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1A: Neonatal resuscitation
#1 The hemodynamic benefits of brief 100% oxygen use during preterm resuscitation with an intact umbilical cord using asphyxiated and non-asphyxiated surfactant deficient ovine model
P Chandrasekharan1*
S Gugino1
J Helman1
N Bradley1
L Nielsen1
M Bawa1
A Mari1
A Prasath1
C Blanco1
M Rawat1
S Lakshminrusimha2
1State University of New York at Buffalo, Buffalo, NY
2UC Davis, Davis, CA
Purpose of Study
The use of 100% supplemental O2 is not recommended in the resuscitation of preterm neonates due to the risk of systemic oxygen toxicity. A recent meta-analysis suggests that more than 50% of preterm infants are born with a heart rate < 100 bpm. Not achieving an HR of ≥100bpm and saturation (SpO2) of ≥80% by 5 min places a preterm infant at a higher risk of morbidity/mortality. Ventilation with an intact cord improves hemodynamic transition in a preterm neonate. In an asphyxiated preterm neonate, the use of 100% O2 with an intact cord could improve alveolar oxygenation with less systemic toxicity due to buffering by umbilical venous return. Our objectives are to study the effect of initiating positive pressure ventilation (PPV) with 100% O2 with and without an intact umbilical cord in asphyxiated and non-asphyxiated preterm lambs.
Methods Used
Preterm lambs (125-127d gestation) were randomized to 4 groups a) AXDCC – asphyxiated (to HR < 100 bpm) and ventilated with an intact cord, b) AXECC – asphyxiated, early cord clamping and PPV, c) NoAXDCC – non-asphyxiated delayed cord clamping, d) NoAXECC – non-asphyxiated, early cord clamping. The cord clamping is delayed in all DCC groups for 5 min. The primary outcome is the incidence of HR of ≥ 100 bpm and SpO2 of ≥80% by 5 min. The secondary outcomes were measures of gas exchange, hemodynamics, and oxidative stress (oxidized to reduced glutathione ratio in the blood). In all the groups PPV was initiated with 100% O2 for 2 min and titrated proportional to the difference in observed and targeted SpO2 every min.
Summary of Results
Asphyxia led to lower PaO2, SpO2, HR and higher PaCO2 at the initiation of PPV. The primary outcome was achieved in 4/7
(AXECC), 6/7 (AXDCC), 5/6 (NoAXECC) & 7/7 (NoAXDCC). By 5 min, the preductal SpO2 was higher in DCC groups despite lower O2 exposure compared to other groups (figure 1B & figure 1C). Intact cord resuscitation led to lower PaCO2 in asphyxiated lambs along with higher peak pulmonary and carotid flow (figure 2). At 5 min, there was no significant difference in oxidized to reduced glutathione ratio between groups (figure 2D).
Groups – AX – asphyxiated (HR < 100 bpm), NoAX – non-asphyxiated, ECC – early cord clamping, DCC – delayed cord clamping. A * p<0.01 by ANOVA – significantly higher than other groups. B * p<0.01 significantly higher than the rest of the groups. C p<0.01– significantly lower O2 requirement than other groups. D *p<0.01 - highest PaO2 compared to rest of the groups
A) p<0.01 lowest PaCO2 levels compared to other groups. B) * p<0.01 – higher PBF than other groups. C) *p<0.01 – higher CBF compared to rest. *denotes significance by ANOVA.
Conclusions
In both asphyxiated and non-asphyxiated preterm lambs, initial use of 100% with an intact cord improved hemodynamic and respiratory transition by increasing peak pulmonary blood flow, with lower oxygen exposure, improved ventilation without any change in oxidative stress markers.
#2 Neonatal resuscitation with laryngeal mask airway (LMA) versus neonatal facemask among unskilled providers
N Sivakumar1*
S Newman-Lindsay2
D Sankaran2
S Lakshminrusimha2
L Donohue2
1UC Davis School of Medicine, Sacramento, CA
2UC Davis Children’s Hospital, Sacramento, CA
Purpose of Study
Effective positive pressure ventilation (PPV) is the single most important component of neonatal resuscitation. The Neonatal Resuscitation Program (NRP) recommends initiating PPV using facemask, and if ineffective despite corrective steps, switch to endotracheal intubation (ETT) or LMA. Pejovic et al (NEJM, 2020) have demonstrated that LMA is safe in the hands of midwives but not superior to facemask in reducing neonatal death or moderate/severe HIE. Time to effective ventilation during simulation by unskilled providers may provide evidence as to whether LMA is superior to facemask as first line ventilation interface in neonatal resuscitation. This study aims to compare time to effective ventilation and assess perceived confidence of pre-clinical medical students (MS) in performing adequate ventilation on a neonatal manikin with LMA and facemask.
Methods Used
Thirty-two pre-clinical MS were recruited and randomized to learning and performing ventilation with either the LMA (Teleflex size 1) or facemask with T-piece resuscitator on a neonatal manikin (Gaumard). Time to effective ventilation was defined as time to ten consecutive breaths reaching preset goal tidal volume in the Gaumard software. Tidal volume was measured by breath-by-breath analysis to assess adequacy and consistency of PPV in 10 consecutive breaths. Perceived confidence was measured by pre- and post-surveys administered prior to and after learning and demonstrating the intervention. The surveys administered utilized a 5-point Likert scale, where 1= ‘not at all confident’ and 5= ‘very confident’.
Summary of Results
Sixteen MS each were randomized to the LMA facemask groups respectively. Time to achieve effective ventilation was shorter with facemask compared to LMA amongst pre-clinical MS (81 seconds vs 171 seconds, p<0.01). Figure 1 presents a screenshot of ten consecutive breaths that met the target tidal volume. Pre-clinical MS reported higher perceived confidence post-intervention with use of facemask when compared to use of LMA (4.6 vs 4, p=0.03). No difference was noted in perceived confidence in other parameters.
Time to effective ventilation and perceived confidence of pre-clinical medical students in performing adequate ventilation with a neonatal face mask and laryngeal mask airway (LMA)
Screenshot of Gaumard software depicting consecutive breaths that meet target tidal volumes. Green bar indicates target tidal volume range, and brackets show ten consecutive breaths of adequate tidal volume
Conclusions
Pre-clinical MS demonstrated a shorter time to effective ventilation and reported higher confidence after learning and demonstrating PPV using the facemask when compared to LMA. Further research is needed to determine if optimization of learning interventions or device improvements will influence unskilled providers’ confidence or performance with an LMA versus facemask.
#3 Randomized trial of 21%, 50% versus 100% inspired oxygen during chest compressions in neonatal resuscitation: goldilocks principle?
C Blanco1*
M Bawa1
A Prasath1
A Mari1
S Gugino1
J Helman1
N Bradley1
J Nair1
S Lakshminrusimha2
P Chandrasekharan1
M Rawat1
1University at Buffalo, Buffalo, NY
2University of California Davis Children’s Hospital, Sacramento, CA
Purpose of Study
Birth asphyxia is associated with high mortality and neurological morbidity due to anoxic brain injury that typically follows a severe ischemia and reperfusion insult. Neonatal Resuscitation Program (NRP) guidelines currently recommend ventilation with 100% oxygen (O2) during chest compressions (CC). Insufficient oxygen delivery can worsen cerebral anoxia while excessive oxygen delivery aggravates oxygen free radical formation and can reduce cerebral blood flow. Optimizing cerebral blood flow and oxygen delivery to the brain during CC may potentially improve outcomes.
The objective of this study is to evaluate whether an intermediate level of inspired O2 (~50%) during CC will increase the incidence and hasten return of spontaneous circulation (ROSC), and result in optimal oxygen delivery to the brain in an ovine model of perinatal asphyxia.
Methods Used
This blinded randomized study used 12 near-term fetal lambs that were randomized into 3 groups prior to asphyxiation: 21%, 50% and 100%. Two minutes after cardiac arrest, positive pressure ventilation (PPV) with 21% O2 was initiated as per NRP guidelines. CC were then carried out 30 seconds after the onset of PPV, and inspired O2 was either continued at 21% (n=4) or increased to either 50% (n=4) or 100% (n=4). The lambs were continuously monitored for evidence of ROSC and were ventilated for 20 minutes after ROSC. Oxygenation, ventilation and hemodynamics were monitored. The ventilator parameters and FiO2 were titrated to achieve normocapnia on the blood gases and to meet the NRP preductal O2 saturation targets.
Summary of Results
All lambs in the 50% group achieved ROSC, while 75% and 50% of the lambs achieved ROSC in the 21% and 100% group, respectively (table 1). The lambs in the 21% group had the lowest pulmonary artery blood flow while the 100% oxygen group had the highest total cumulative O2 exposure at ROSC. The lambs in the 50% group had the lowest total cumulative O2 exposure after ROSC. The oxygen delivery to the brain throughout the post-ROSC period was significantly higher in the 50% group (p< 0.05) compared to the 21% and 100% groups, as was the mean carotid artery blood flow (figure 1).
Return of spontaneous circulation and hemodynamic parameters
Oxygenation and hemodynamic parameters after achieving return of spontaneous circulation in lambs ventilated with 21%, 50% and 100% inspired oxygen during chest compressions.
Changes in total cumulative oxygen exposure (A), oxygen delivery to the brain (B), mean pulmonary artery blood flow (C) and mean carotid artery blood flow (D) over 20 minutes post-return of spontaneous circulation. * Significantly different from the 21% group. ‡ Significantly different from the 100% group.
Conclusions
Use of 50% inspired oxygen during CC for cardiac arrest yielded the highest ROSC rates, higher mean carotid artery blood flow and oxygen delivery to the brain, yet lower total cumulative oxygen exposure after ROSC, compared to 21% and 100% oxygen.
#4 Initial use of 100% but not 60% or 30% oxygen achieved a target heart rate of 100 and preductal saturations of 80% faster in a bradycardic preterm model
M Bawa1*
S Gugino1
J Helman1
N Bradley1
L Nielsen1
A Mari1
A Prasath1
C Blanco1
S Mani2
P Rivera Hernandez1
A Gupta1
J Flores1
J Nair1
M Rawat1
S Lakshminrusimha3
P Chandrasekharan1
1University at Buffalo, Buffalo, NY
2ProMedica Toledo Children’s Hospital, Toledo, OH
3UC Davis Childrens Hospital, Sacramento, CA
Purpose of Study
In bradycardic preterm neonates who do not require chest compressions(CC), failure to achieve a heart rate (HR) of ≥100 bpm & peripheral oxygen saturation (SpO2) of ≥ 80% by 5 min increased the risk of mortality 18 times. It remains unknown if initiating resuscitation with 30% oxygen (O2) in an asphyxiated preterm neonate with surfactant deficiency, based on current recommendations, is sufficient to achieve this target by 5 min.
We wanted to evaluate the effect of initiating PPV with 30% O2 (OX30), 60% O2 (OX60) & 100% O2 (OX100) on a) primary outcome – achieving a combined HR of ≥100 bpm & peripheral SpO2 of ≥ 80% by 5 min b) secondary outcomes – Time to achieve primary outcome, effect on gas exchange, pulmonary/systemic hemodynamics, oxygen delivery to brain and oxidative injury.
Methods Used
Preterm lambs (126-128d, ≡ < 28-week human neonate) were asphyxiated to achieve HR < 100bpm. Once target HR was achieved, positive pressure ventilation (PPV) was initiated with OX100, OX60, and OX30 for 2 min and titrated based on recommended preductal SpO2. The titration of O2 was proportional to the difference between observed SpO2 and target SpO2 and was performed every min. Data on gas exchange and hemodynamics was collected continuously for the first ten min.
Summary of Results
Characteristics of the lambs are shown in fig 1a. Four in OX100 & two in OX60 achieved primary outcome by 5 min, while none achieved in OX30. Time taken to achieve the primary outcome in OX100 (6±2 min) was significantly lower (p-0.042), compared to OX30 (10±3 min). With OX60 it took 8±3 min to achieve the target. The preductal SpO2 was significantly higher with OX100 compared to OX30 (figure 1). Oxygen concentration used during the first 10 min of PPV with OX100 was significantly lower than OX30 and higher than OX60 (figure 1). The arterial oxygenation (PaO2) and the peak pulmonary blood flow (PBF) were lowest in the OX30 group (figure 1 & 2). There was no difference in the left carotid blood flow between the groups (figure 2B). O2 delivery to the brain (figure 3A) and the oxidized to reduced glutathione ratio (figure 3B) was not different between the groups.
OX100 – initiate resuscitation with 100% oxygen, OX60 – initiate resuscitation with 60% oxygen, OX30 – initiate resuscitation with 30% oxygen. A) Shows the characteristics of preterm lambs used in the study. B) Shows the preductal saturations in different groups. The dotted line represents the 5 min and 80% SpO2 mark. C) Oxygen concentration in percentage. D) Arterial oxygenation (PaO2) in mmHg. The x-axis on all line graphs represent the events (from asphyxia to 10 min of ventilation). All continuous data in the line graphs are represented as average and standard deviation. *denotes significance by ANOVA as shown.
Conclusions
In asphyxiated preterm lambs, an initial O2 of 100%, decreased the duration to achieve HR of ≥ 100 bpm & SpO2 ≥ 80% compared to 60% & 30%. The arterial oxygenation and peak pulmonary blood flow were lowest with OX30. There was no difference in oxidative stress between the groups. Although 100% O2 reduced the time to achieve the primary outcome, more translational studies are required to understand the pulmonary and cerebral oxidative stress secondary to higher oxygen exposure in the background of asphyxia.
#5 Randomized trial of preductal target SpO2 of 90–94% vs. 95–99% in neonatal ovine hypoxic respiratory failure
HM Joudi*
P Vali
A Lesneski
M Hardie
V Hammitt
K Shulman
R Valdez
E Giusto
D Sankaran
S Lakshminrusimha
University of California, Davis, Davis, CA
Purpose of Study
There is considerable variation in clinical oxygen saturation (SpO2 ) targets in the management of term infants with meconium aspiration syndrome (MAS) and pulmonary hypertension of the newborn (PPHN). The optimal SpO2 in term neonates with severe lung disease and PPHN is not known. We hypothesize that a lower SpO2 target range (90-94%) will not compromise pulmonary blood flow and oxygen delivery to the brain and reduce the risk of oxidative stress compared to a higher SpO2 target range (95-99%).
Methods Used
Fifty-six near-term (~140d gestation; term is 145d) fetal lambs were partially exteriorized and instrumented to measure left pulmonary blood flow (Qp) and carotid blood flow (Qca). Lambs were intubated and meconium was instilled into the trachea. Umbilical cord was occluded to induce asphyxia and gasping. Lambs were randomized to 1) low preductal SpO2 target range (90-94%) or 2) high SpO2 target range (95-99%). Lambs were delivered and ventilated for 6h. Hemodynamic data was continuously measured. Serial blood samples were collected for blood gases analysis. Brain, lung and plasma were analyzed for markers of oxidative stress.
Summary of Results
There was no difference in baseline characteristics between groups. Lambs randomized to low SpO2 had significantly lower PaO2compared to the high SpO2 group (figure 1). There was no difference in pulmonary and carotid blood flow between groups. Xanthine/hypoxanthine and methionine sulfoxide/methionine ratios were similar in the lungs, plasma and brain. Plasma lactic acid concentrations were higher in the low SpO2 group but there was no difference in brain or lung lactic acid concentrations (table 1).
Oxidative stress markers based on SpO2 categories
Conclusions
In a lamb model of MAS and PPHN, targeting lower SpO2 at 90-94% had no effect on pulmonary and carotid blood flow or oxidative stress markers. Clinical studies comparing these target SpO2 ranges are warranted.
#6 Side vs over-the-head chest compressions in neonates: does rescuer height alter efficacy?
G Gomez*
J Nair
University at Buffalo, Oishei Children’s Hospital, Buffalo, NY
Purpose of Study
Current recommendations for neonatal chest compressions (CC) recommend the 2-thumb technique which may be performed from the side or from above the head (Wykoff, 2015) to facilitate easy placement of umbilical catheters. CC from ‘over the head’ (Head) appears as effective as the lateral position (Side) in a small manikin study (Cheung, 2020). Ergonomic factors such as rescuer and bed height may affect efficacy of neonatal CC. We hypothesized that in a simulated resuscitation, rescuer height would influence efficacy of CC, both at the Head and Side positions.
Methods Used
NRP certified providers were recruited to perform CC on a manikin (Baby Hal, Gaumard® Scientific), from the head and side of the warmer, kept at a fixed height (98cm). Participant height was categorized into ‘below-average’ (BA) vs. ‘above-average’(AA) height groups using cut-off points representing average US male and female heights (175.4 cm and 161.5 cm, CDC/National Center for Health Statistics data, 2017). Each provider performed 2min of CC at a 3:1 C:V ratio from Head or Side. After a 20-min recovery period, providers crossed over to the other group. Outcomes measured were target CD (at least 1/3rd of AP diameter) achievement, on target CC (%) – the percentage of adequate CC and rate of CC. Providers’ performance was evaluated using OMNI® 2 control tablet (Gaumard® Scientific), featuring CPR feedback. A 5-point Likert scale assessed perception of fatigue and difficulty after CC in each position. Graphpad Prism software was used for statistical analysis.
Summary of Results
27 participants were recruited. Complete CC feedback data was available for 25 participants. Overall there was difference between head vs side on target CC%, target CD achievement or CC rate. However, AA group had a higher on target CC% (figure 1a) and target CD achievement (figure 1b) from the side vs head. No significant differences were noted in BA group. More BA rescuers expressed moderate to severe fatigue than AA, in both positions. Both AA and BA reported more fatigue in the side compared to head (AA: 15.4% vs 38.5%, BA: 33.4% vs 83.4%) (figure 2).
Conclusions
Rescuer height can impact CC efficacy, with AA demonstrating increased on target CC percentage as well as target CD achievement. Height also influenced fatigue perception with BA expressing more fatigue than AA. However CC in side position increased fatigue perception significantly after 2 min in both height groups. We conclude that while AA rescuers had a slightly increased efficacy of CC from side, increased fatigue perception in this position may limit these benefits in a longer resuscitation. Awareness of height differences could determine specific roles for resuscitation team members.
#7 The impact of heart rate availability on workload and performance during simulated newborn resuscitations
Y Lee1*
D Elachi2
J Bush4
R Miller2
C Thomas3
C Chang2
1Department of Pediatrics, New York Presbyterian Weill Cornell Medicine, New York, NY, United States
2Division of Newborn Medicine, Weill Cornell Medicine, New York, NY, United States
3Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, United States
4Division of Neonatology, Children’s National Hospital, George Washington University, Washington, DC, United States
Purpose of Study
The 2020 Neonatal Resuscitation Program (NRP) guidelines recommend the use of continuous HR monitoring with the initiation of positive pressure ventilation (PPV). The impact of continuous HR availability on cognitive demand and clinical performance during the early phases of neonatal resuscitation is unclear. The NASA-Task Load Index (TLX) is a widely used, validated tool that assesses workload and may be used to evaluate this impact. We aimed to assess the impact of intermittent vs continuous HR availability on adherence to the NRP algorithm and subjective workload in simulated scenarios of neonatal resuscitation.
Methods Used
NRP trained nurses were recruited to participate individually in a simulated delivery room scenario and randomized to receive a continuous HR starting at 60 seconds (s) or 90s. A third group was later recruited and provided an intermittent HR only when/if verbally requested. Participants were presented with an apneic baby whose HR was <100 beats/minute (bpm) and gradually decreased until the ventilation corrective steps were performed and effective ventilation was achieved. Time to initiation of PPV, time to start of ventilation corrective steps and number of corrective steps performed were recorded utilizing the NeoNatalie Live manikin (Laerdal Medical). The NASA-TLX was administered post-simulation to assess workload. The Kruskal-Wallis test was used to compare variables among the 3 groups, and the Wilcoxon-rank sum test was utilized for pairwise comparisons.
Summary of Results
Participants of similar experience were assigned to receive a continuous HR at 60 s (n=12) or 90s (n=12), or an intermittent HR when requested (n=9). There were no significant differences in time to initiate PPV or the ventilation corrective steps between the three groups. There was a trend toward more ventilation corrective steps completed when a continuous HR was available (at either 60s or 90s) compared to when it was intermittently provided (4 vs 3, p=0.091) (table 1). The average workload was similar between groups, with a trend towards increased frustration when HR was available earlier (most prominently seen when comparing the 60s vs intermittent HR groups) (45 vs 20, p=0.06) (figure 1). There was also a trend towards increased mental demand the earlier a continuous HR was available (seen with HR at 60s vs 90s; 62 vs 50, p=0.08).
NASA-TLX survey response
Participant performance
Conclusions
In this pilot study, availability of a continuous HR early on in delivery room resuscitation impacted the cognitive load and performance of single resuscitators. Further studies should continue to define these effects. NRP training should include specific preparation and practice for utilizing continuous HR availability in neonatal resuscitation.
#8 Initiating resuscitation with chest compressions and ventilation in a neonatal cardiac arrest model significantly reduced the time to establish return of spontaneous circulation
A Prasath*
S Gugino
J Helman
N Bradley
L Nielsen
M Bawa
C Blanco
A Mari
J Flores
B Mathew
M Rawat
P Chandrasekharan
Jacobs school of Medicine, University at Buffalo, Buffalo, NY
Purpose of Study
When neonates are born without a heart rate, they are at higher risk of mortality and morbidity despite effective resuscitation. Current practice to provide effective positive pressure ventilation (PPV) before starting chest compressions (CC) is important when the heart rate (HR) is < 60 bpm due to birth asphyxia. But when the HR is ‘0’, starting CC after 30s of effective PPV through a secured endotracheal tube (ETT) or laryngeal mask airway (LMA), which could take at least 2 min may be detrimental. With recent recommendations to continue resuscitation for 20 min, initiating early CC with PPV could reduce the time to achieve the return of spontaneous circulation (ROSC). To evaluate the effect of immediate CC and face mask PPV on I) timing and rates of ROSC, II) gas exchange and hemodynamics, compared to delayed initiation of CC (after 2 min) in an ovine neonatal model of asphyxia.
Methods Used
Near-term lambs (139-140d) after instrumentation & post cord occlusion induced cardiac arrest (2 min after HR – 0 bpm) were randomized to i) controls – initiate resuscitation with facemask (FM) PPV (21%O2 for 30s, then 100%O2), intubate at 2 min, followed by CC&PPV in the ratio of 3:1 until ROSC or up to 20 min, ii) Study – Start CC& FacemaskPPV (21%O2 for 30s, then FM100%O2) in the ratio of 3:1 and intubate at 2 min if ROSC is not achieved or up to 20 min. IV epinephrine was administered after 5 min and subsequently every 3 min for a total of 4 doses If lambs achieve ROSC, they are ventilated for 1 hour and euthanized. Time and rates of ROSC, blood gas, continuous peak carotid (CBF) & pulmonary blood flows (PBF) were recorded.
Summary of Results
Eleven lambs were randomized to controls (N-6) and study (N-5) (figure 1a). Compared to controls (figure 1a & 1b), the time to achieve ROSC was significantly shorter in the study group (figure 1a & 1c). The pH and arterial carbon dioxide levels (figure 2 a & b) were non-significantly lower in the study group signifying gas exchange from the beginning of resuscitation. The arterial oxygenation was not different (figure 2c). Peak CBF was significantly higher during resuscitation in the study compared to controls (figure 3a), while the PBF was not different (figure 3b).
Conclusions
Initiation of resuscitation with CC and FM PPV reduced the time to achieve ROSC while preparing and placing an ETT at 2 min in a complete cardiac arrest model. Clinical studies are needed to validate our findings in terms of mortality and neurodevelopmental outcomes.
1B: Emergency medicine
#9 A novel method for the assessment of capillary stasis (no-reflow) after cardiac arrest
V Gunasekaran1*
AL Vazquez2
B Nelson2
A Toader2
P Wang2
J Stezoski2
M Manole1
1University of Pittsburgh Medical Center, Pittsburgh, PA
2University of Pittsburgh, Pittsburgh, PA
Purpose of Study
Brain injury is the major cause of morbidity after resuscitation from pediatric cardiac arrest (CA). Post-CA, capillary stasis produces cortical hypoperfusion and neuronal injury. Current methods to evaluate capillary stasis are subjective, time-consuming, and can evaluate only a few individual vessels serially post-CA. The objective of our study is to characterize capillary stasis in mice post-CA and to develop a comprehensive method of volumetric assessment of capillary stasis.
Methods Used
Mice (n=4) underwent tracheal intubation, mechanical ventilation, arterial and venous femoral catheterization. A 4 mm cranial window was placed over the parietal cortex. We induced CA for 5 minutes, and then resuscitated the mice with chest compressions and epinephrine (iv). We imaged the motor cortex pre-CA and serially post-CA for 1 hour using in vivo multiphoton microscopy (figure 1).
We assessed capillary stasis using two methods: a qualitative assessment of capillary red blood cell (RBC) flow and a quantitative assessment of capillary RBC flux variance. The capillary flow was visually qualified as normal flow, slow flow, and no flow. Capillary flux variance images were processed and analyzed in MATLAB. We generated colorimetric flow maps and calculated the coefficient of variance to assess RBC signal fluctuations in capillaries. The RBC flux variance for the capillaries was grouped into 3 categories: high variance (normal flow, red), medium variance (slow flow, aqua), low variance (no flow, blue) (figure 2). We compared RBC flow with RBC flux variance using linear regression.
Summary of Results
We assessed flow in 574 capillaries pre-CA and 419 capillaries post-CA. At baseline, we observed normal flow in most capillaries (94±3% and 90±6%, flow and flux variance method, respectively). Slow and no flow were rarely observed at baseline (6±2% and 10±3%, flow and flux variance method, respectively). Post-CA, slow and no flow increased to 23.1±7% for the capillary flow method and 21±7% for the capillary flux variance method (figure 2), with no difference between methods (p=0.9). There was a strong association between the capillary flow qualitative assessment and the capillary flux variance quantitative assessment, correlation coefficient 0.99 [r2=0.99, 95% CI: 0.92-0.99, p<0.0001].
Experimental setup – A representative mouse that undergoes imaging. Arterial and venous catheters and endotracheal tubes are placed. The mouse is positioned under the multiphoton microscope for imaging
Abstarct #9 Figure 2 Capillary stasis, quantified as the capillary red blood cell (RBC) flux variance at baseline and post-CA in a representative mouse. Left Panels: Vascular Label images. The micro-vasculature (red) was imaged for 2 min and RBC flux was recorded at baseline (pre-CA) and at 30 min post-CA in a large area of the capillary bed. Texas Red dextran was administered iv (70kDa, 3%). Right Panels: Flux Variance Index (coefficient of variance) was used to quantify signal fluctuations in capillary flow. The intensity of the capillary signals fluctuates as RBCs pass through them. Hence, normal capillary perfusion is represented by dark orange or red color, and slow or no perfusion is represented by yellow, green, or light blue color. Post-CA, capillary flow is reduced due to intermittent stalling or arrested RBC flow in many capillaries
Conclusions
Using in vivo multiphoton microscopy, we were able to identify capillary stasis, previously described ex-vivo as the ‘no-reflow’ phenomenon, in mice post-CA. The quantitative method of capillary flux variance correlates well with the qualitative analysis of capillary stasis and is a feasible, efficient, and objective method to evaluate capillary stasis. This method can be used to assess the effect of neuroprotective therapies on capillary blood flow post-CA.
#10 Pediatric age-adjusted shock index as a clinical predictor of hospital admission in children presenting to the emergency department
M Adhikary1,2*
EJ Silver2
DM Fein1,2
1Children’s Hospital at Montefiore, Bronx, NY
2Albert Einstein College of Medicine, Bronx, NY
Purpose of Study
Shock index, defined as the ratio of heart rate to systolic blood pressure, has been shown to be a valuable prognostic tool when assessing shock severity and anticipating patient morbidity and mortality in trauma patients. Pediatric age-adjusted shock index (SIPA) has been validated in multiple studies to identify and predict mortality in children with blunt trauma. Recent research has shown that triage shock index calculated from the emergency department shows promise as a clinical metric in the adult population as a predictor of hospital admission and inpatient mortality. Literature regarding utility of age-adjusted shock index in the general pediatric population is lacking. We seek to determine whether triage pediatric age-adjusted shock index can be used to predict disposition from the pediatric emergency department (PED).
Methods Used
This was a retrospective chart review of all patients aged 4-20 years who were either admitted or discharged from a quaternary care PED in 2019. Patients with incomplete charts, and triage vital signs missing heart rate or blood pressure were excluded. Initial shock index values were characterized as high or low as established in prior studies based on four separate age categories with different cutoff values. Association between high pediatric age-adjusted shock index and inpatient admission was evaluated overall and within age groups. Relationship of high pediatric age-adjusted shock index and clinical characteristics were also examined. Chi-square analysis was used for all comparisons.
Summary of Results
There were 29476 eligible PED patient encounters occurring in the study period, with 2979 (10.1%) resulting in hospital admission and 6422 (21.8%) with a high triage pediatric age-adjusted shock index. High triage pediatric age-adjusted shock index was associated with younger age (< 12-year-old), male gender, and emergency severity index (ESI) level 1-2 (table 1). High triage pediatric age-adjusted shock index was associated with significantly greater odds of hospital admission overall and within each age group (table 2). Among admissions, high triage pediatric age-adjusted shock index was also associated with higher odds of pediatric intensive care unit admission (OR 3.2; 95% CI 2.5-4.3) and rapid response on the in-patient unit (OR 3.9; 95% CI 1.8-8.8).
Relationship of high SIPA to clinical characteristics
Association between SIPA and admission
Conclusions
Elevated triage pediatric age-adjusted shock index is associated with higher odds of admission. Elevated triage pediatric age-adjusted shock index shows promise as a clinical metric in the general pediatric ED population and should be further studied.
#11 Utility of emergent magnetic resonance imaging in children with persistent traumatic neck pain without radiographic injury
WC Sokoloff*
V Mirisis
J Rocker
Cohen Children’s Medical Center, New Hyde Park, NY
Purpose of Study
Pediatric patients with traumatic neck pain often require radiographic imaging to evaluate for rare, but debilitating cervical spine (C-spine) injuries. However, many alert patients without injuries seen on CT continue to have persistent neck pain and undergo emergent MRI to evaluate ligamentous or non-visualized bony injuries. The primary purpose of this study is to describe the utility and resource burden of cervical spine MRI in the emergent setting for alert children with persistent midline neck pain, despite a normal cervical spine CT. A secondary aim is to describe the subsequent management of those injuries identified by MRI.
Methods Used
A retrospective review was performed of children age 8-18 years-old presenting over a 6-year period to a Level 1 pediatric trauma center, who underwent both CT and MRI imaging for suspected C-spine injury. Patients with traumatic C-spine injuries on CT were excluded, as well as those with: predisposing medical conditions, those endorsing neurological symptoms, and those who were intoxicated, obtunded, disoriented, or unable to reliably participate in a physical exam. Documentation from the initial outpatient neurosurgical follow-up was also reviewed for each patient with a clinically significant injury.
Summary of Results
A total of 154 patients met inclusion criteria, of whom 89% had no clinically significant injury identified on MRI. Of those with a clinically significant injury found on MRI (n=17), none required surgical intervention and all were managed with a hard cervical collar and outpatient follow-up. No patient was admitted for management of their C-spine injury. The mean time from a normal cervical spine CT result being available to an order for admission or discharge was 542 minutes (73-1734 minutes, SD: 268 minutes) with no statistical difference between those with and without a significant injury (p=1.0). The majority of clinically significant injuries occurred secondary to motor vehicle collisions (6/17) or falls from heights (5/17) and 47.1% (8/17) of the mechanisms did not meet criteria for a trauma team activation or consult.
Patients with clinically significant injuries
Conclusions
The vast majority of children who are alert and endorse persistent traumatic C-spine tenderness despite a normal cervical spine CT, do not have a clinically significant injury identified by MRI. Those who do, appear to require minimal management with a hard cervical collar as no C-spine injury in this cohort required hospitalization or surgical intervention. ED management with a hard collar and outpatient reassessment may be a safe, resource-conscious and reasonable option for this population.
#12 Characteristics of patients presenting with chest pain to the pediatric emergency department in an inner-city community hospital
RO Akiyode1*
C Onwudiwe1
E Augustine2
G Augustine1
1BronxCare Health system, New York, NY
2Northern Highlands Regional High School, Allendale, NJ
Purpose of Study
Chest pain is a common complaint in children and adolescents seeking care in the emergency department (ED) and is a common reason for referral to the pediatric cardiologist. Despite the benign etiology of most pediatric chest pain, this symptom often leads to multiple diagnostic testing in an attempt to exclude life-threatening causes of chest pain and to allay the anxiety of patients, their families, and providers.
We, therefore, set out to describe the etiology and demographic characteristics of pediatric patients presenting with chest pain to the ED of an inner-city hospital.
Methods Used
A retrospective chart review of patients presenting to our pediatric ED with a primary complaint of chest pain between January 2018 to December 2020 was performed. Demographic and clinical data, laboratory tests, electrocardiography(EKG), final diagnosis, and disposition were sorted for assessment. Multivariable adjusted logistic regression models were used to determine predictors of having workup done.
Summary of Results
We reviewed 208 medical records. Subjects’ ages ranged from 3 to 21 years with a mean (SD) of 16 (4.8) years, with females comprising 52% (n=108). Twenty-one (10%) subjects analyzed reported substance use and the most common substance used was marijuana (90%).
At presentation, 206 (99%) had no respiratory distress. EKG was performed in 193 (92.8%) subjects, with only 2 being reported as abnormal (premature atrial contractions and sinus tachycardia). Chest x-ray was done in 195 (94%) subjects, of which 189 (97%) were reported as normal. Abnormalities found include atelectasis, pulmonary infiltrates/pneumonia and cardiomegaly. Serum troponin was measured in 44 subjects (21.2%), all of which were within normal limits.
Subjects older than 14 years were more likely to have EKG [OR = 6.71 (95% CI: 1.49-30.2) and serum troponin levels [OR=3.23 (95% CI: 1.02-10.16) done, unlike chest x-rays which appeared to have no relationship with age.
Chest pain improved in 203 (97.6%) subjects and they were discharged home from the ED. Four subjects were admitted for pneumonia and one for tuberculosis. The final diagnoses at discharge are represented in table 1.
Final diagnoses of patients presenting with chest pain
Conclusions
Extensive workup of patients presenting in the ED with chest pain remains common despite prior studies showing most cases are idiopathic. Our findings show that even among our underserved population with significant substance use in adolescents, the yield of investigations such as EKGs, chest x-rays, and serum troponin remains very low. Our study also shows that most cases of chest pain are idiopathic and benign. Therefore, the need for diagnostic testing should only be individualized to patients with strong clinical suspicion of a serious underlying etiology.
#13 High-risk markers and infection rates in febrile infants aged 29–60 days presenting to the emergency department during the COVID-19 pandemic compared with previous years
K Schissler*
S Stewart
T Phamduy
M Brimacombe
I Waynik
E Hoppa
Connecticut Children’s, Hartford, CT
Purpose of Study
During the COVID-19 pandemic there was a change in the utilization of the emergency department (ED) for many reasons, including a decrease in transmission of communicable childhood infections and avoidance of situations that could result in exposure. Caregivers are educated on the importance of bringing neonates to the ED if febrile, however for infants aged 29-60 days, there may not be the same urgency especially during a pandemic. In this population there may have been a delay in ED presentation, leading to patients presenting with increased clinical and laboratory markers associated with a higher risk of serious bacterial infection. The objective was to evaluate how the COVID-19 pandemic affected the clinical and laboratory high-risk markers as well as infection rate in infants aged 29-60 days presenting to the ED with fever.
Methods Used
Retrospective chart review of infants evaluated in the ED from March 11-December 31, 2017-2020 at a free-standing children’s hospital. Patients were identified using a dataset derived from the hospital’s clinical pathway for febrile infants aged 29-60 days. Inclusion, exclusion and high-risk criteria are included in table 1. Data was reviewed by quality data specialists and then reviewed by a physician to ensure proper categorization and infectious diagnosis. Patient demographics, categorization as high-risk, and type of infection were collected (table 2). Data was analyzed using chi-square and Fisher exact tests. A p-value < 0.05 was considered significant.
Summary of Results
251 patients over the 4 years met inclusion criteria. The ED visits for this patient population decreased in 2020 compared to prior years. However, the proportion of visits for this patient population to all ED visits remained similar across all 4 years (p = 0.66). There was no significant difference in patient demographics as seen in Table 2. Year 2020 had the highest rate of urinary tract infection (26%) and bacteremia (11%). The rate of the high-risk criteria of ill-appearance, white blood cell count (WBC), and urinalysis (UA) were highest in 2020. Comparison of the cumulative data from 2017 through 2019 to 2020 data showed a significant difference in the proportion of patients presenting with high-risk WBC (p = 0.028) and UA (p = 0.034), but no significant difference in high-risk ill-appearance (p = 0.208).
Patient demographics
Conclusions
In 2020 there was a higher rate of urinary tract infections and bacteremia as well as a significantly greater proportion of patients presenting with high-risk WBC and UA in this patient population. This suggests that during the COVID-19 pandemic, a lower rate of community viral infection due to pandemic mitigation strategies and possibly later presentation of febrile infants to the ED led to these results.
#14 Universal suicide screening in a pediatric emergency department is feasible: even during a pandemic
K Volz1*
D Chenard1
S Sacco2
K Borrup1,2
S Rogers1,2
1Connecticut Children’s, Hartford, CT
2University of Connecticut, Storrs, CT
Purpose of Study
Suicide is the 2nd leading cause of death for youth age 10-24 in the United States. Suicide rates in youth have been climbing over the last decade, and focus on prevention should be a priority. Implementation of universal suicide risk screening in pediatric emergency departments (PED) may provide early detection and intervention for at risk youth.
Methods Used
This retrospective chart review study examined youth ≥10 years old presenting to the PED. Records from 09/2019-08/2021 were searched to determine suicide risk using a validated suicide screening tool by nursing staff. Data were described with appropriate summary statistics (e.g., proportions) and compared by relevant covariates (e.g., gender) with appropriate test statistics including chi square and z-test analysis.
Summary of Results
Over a 2-year period, 31,344 children between the ages of 10-21 presented to the PED. Of those patients, 26,992 (86%) were screened for risk of suicide, which did not show a significant change during the pandemic (table 1; Z=-0.52, p=0.61); minimum compliance rate was 83.8% and maximum was 89.4%. Of those screened, 5039 (19%) of patients screened positive for suicide risk; 1738 (7%) had a medical chief complaint which was significantly lower compared to 3077 (11%) that had a behavioral health chief complaint (χ [1, n=22889] = 6273.2, p< 0.001). Females had a significant association with positive screens (χ [1, n=26992] = 9.3, p=0.002). Non-Hispanic or Latino patients also had a significant association with positive screens χ [1, n=26992] = 79.9, p< 0.001.
Staff compliance from 9/2019 to 8/2021
Conclusions
Universal suicide risk screening for youth is feasible in a PED. This was demonstrated by higher-than-expected rates of staff compliance with completing universal suicide screening. There has been no significant change in screening compliance rates during the COVID pandemic. Suicidal thoughts and/or behaviors were prevalent in a significant proportion of children presenting to the PED with both medical and behavioral health chief complaints. Identifying all at risk youth and providing them with appropriate resources may improve patient safety.
#15 Neighborhood social vulnerability, emergency department visits, and hospital readmissions in infants with bronchopulmonary dysplasia (BPD)
T Nelin1*
N Yang1
S Lorch1
S DeMauro1
N Bamat1
E Jensen1
K Gibbs1
A Just2
H Burris1
1Children’s Hospital of Philadelphia, Philadelphia, PA
2Icahn School of Medicine at Mount Sinai, New York, NY
Purpose of Study
Preterm infants with BPD are at risk for adverse health outcomes after discharge. Whether neighborhood factors affect healthcare utilization in infants with BPD is unknown. We aimed to quantify the association of the CDC Social Vulnerability Index (SVI) at the census tract level with acute respiratory illness in the first year after NICU discharge in infants with BPD.
Methods Used
We generated a dataset comprising infants with BPD from a local research registry and the Children’s Hospital of Philadelphia electronic health record. Included infants were born <32 weeks gestation (GA) between 2010-2020 and met criteria for BPD at 36 weeks post-menstrual age. We geocoded each patient’s address at hospital discharge to assign a CDC SVI value from 2018. SVI includes 15 social factors (e.g., census tract poverty, education, household structure, demographics, housing & transportation) and ranges from 0-1; higher SVI values indicate more vulnerability. Logistic regression models including census track as a random effect were used to quantify associations of SVI with the primary outcome of acute respiratory illness defined as an ED visit or readmission in the first year after NICU discharge, adjusting for GA, sex, birth year, respiratory support at 36 weeks, race, ethnicity, and insurance. A secondary analysis restricted to metro Philadelphia was performed.
Summary of Results
540 infants met inclusion criteria. Table 1 shows bivariate associations of characteristics and SVI with acute respiratory illness. Per standard deviation increment increase in SVI, infants had higher odds of acute respiratory illness in unadjusted (OR 1.48, 95%CI: 1.22-1.79) and adjusted models for GA, sex, birth year, and respiratory support at 36 weeks (aOR 1.51, 95%CI: 1.24-1.84) (table 2). Further adjustment for patient race, ethnicity, and insurance attenuated the association (aOR 1.18, 95%CI: 0.93-1.49). Results were similar when restricted to metro Philadelphia.
Bivariate associations of cohort characteristics with acute respiratory illness (ED visit or hospital readmission) among infants with BPD
Unadjusted and adjusted associations of social vulnerability index with acute respiratory illness (ED visit or hospital readmission) in the year after discharge
Conclusions
In preterm infants with BPD, census tract SVI was associated with an ED visit or hospital admission in the year after NICU discharge in models adjusted for severity of illness. However, this association may be driven by insurance and other factors associated with race and ethnicity. Larger studies from broader geographic regions are required to clarify the relationship between SVI and healthcare utilization in patients with BPD.
#16 Quality improvement: management of pelvic inflammatory disease in a pediatric emergency department
S Andreas1*
S Smith1,2
E Lardieri1
A Bennett1,2
1University of Connecticut, Farmington, CT
2Connecticut Children’s, Hartford, CT
Purpose of Study
Adolescent females are at high risk for developing pelvic inflammatory disease (PID) which causes long-term sequelae including chronic pain, recurrent PID and lower genital tract infections, and infertility. PID is often misdiagnosed in the Emergency Department (ED). The purpose of this study is to identify gaps in the identification and treatment of PID in a pediatric ED and to implement interventions to improve care.
Methods Used
This quality improvement project conducted in an urban pediatric ED included adolescent females age 14 to 20 who presented with a chief complaint of abdominal pain, pelvic pain, or vaginal symptoms. Exclusion criteria were patients without PID symptoms or received another medical diagnosis. Baseline data was collected from March 2019 through June 2019. Charts were audited by trained pediatric residents and reviewed by an adolescent medicine physician and pediatric emergency medicine fellow, with expertise in the management of PID. The baseline data included age, type of primary provider, gender of provider, documentation of sexual history, STI testing, documentation of a bimanual exam, and antibiotic therapy. Initial educational interventions began in August 2019, followed by introduction of a best practice advisory (BPA) in the hospital’s electronic medical record in November 2019, and confidential STI testing in August 2020.
Summary of Results
There were a total of 798 patients, mean age 16 years (+/- 1.2). Residents were the primary provider for a majority of patients (53%), followed by midlevels (37%), fellows (5%), and attendings (5%). Sexual history was documented 71% of the time, with increasing documentation as patients got older. Documentation of sexual history was similar by race. In patients with unknown or positive sexual history, STI testing was obtained 22% of the time. Bimanual exams were offered in patients with unknown or positive sexual histories 15% (N=70) of the time, with 25% of these being positive. 58% (N=23) of patients were correctly diagnosed with PID based on the exam. 48% of patients who met criteria for PID were correctly treated and 52%were not treated with antibiotics. During the course of the project, sexual history documentation slightly improved but did not correlate with any specific intervention. STI testing and bimanual exams also improved slightly throughout the course of the project, with the largest impact coming after the EPIC BPA was initiated.
Run chart on the documentation of sexual history from March 2019 – May 2021
Run Chart on the performance of bimanual exams between March 2019 and May 2021
Conclusions
Among adolescents presenting to a pediatric ED with symptoms concerning for PID, 46% received an appropriate history, exam, diagnosis and treatment of their chief complaint. Changes in electronic medical record alerts and testing had the greatest impact on provider change.
1C: Developmental biology/basic & translational
#17 Deletion of cyclophilin D alters metabolic transitions in the developing heart
G Beutner1
JR Burris1
MP Collins1
D FangniboHanvi1
ED Cohen1
MA O’Reilly1
PS Brookes1
K de Mesy Bentley2
GA Porter1*
1University of Rochester Medical Center, Rochester, NY
2University of Rochester, Rochester, NY
Purpose of Study
During cardiac development, cellular energy production evolves from anaerobic glycolysis in the embryo to lipid-fueled, aerobic oxidative phosphorylation (OXPHOS) in the mature heart. The mechanisms that control these changes and activation of mitochondrial electron transport chain (ETC) remain unclear, but this maturation requires closure of the mitochondrial permeability transition pore (mPTP), which is controlled by the chaperone protein, cyclophilin D (CyPD). The objective of this study was to test the hypothesis that CyPD regulates activation of the ETC activity and the maturation of cardiac myocyte bioenergetics during development.
Methods Used
Mouse hearts were harvested from wild type (WT) and CyPD null hearts from embryonic day (E)9.5 to adult. Samples were examined by electron microscopy for changes in cellular and mitochondrial structure, liquid chromatography/mass spectrometry for metabolomic profiling, oxygen consumption and enzyme assays for ETC function, gel electrophoresis/immunoblotting for ETC protein expression and complex assembly, and calcium retention capacity for mPTP activity.
Summary of Results
As the heart develops, there are increases in myocyte differentiation and size, and, in each myocyte, mitochondrial number, size, and complexity also increase with specific transitions at the end of the embryonic period and immediately after birth. Metabolomic profiling demonstrated changes in glycolysis, the TCA cycle, and redox state during development and also suggested that these changes may facilitate proliferation around the time of birth. Activation of ETC complexes I, III, IV, and V occurs in the mid-embryonic period, while complex II activity is relatively stable during development, and assembly of more efficient ETC supercomplexes begins to occur at the embryonic/fetal bioenergetic transition. Calcium retention assays demonstrated a gradual decrease in the probability of mPTP opening during cardiac development. CyPD expression increased, but the specific enzymatic activity of CyPD decreased, during cardiac development. For most assays tested, these transitions occurred earlier during cardiac development in CyPD null mice.
Conclusions
Cellular bioenergetic profile changes during cardiac development with two transitions at the end of the embryonic period and immediately after birth. Deletion of CyPD causes these two transitions to occur earlier in development, suggesting that CyPD and closure of the mPTP controls mitochondrial activation during cardiac development.
#18 HMGB1 and cerebral edema in the hypoxic piglet brain
V Stoffel1*
R Saab1
R. Grothusen J2
K McRae3
F Tuzer1
S Malaeb1
1Drexel University College of Medicine, Philadelphia, PA
2University of Pennsylvania, Philadelphia, PA
3St. Christopher’s Hospital for Children, Philadelphia, PA
Purpose of Study
Perinatal asphyxia and cardiac arrest remain leading causes of neurodevelopmental imapriment in infants and children. Cerebral edema post cerebral hypoxic-ischemic injury is associated with poor prognosis and lifelong disability risk in infants and children. Cerebral edema can be detected by diffusion-weighted MRI. However, MRI has limited availability shortly after an insult, hindering its application, hence the need for other markers of neuropathology. Necroptosis is a caspase-independent cell death process involving cellular swelling, ruptured cellular membrane, and nuclear content spillage. High Mobility Group Box Protein 1 (HMGB1) is a non-histone DNA-binding protein released early amongst damage-associated molecular patterns (DAMPs) post-injury. It is a marker of necroptosis and is elevated during an inflammatory condition. We have shown that HMGB1 is increased shortly after cerebral hypoxia in piglets. The validity of HMGB1 as a marker for cerebral edema has not yet been established. Therefore, the purpose of the present study is to determine the relationship between cerebral HMGB1 expression and degree of cerebral edema in hypoxic piglets.
Methods Used
Anesthetized male piglets (3-5 days old) were ventilated at FiO2 0.21 x5 hrs (Nx) or FiO2 0.06 x1 hr (Hx), returned to FiO2 0.21 x4 hrs at normal body temperatures, then euthanized for brain harvest. Cerebral water content (g H2O/g dry tissue) was used as a marker of cerebral edema, and lactate levels (μMol/g tissue) were measured to determine cerebral energy in frozen samples of the cerebral cortex. Cytosolic fraction was collected by centrifugation at 40,000xG of a nucleus-free tissue homogenate. HMGB1 expression relative to cytoskeletal protein vinculin determined by Western blot was expressed as normalized ratios to a normal control.
Summary of Results
Hypoxia exposure resulted in consistent hypoxemia, hypotension, metabolic acidosis, and cerebral lactic acidosis (P < 0.05; table 1). Both HMGB1 and cerebral water content were significantly increased in Hx compared to Nx (P < 0.05) [figure 1A; figure 1B]. We observed a strong linear correlation between HMGB1 levels in the brain and cerebral water content (R = 0.86; P < 0.01) [figure 1C].
Physiological parameters during hypoxia exposure
HMGB1 expression (A) and cerebral water content (B) in normoxic (Nx; open bars) and hypoxic (Hx;closed bars) piglet brains. M ± SD. *P < 0.05 vs. Nx. (C) Linear correlation analysis between cerebral water content (g H2O/g dry tissue) and HMGB1expression(HMGB1:Vinculin normalized ratios) in piglet brain tissue. Each point represents a single animal
Conclusions
Increased HMGB1 in the piglet brain correlated with increased cerebral edema after hypoxia. Cerebral edema can be vasogenic, cytotoxic, or both. Vasogenic edema involves the breakdown of the blood-brain barrier, whereas cytotoxic edema involves cellular swelling and rupture, with a worse prognosis. We speculate that a worse hypoxic injury involves hypoxia-induced necroptosis, activating mechanisms leading to cellular swelling and the release of HMGB1. There is potential for HMGB1 to be used as a marker of the severity of hypoxic brain injury.
#19 Role of IL-10 in mediating circadian regulation of lung injury from influenza A virus
K Forrest1*
A Naik1
S Tang2,3
S Sengupta1,3
1Children’s Hospital of Philadelphia, Philadelphia, PA
2University of Pennsylvania, Philadelphia, PA
3University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
Purpose of Study
Circadian rhythms provide an anticipatory mechanism for all living organisms. Such rhythms are evident in various facets of the immune response. Our published work shows that circadian rhythms confer a time-of-day specific protection from Influenza A Virus (IAV) infection. Mice infected at dawn had 3-fold better survival than those infected at dusk. While both groups had comparable viral titers, the lungs from the dawn group had higher IL-10 mRNA expression than lungs from the dusk group. However, the role of IL-10 in the circadian gating of IAV is unknown. We hypothesized the circadian gating of the IAV infection at least in part is mediated by the immunoregulatory cytokine IL-10. Our aim was to determine if the loss of IL-10 signaling abrogates circadian protection by worsening inflammation and immunopathology induced by IAV and not by direct effect on viral burden.
Methods Used
8-16-week-old C57bl/6J mice were infected with 35 PFU of PR8 at either dawn or dusk. Mice were either treated with Il10R1 antibody or IgG 1-, 3-, and 5-days post infection (d.p.i). IL10R1 antibody blocks downstream IL10 signaling. Lung and bronchioalveolar lavage (BAL) were harvested at serial time points following IAV infection.
Summary of Results
In mice with intact IL-10 signaling, those infected at dawn had almost three times lower mortality than those infected at dusk. However, blocking IL-10 signaling abolished the circadian protection, with both groups having comparably high morbidity and mortality. Upon histological analysis, we found mice without intact IL-10 signaling had similarly worse immunopathology which was comparable to that of the mice infected at dusk wherein IL-10 signaling was intact. Interestingly, the viral titers were similar across all groups at 5 and 8 d.p.i., indicating no difference in viral clearance. Analysis of BAL fluid 5 d.p.i showed that in the absence of IL10 signaling the BAL count was higher, suggestive of higher inflammation.
Conclusions
We conclude that IL-10 contributes to the circadian gating of IAV infection outcomes. Loss of IL-10 signaling abolishes the circadian protection from IAV infection via the inflammatory response rather than impacting viral clearance. In future, we plan on identifying the cellular source and target(s) of IL-10 in the context of circadian regulation of IAV infection outcome.
#20 Differential susceptibility to propofol and ketamine in primary cultures of young astrocytes
A Murtha1*
L Huang2
F Tuzer1
M Green3
C Torres1
S Malaeb1
1Drexel University College of Medicine, Philadelphia, PA
2New York University Grossman Medical School, New York, NY
3Sidney Kimmel Medical College, Philadelphia, PA
Purpose of Study
The implication of astrocytes in nervous system processes and neurodegenerative conditions indicate that these cells are essential for brain function. Anesthetics are of concern as studies have shown detrimental neurodevelopmental effects in infants and young children. As such, the need remains for safer anesthesia for the developing brain. Therefore, the purpose of the present study is to compare the susceptibility of young astrocytes in primary cultures to propofol versus ketamine, two commonly used intravenous anesthetics.
Methods Used
Human fetal astrocytes from ScienCell Research Laboratories were grown at 37°C, 5% CO2 in room air and media supplemented with 2% fetal bovine serum and penicillin/streptomycin. Cells were seeded at 100 cells/mm2 and cultured until 70-80% confluence. Equal volumes of the same cell suspension stock were added to wells at the start of incubation. Baseline controls were cultured without additives. Propofol was emulsified with Dimethyl sulfoxide (DMSO), then added to media in concentrations of 30, 100, and 300 μM. DMSO alone served as a corresponding vehicle control to propofol. Ketamine was added to media in concentrations of 30 and 300 μM. The range of drug concentrations used correlate to amounts found in patients anesthetized with these agents. After 7 hours, cells were counted using flow cytometry in 71μL aliquots and assessed using Guava ViaCount® Reagent to distinguish the viability of cells based on differential permeabilities of two DNA-binding dyes.
Summary of Results
Astrocytes cultured in baseline control media showed cell counts of 375 ± 56 cells/aliquot. Cell counts of astrocytes incubated with propofol+DMSO saw a 39.2% reduction when compared to baseline control (p < 0.01). Cells in propofol+DMSO also had count reductions vs. DMSO and vs. ketamine (both p < 0.01) [figure 1]. For dose response cell count, propofol+DMSO showed reductions vs. baseline control (30 and 300 μM, p < 0.01 and 100 μM, p < 0.05), vs. DMSO (30 and 300 μM, p < 0.05), and vs. 300 μM ketamine (p < 0.05) [figure 2]. There was no significant difference in total or dose response in cell counts of DMSO or ketamine vs. control. For viability, only 300 μM propofol+DMSO had reductions vs. baseline control and vs. ketamine (both p < 0.05) [figure 3]. The results demonstrated significant effects of propofol, even at low concentrations.
Cell Counts of Young Astrocytes to DMSO, Propofol, and KetamineAverage cell count of young astrocytes per exposure after 7 hours of incubation in different media, expressed as a percentage of best growth in control media for each set of experiments, and presented as means +SD. Legend: control (N= 4; white bar), DMSO (N= 12; dark gray bar), propofol+DMSO (N= 12; light gray bar), ketamine (N= 6; hatched bar). *p < 0.05 and **p < 0.01 vs control; +p < 0.05 and ++p < 0.01 vs DMSO; #p < 0.05 and ##p < 0.01 vs propofol+DMSO. ANOVA with Bonferroni correction for post-hoc comparisons.
Cell count and viability dose response of young astrocytes to DMSO, propofol, and ketamineAverage cell count (A) and percent viability (B) of young astrocytes per dose after 7 hours of incubation in escalating strengths of different media (30 μM, low; 300 μM, high; 100 μM of DMSO and propofol+DMSO not shown), expressed as percent of best growth in control media for each set of experiments and presented as means +SD. Legend: control (N= 4; white bar), low DMSO (N= 3; 30 μM dark gray bar, left), high DMSO (N= 6; 300 μM dark gray bar, right), low propofol+DMSO (N= 3; 30 μM light gray bar, left), high propofol+DMSO (N= 6; 300 μM light gray bar, right), low ketamine (N= 3; 30 μM hatched bar, left), high ketamine (N= 3; 300 μM hatched bar, right). *p < 0.05 and **p < 0.01 vs control; +p < 0.05 and ++p < 0.01 vs DMSO; #p < 0.05 and ##p < 0.01 vs propofol+DMSO. ANOVA with Bonferroni correction for post-hoc comparisons.
Conclusions
The data show differential susceptibility of young astrocytes to propofol than ketamine. The observed cell count reduction may be related to adverse effects of propofol on mitochondrial function and free radical production as described in previous studies. We speculate that ketamine may have a more favorable safety profile in infants and children.
#21 Early white matter tract changes in neonates with prenatal opioid exposure: a pilot study
P Sikka1*
N Madan1,2
E Yen1,2
1Tufts University School of Medicine, Boston, MA
2Tufts Medical Center, Boston, MA
Purpose of Study
The impact of prenatal opioids on white matter tract development shortly after birth is not well understood. This pilot study aims to evaluate and compare white matter changes in opioid- and non-exposed neonates.
Methods Used
Brain MRI was acquired within 48 hours of birth using a ‘feed-and-swaddle’ method in 10 opioid-exposed neonates born at > 34 weeks gestational age (GA), prior to the start of pharmacotherapy, and 11 healthy sex- and age-matched non-exposed neonates. Diffusion tensor imaging (DTI) was acquired for each patient with a baseline image (b = 0 s/mm2) and 15 different diffusion orientations (b = 1,000 s/mm2). Single-subject and group-level DTI analyses were carried out using FMRIB’s Software Library (www.fmrib.ox.ac.uk/fsl), including corrections for eddy current-induced distortions and gross subject movement. Slices with signal loss caused by subject movement coinciding with the diffusion encoding were detected and replaced by predictions made by a Gaussian Process. To determine differences in white matter between the two groups, voxel-wise whole tract analysis of the fractional anisotropy (FA) data was performed with Tract Based Spatial Statistics using a pipeline optimized for neonatal DTI data (thresholded at FA > 0.19), with sex and GA at birth listed as covariates. All FA data were subject to permutation (10,000) testing and family-wise error correction for multiple comparisons following threshold-free cluster enhancement (TFCE). Continuous data were analyzed using a t-test, and categorical data using Chi-square. Significance was set at p ≤ 0.05.
Summary of Results
Opioid-exposed neonates had lower birth weight and head circumference percentiles (p = 0.05) and length percentile (p = 0.07) compared to non-exposed controls. Following adjustment for sex and GA, the opioid-exposed cohort showed qualitatively reduced FA with no significant difference in quantitative FA from the non-exposed cohort (0.299 ± 0.020 vs. 0.300 ± 0.021 respectively, p = 0.52). Decreased FA was observed in multiple bilateral white matter pathways involving the anterior and posterior corona radiata, inferior fronto-occipital fasciculus, superior and inferior longitudinal fasciculi, corpus callosum, anterior and posterior thalamic radiations, cingulum, internal and external capsules, amygdala, corticopontine, and corticospinal tracts (p > 0.05, TFCE corrected).
Demographic characteristics and diffusion tensor imaging measurements of neonates enrolled in the study
Conclusions
Opioid exposure in utero is associated with microstructural changes within major white matter tracts, demonstrated by reduced FA in the amygdala and cerebral cortex. Our work is limited by a small sample size. However, obtained immediately after birth, our DTI data reveal early white matter tract changes in opioid-exposed neonates. As reduced FA has been linked with long-term cognitive and motor deficits, our preliminary study holds important insights into the effects of opioid exposure on neonatal brain development.
#22 Prenatal brain maturation in neonates with congenital diaphragmatic hernia
S Johng1*
D Licht1
H Hedrick1
N Rintoul1
R Linn1
R Xiao2
S Massey1
1Children’s Hospital of Philadelphia, Philadelphia, PA
2Hospital of the University of Pennsylvania, Philadelphia, PA
Purpose of Study
Infants with congenital diaphragmatic hernia (CDH) are at increased risk of neurodevelopmental impairment (NDI). It is unknown whether abnormal neurodevelopment is due to a congenital difference in development, or the sequelae of critical illness. One strategy is to examine prenatal neuroimaging to assess brain development prior to the infant’s exposure to critical illness after delivery. We assessed prenatal brain maturation according to a fetal Total Maturation Score (fTMS) in neonates with CDH compared with healthy controls. This study is the first to examine fTMS in CDH infants.
Methods Used
We conducted a retrospective cohort study using data from a quaternary single-center clinical registry. Our study cohort consisted of inborn neonates with an antenatal diagnosis of CDH between 2014 and 2020 and and prenatal neurologic magnetic resonance imaging (MRI) between 25 and 35 weeks gestational age (GA). The fTMS in the CDH population were compared to historical controls. The relationship between fTMS and actual GA was assessed with linear regression models. Key prognostic and prenatal variables of CDH were tested as potential modifiers of fTMS using linear regression models. An unpaired t-test was used to compare early (<30 weeks) versus late (>30 weeks) fTMS differences.
Summary of Results
48 infants met inclusion criteria for the prenatal study population, and 41 of these were inborn and included in the postnatal study population (table 1). Compared with normal controls, fTMS in CDH patients were significantly delayed (p-value < 0.001) (figure 1A). Delay in fTMS emerged after 30 weeks’ gestation (p-value = 0.001) (figure 1B). There was no significant difference in fTMS based on CDH severity, intrathoracic liver position, right versus left CDH, gender, need for extracorporeal membrane oxygenation, or in-hospital mortality. CDH placentas had a higher proportion of fetal vascular malperfusion (56%) compared with previously published controls (7-20%).
(A) The relationship between fTMS and actual gestational age in CDH infants versus normal controls was assessed using linear regression models, and the slopes of the cohorts’ correlations were significantly different (CDH 1.04, Control 1.27, p <0.001). On visual inspection of the correlations, the divergence in fTMS between CDH infants and normal controls appeared to occur after 30 weeks‘ gestation; (B) A comparison of delta values (Calculated Gestational Age minus Actual Gestational Age) demonstrates that, when stratified by gestational age < or > 30 weeks‘ gestation, the delay of fTMS in CDH infants was only significant at >30 weeks’ gestation. An unpaired t-test comparing delta values between CDH and control infants was only significantly different at >30 weeks’ gestation (Less than 30 weeks: Control delta mean 0.11 versus CDH delta mean 0.02, p-value = 0.65; Greater or equal to 30 weeks: Control delta mean -0.20 versus CDH delta mean -1.11, p-value = 0.001).
Conclusions
Prenatal brain maturation in CDH patients is delayed after 30 weeks’ gestation, and may be due to placental pathology given a high proportion of fetal vascular malperfusion. The etiology and clinical impact of prenatal brain immaturity in CDH infants needs further investigation, starting with reporting neurodevelopmental outcomes in our study cohort. It is crucial to better understand how placental pathology contributes to abnormal neurodevelopment, and examine potential modifiable factors that could improve prenatal health in the CDH population.
#23 Cathelicidin anti-microbial peptide (CAMP) is toxic during neonatal influenza virus infection
N Ugwu1*
A Rao2
Cort l2
A Carey1,2
1St. Christopher’s Hospital for Children, Philadelphia, PA
2Drexel University College of Medicine, Philadelphia, PA
Purpose of Study
To determine the role of CAMP in the innate immune response and subsequent pathogenesis during neonatal influenza virus infection.
Methods Used
Wild-type (C57BL/6) and CAMP deficient (CAMP-/-) 3-day old neonatal and 8-week old adult mice were infected intranasally with influenza A virus/Puerto Rico/8 (PR8) and tracked for survival. In separate experiments, murine neonatal lungs were harvested at 1-, 3- and 6-days post-infection (DPI). Bronchoalveolar lavage fluid (BALF) and whole lungs were analyzed by flow cytometry for cellular infiltration. Animal work was conducted according to approved IACUC protocols.
Summary of Results
Three-day old CAMP-/- murine neonates had improved survival compared to wild-type (75% versus 14%, p<0.01). This is in direct opposition to adult mice, where CAMP-/- and wild-type mice had similar weight loss, an important indicator of adult influenza-related morbidity. At 1- and 6-DPI, neonatal CAMP-/- mice had increased absolute numbers and frequency of alveolar macrophages (AM) compared to wild-type mice (p<0.01). In contrast, AMs, lymphocytes, monocytes and neutrophils were increased in the lung interstitium of wild-type neonates compared to CAMP-/- mice at 1 DPI (p<0.01).
Conclusions
Neonatal CAMP-/-, but not adult, mice are protected during influenza virus infection, which demonstrates an age-specific role of CAMP. CAMP-/- neonates have a more targeted initial immune response, with specific recruitment of AMs to the site of infection, the alveoli. Their wild-type counterparts demonstrate a general increase in interstitial cellular infiltration. This targeted response potentially plays a role in the improved CAMP-/- survival, as AMs are critical to the control of inhaled pathogens. Further studies using our murine model will further investigate the role of AMs as the first-line of defense during neonatal respiratory viral infection.
#24 Mdivi-1: Surprising effects on neuroinflammation
BM Hung*
J Waddell
University of Maryland Medical Center, Baltimore, MD
Purpose of Study
Hypoxic-ischemic encephalopathy (HIE) is a major cause of cerebral palsy and associated disabilities in children. Current standard of care is therapeutic hypothermia, which improves survival and neurological outcomes into middle childhood. However there are still many infants who die or survive with disabilities. Interventions that can complement hypothermia are necessary. Mdivi-1 is a putative mitochondrial fission inhibitor with demonstrated neuroprotective effect in adult animal models. Neuroprotective efficacy in the developing brain remains tested.
Methods Used
Male and female rat pups underwent a modification of the Rice-Vannucci hypoxic ischemic brain injury method. Briefly, pups undergo a unilateral carotid artery ligation followed by 60 min of hypoxia (8% O2: 92% N2). Pups were then randomly assigned to normothermic or hypothermic conditions. After 4 hours pups were randomly assigned to drug condition and treated with a vehicle or midivi-1. Two injections of mdivi-1 (2mg/kg) were given at 0 and 24 hours. Tissue was collected 12 or 24 hours after HI. Tissue collected 12 hours after HI was processed for nanostring quantification of mRNA. Tissue collected 24 hours after HI was processed for immunohistochemistry. Both 3-NT, a marker of inflammation, and cerebral hemisphere volume were measured.
Summary of Results
The 3-NT analysis showed a statistically significant decrease in inflammation in the HI+mdivi group compared to the HI group. In the HI+hypothermia group, there was a trend toward decreased inflammation after treatment with mdivi, but variability remained high. Nanostring quantification of mRNA showed increased inflammation in females pups compared to male pups, and a reduction of inflammation by mdivi-1 administration. Mdivi-1 administration coupled with hypothermia appeared to reduce tissue loss compared to either alone.
Conclusions
Mdivi alone decreases inflammation in hypoxic ischemic neonatal brain. We also observe a novel sex difference in the inflammatory response after HI. The mechanisms of mdivi-1 appear to be much broader than inhibition of mitochondrial fission. It is possible that mdivi-1 could be used as an adjuvant therapy in addition to hypothermia.
2A: Neonatal pulmonary
#25 Gene variant affecting the hippo signaling pathway is correlated with bronchopulmonary dysplasia in extremely low birthweight infants
NR Palla1*
V Trinh1
L Parton1,2
1New York Medical College, Valhalla, NY
2MFCH at WMC, Valhalla, NY
Purpose of Study
Bronchopulmonary dysplasia (BPD) is one of the most common causes of death and morbidity in extremely low birth weight (ELBW) infants. It is characterized by exposure to environmental stimuli such as: mechanical ventilation-pressure, volume; hyperoxia; and inflammation; within a background of genetic susceptibility. Impaired lung development affects the respiratory epithelium, the vascular endothelium, and the extracellular matrix. The Hippo signaling pathway is known to play a key role in tissue growth suppression and modulation in lung development, physiology, and injury. Specifically, variants of yes-associated protein (YAP), transcriptional co-activator with PDZ-binding motif (TAZ) and transcription enhancer factor (TEA/ATTS) domain (TEAD) are important regulators of the Hippo pathway and are associated with changes in lung function in asthma and in small-cell lung cancer. Perturbations to YAP, TAZ and TEAD of the Hippo pathway result in altered pulmonary tissue growth and vascular development. Because alterations in pulmonary lung and vascular development are also characteristic of BPD, we hypothesize that genetic variants in YAP, TAZ and TEAD of the Hippo pathway are associated with the development of BPD in ELBW infants.
Methods Used
DNA extracted from buccal swabs collected from ELBW infants following IRB-approved parental consent was subjected to allelic discrimination using specific Taqman probes for rs10895256, rs2846836, rs1820453, rs16861979, rs2304733, rs6918698 and rs11225163 during RT-PCR. Statistics included Chi-square, t-test, and z-test, with significant p value ≤0.05.
Summary of Results
Demographic characteristics did not differ between those with BPD and those without BPD except for gestational age and postnatal steroids (table 1). TEAD variant rs2304733 was found to have a significantly different genotype distribution in the BPD group compared to the Non-BPD group (p=0.05) (table 2). There were no statistical differences in the genotype distributions of the other YAP1 or TAZ variants tested.
Demographic or TEAD SNP rs2304733 for infants with and without BPD
Genotype distribution for TEAD SNP rs2304733 for infants with and without BPD
Conclusions
The TEAD variant rs2304733 is associated with BPD in ELBW infants. We speculate that while preterm birth perturbs the HIPPO pathway and accelerates pulmonary growth suppression, this specific TEAD genetic variant may play a role in modulating YAP/TAZ nuclear localization, contributing to increased susceptibility to BPD.
#26 Prenatal inflammation primes pulmonary immune cells to postnatal hyperoxia-induced lung injury
S Anbalagan*
M Babak
L Glazewski
A Hesek
D Alapati
Nemours Children’s Hospital, Wilmington, DE
Purpose of Study
Bronchopulmonary dysplasia (BPD) is a multifactorial disease caused by a combination of prenatal and postnatal environmental insults that predisposes to lifelong respiratory morbidities. Resident pulmonary immune cells regulate host immune response to airborne toxins and microbes and are thus crucial in respiratory disorders. We previously showed that combined prenatal inflammation induced by chorioamnionitis and postnatal inflammation induced by hyperoxia in neonatal rats led to significantly altered pulmonary-specific immune cell gene expression that persisted long-term. However, mechanisms by which prenatal inflammation primes the pulmonary immune cells to postnatal lung injury are unknown.
Purpose of the study is to quantify differences in resident pulmonary immune cell composition in response to hyperoxia-induced lung injury subsequent to prenatal priming induced by chorioamnionitis in a double-hit rat model of BPD. We hypothesized that pulmonary immune cells are primed by prenatal inflammation resulting in altered pulmonary immune cell composition in response to postnatal hyperoxia.
Methods Used
Pregnant Sprague-Dawley rats were injected with intra-amniotic lipopolysaccharide (LPS) (1ug) or normal saline (NS) at 20 days of gestation. Upon delivery, pups were placed in a hyperoxia chamber with 85% O2 or room air (RA) for 14 days. Pups were euthanized on postnatal days 1 (P1) and 14 (P14). Single-cell suspension of the lung was stained with DAPI and rat-specific fluorochrome-conjugated antibodies to CD45, CD3, CD4, CD8, CD161, CD43, and CD45R for flow cytometry. Data were analyzed using FCS Express™ software. Statistical analysis was performed using Mann-Whitney test for two groups and ANOVA test for three groups.
Summary of Results
On P1, prenatal LPS exposure decreased CD3+CD4+ T-cells (3.5±0.8% vs 1.9±0.2%; NS+RA vs LPS+RA), CD3+CD8+ T-cells (2.7±0.9% vs 1.4±0.2%; NS+RA vs LPS+RA) and CD45R+ B-cells (44.9±6.3% vs 30.8±3.1%; NS+RA vs LPS+RA)(p=0.0079). In contrast, CD161+ cells (49.8±7.2% vs 66.5±3.3%; NS+RA vs LPS+RA) and CD43+ monocytes were significantly increased compared to control pups (p=0.0079) (figure 1). Secondary exposure to postnatal hyperoxia increased CD161+ cells in LPS+O2 group compared to NS+O2 (6.1±2.4% vs 52.9±12.7%; NS+O2 vs LPS+O2, p < 0.0001) but decreased CD43+ cells (32.9±3.5% vs 25.5±1.7%; NS+O2 vs LPS+O2, p=0.0009) (figure 2).
Postnatal day 1 pulmonary immune cell composition
Postnatal day 14 pulmonary immune cell composition
Conclusions
Chorioamnionitis induced priming of neonatal lung immune cells results in differential response to postnatal hyperoxia, which may have clinical implications in the subset of preterm infants with respiratory failure who are exposed to chorioamnionitis prenatally.
#27 Lung ultrasound assessment of pulmonary edema in neonates with chronic lung disease before and after diuretic therapy
G Kasniya1,2*
J Cerise3
B Weinberger1,2
D Kurepa1,2
1Cohen Children Medical Center at Northwell Health, New Hyde Park, NY
2Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY
3Feinstein Institutes for Medical Research, Manhasset, NY
Purpose of Study
Chronic lung disease (CLD) in preterm infants is characterized by impaired alveolarization, inflammation, and capillary leak. Clinically, it presents with atelectasis, pulmonary edema, and pulmonary hypertension. Treatments include ventilation strategies, nutrition, corticosteroids, and diuretics. More than 58% of extremely preterm neonates receive diuretics in the NICU. Point-of-care lung ultrasound (LUS) can be used to identify pulmonary edema based on the presence of ‘B-lines’ over the affected areas.
Our objective was to evaluate pulmonary edema using LUS before and after initiation of diuretic therapy for infants with CLD, and to compare with infants with CLD not receiving diuretics. Oxygen requirements were also assessed in both groups.
Methods Used
Preterm infants (median gestational age 27 weeks) were recruited at a median of 34 weeks corrected gestational age based on the persistent requirement for supplemental oxygen and/or positive end-expiratory pressure. Infants in the study group were started on diuretics at the discretion of their physicians and compared with the control group of matched infants not receiving diuretics. LUS exams were performed within 1 day before the start of diuretic treatment (day 0), and on days 1, 3, and 6 after the first dose of diuretic. For each exam, anterior, lateral, and posterior areas of the lung on each side, each including 3 intercostal spaces, were scanned for B-lines. A 10-second video of each area was recorded and scored, and a composite pulmonary edema severity (PES) score of 0 to 5 was calculated based on the total number of B-lines. Oxygen requirement was recorded on days 0, 1, 3, and 6.
Summary of Results
51 infants were enrolled (28 study, 23 control). The groups were similar for gestational age, post-conceptional age at enrollment, use of caffeine and prenatal steroids, and gender, as well as for the incidence of chorioamnionitis, small for gestational age, and patent ductus arteriosus (table 1). PES scores decreased significantly in the study group, but not the control group, during the study period (p<0.0001) and were significantly lower in the study group than the control group on days 3 and 6 (figure 1a). Also, FiO2 decreased significantly in the study group during the study period (p=0.0001) and was lower in the study group compared to controls on day 3 (figure 1b).
Demographics
a) Pulmonary edema scores. * Study group different from control group, day 3 p<0.0001, day 6 p=0.01; b) FiO2. * Study group different from control group, day 3 p=0.017
Conclusions
Diuretic use is associated with decreased lung edema and improved oxygenation in infants with CLD during the first week of treatment. LUS scoring of pulmonary edema in CLD may be an effective tool to assess the efficacy of diuretic therapy.
#28 Do extremely low birth weight (ELBW) infants tolerate extubation to neurally adjusted ventilatory assist (NAVA) better than conventional non-invasive positive pressure ventilation (NIPPV)?
K Louie1*
S Amatya2
L Parton1
1Maria Fareri Children’s Hospital, Valhalla, NY
2Milton S. Hershey Medical Center, Hershey, PA
Purpose of Study
Infants weighing less than 1 kg at birth (ELBW) are at high risk for the development of bronchopulmonary dysplasia (BPD) and ventilator-induced lung injury (VILI), in part because of the need for mechanical ventilation utilizing an endotracheal tube (MVET). Various noninvasive (NIV) strategies have been utilized following elective extubation to prevent the need for reintubation. Continuous positive airway pressure (CPAP) and NIPPV are modalities frequently used. Studies have shown decreased elective extubation failure when placed on NIPPV compared to CPAP. Furthermore, synchronized noninvasive positive pressure ventilation (sNIPPV) utilizing NAVA compared to NIPPV has demonstrated improvements in pulmonary mechanics, work of breathing, and extubation success in preterm infants. To our knowledge, there are no randomized controlled trials comparing sNIPPV using NAVA with NIPPV in ELBW infants during elective extubation. This study investigates the effectiveness of extubation from conventional mechanical ventilation (MVET) to sNIPPV using NAVA or NIPPV in ELBW infants.
Methods Used
Consented ELBW infants are randomized to sNIPPV using NAVA or NIPPV in a one to one computer-generated scheme. Patient demographics are collected and infants are assessed for duration infant remain extubated. The Institutional Review Board (IRB) of New York Medical College approved this study.
Summary of Results
At the time of analysis our data included 47 ELBW infants of which 27 were randomized to NIPPV and 20 to NAVA. The average birth weight was 782 (153) grams [mean (SD)] and 808 (158) grams in the NIPPV and sNIPPV groups, respectively. There were no statistically significant differences between the two group demographics. Median time to reintubation was 2 (1, 9) [median (IQR)] days in the NIPPV group and 2 (1, 5) days in the NAVA group, which was not statistically significant. Overall there was a 40% extubation failure across the groups. There were no infants in the sNIPPV group requiring oxygen at time of discharge compared to 9 in the NIPPV group (p = 0.006).
Conclusions
This interim analysis has shown similar extubation failure among ELBW infants in comparison to prior studies. While there were no statistically significant differences in extubation success, time to reintubation, BPD, or length of stay there were no infants in the NAVA group discharged home on oxygen, which may improve outcome variables not measured in this study. The use of NAVA may be a possible alternative mode of NIV in the ELBW population.
#29 Early versus late caffeine and/or non-steroidal anti-inflammatory drug (NSAIDs) on biomarkers of lung inflammation in neonatal rats exposed to intermittent hypoxia
KS Bhatia*
C Cai
JV Aranda
SJ Wadowski
KD Beharry
SUNY Downstate Health Sciences University, Brooklyn, NY
Purpose of Study
Immature respiratory control, prematurity, intermittent hypoxia (IH), and resulting inflammation, contribute to the development of chronic lung disease in preterm infants. Early caffeine therapy has been shown to be associated with reduced lung inflammation. Cyclooxygenase inhibitors, such as ibuprofen have also been shown to improve lung mechanics in animal models.
We tested the hypotheses that: 1) Caffeine and NSAID co-treatment has synergistic benefits for reducing IH-induced inflammation in the neonatal rat lungs, and 2) early postnatal treatment during IH is more beneficial than late treatment during reperfusion/reoxygenation.
Methods Used
Newborn rats (n=18/group) were exposed to brief hypoxia (12% O2) during hyperoxia (50% O2) from birth (P0) to P14) or room air (RA). For early, the pups were administered: 1) a single daily IP injection of caffeine citrate (Cafcit, 10 mg/kg loading on P0, followed by 5 mg/kg maintenance from P1-P14); 2) ketorolac topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Neoprofen, 10 mg/kg loading dose on P0 followed by 5 mg/kg/day on P1 and P2); 4) caffeine+ketorolac co-treatment; 5) caffeine+ibuprofen co-treatment; or 6) equivalent volume saline. On P14, animals were placed in RA with no further treatment. For late, the pups received similar treatments from P15-P17 (ibuprofen) or P15-P21 (caffeine and/or ketorolac). At P21, lungs (n=6/group) were assessed for growth and biomarkers of inflammation (IL-1, TNFα, IL-6, IL-10).
Summary of Results
Neonatal IH resulted in reduced weight accretion and lung/body weight ratios in both early and late groups. Early ibuprofen was beneficial for preserving bodyweight accretion and lung/bodyweight ratios. All late treatments were beneficial. Similarly, early caffeine/NSAID co-treatment resulted in effective decreases in pro-inflammatory cytokines (IL-1B, TNF-alpha, and IL-10) compared to late treatments (figure 1; Panels A, C, E are Early; Panels B, D, F are Late).
Effect of caffeine and/or NSAIDs on lung growth and cytokines in neonatal IH
Conclusions
Our data show that neonatal IH is deleterious to lung and body growth. Early caffeine with or without ibuprofen is preferable, and confer synergistic effects for reducing IH-induced lung inflammation. The anti-inflammatory effects of caffeine may explain in part, its beneficial effects on the decreased risk for bronchopulmonary dysplasia.
#30 Does elevated midline head position in periviable lambs alter hemodynamic response to surfactant?
A Mari*
M Bawa
S Gugino
J Helman
N Bradley
C Koenigsknecht
A Prasath
P Chandrasekharan
M Rawat
J Nair
University at Buffalo, Buffalo, NY
Purpose of Study
Surfactant administration (Surf) may cause variable changes in cerebral hemodynamics such as an increase (Saliba,1994; Rabe,1991) or decrease in cerebral blood flow (Cowan, 1991) and pulmonary artery pressure (Hamdan,1995). Differences in timing/type of Surf and exposure to antenatal steroids also may be contributing factors (Katheria,2013). Lack of autoregulation in ELBW infants predisposes to swings in cerebral blood pressure (BP) which may contribute to intraventricular hemorrhage (IVH). Elevated head positioning (EMHP) after admission to the NICU may decrease severe IVH, improve oxygenation and survival (Kochan,2019). We hypothesized that EMHP during Surf in a periviable ovine model would decrease hemodynamic fluctuation and improve cerebral oxygen delivery (DO2).
Objective
To evaluate the effect of 15° EMHP during Surf on BP, carotid (CBF) & pulmonary (PBF) blood flow and DO2 in a periviable ovine model.
Methods Used
120d gestation beta-mature lambs, were randomized into elevated (ELEV: 15° elevation) or standard group (FLAT). Lambs were resuscitated per NRP guidelines with delayed cord clamping and initial FiO2 of 0.3. 3ml/kg of intratracheal Surf was administered after 5 min. PBF, CBF, BP, HR, and pulse oximetry (SpO2) were monitored continuously using Biopac and Nonin systems. Blood gases were collected before and after Surf. Graphpad PRISM software was used for statistical analysis using appropriate tests.
Summary of Results
Baseline characteristics were similar (table 1). There was no significant difference in CBF with Surf (figure 1a). PBF was significantly higher in the ELEV group around Surf. Slight increase in PBF after Surf was seen in both groups (figure 1b). BP (figure 1c) was similar between groups. DO2 went up post Surf in both groups, but the response was similar in FLAT and ELEV (figure 1d).
Baseline demographics
Hemodynamics and oxygen delivery during surfactant administration. Blue bar represents approximate period of surf administration. 1a) CBF b) PBF c) MBP and d) oxygen delivery in the two groups are represented.
Conclusions
In our model, EMHP during Surf improved PBF but had no significant effect on systemic hemodynamics. While reduced pulmonary vascular resistance and increased ductal left-to-right shunting after Surf may improve PBF and DO2 in both groups, we speculate that improved ventilation of the lungs and better Qp:Qs matching with ELEV contributes to significantly higher PBF. Further human studies of hemodynamics during Surf in ELEV are needed to assess benefits.
#31 Validation of extubation readiness tool in extremely premature neonates at a regional perinatal center
K Rao1*
M Bawa1
K Kolden2
A Reynolds1
D Handa1,2
M Leaderstorf3
V Elberson1
L Sandin2
M Rawat1
P Orbank3
P Chandrasekharan1
1University of Buffalo, Buffalo, NY
2Oishei Children’s Hospital, Buffalo, NY
3John R. Oishei Children’s Hospital, Buffalo, NY
Purpose of Study
In neonates born extremely premature, prolonged invasive mechanical ventilation with an endotracheal tube and failure to extubate are factors associated with increased mortality and morbidities such as bronchopulmonary dysplasia, retinopathy of prematurity requiring prolonged hospitalization leading to poor outcomes. In the absence of accurate tools to assess extubation readiness, many infants fail their extubation attempt which also increases complications. Gupta et al. have developsed a valuable online calculator that could be helpful to assess the chances of extubation success in extremely preterm neonates. Our objective was to a)validate the extubation readiness calculator in our cohort at a regional perinatal center to predict successful extubation and b) understand if the same factors used in the extubation calculator are applicable to our patient population.
Methods Used
Neonates < 29 weeks, who were admitted to our newly built state-of-the-art tertiary NICU over a 2-year period who were on invasive mechanical ventilation, and had an elective extubation attempt within 60 days of age were included. The primary outcome was to validate the extubation success using the calculator, defined as surviving for at least 5 days after extubation, without a need for reintubation. A receiver operating characteristic curve (ROC) analysis was done. The secondary outcome was to model factors associated with predicting extubation readiness in the calculator. Infants who died or had unplanned extubation were excluded.
Summary of Results
There were 118 infants between 2018 and 2019 who were included. Of the eligible infants, 66% were successfully extubated while 34% of them failed (figure 1). At the time of extubation, these infants were larger, born at older gestation, and had higher pre-extubation pH and lower oxygen (O2 ) requirements than those who failed extubation (figure 3). The ROC analysis for the extubation readiness calculator in our cohort was statistically significant with various validity models shown in figures 2a & 2b. Only the mode of delivery and weight at extubation were statistically significant in our model to predict extubation readiness i.e vaginal delivery and higher birth weight favoring extubation success. This could also be secondary to the fact that our median time of extubation is 9 -10 days after birth as opposed to 3-4 days in the study by Gupta et al.
A regression model of factors used in assessing extubation success in the calculator from our cohort
Conclusions
In our cohort that included data for 2 years, with our current practice, the calculator was validated in infants who were extubated with variable chances of success rate. As time and change in different neonatal intensive care unit practices evolve, the predictor variables for successful extubation will vary decreasing rates of BPD and mortality.
ANS antenatal steroids, GA gestational age, RSS respiratory severity score. Data are represented as median (interquartile range) unless specified.
* p <0.05 – data analyzed by chi-square for categorical variables and Wilcoxon Rank sum test for non-parametric continuous variables.
RSS respiratory severity score
*p <0.05 – data analyzed by chi-square for categorical variables and Wilcoxon Rank sum test for non-parametric continuous variables.
#32 A novel method of measuring peep on bubble nasal CPAP (bnCPAP), using a vascular pressure monitoring device (VPMD)
B Tehreem*
A Bhutada
A Gupta
Suny Downstate Medical center, Brooklyn, NY
Purpose of Study
BACKGROUND bnCPAP is a prevalent noninvasive form of respiratory support in neonates. However, pressure delivery can be unreliable and lead to complications, lower pressures can cause atelectasis and higher pressure can cause air leaks. Continuous monitoring and recording of PEEP are vital, but no such method is currently available. We introduce a novel method for continuously measuring PEEP on bnCPAP using VPMD at the expiratory limb of the nasal prong.
OBJECTIVE
VPMD can be used accurately to continuously measure and record PEEP
Methods Used
This is a prospective, observational trial of neonates requiring bnCPAP. VPMD measurements (in mm of Hg =1.36 cm of H20) at the nasal prongs were displayed as central venous pressure (CVP) on the monitors. Data were continuously recorded per millisecond for 24 hrs using Philips IntelliVue MP70 Neonatal Monitors and ixTrend 2.0 software and saved to a Microsoft Excel file. Spot measurements were recorded 8 hourly using a standard pressure monitoring manometer-AG Cufill (Hospitech). Simultaneous measurements were recorded for set PEEP, VPMD, and Cufill. Data were analyzed using Freidman’s two-way analysis of variance ANOVA
Summary of Results
20 patients were enrolled. Data analysis was performed on 18. There were no differences between the medians of the CVP, PEEP and Cufill values. There were no statistically significant differences between CVP and PEEP ( p-value 0.6), CVP and Cuffil (p-value 0.2) and between PEEP and Cufill (p-value 0.08). Babies stayed within 1 cm of set PEEP for 68.1% of the time, within 2 cm for 80.5% of the time, and within 3 cm for 89.5% of the time.
p-values showing no statistically significant differences between CVP and PEEP, CVP and Cuffill and between PEEP and Cuffill.
VPMD set up and Cuffill syringe. VPMD was connected to the expiratory limb of nasal prongs.
Conclusions
VPMD can be used to continuously monitor PEEP. This device is feasible, easily accessible, and can reliably monitor and record pressures. It provides an objective, bedside tool for accurate measurement of PEEP and set alarm limits. Alarm limits can alert staff about any leakage, disconnect, or changes in pressures to avoid complications of low and high PEEP.
2B: Social determinants of health
#33 The maternal vulnerability index is associated with infant mortality in the United States
D Murosko*
J Radack
B Formanowski
M Passarella
EG Salazar
D Montoya-Williams
C McGann
M Pena
K Paul
H Burris
S Handley
S Lorch
Children’s Hospital of Philadelphia, Philadelphia, PA
Purpose of Study
The Maternal Vulnerability Index (MVI) is a novel index that examines 43 indicators along six themes (reproductive healthcare, physical health, mental health and substance abuse, general healthcare, socioeconomic determinants and the physical environment) to quantify susceptibility to poor pregnancy outcomes. While MVI has been associated with maternal mortality risk, the association of MVI with infant mortality (IM, death before 1 year of age) has not been examined.
Methods Used
This retrospective cohort study analyzed national linked birth-death certificate data from 2012-2014 of singleton infants born at 22 0/7 – 44 6/7 weeks (or 400–8000g if gestational age [GA] was unavailable). The primary outcome was IM. Multivariate logistic regression determined the association between a 20-point change in MVI and risk of IM clustered at the county level, using fixed effects by state, after adjusting for maternal demographics and health indicators, infant GA and rurality. We evaluated the association of IM with each of the 6 sub-themes. To assess concordance between MVI and IM at the county level, we calculated the kappa statistic between MVI and IM dichotomized at the national median values.
Summary of Results
Compared to mothers in the lowest MVI categories, mothers with higher MVI were more likely to be younger, be on Medicaid, have inadequate prenatal care, smoke during pregnancy and be Black or Alaskan Natives/American Indians. Of the 11,456,232 infants in the cohort, 59,056 (0.52%) died before 1 year. IM increased with increasing MVI (0.38% in the lowest MVI quintile vs. 0.70% in the highest, p < 0.001). In the unadjusted model, a 20-point increase in MVI was associated with higher odds of IM (OR 1.18, 95% CI 1.16-1.20); this persisted in the adjusted model (OR 1.06; 1.04-1.07). IM was associated with all themes in the adjusted models except for the physical environment, and was most strongly associated with physical health, mental health and substance use, and socioeconomic determinants (Table 1). There was 60.8% agreement between the dichotomized MVI and IM across the US (Figure 1) (k = 0.217); agreement was similar by region and rurality.
Association between MVI and infant mortality, overall and stratified by MVI theme
Association of high or low MVI with high or low IM rate. High MVI is defined as greater than national median MVI. High IM rate is defined as greater than national median infant mortality rate
Conclusions
MVI is associated with IM in the US. After adjusting for perinatal characteristics, this association persisted, indicating that MVI may be a useful proxy measure when seeking to adjust for maternal characteristics in the absence of individual-level data. MVI may also prove useful for capturing typically unmeasured geographic-based factors, particularly aspects of community-level physical health, mental health, substance use and socioeconomics. Further research is needed to better understand the local influences leading to discordance between MVI and mortality at the individual county level.
#34 Health-related social needs in a pediatric emergency department
G Soma1*
V Shabanova2
T Vargas3
M Sharifi2
M Gaeta2
G Carlotta-McDonald4
M Landock4
K Kourouma4
B Emerson2
G Tiyyagura2
1Yale School of Medicine, New Haven, CT
2Yale University School of Medicine, New Haven, CT
3University of California-Davis, Davis, CA
4Yale-New Haven Hospital, New Haven, CT
Purpose of Study
Background
The pediatric emergency department (PED) serves as a safety net for vulnerable children, but efforts to describe and intervene upon health-related social needs (HRSNs) in this setting are limited.
Objectives
To describe the burden of HRSNs in publicly insured children who present to a tertiary care PED.
To examine the extent to which HRSNs are associated with PED utilization. Utilization was dichotomized as high (accessing the PED > 2 times) vs. regular (accessing the PED once) within the past 12 months.
To describe the impact of patient navigation (PN) on the burden of HRSNs in a group of high–frequency PED utilizers.
Methods Used
We conducted a cross-sectional survey of Medicaid beneficiaries presenting to a tertiary care PED between November 2018 and May 2019. The Accountable Health Communities tool was used to screen for five core areas of HRSN: housing instability, food insecurity, transportation needs, utility needs, and personal safety. Self-reported PED utilization was also collected. Surveys were completed on tablets by caregivers of patients <13 years of age and by patients if ≥ 13 years of age and were offered in English and Spanish. Patients with high PED utilization were offered PN for one year to connect with community resources based on identified needs.
T-tests and Chi-square analyses were used to summarize the association between HRSNs and PED utilization. Logistic regression was used to investigate these relationships. One-year outcomes of PN on the resolution of HRSNs are reported.
Summary of Results
1046 patients or caregivers were screened for the study and 906 (86.6%) consented to participation. Most families (56.0%) had unmet HRSNs (Table 1). Patients with HRSN were more likely Spanish speaking (19.8% vs. 14.4%, p = 0.04), and had an annual family income < $25,000 (40.5% vs. 20.7%, p<0.01) compared to patients without HRSN. Patients without HRSN more often identified as White non-Hispanic (10.4% vs. 3.9%, p<0.01) compared to patients with HRSN. The most common HRSN identified was food insecurity (36.3%), followed by housing instability (30.1%), utility needs (29.5%), transportation needs (18.4%), and concern for personal safety (0.7%).
Patients with HRSN were more likely to be high PED utilizers (58.4% vs. 51.5%; OR = 1.30; 95% CI, 0.99 – 1.72) (figures 1a, 1c) and an increasing number of HRSN was associated with high frequency PED utilization (p<0.01) (figure 1b). Of those who received PN, 50% of HRSNs were resolved (figure 1d).
Description of the patient cohort
Conclusions
There is a high-burden of HRSN in the PED and a burden of HRSN may predict high-frequency PED utilization. PN can help to alleviate these needs.
#35 Neighborhood walkability as a risk factor for preterm birth phenotypes in two Philadelphia hospitals from 2013 – 2016
T Kash1*
R Ledyard2
A Mullin3
H Burris2
1University of Pennsylvania, Philadelphia, PA
2Children’s Hospital of Philadelphia, Philadelphia, PA
3Tufts University School of Medicine, Boston, MA
Purpose of Study
One in ten infants is born preterm in the U.S. with large racial disparities; Black infants are 50% more likely than white infants to be born preterm. The etiology of preterm birth (PTB) remains poorly understood. Some data suggest that neighborhood factors may play a role. Walkability, or how easily individuals can walk to amenities, is one way in which urban planners may affect health through encouraging physical activity. We hypothesized that walkability might be associated with decreased risk of PTB and that associations would vary by PTB phenotype. PTB is heterogeneous and can be either spontaneous (sPTB) from conditions such as preterm labor and preterm premature rupture of membranes or medically indicated (mPTB) from conditions such as fetal growth restriction or preeclampsia. We analyzed associations of neighborhood walkability with sPTB and mPTB in a diverse Philadelphia birth cohort.
Methods Used
We conducted a retrospective cohort study using data from two Philadelphia hospitals (2013-2016). We performed multivariable, multinomial, mixed effects, logistic regression models to quantify associations of walkability with PTB, sPTB, and mPTB. Walkability was quantified using data provided by www.walkscore.com neighborhood Walk Score ranking values spatially joined to patient residential geocodes, with higher scores indicating more walkability. Given racial residential segregation in Philadelphia, we also explored whether walkability might contribute to racial disparities in PTB by testing for interactions using a race*walkability term.
Summary of Results
Patient characteristics and average neighborhood Walk Score stratified by birth outcome are shown in table 1. In models adjusted for maternal age, BMI, insurance status, parity and neighborhood deprivation, walkability (per 10-point increment) was associated with decreased odds of mPTB (aOR 0.90, 95% CI: 0.83, 0.98) but not sPTB (aOR 1.04, 95% CI: 0.97, 1.12) (table 2). We also found that walkability may not be equally protective for mPTB for all patients with different effect estimates for white (aOR 0.87, 95% CI: 0.75, 1.01) and Black patients (aOR 1.05, 95% CI: 0.92, 1.21) (interaction p=0.03).
Characteristics of patients residing in philadelphia who gave birth from Oct 23, 2013 through Oct 22, 2016 (n=19,203) by preterm birth (PTB), spontaneous PTB (sPTB), and medically indicated PTB (mPTB)
Unadjusted and adjustedaodds ratios (OR) of PTB, sPTB and mPTB per 10 point increase in walk score† in all patients and then in models stratified by race/ethnicity
Conclusions
In this diverse cohort, walkability was associated with decreased odds of mPTB but effect estimated varied by race/ethnicity. These results may suggest walkability may not have equal benefits across cities with substantial segregation. Measuring health effects of neighborhood characteristics across populations is key for urban planning efforts focused on health equity.
#36 Screening for social determinants of health in centeringparenting
SM Leib
I Navarro*
K Blankenhorn
C Waggoner
A Paoletti
Einstein Medical Center Philadelphia, Philadelphia, PA
Purpose of Study
Screening for social determinants of health is an important part of well child care. CenteringParentingR is a model of group well child visits that emphasizes family centered care and community building. The objective of this study is to examine rates of screening for social determinants of health and maternal postpartum depression during Centering visits compared to traditional well child visits.
Methods Used
In Centering a cohort of 6-8 same age infant/parent dyads meet with a pediatric provider for shared well child visits and facilitated group discussions for the first 2 years of life. Our clinic sees children in Centering and traditional well child visits.
This case control study included randomly selected infants born 10/1/2014 – 02/18/19 with 5 or more well visits, either in Centering or traditional visits, by 2 years of age at an academic center that serves an urban, minority, publicly insured population. Infants in Centering were matched 1:2 with infants in traditional visits (controls). Using electronic records, we examined rates of screenings for social determinants of health using the Safe Environment for Every Kid Parent Questionnaire (SEEK) at 2, 6, 24 months and for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS) at birth, 4, 6 months.
Summary of Results
The study population included 115 infants in Centering and 220 infants in traditional visits. There were no significant demographic differences between infants in Centering and controls for maternal mean age (26.5 years), race/ethnicity (71% African American, 19% Hispanic, 3% White, 3% Asian), and Medicaid (87%). Mothers in Centering were more likely to be primiparous than mothers in traditional visits (54% vs 37%, p<0.01) and to have behavioral health diagnoses at delivery (17% vs 5%, p<0.001).
At 2 months of age, infants in Centering were more likely to be screened for social determinants of health than infants in traditional visits (90% vs 59%, p<0.001). At 4 months of age, mothers in Centering were more likely to be screened for postpartum depression (59% vs 31%, p<0.001). SEEK screening rates at the 24-month visit were comparable (56% vs 51%, p=NS). Infants in Centering completed more SEEK screenings than infants in traditional care throughout their well child care (p<0.01).
Conclusions
Infants seen in Centering visits were more likely to be screened for social determinants of health and maternal depression than infants seen in traditional visits. Improved screening rates may allow for greater opportunities to provide resources and address social determinants of health that directly impact the health and wellbeing of children and families.
#37 Caregiver perceptions of firearm education
R Shah1,2
S Rogers1,2
B Campbell1,2
K Borrup1
J Knod1,2
G Lapidus1
S Kadian3
M Mizra3
D Chenard1
S Smith1,2,3*
1Connecticut Children’s, Hartford, CT
2University of Connecticut Health Center, Farmington, CT
3University of Connecticut, Storrs, CT
Purpose of Study
Youth suicide has increased at an alarming rate and is now the second leading cause of adolescent death in the United States. The presence of a firearm is correlated with a significant increased risk of suicide death. It is unclear from whom caregivers receive information on firearm safety, and would be most receptive.
The objective of this study was to determine the frequency and venue of firearm education for a cohort of adult caregivers who presented to the pediatric emergency department; specifically, a) if/where they currently receive information b) where they prefer to receive information, and c) knowledge of best safety practices.
Methods Used
This tablet-based anonymous survey was given to a convenience sample of parents in a large, urban tertiary-care hospital between November 2020 and November 2021. Any caregiver who provided shelter for the child at least 20 hours/week was eligible. It was available in both English and Spanish.
Summary of Results
A total of 485 subjects participated:16.9% reported having a firearm in their home, 21.9% reported receiving firearm safety information in the last two years, with 13.0% from their child’s primary care physician. Caregivers reported currently receiving firearm safety information from a police department (17.1%) and guns’ rights organizations such as the National Rifle Association (16.7%). There was an association between having a firearm in one’s home and receiving safety information in the last two years (p=0.03). 29.1% were aware of American Academy of Pediatrics (AAP) best practices for firearm storage. Knowledge of the AAP recommendations and owning a firearm were correlated (chi-square= 33.1, p<0.01). Having a firearm in one’s home was correlated with not believing pediatricians should discuss firearm safety with families (chi-square = 10.9, p<0.01). Rates of firearm possession were similar between parents who reported mental health concerns (31.1%) for their children and those who did not.
Conclusions
The majority of caregivers did not recall receiving information about firearm safety in the last two years and were unaware of AAP best practices for storage. Most firearm education is not provided by pediatricians. There may be opportunities for pediatricians to partner with organizations to disseminate high-quality information related to firearm safety.
#38 Assessment of central precocious puberty care for racial and socioeconomic disparities
S Chau1
V Wu2*
M Yau2
1NYU, New York, NY
2Mount Sinai Kravis Children’s Hospital, New York, NY
Purpose of Study
Health disparities, especially ones that highlight racial and socioeconomic differences, continue to be a major problem within the United States. Central Precocious Puberty (CPP) is a condition in which the onset of puberty in girls occurs younger than eight years and in boys younger than nine years. Timing of pubertal development varies by race and cultural perception of puberty may differ. Gonadotropin releasing hormone agonists (GnRHa) can aid in delaying pubertal symptoms. We aimed to better understand whether a relationship exists between treatment for CPP and insurance type, and CPP and racial differences.
Methods Used
We retrospectively reviewed medical records of 66 females (38 White, 24 Non-white) with CPP treated with a GnRHa from ages 3 to 11 years and collected data on patients’ race, insurance type (17 with Medicaid, 49 with private insurance), medication type (histrelin or leuprolide), age of their first consultation, and length of treatment. CPP diagnostic criteria were breast development at <8 years old, measurable pubertal luteinizing hormone and/or estradiol concentrations, and bone age advancement.
Summary of Results
Mean age was 7.8±1.9 years at first visit and treatment duration was 2.2±1.4 years. The age of the first visit was significantly earlier for those with Medicaid (6.8±2.1 years) compared to those with private insurance (8.2±1.8 years, p < 0.02). There was also a significant difference between race and age of first appointment, with non-White patients being seen earlier compared to White patients (7.1±1.9 years versus 8.2±1.9 years, p < 0.02). There was no significant difference between insurance type and length of GnRHa treatment (p = 0.60).
Conclusions
A lack of difference in such factors demonstrates a commitment to equity of care for all patients regardless of race or insurance coverage. The earlier presentation of non-White patients is consistent with normal racial differences in age of puberty onset. Assessment of treatment practices should occur on a continual basis as it plays an integral part in ensuring quality patient care.
#39 Caregiver Risk factors and reasons for nonparticipation in the WIC program
Y Faryna1*
J Slifer1
J Dong1
A Clonan1
S Smith1,2
1University of Connecticut, Storrs, CT
2Connecticut Children’s Medical Center, Hartford, CT
Purpose of Study
Children’s WIC coverage rates nationally and in Connecticut (CT) have gradually decreased over the decades and substantially trail behind Infants’ and Pregnant/Postpartum Women’s coverage rates. The COVID-19 pandemic compounded this issue; SNAP and Medicaid enrollments increased while WIC enrollments continued to lag. Under these conditions, childhood food insecurity and nutrition-related health disparities persist. More information is needed to identify risk factors and reasons for caregiver nonparticipation in WIC to inform potential family-centered interventions to decrease attrition.
Methods Used
This is a single-center cross-sectional survey study. Inclusion criteria were caregivers of WIC-eligible children who are recipients of Medicaid and present to an urban pediatric emergency department in Hartford, CT. Questions focused on caregivers’ sociodemographic characteristics and attitudes, knowledge and experiences related to the WIC program. Data were analyzed using exploratory methods and logistic regression, p-values <0.05 considered significant.
Summary of Results
288 caregivers met inclusion criteria. Many sociodemographic factors were similar between participants and nonparticipants (table 1). However, an association existed between nonparticipation (NP) and gender, number of adults in a household and presence of healthcare provider-dispensed education on health benefits of WIC. The risk of NP for male compared to female caregivers was 1.6, 95% CI (1.1, 2.0), p=0.02. For caregivers in two-adult households compared to one-adult households the risk of NP was 1.5, 95% CI (1.1, 2.0), p=0.02. The risk of NP for caregivers lacking compared to possessing healthcare provider-sourced education on health benefits of WIC was 1.7, 95% CI (1.3, 2.0), p<<0.01. Nonparticipating caregivers reported not needing WIC services, not knowing how to apply and being ineligible. Caregivers also disclosed barriers related to WIC appointment/clinic availability and accessibility (table 2).
SDC
Caregivers’ perspectives
Conclusions
Risk factors for WIC nonparticipation by caregivers of WIC-eligible children include identifying as male, living in a two-adult household and lacking healthcare provider-sourced education on health benefits of WIC. This suggests that clinical interventions during primary care visits, with attention to two-adult households and males with WIC-eligible children, may be a key step to decreasing WIC attrition. Further qualitative research is needed to fully grasp nonparticipating caregivers’ attitudes towards WIC.
#40 The association between the maternal vulnerability index and preterm birth in the US
EG Salazar1*
D Montoya-Williams1
M Passarella1
C McGann1
K Paul1
D Murosko1
M Pena1
R Ortiz2
S Lorch1
H Burris1
S Handley1
1Children’s Hospital of Philadelphia, Philadelphia, PA
2NYU Grossman School of Medicine, New York, NY
Purpose of Study
The Maternal Vulnerability Index (MVI) is a novel index that quantifies maternal vulnerability to poor pregnancy outcomes. The MVI includes indicators of reproductive healthcare, physical health, mental health and substance abuse, general healthcare, socioeconomic determinants, and physical environment. MVI has been associated with maternal death. This study examined the association of MVI and preterm birth (PTB).
Methods Used
This is a retrospective cohort study using 2018 National Vital Statistics birth certificate data of singleton infants born between 220/7-446/7 wks gestational age (GA) without anomalies. The primary outcome was all PTB (<37 wks GA). Secondary outcomes were stratified GA subgroups: extremely preterm (<29 wks GA), moderate preterm (290/7–336/7 wks GA), and late preterm (340/7-366/7 wks GA). We examined the association of MVI (5 levels, very low to very high) and PTB (all and by GA subgroup) using multinomial logistic regression clustered by county with a state fixed effect after adjusting for maternal demographics and preexisting conditions. We then defined areas with high MVI and PTB as greater than national median values and examined the geographic distribution of the concordance and discordance (quantified using kappa [K]) of high and low MVI with high and low PTB at the county level.
Summary of Results
Of 3,659,099 infants, 8.2% were born preterm (0.6% extremely, 1.5% moderately, and 6.1% late preterm). As MVI increased from very low to very high, PTB rates increase from 7.0% to 10.2%, which was observed for all GA subgroups. Compared very low MVI infants, very high MVI infants had lower birth weight and were more likely to be born to people who were younger, Black, Medicaid insured, less educated, had higher BMI, hypertension, inadequate prenatal care, smoking during pregnancy, lived in rural areas and were from the South census region. The relationship of higher MVI and increased PTB was present in the unadjusted (very high MVI: OR 1.50, 95% CI 1.45-1.56) and adjusted (very high MVI: aOR 1.07, 95% CI 1.009-1.13) analysis. This persisted with GA stratification and was significant at all MVI levels among extremely preterm infants (table 1). Concordance between high MVI score and high PTB prevalence varied across the US (figure 1) and by rurality (metropolitan K=0.43, micropolitan K=0.38, non-core K=0.29).
Models of association between MVI and PTB, overall and stratified by GA groups
Association of high or low MVI with high or low PTB rate
Conclusions
The MVI is associated with PTB, with stronger associations in infants of lower GA. Though association’s strength is reduced in adjusted models, the persistent effect suggests that MVI is a useful composite measure for maternal community exposures. While counties with concordant high MVI and PTB tended to be in the southeastern US, the relationship of MVI and PTB varies throughout the US and should be further characterized.
2C: Adolescent/public health
#41 Perception of pre-exposure prophylaxis to HIV among adolescents in the Bronx
A Cortes Fernandez1,2*
N Scott1,2
K Joy Armada3
J Adjo1,2
D Rubin1,2
1St Barnabas Hospital, Bronx, NY
2CUNY School of Medicine, New York, NY
3Downstate Medical Scool, Brooklyn, NY
Purpose of Study
Introduction
CDC reports that youth 13 to 24 years of age accounted for 21% of all new HIV diagnoses in the US. Emtricitabine/tenofovir for Pre-Exposure Prophylaxis (PrEP) provides a 92-99% reduction in HIV risk for HIV-negative individuals and is an important tool in the prevention of HIV. Due to the increased incidence of HIV in this population, perceptions about this effective method of HIV prevention are important.
Objective
Explore PreP perception among adolescents in a community health center.
Methods Used
This cross-sectional study enrolled a convenience sample of adolescents (13 to 21 years old). Data was collected using a self-administered questionnaire regarding demographics, sexual orientation, sexual behaviors, familiarity with PreP, and attitudes. This questionnaire included a short definition, a statement, and multiple choice answers based on participants’ perceptions of PREP.
Summary of Results
103 adolescents participated in the study with a mean age of 16.62.07 years, 72.8% identified themselves as Hispanic. 61.2% as female, 35% as male, and 3.9% as non-binary. 44.7% reported having sexual intercourse in their life. 83.4% identified as heterosexual, 18.5% as bisexual, and 4% as homosexual.
34.8% denied being tested for HIV and 47.8% for other STIs, during the past 12 months. The mean age of first sexual intercourse was 15 1.6 years, and the average number of sex partners was 2.5.
82.5% reported being not at all familiar with PREP. 61.2% reported not having learned about PreP to prevent HIV, 9.8% learned about it from a healthcare provider, 7.8% on the internet, and 4.9% on school. Only 2.9% reported being prescribed PreP, and 2.9% reported having friends that use it.
On the statement that ‘PrEP should be widely available’ 45.6% reported not knowing enough about it, and 38% agreed with it.
On the statement, ‘If PrEP was available, how likely would you be to use it to prevent HIV infection’, 60.2% reported not knowing enough about it, 35% agreed with it.
No significant association was found between sexual behaviors and PrEP perceptions.
Conclusions
This study explores PrEP perceptions among adolescents in NYC. Most teenagers reported not being familiar with PrEP, but they agreed that it should be widely available. More than a third of the sexually active adolescents denied being tested for HIV in the past year, indicating that a need for increased sexual education including HIV prevention from reliable sources such as health care providers.
#42 Prevalence of cardiometabolic risk in US children and adolescents using TG/HDL-C: are there differences based on age subgroups?
AO Awujoola*
P Torga
J Valencia
SP Kant
Bronxcare Health System, Bronx, NY
Purpose of Study
Evaluation for cardiometabolic risk is critical among children and adolescents as it can predict morbidity in adulthood. Among other lipid ratios, TG/HDL-C ratio has been reported to have high predictive accuracy as a clinical marker for atherogenic dyslipidemia and metabolic syndrome. Given the endocrine changes of puberty, exploring the prevalence and risk among different age subgroups of children and adolescents – prepubertal, pubertal, and post-pubertal adolescents is important. This is the first study, we are aware of that examines the relationship between TG/HDL-C in different adolescent age groups. Therefore, we aim to evaluate the prevalence of high TG/HDL-C in these age subgroups and to determine if there are any significant differences in TG/HDL-C levels based on age stratifications.
Methods Used
We conducted a cross-sectional analysis of children 9 – 21 years from the NHANES 2011–2018. Age was stratified into 9-11 (pre-pubertal), 12–16 (pubertal), and 17–21 (post-pubertal). We used a TG/HDL-C ratio cut-off of 2.5 to determine high versus low levels. Currently, there is no set cut-off for TG/HDL-C. However, existing literature has shown increased cardiometabolic risk at ratios between 2 to 3. We utilized chi-square test to determine whether dichotomized TG/HDL-C ratio differs by age categories and other sociodemographic parameters. Furthermore, a multivariate logistic regression analysis was performed to determine association between the age subgroups and high TG/HDL-C ratio.
Summary of Results
Of the 1685 study subjects, females constituted 51%, 34% were pre-pubertal, 45% pubertal, 21% post-pubertal, and 27.5% had a high TG/HDL-C ratio. Compared to normal TG/HDL-C, adolescents with high TG/HDL-C are more likely prepubertal group(37.9% vs 32.6%), post-pubertal (22.1% vs 20.6%), and less among the pubertal group (40.1% vs 46.8%). (Table 1). After adjusting for race and gender, those in the pre-pubertal age group have increased odds of having high TG/HDL-C (>2.5) (OR 1.36 95% C.I 1.067 -1.734) compared to the pubertal group. Although the post-pubertal group also has increased odds of having high TG/HDL-C (>2.5), it was only marginally significant (OR 1.25 95% C.I 0.947 -1.671).
Characteristics of Subjects Based on TG/HDL-C Level. Categorical variables are presented in counts (frequency and percentages) and comparisons between groups are made using Pearson chi-square statistics. P<0.05
Factors independently associated with elevated TG/HDL-C. The multivariate analysis result is presented. aOR >1 denotes factors that are associated with increased odds of elevated TG/HDL-C, while aOR <1 denotes factors that are associated with decreased odds of elevated TG/HDL-C. Statistical significance was set at (P<0.05) with a 95% confidence interval that excludes null value of 1
Conclusions
US children and adolescents may be at increased risk of cardiometabolic disease. Our study showed that the prepubertal group may be more vulnerable with increased odds of high TG/HDL-C compared to the pubertal group, however, this may be due to the pubertal effect on lipid metabolism. Since the odds of a high TG/HDL-C ratio is also marginally significant in the postpubertal group, this suggests that postpubertal screening may be more valuable and actionable. Follow-up screening at age 17-21 years should be emphasized, as this may help to predict adolescents with increased cardiometabolic risk.
#43 National variation in the black immigrant birth advantage & the role of county-level risk factors
O Amuzie*
N Yang
A Barreto
S Lorch
D Montoya-Williams
H Burris
Children’s Hospital of Philadelphia, Philadelphia, PA
Purpose of Study
Immigrant Black people have lower risks of adverse birth outcomes compared to US-born Black people. However, it is not known whether the Black foreign-born birth advantage varies across the country, nor how county-level markers of disadvantage are associated with variation in nativity disparities in Black birth outcomes.
We examined how gestational length disparities by nativity among Black people in the US vary across the country and how county-level disadvantage and segregation associate with regional variation.
Methods Used
This was a cross-sectional analysis of US birth certificates (2011-2014) for non-Hispanic Black people with singletons. Linear regression explored associations between nativity and gestational length, adjusting for maternal demographics and medical risk factors, clustering by county, with state as a fixed effect. These same models were then run within each US county that had at least 100 total births, with a minimum of 10 births to foreign-born Black people. Counties with a significant positive β estimate for foreign-born (vs. US-born) gestational length were designated as ‘immigrant advantaged.’ Counties were designated as ‘immigrant disadvantaged’ if the estimate was significantly negative, and ‘neutral’ if non-significant. We then performed multinomial logistic regression to model associations of county-level risk factors such as socioeconomics, rurality, and racial and economic segregation with odds of a county being immigrant advantaged, disadvantaged, or neutral.
Summary of Results
In our cohort of 1.9 million births, foreign-born Black people had longer gestational lengths (β = 0.29 wks, 95% CI 0.27, 0.30) than US-born Black people, and were more often privately insured with higher levels of education (Table 1). There were 133 immigrant advantaged counties, 4 disadvantaged, and 440 neutral. Counties with a higher proportion of residents with some college education and a higher proportion of foreign-born residents had higher odds of having an immigrant gestational advantage (Table 2). Counties with higher proportion of white residents had lower odds of an immigrant advantage.
Material characteristics amongst live births to non-hispanic blank people from 2011–2014 in the US1 (N=1,925,771)
Conclusions
Among Black birthing people in the US, the foreign-born gestational length advantage is not uniform across the country. While counties with more foreign-born residents were more likely to be protective for immigrants, counties with more White residents were less likely to be. Our findings indicate the need to understand how the relationship between immigrant enclaves and structural racism affects nativity birth inequities.
#44 Standardized yoga & meditation program for stress reduction for adolescents with irritable bowel syndrome
S Topfer1*
M Wozniak1
N Morris1
B Pradhan2
A Kushnir2
K Kaminski1
1Cooper Medical School of Rowan University, Camden, NJ
2Cooper University Hospital, Camden, NJ
Purpose of Study
IBS, or Irritable Bowel Syndrome, is the most common cause of general recurrent abdominal pain (RAP) in children. This discomfort often significantly impacts the patient’s life, leading to emotional stress, decreased quality of life due to necessary changes in daily living to accommodate bathroom patterns, as well as anxiety and depression. Since IBS is often accompanied by anxiety, along with other psychological and quality of life issues, we are proposing that practicing yoga and mindfulness will decrease anxiety and increase quality of life for patients with IBS. The objective is to measure the impact of a brief, at-home, 6-week twice per week Standardized Yoga & Meditation Program for Stress Reduction (SYMPro-SR) program on anxiety, IBS symptoms, and quality of life in children ages 12-21 years old diagnosed with Irritable Bowel Syndrome.
Methods Used
Using charts from pediatric gastroenterology office from January 2020 to September 2021, we identified and reached out to children ages 12-21 who suffered from IBS. If their parents and they agreed to participate in the study, they filled out the Screen for Child Anxiety Related Disorders, Pediatric Quality of Life Inventory questionnaires and Children Somatic Symptoms Inventory before and after a 6- week online yoga course. A yoga and mindfulness course was created as YouTube videos and access was granted to participants. Results of the questionnaires total scores and sub-scales were analyzed. ANCOVA was performed for repeated measures incorporating age, sex, baseline scores, etc. as covariates.
Summary of Results
In this pilot study, 40 subjects were approached and 8 completed the videos. There were 4 females (50%), 6 Caucasian subjects (80%), 1 Asian subject (10%) and 1 African-American subject (10%). There were 4 subjects with IBS constipation (50%) and 4 with IBS mixed-type (50%). There was significant improvement in Pediatric Quality of Life post intervention (p = 0.01). The SCARED test was subdivided into six sections. The SCARED anxiety section significantly decreased post intervention (p = 0.01). There was a trend for improved outcomes in SCARED panic disorder and separation anxiety post intervention (p = 0.07 and 0.08 respectively). There was a post intervention improvement in a number of variables in the CSSI scale. Four of the 24 symptoms in the CSSI significantly improved post intervention.
Conclusions
Teenagers with IBS were able to complete yoga videos at home, with improvement in quality of life, certain aspects of anxiety and a few somatic symptoms.
#45 A warm approach to reduce hypothermia in preterm infants in a resource limited setting
AO Gupta1,2*
H Ramdial1,2
J McKeever2
1Nemours Childrens Health, Wilmington, DE
2Inspira Medical Center, Vineland, NJ
Purpose of Study
Hypothermia at birth can lead to significant morbidity and mortality in neonates. Due to greater evaporative, convective, conductive and radiation heat losses, and diminished physiologic response to cold stress, preterm infants are at higher risk for hypothermia. NRP added an increased focus on ‘warm and maintain normal body temperature’ in latest revision to address hypothermia in neonates.
Our AIM was to decrease the admission hypothermia (AH) in preterm neonates born at ≤ 36 weeks of gestation to less than 10% of total preterm births within one year.
Methods Used
A quality improvement (QI) project was performed at Level III NICU located in a rural community hospital from April 2019 to December 2021. Preterm infants born at ≤36 weeks of gestational age (GA) were included. AH was defined as temp <97.70F at the time of NICU admission. A Fishbone diagram was developed using the baseline data and ongoing NICU practices. A comprehensive checklist (figure 1) was created using a standardized bundled approach for data collection and to address the contributing factors leading to AH. A multidisciplinary QI team was convened, the team provided education to their respective groups. Infants were categorized based on the mode of delivery (C-section vs Vaginal delivery) and GA at birth (≤32 weeks vs >32 weeks). A statistical process control chart (figure 2) was created to monitor the progress, monthly team meeting was held and evidence-based measures were periodically enacted.
Summary of Results
Total of 301 infant born at ≤36 weeks of GA and admitted to NICU from April 2019 to Dec 2021. Overall, 65% infants were born by CS and 35% by VD, 26% were at <32 weeks GA and 74% at >32 weeks. Baseline data revealed >50% AH in preterm neonates and low ambient temperature (AT <720F). Incidence of AH reduced from 50% in April 2019 to <10% by Sept 2019 and then sustained for more than 2 years for >85% of the months (figure 2). Intermittent fluctuation in AH was noted primarily for infants born by VD and <32 weeks GA, due to low numbers. A direct correlation was noted with low AT (<720F) and AH (figure 2) with 60% of infants developed AH when the AT was <720 F. Incidence of low ambient temperature reduced from 50% in April 2019 to <10% and sustained for majority of months over >2 years.
Hypothermia prevention checklist
Monthly run charts. 3a: Comparison of infants born by C-Section and Vaginal delivery; 3b: Comparison of infants born at <32 weeks or >32 weeks of gestational age; 3c: Effect of low Ambient temperature on admission hypothermia in preterm infants
Conclusions
A multidisciplinary approach and implementation of a standardized evidence-based best practices resulted in significant reduction in the incidence of admission hypothermia in preterm infants born at ≤ 36 weeks gestation. A direct correlation of admission hypothermia and low ambient temperature was identified.
#46 Culturally sensitive nutrition intervention for children of dominican heritage with obesity
J Campos*
L Cochran
D Rubin
J Adjo
SBH Health System, Bronx, NY
Purpose of Study
Background
Childhood obesity has recently increased two-three fold in the United States placing children at risk for significant health problems. Culture influences food preferences, child-feeding practices, intake, and desirable body size. Hispanic families consume the highest intake of sugar-sweetened beverages and saturated fats. Culturally sensitive dietary interventions have been successful in modifying nutritional behaviors, but some are too lengthy for practical use.
Objective
To assess efficacy of a brief culturally sensitive diet intervention for children with obesity.
Methods Used
Design/Methods
Randomized clinical trial of children of Dominican Heritage, 5-11 years old with BMI > 95%-ile. Subjects defined as Dominican Heritage if one or both parents were born in the Dominican Republic. Control group subjects received nutrition counseling using the standard NYC DOH My Plate Planner Tool. Experimental group subjects received a 10 minute nutrition counseling with the culturally sensitive Plate Planner. All subjects completed E-KINDEX validated dietary screening tool to assess obesogenic dietary habits before and 2 months after intervention. Statistical analysis focused on differences between the two groups’ behavior changes and healthy eating habits.
Summary of Results
Thirty subjects enrolled in the study. Participants were 5-11 years of age with equal males and females. All subjects had BMI >98%ile and 63.3% had BMI >99%ile. At baseline, 86.7% of participants in both groups showed high E-KINDEX scores (>60 points), reflecting obesogenic dietary habits. After the intervention, 86.7% of subjects in the experimental group obtained significantly lower E-KINDEX score (<60 points) compared with only 13.3% in the control group. 73.3% of subjects in experimental group showed improvement in their food choices vs 40% in the control group (P=<0.06). There was a significant difference in adherence to the diet between experimental group (86.7%) and control groups (53.4%) (P=<0.04).
Conclusions
Brief, culturally sensitive dietary interventions for young children with obesity is a feasible measure that can be implemented in the primary care setting and result in behavior change.
#47 Trends in cannabis use disorder among pediatric hospitalizations in the United States, 2009–2019
SA Mensah1*
N Parmar2
J Umscheid3
R Turkson4
R Vasudeva3
P Bhatt5
K Donda6
H Doshi7
S Pemmasani8
T Parekh9
F Dapaah-Siakwan10
1Tarkwa Municipal Hospital, Tarkwa, Ghana
2East Tennessee Children’s Hospital, Alcoa, TN
3University of Kansas School of Medicine Wichita, Wichita, KS
4Unaffiliated, Lowell, MA
5United Hospital Center, Bridgeport, WV
6University of South Florida, Tampa, FL
7Pediatrix Medical Group, Fort Myers, FL
8Icahn School of Medicine at Mount Sinai, Elmhurst, NY
9George Mason University, Fairfax, VA
10Valley Children’s Hospital, Madera, CA
Purpose of Study
As of 2021, marijuana is allowed for medical use in 36 states in the United States (US) while recreational use is allowed in 13 states. A few single-center studies from the US suggest that marijuana exposure or use in children is increasing but it is unknown if this trend is nationwide. To examine the trends in the prevalence of cannabis use disorder (CUD) in pediatric hospitalizations aged 11-21 years in the US from 2009 through 2019.
Methods Used
This is was a repeated cross-sectional analysis of pediatric hospitalizations aged 11-20 years within the Healthcare Cost and Utilization Project’s Kids Inpatient Database (KID) from (2009, 2012, 2016, and 2019). KID is the largest, all-payer inpatient pediatric administrative database in the US, and it is released every 3 years. International Classification of Diseases (ICD-9 and ICD-10) diagnostic codes were used to identify CUD hospitalizations. Transfers were excluded to avoid double counting of hospitalizations. The outcomes of interest were the changes over time in the prevalence of CUD among pediatric hospitalizations and the trends in length of stay (LOS) and inflation-adjusted hospital cost of hospitalizations with CUD. The prevalence rate of CUD was expressed as the number of hospitalizations with CUD per 1,000 pediatric hospitalizations. The exposure variable was a calendar year. The Chi-square test for trend was used to analyze the changes in the prevalence rate of CUD. Linear regression was used to assess the trend in LOS and hospital costs. P-value <0.05 was considered significant.
Summary of Results
Out of 5.57 million pediatric hospitalizations aged 11-20 years, 292,816 were associated with CUD during the study period (prevalence of 52.5 per 1,000). The overall prevalence rate of CUD among pediatric hospitalizations (per 1,000 hospitalizations) increased by 132% from 33.2 to 77.1 between 2009 and 2019 (figure 1). The prevalence rate increased significantly for all age groups, genders, races, and census/geographic regions (table 1). The percentage increase in the prevalence of CUD between 2009 and 2019 was highest in Hispanics (241%), age group 11-13 years (179.2%), females (189.7%), the South region (182.8%), and those with Medicaid (164.3%). Mean LOS was 5.1 days and it decreased from 5.3 to 5.1 days. The mean hospital cost per hospitalization associated with CUD was $7,088 and there was a significant increase from $6,580 in 2009 to $7,353 (P < 0.001).
Trends in the prevalence of CU per 1,000 hospitalizations by age group, gender, race, and hospital region
Trends in cannabis use among pediatric hospitalizations aged 11-21 years in the United States, 2009-2019
Conclusions
There was a significant increase in CUD among pediatric hospitalizations aged 11-21 years in the US from 2009 through 2019. This was associated with significant resource use. The implications of these on the medical and mental health of children and society at large require further investigation.
Fellows case competition
#49 Desaturations in a term infant
K Nyman*
S Patel
J Diaz
University of Maryland Medical Center, Baltimore, MD
Case Report
History
On day of life 1, a term infant born to a 23-year-old G4P3013 mother was evaluated in the nursery for multiple episodes of cyanosis associated with respiratory distress and hoarse cry. These events were precipitated by feeding and associated with copious secretions as well as desaturation down to 70% SpO2. He was transferred to the NICU for further evaluation and management. With the help of multiple pediatric subspecialties, the infant underwent diagnostic testing over the course of several weeks. He continued to have periodic cyanotic events despite differing levels of respiratory support and varied feeding strategies.
He was born by forceps assisted vaginal delivery with a routine resuscitation; APGARs of 8 and 9.
Maternal labs unremarkable.
Physical Examination:
Temp: 36.4 °C, Pulse: 180, Resp: 76, BP: 81/40, SpO2: 92%, birthweight 2.74kg
Well-appearing. Mild microcephaly. Palate intact with a hoarse cry. Cardiopulmonary exam within normal limits. Neurological exam notable for periods of hypertonia and hypotonia.
Labs and Diagnostics:
Blood culture: no growth
Urine CMV negative
HSV negative
CSF unremarkable
Nostrils patent bilaterally
CXR confirmed normal passage of NG tube into the stomach
Laryngoscopy: normal movement of the vocal cords
Upper GI study: normal
Head US: normal
MRI brain with spectroscopy: elevated peak of lactate
EEG: normal
Sleep study: moderate OSA
ECHO: normal
Ophthalmologic exam: normal
Lactate, blood amino acids, uric acid, urine pyridoxine-dependent epilepsy, urine organic acids, urine ketones: all normal
Rapid whole exome sequencing found two missense mutations in the CHRNA1 gene on chromosome 2q31
Final Diagnosis:
Fast-channel congenital myasthenia syndrome 1B
Discussion
The initial differential included tracheoesophageal fistula, vocal cord paralysis or paresis, choanal atresia, seizure, inborn errors of metabolism, mitochondrial disease, glycogen storage disorders and neuromuscular disorders. Desaturations and apnea are common symptoms prompting healthy babies from the nursery to undergo evaluation in the NICU. In our case, while many common etiologies were ruled out early on, the diagnosis was primarily made by whole exome sequencing.
Fast-channel congenital myasthenia syndrome (FCCMS) presents with early-onset progressive muscle weakness. There is dysfunction in the post synaptic neuromuscular junction from defects in the acetylcholine receptor. Inheritance can be autosomal dominant or recessive. FCCMS only affects skeletal muscle, therefore cardiac and smooth muscle are spared. Due to the fatigable skeletal muscle, the clinical manifestations include respiratory insufficiency with desaturations, apnea, and cyanosis. Other symptoms include stridor, hoarse cry, poor suck, ptosis, and generalized weakness.
After treatment with pyridostigmine (acetylcholinesterase inhibitor) the infant’s symptoms improved. He was able to feed by mouth and his cyanotic spells resolved.
#50 Ketamine use in a newborn with hemi-megalencephaly and super-refractory status epilepticus: a case report
V Mandal1*
A Andrews2
F Tirol2
S Kaushal2
P Pergami2
1Inova Alexandria Hospital, Alexandria, VA
2MedStar Georgetown University Hospital, Washington D.C
Case Report
Background
Hemimegalencephaly (HMG) is a well-known cause of refractory seizures in neonates. Ketamine is an N-methyl-d-aspartate (NMDA) receptor antagonist that is increasingly used to treat refractory status epilepticus (RSE) in adults and older children. To our knowledge, its use in neonates is limited to case reports. Although attractive for use in these patients, concerns regarding potential ketamine-mediated neurotoxicity in the immature brain remain.
History
We present a neonate with partial HMG and super-refractory status epilepticus (SRSE) since birth who was successfully controlled by the addition of ketamine to her anti-seizure medications (ASM) from days of life (DOL) 5 to 18. Prior failed ASM included midazolam infusion (Fig.1). Addition of ketamine at 3.5 mg/kg/hour (max. infusion rate) decreased seizures from almost continuous status epilepticus (SE) to discrete seizures lasting less than one hour (DOL 9), and ultimately brought seizure duration down to a median of 3-5 min, max. 20 min, with cycles of focal ongoing SE. Brain MRI at DOL 64 demonstrated frontal-dominant cystic white matter degeneration. The role of ketamine in the development of this finding is uncertain, although declining cardiac ejection fraction (39% at DOL 21) could have resulted in perfusion deficit. At 8 months of life, functional hemispherectomy was safely and successfully performed, leading to seizure cessation up to the time of writing (14 months of life).
Discussion
Animal models have shown upregulation of NMDA receptors in ketamine exposed neurons in developing brains leading to increased intracellular Ca2+, generation of reactive oxygen species and apoptosis. In these models significant apoptotic neurodegeneration was observed in the frontal cortex and several other brain regions following high doses of ketamine administration. It is unclear if the neuroprotective effects of ketamine shown in a pilocarpine-induced rat model of SE is due to lower seizure burden in the ketamine vs placebo-treated group. Despite potential ketamine neurotoxicity, the relative benefit of this agent in RSE control and the decreased use of other ASM is undisputable. This pertains to our case given the distribution and degree of cystic degeneration on MRI is unlikely due to vigabatrin toxicity, but potentially, to relative demand ischemia given depressed cardiac output in the context of SRSE. Ketamine infusion did not overlap with peak cardiac dysfunction for this patient; however, it was employed prior to the interval MRI depicted (Fig.2). Thus, the cystic degeneration could also be multifactorial in cause.
Timing of anti-seizure medication (y-axis) at days of life (x-axis)
MRI at DOL 11 and DOL 64
Conclusion
In this patient, ketamine was effective in controlling SRSE. It’s association with changes identified on MRI is unclear, but potential side effects need to be weighed on a case-by-case base. Further studies are necessary to establish the safety and efficacy of ketamine use in neonates.
#51 Respiratory distress in a neonate – when boards meet real life
M Bawa*
V Elberson
P Rivera Hernandez
G Perez
J Nair
University at Buffalo, Buffalo, NY
Case Report
A male infant is born at 37w to a 34-year-old G3P2 mother by vaginal delivery after an uncomplicated pregnancy. Prenatal screens are negative. The patient had a birth weight of 2,620 g, with Apgar scores of 9 and 9. On day 2 after birth, had increased work of breathing which prompted transfer to a level II NICU for further management.
On arrival to the unit, the infant is tachypneic with mild chest wall retractions and thick nasal secretions. A CBC and blood culture were collected and empiric antibiotic therapy was started. Respiratory viral panel and COVID test are negative. A chest radiograph shows a middle lobe opacity concerning for pneumonia (figure 1). His clinical status failed to improve and on day 4 after birth, supplemental oxygen was provided. The primary team consulted ENT and Pulmonology services. Flexible laryngoscopy showed a normal anatomy. Pulmonology recommended transferring to our NICU for a chest CT with bronchoscopy.
Our differential diagnosis for this neonate with respiratory distress that fails to improve over time or with antibiotics was broad, but further testing revealed this infant’s condition.
A CBC, CRP and a blood gas were collected on admission and were normal. ID service was consulted. A Chest CT showed bilateral atelectasis. Bronchoscopy showed a normal anatomy. Bronchoalveolar lavage was sent. Umbilicus swab was positive for MRSA, nasal wash/sputum culture/bronchoalveolar fluid also grew moderate S. aureus. Nasal ciliary biopsy sent for electron microscopy.
Positive umbilicus and nasal swab, and subsequently BAL for MRSA led to a diagnosis of MRSA neonatal rhinitis. Therapy with IV vancomycin was initiated and later changed to oral clindamycin to complete a total of 14 days of therapy.
The neonate was weaned off oxygen support on day 11. His clinical symptoms improved. He was discharged on oral clindamycin with follow up appointments with pulmonology and ID clinics. His ciliary biopsy showed absence of outer and inner dynein arms, compatible with the diagnosis of primary ciliary dyskinesia (PCD) (figure 2). Genetic testing for PCD showed mutations in the DNAAF1 and CCDC40 genes.
This neonate was diagnosed with primary ciliary dyskinesia (PCD) but his presentation at birth was nonspecific and the differential diagnosis was broad. There is no gold standard diagnostic test for PCD and high clinical suspicion is important. Since it is most likely an AR inheritance, screening of family members is essential.
Initial management of neonates may include measures that manage the respiratory distress, airway clearance to prevent respiratory infections and treat bacterial infections. Chest physiotherapy may help if recurrent atelectasis. Flexible bronchoscopy and bronchoalveolar lavage may help both to diagnose and treat the underlying infection. Antibiotic therapy based on organism growth for exacerbations may prevent development of bronchiectasis.
#52 Feeding aversion in an infant eluding to a rare renal pathology
E Vargas*
M Williams
S Mason
Connecticut Children’s, Hartford, CT
Case Report
History: An 8-month-old male with no significant medical history presents to the ED with two months of decreased oral intake (initially solids, then liquids), two weeks of postprandial emesis, fatigue, and decreased wet diapers. Initial labs demonstrate severe electrolyte derangements, acute kidney injury, high anion-gap metabolic acidosis, anemia, and transaminitis. Admitted to the PICU.
Family History: Maternal congenital partial hearing loss
Physical examination findings:
Initial vital signs within normal limits.
Constitutional: Awake, fatigued, highly irritable, not making tears
HEENT: Anterior fontanelle flat, TM normal b/l, moist mucous membranes
Neck: Normal ROM, supple, no lymphadenopathy
Cardiac: Tachycardia, no murmur
Pulmonary: Tachypnea, mild subcostal retractions, clear breath sounds b/l
Abdominal: Hypoactive bowel sounds, soft, non-distended non-tender abdomen, no organomegaly
GU: No scrotal edema
MSK: Normal ROM
Neurologic: Alert, normal suck, good tone
Skin: Delayed capillary refill, pale, no rash or edema
Laboratory or Diagnostic imaging or Procedures:
WBC 19.6, no left shift; hematocrit 18; platelet count 332,000
Na+ 109, K+ 4.6, Cl- 80, HCO3 4, Gluc 90, Ca2+ 9.6, Mg 1.8, Phos 8.2, BUN/Cr 164/8.3, anion gap 30, albumin 4.3, AST/ALT 79/117, total bilirubin 0.2, coagulation studies normal
VBG: 7.1/15.6/56/4.9/79/-25
UA: clear, pH 5, gluc 150, small hgb, trace ketones, large leukocytes, neg nitrates, WBC 6, moderate protein, SG 1.006
Renal Ultrasound: Enlarged, markedly echogenic kidneys bilaterally without hydronephrosis. Normal renal vascular flow.
Renal Biopsy: Extensive calcium oxalate crystals and 70% fibrosis of renal tubules. Tubular atrophy and interstitial fibrosis, diffuse and severe with abundant calcium oxalate deposits, consistent with advanced oxalate nephropathy.
Plasma oxalate level: 8.5 mmol/L (reference range <2.5)
Final Diagnosis: Primary Hyperoxaluria Type 1 (PH1), confirmed by genetic testing.
Light microscopy of kidney biopsy with severe tubulointerstitial inflammation
Polarized light of kidney biopsy with extensive oxalate crystal deposition
Discussion
PH1 is a rare inborn error of metabolism with a high mortality risk, characterized by deficiency in a liver-specific enzyme, alanine-glyoxylate aminotransferase (AGT). Oxalate overproduction and excessive urinary excretion cause insoluble calcium oxalate crystal deposits in the kidney and urinary tract. As renal involvement progresses, glomerular filtration rate declines, leading to further oxalate accumulation, end-stage renal disease, and ultimately systemic oxalosis with deposits in organs including the bone, heart, joints, nervous system, retina, skin, soft tissues, and vessels. Pyridoxine is an adjunctive treatment as it is metabolized into the main co-factor of AGT. Not all patients are responsive and dialysis may only remove up to 25% of daily hepatic oxalate production. Optimal therapeutic outcomes are achieved by a combined hepato-renal transplantation. Studies show the median time between initial symptoms and diagnosis is over five years, making diagnostic delay a crucial issue.
#53 Unusual case of lower extremity pain in pediatric patient with osteogenesis imperfecta
A Amin*
M Ali
K Wong
Rutgers University New Jersey Medical School, Newark, NJ
Case Report: History
An 11-year-old male with history of Osteogenesis Imperfecta (OI), presented to the pediatric emergency department with bilateral lower leg pain after a trip and fall. Past medical history was significant for unknown type of OI – ‘mildest form’ per mother’s report. The patient has had ten previous fractures, most recently three years ago.
Physical Examination Findings
Vital signs: T 36.6°C, BP 102/57, HR 86, RR 18, SpO2 100% RA. Patient was in acute distress requiring IV morphine for relief. Physical exam was significant for tenderness and swelling of the distal femurs and proximal tibias bilaterally with decreased range of motion at the knees. Distal pulses and sensation were intact.
Diagnostic Imaging and Procedures: Radiographs of bilateral femurs, knees, tibias, and fibulas were negative for fracture or dislocation. On re-evaluation, patient continued to have severe pain in both lower extremities and became hysterical with each attempt to reexamine him.
After consulting with orthopedic surgery, patient was splinted under procedural sedation for CT of bilateral lower extremities to evaluate for occult fracture. Given patient‘s significant pain despite IV analgesics, compartment pressures were measured and found to be elevated (right anterior 31 mmHg, left anterior 75 mmHg). Patient was taken to the OR for emergent bilateral anterior and lateral compartment decompressive fasciotomies.
Post-operative MRI imaging of bilateral knees revealed acute intra-articular Salter-Harris III fractures of bilateral tibial epiphyses. Patient underwent additional procedures for fasciotomy closures, tendon avulsion repair, and internal fixation of the fractures. He was discharged home and has since recovered appropriately.
Final Diagnoses: Bilateral Tibial Tubercle Fracture; Bilateral Anterior Compartment Syndrome
MRI Left Knee: nondisplaced fracture (blue arrow) from tibial epiphysis to physis, consistent with Salter-Harris III fracture. Sclerotic bands within proximal tibia consistent with Osteogenesis Imperfecta.
MRI Right Knee: nondisplaced fracture (blue arrow) from tibial epiphysis to physis, consistent with Salter-Harris III fracture. Sclerotic bands within proximal tibia consistent with Osteogenesis Imperfecta.
Discussion
Osteogenesis Imperfecta (OI) is a group of inherited connective tissue disorders caused by genetic defects in collagen processing and bone mineralization (i.e. COLA1A gene). The inherently weaker bones of these patients are prone to fractures, so the use of advanced imaging like CT or MRI may be warranted in the setting of negative radiographs.
Fractures and the ensuing edema threaten Acute Compartment Syndrome (ACS) in all patients, but patients with OI are at a heightened risk secondary to their generalized fragility of connective tissue, including that which comprises vascular walls. ACS is defined as an acute rise in pressure in a muscle group enclosed by inelastic fascia, which compromises blood supply and results in ischemia and myonecrosis. Given the high morbidity associated with ACS, it is paramount to remain suspicious in pediatric patients exhibiting any of the traditional 5 P’s – pain, pallor, paresthesia, paralysis, and pulselessness – or the pediatric-focused 3 A’s – anxiety, agitation, and increasing analgesic requirement – especially in the setting of connective tissue diseases like OI.
#54 A case of transient hyperthyroidism due to acute suppurative thyroiditis in a pediatric patient
L Crawford*
J Gupta
Pediatric Endocrinology, Golisano Children’s Hospital, University of Rochester, Rochester, NY, United States
Case Report
Acute suppurative thyroiditis is a rare and potentially life-threatening cause of thyroid inflammation in children requiring prompt recognition and management. Relatively few case reports have documented hyperthyroidism in conjunction with acute suppurative thyroiditis.
History: A 9-year-old boy presented to the hospital with one week of progressive fevers and anterior neck pain with limited range of motion in his neck in addition to night terrors, emotional lability, and headaches. His parents began to notice a change in his voice and swelling in his neck one day prior to presentation.
Physical Exam: On initial exam, he was afebrile and hemodynamically stable with a tender and firm anterior neck mass with limited range of motion in his neck.
Diagnostic Testing: Laboratory testing was remarkable for neutrophilia without leukocytosis, elevated inflammatory markers (ESR, CRP), and hyperthyroidism (TSH 0.01 uIU/mL, FT4 2.7 ng/dL, FT3 3.6 pg/mL, T3 146 ng/dL). Ultrasound and subsequent CT imaging of the neck were concerning for a heterogeneous collection in the region of the left thyroid (see figure 1).
Diagnosis: Acute Suppurative Thyroiditis and Adenitis
Clinical Course: He was initiated on intravenous ampicillin-sulbactam with minimal clinical improvement. Subsequently the patient was taken to the operating room for incision and drainage, resulting in rapid clinical improvement in pain. Cultures of the drainage grew pan-sensitive Streptococcus anginosus, a bacterium commonly associated with oral flora. The patient was transitioned to amoxicillin-clavulanate to complete a three-week course of oral antibiotics. On post-operative day 15, his hyperthyroidism had resolved (TSH 2.82 uIU/mL, FT4 1.2 ng/dL, FT3 4.0 pg/mL, T3 147 ng/dL) and inflammatory markers trended down. He will have further testing to determine if any anatomical abnormality (such as a pyriform sinus fistula) is present that may have predisposed him to developing acute suppurative thyroiditis.
Thyroid function tests
CT imaging
Discussion
Hyperthyroidism as a complication of acute suppurative thyroiditis is a rare phenomenon thought to be the result of the release of preformed thyroid hormone from damaged thyroid follicles. This has been documented in the literature a handful of times in adult patients, though there are even fewer case reports documenting this finding in pediatric patients. Generally, in reported cases and in our patient, appropriate treatment of acute suppurative thyroiditis with incision and drainage and antibiotic therapy results in the resolution of hyperthyroidism.
#55 Maternal SARS-CoV-2 infection in the second trimester and ventriculomegaly and developmental delay in an infant
VM Castro Diaz1*
N Cordero1
S Elshahawy1
J Escalona1
H Phan2
SM Parab1
1Richmond University Medical Center, Staten Island, NY
2NYS Institute of Basic Research in Developmental Disabilities, Staten Island, NY
Case Report
History: Mother is a 23 year old gravida 4 para 1021, with a history of type 1 diabetes since 12 years of age. Prenatal sonogram at 20 weeks of gestation showed normal fetal anatomy with an EFW 21st percentile & 2-vessel cord. She was admitted at 23 weeks of gestation for acute hypoxic respiratory failure secondary to SARS-CoV-2 pneumonia, diabetic ketoacidosis & acute kidney failure. She refused intubation in spite of saturations in low 80s & was treated with high flow nasal cannula, non-rebreather mask, & nasal CPAP. She received convalescent plasma, Remdesivir, Tocilizumab, steroids, hydroxychloroquine, ceftriaxone & azithromycin, and was discharged home on oxygen after 29 days. Prenatal sonogram at 29 weeks of gestation demonstrated severe IUGR (abdominal & head circumference, fetal weight and femur length all < 3rd percentile), ventriculomegaly & a 2-vessel cord. Fetal MRI showed severe lateral ventriculomegaly of the brain, diffuse white matter parenchymal edema, bilateral germinal matrix & intraventricular hemorrhage & severe parenchymal volume loss. Mother was lost to follow up until time of delivery.
Physical examination
An infant female was born at 39 weeks of gestation via repeat cesarean-section. She was admitted to NICU for severe IUGR. The newborn’s birth weight was 2126 g, head circumference 30 cm, length 43.5 cm (all <3rd percentile). Baby had mild hypertonia and tremors, rest of the exam was normal. The newborn was treated for TTN with NCPAP, hypoglycemia requiring IVF and hyperbilirubinemia requiring phototherapy and was extremely slow to feed.
Diagnostic work-up
CBC, BMP, LFT & CSF microscopy were normal, SARS-CoV-2 PCR was negative. SARS-CoV-2 IgM was negative in serum & CSF, but IgG was positive in serum & CSF. Baby’s titers were slightly higher than mother’s. US & MRI confirmed ventriculomegaly due to volume loss, a component of hydrocephalus was suspected due to presence of intraventricular hemorrhage, however there was no evidence of raised ICP. Retinal exam, hearing and BAER were normal. Chromosome analysis was normal & Zika titers were negative. The newborn was discharged home after 20 days with weighing 2580 g and head circumference of 32 cm. Placental was 222 g with <10% infarction and moderate acute chorioamnionitis. Infant has significant developmental delay at 1 year of age.
MRI T1 sagital
MRI T2 coronal
Discussion
There is definitive evidence of adverse neonatal outcomes in third trimester maternal SARS-CoV-2 infection, effects of earlier infections are not well reported. In our case the neurological injury can’t be attributed definitively to fetal SARS-CoV-2 infection as IgM was negative, but the interval of 16 weeks between maternal infection and delivery need to be taken into account. Maternal illness likely contributed to severe acute on chronic fetal hypoxia which resulted in IUGR and in utero IVH with resultant CNS tissue loss and ventriculomegaly.
#56 Adolescent with rapidly enlarging jaw swelling
S Ramesh*
NE Abreu Roa
S Manwani
BronCare Health Systems, Bronx, NY
Case Report
HISTORY: Previously healthy 17-year female with a week of right facial pain presented with an acute one-day onset of right jaw swelling and poor oral intake. She had prior dental caries despite good oral hygiene.
PHYSICAL EXAM & DIAGNOSTICS: In ER, she was febrile (100.4F) with trismus, and right-sided jaw swelling with overlying tenderness and induration. Labs showed leukocytosis, elevated CRP, and Head CT showed periodontal disease of right 1st molar with soft-tissue infiltration and regional lymphadenopathy. Bedside incision and drainage were unsuccessful in expressing pus. She was admitted to the inpatient unit for antibiotic therapy and pain control in view of facial cellulitis possibly secondary to an odontogenic source.
HOSPITAL COURSE: Admission exam showed an indurated right submandibular swelling and caries in tooth #30 (right 1st mandibular molar) that was tender to palpation/percussion, without uvular deviation or elevation of the floor of the mouth. She received IV Ketorolac, IV Clindamycin, and oral chlorhexidine rinses. Wound cultures showed mixed gram positive-gram negative cocci and gram variable bacilli on Gram stain. The infected tooth (#30) was extracted on the day of hospitalization (DOH) 2. However, on DOH 4 (POD 2) she spiked fevers (101F) with worsening swelling, voice changes, and trismus. She received IV Dexamethasone and antibiotics switched to IV Meropenem and Vancomycin. Emergent contrast CT showed ring-enhancing contiguous fluid collection within the oral cavity along with bilateral nodules concerning an abscess, suggestive of Ludwig’s angina. On DOH 6, the patient underwent emergency surgical exploration and debridement of bilateral submandibular and submental areas. Intra-operatively, no purulent material was expressed. Cultures grew rare gram-positive cocci, but no single organism was isolated. The patient was discharged home (DOH 12) after clinical and laboratory improvement on PO Linezolid and Augmentin. She has had an uneventful outpatient follow-up.
FINAL DIAGNOSIS: Ludwig’s Angina
Contrast neck CT shows a ring-enhancing fluid collection (yellow arrow) that is contiguous and concerning for an abscess. Periodontal changes (red arrow) may be consistent with post-surgical findings.
Discussion
Ludwig angina is a rapidly enlarging, life-threatening cellulitis of deep spaces of neck that presents with edema of the soft tissues and floor of the oral cavity. Mandibular molars (#19 and 30) are the common culprit, especially because the roots of these molars penetrate the inner cortex of the mandible and serve as a gateway for dissemination. The infection then extends from the submandibular region and spreads by continuity rather than by lymphatics. Ludwig angina is a clinical diagnosis and cultures have low diagnostic yield. Contrast CT (95% sensitivity) can aid in the diagnosis. Airway management, broad-spectrum antibiotics, and steroids are first-line treatments, along with early surgical debridement to improve prognosis, lower the rates of airway compromise, and prevention of further complications.
3A: Quality improvement
#57 A quality improvement project to decrease nasal pressure injuries in a neonatal ICU
V Dumpa1*
L Rios2
C Tiozzo1
L Pitter2
M Quintos Alagheband1
M Kim1
1NYU Long Island School of Medicine, Mineola, NY
2NYU Langone Hospital – Long Island, Mineola, NY
Purpose of Study
Early use of non-invasive ventilation (NIV) in neonates decreases the risk of lung injury and is the preferred mode of ventilation even in extremely premature neonates. Preterm infants are at an increased risk of nasal injuries due to the continuous pressure from the interface on their fragile skin. With the increasing use of NIV, the incidence of nasal pressure injuries (PI) in the neonatal intensive care unit (NICU) is estimated to be as high as 60%. These injuries can cause pain, infection, and rarely damage to underlying nasal cartilage leading to severe nasal deformities. After observing an increased incidence of NIV-related PI in our NICU, we launched a quality improvement project to tackle this problem.
The objective of this study is to decrease the rate of nasal PI by 30% from a baseline of 0.36 injuries/100 NIV days to a goal of 0.25 injuries/100 NIV days by December 2020. The secondary aim is to eliminate any serious harm nasal PI (stage 3 and beyond as per the national pressure injury advisory panel staging).
Methods Used
An interdisciplinary team was formulated in late 2017 and the collection of data on NIV-related PI and NIV days was started. We conducted a series of plan-do-study-act (PDSA) cycles focused around early detection of injury, change of NIV interface and alternating mask and prongs at the first sign of injury, use of nasal cannulaide as a protective barrier, engagement of both frontline nursing and respiratory therapy staff to do daily skin checks, and increased involvement of wound care nursing. NIV-related PI rates/100 NIV days were analyzed monthly using run charts (figure 1).
Summary of Results
Through this series of PDSA cycles, we were able to significantly decrease our rate of nasal PI from a baseline of 0.34 from January 2018 to Q2 2019 to 0.24 injuries/100 NIV days by December 2020, with a continued improvement noted in 2021 with a rate of 0.11 injuries/100 NIV days. There was no serious harm nasal PI after 2019. A spike of events was noted in the second quarter of 2020 during the COVID-19 surge in New York. This increase is likely secondary to the strain on healthcare resources during that time.
Run chart showing the nasal PI rates during the study period with the interventions at different time periods. There was a significant centerline shift in the median nasal PI rate from a baseline of 0.34 from Q1 2018-Q2 2019 to 0.18 thereafter. The star denotes the increased incidence during the COVID-19 surge
Conclusions
Using quality improvement methodology, we identified opportunities for improvement and instituted measures to decrease nasal PI in neonates. Multidisciplinary collaboration, accessibility to alternative interface(s) if needed, and the use of a barrier between interface and skin are effective strategies to decrease nasal PI in the NICU.
#58 Decreasing peripheral intravenous infiltration and extravasation rates in children- a quality improvement initiative
V Dumpa
D Mody*
M Dziomba
D Thomas
M Quintos Alagheband
NYU Langone Long Island, Mineola, NY
Purpose of Study
Background
Intravenous fluid therapy and medications via peripheral intravenous catheters are an essential part of the inpatient management of pediatric and neonatal patients. The innate nature of children being active poses significant risk of dislodgement of these catheters. This can cause peripheral intravenous infiltration or extravasation (PIVIE) of fluids and medications in surrounding tissue, resulting in tissue necrosis, ulceration or rarely compartment syndrome requiring reconstructive surgery. These events increase hospital acquired harm to the patients, the number of painful procedures, length of stay, cost and patient dissatisfaction. After a severe case of PIVIE was noted in a neonate in our institution in 2016 that resulted in a scarring injury, we identified that there are opportunities to improve and designed a quality improvement project to decrease PIVIEs.
Objective
To decrease the number of total PIVIEs (mild, moderate and severe) in neonatal and pediatric patients under the age of 18 years by 50% from a baseline rate of 2.05 per 1000 patient days over a period of 2.5 years. The secondary aim is to eliminate serious harm PIVIEs (moderate/severe).
Methods Used
The study was conducted at an academic medical center from May 2019 to October 2021. PIVIEs were staged based on guidelines from the Children’s Hospitals’ Solutions for Patient Safety network. The Plan-Do-Study-Act (PDSA) method of quality improvement was used for this project. An existing interdisciplinary PIVIE prevention team conducted 3 PDSA cycles during the study period to institute, modify and improve the action plans aimed to decrease PIVIE. Some of the major action items included standardization of intravenous catheter securement, use of new intravenous catheter kits with transparent taping, and engagement of frontline staff and family (figure 1).
Summary of Results
After the PDSA cycles, the overall rate of PIVIEs decreased from a baseline of 2.05 to 0.46 per 1000 patient days during the active intervention period of 11/19 to 10/21 (figure 2). The serious harm (moderate/severe) PIVIE rate decreased from 0.64 to 0/1000 patient days during those time periods (figure 3).
Conclusions
Identification of opportunities for improvement and implementation of evidence-based practices led to a decrease in the rates of PIVIE in our institution. Although improvement in outcome measures was noted, additional work is needed in key areas such as documentation of PIV care in electronic medical record and consistent approach to early identification and management of PIVIEs. Frontline staff engagement is essential to sustain any quality improvement initiative.
#59 Reducing unplanned extubations (UE) in a level IV neonatal intensive care unit (NICU)
SM Cullen*
E Ahn
L Mrija
K Jonas
C Blake
R Hemway
K Mohrman
J Perlman
SN Osorio
P Tiwari
New York Presbyterian-Weill Cornell, New York, NY
Purpose of Study
UE is a frequent problem in the NICU due to short distances for optimal positioning, oral secretions impeding endotracheal tube (ET) securement, and use of minimal sedation. It has been associated with various adverse outcomes including increased oxygen requirement and need for CPR. Our objective was to reduce the rate of UE from 2.9/100 ventilator days in 2020 to < 1/100 by July 2022.
Methods Used
This ongoing quality improvement study utilized the Model for Improvement. A key driver diagram was developed and interventions derived from tertiary drivers (figure 1). The apparent cause analysis form and UE care bundle were adapted from the Solution for Patient Safety Network. Measures used include compliance with the UE care bundle (process), completion of apparent cause analysis (ACA) forms (process), UE/100 ventilator days (outcome), and number of adverse events during management of UEs (balancing). Statistical process control charts (U-chart and P-chart) were used to display and analyze data. Associates in Process Improvement rules for special cause were applied.
Summary of Results
Baseline rate of UE was 2.8/100 ventilator days in early 2019 (figure 2). Previous years’ PDSA cycles demonstrated an increase in UE rate to 4.5 with introduction of in-line suctioning devices and decreased to 1.6 following identification of staff champions, nursing education, and adherence to respiratory therapist led audits and ACA forms. This past year’s PDSA cycles, including standardization of ET taping, post-event debriefs, and introduction of a high risk procedure card at bedside, have decreased the yearly rate of UE to 1.5 in 2021, from 2.9 and 3.4 in 2020 and 2019, respectively. Compliance with UE care bundle ranged between 61-100%, and exceeded 90% since December 2020. No adverse events were reported.
Conclusions
Identifying champions, audits, ACAs and nursing education demonstrated a reduction in the UE rate center line, while standardized ET taping, post event debriefs, and high risk procedure cards has helped reduce the yearly rate of UE. This QI initiative demonstrates that various interventions are needed to solve a multifactorial safety event, and various methods for measuring success are necessary to detect initial improvement from PDSA cycles. Next steps include utilizing a process map for post-event debriefs and introduction of bedside airway cards.
#60 Improving developmental-behavioral follow-up rates of neonatal intensive care unit graduates
A Bhatia*
M Dehnert
C Calilap-Bernardo
A Rahman
Staten Island University Hospital, Northwell Health, Staten Island, NY
Purpose of Study
8.3% of all live births are infants of low birth weight (LBW), and 10.2% are preterm. Preterm and LBW infants are at high risk for short and long-term complications, including poorer neurodevelopmental outcomes. Infants that receive earlier therapies and educational interventions have improved outcomes in cognition, behavior, and motor skills. However, rates of follow-up for the high-risk infant remains low.
At Staten Island University Hospital (SIUH), infants at risk for neurodevelopmental complications are identified and referred to follow-up with the department of developmental-behavioral pediatrics (DBP). The goal of this quality improvement project is to increase overall follow-up at DBP appointments following discharge from the NICU.
Objective
Improve follow-up attendance rates with DBP for at-risk infants discharged from the NICU. Specifically, our goal is to increase attendance at initial DBP appointments from a baseline of 29.2% to 50% within 18 months.
Methods Used
This quality improvement project is a collaboration with SIUH NICU and the department of DBP. To assess our primary SMART aim, a core multi-disciplinary team (NICU, DBP, pediatrics rehab, social work), identified multiple primary drivers to guide the success.
Infants referred were based upon 14 pre-identified criterion. Our first PDSA cycle began on January 24, 2021. Multiple PDSA cycles continued, some simultaneously, based upon the primary drivers. To date, emphasis is on standardization of referrals, education of nursing and medical team, and education of parents (figure 1).
Summary of Results
Demographic data is shown in table 1. The mean gestational age of patients referred to date was 35.1 weeks. The most common reason for referral was prematurity (<35 weeks GA).
Baseline data (2019) showed an attendance rate of the high-risk infant at DBP clinic of 29.2%. 2020 data was excluded due to the Covid-19 epidemic. Through the PDSA cycles to date, there is an increase in appropriate referrals to above 95% and an overall increase in attendance to 54.7% to date.
Description of infants who attended follow-up versus were lost to follow-up
Run chart demonstrating 2021 DBP follow-up rates
Conclusions
A multi-disciplinary approach has led to increased identification of infants require follow-up with DBP and has led to an increase in attendance of the high-risk infant. Future directions include collaboration with community pediatricians, emphasis on retention of infants beyond one visit, and analysis of impact on long-term neurodevelopmental outcomes
#61 Improving immunization rates of infants admitted to a tertiary neonatal intensive care unit (NICU)
I Avulakunta1*
T Morgan-Joseph1
A Rechnitzer2
S Nafday1,2
1Children’s Hospital at Montefiore, Bronx, NY
2Albert Einstein College of Medicine, Bronx, NY
Purpose of Study
Preterm and term infants are at increased risk of vaccine-preventable infections. Several studies have shown that there is a delay in the timely immunization of hospitalized infants. The Centers for Disease Control and Advisory Committee on Immunization Practices recommend the administration of the hepatitis B vaccine (HBV) within 24 hours to all stable infants born with a birth weight >2000 gm. The New York state department of health recommends HBV birth dose within 12 hours of life to reduce the perinatally acquired hepatitis B infection. The US national estimated birth dose HBV rate was 71.1% in 2014 with NYC average of 72%. Figure 1 shows the baseline rates of immunization in our NICU. The objective of our study is to improve the Birth dose HBV rate by 25% from baseline and to improve HBV at 1 month, and the 2nd and 4th-month immunization rates to > 90%
Methods Used
In May 2019, we instituted a quality improvement project to improve the timely immunizations of term and preterm infants admitted to our level IV NICU. Baseline data was acquired for a period of 1 year from April 2019 to April 2020 (figure 1). A multidisciplinary team was assembled; key drivers and Ishikawa diagrams were constructed to identify the barriers to immunization (figure 2). We implemented quarterly Plan-Do-Study-Act cycles (PDSA) to institute, modify and improve our immunization rates per institute of healthcare improvement model. The primary outcome measures were timely immunization of birth dose HBV administration within 12 hours for eligible infants and subsequent immunizations within one week of recommended schedule.
Summary of Results
After four PDSA cycles over a period of 16 months from July 2020 to November 2021, the rate of HBV increased from 22.5% to 71% and HBV at 1 month, and 2nd and 4th-month immunizations have increased to 100%. Monthly ongoing education for the providers, revising our immunization policy, the intervention of nurses in obtaining the consent, a reminder on immunization status in the resident sign out, bundling 1-month Hep B consent with our unit-specific protocols were some of the most effective interventions.
Showing baseline data for birth dose HBV, HBV at 1 month, 2nd month & 4th-month immunizations
Ishikawa diagram showing barriers to immunizationRun charts showing the trend of immunizations.
HBV birth dose immunization
HBV at 1 month
2nd-month immunization
4th-month immunization
Conclusions
Using the QI methodology, we identified barriers to the delay in the immunization schedule. Multidisciplinary collaboration, provider, and staff education with implementation of PDSA cycles are effective in improving the immunization rates in a timely manner of infants admitted to NICU.
#62 Improving the rate of early breast milk expression in mothers with premature infants
AE Ng1*
K Sundar1
L Feldman-Winter1,2
K Hunter2
A Kushnir1,3
1Cooper Medical School at Rowan University, Camden, NJ
2Cooper University Healthcare, Camden, NJ
3Cooper University Hospital, Camden, NJ
Purpose of Study
To improve the rate of early human milk expression (HME) among all mothers with Neonatal Intensive Care Unit (NICU)-hospitalized infants to 80% over 4-months through standardized documentation of lactation assistance in maternal postpartum flowsheets.
Methods Used
The rate of early HME among mothers of NICU patients in a tertiary hospital in urban New Jersey was determined by conducting in-person/phone interviews using a survey instrument adapted from a Baby-friendly Hospital Initiative auditing tool. Interviews were conducted for 1 year Pre-Intervention (Pre-I) and 4 months Post-Intervention (Post-I). The intervention entailed additional documentation of whether lactation assistance was provided or offered to the mother on her postpartum flow sheet. The type of lactation support remained the same throughout the intervention, and included an interactive hand expression and pumping tutorial. Women in Pre-I and Post-I were sub-grouped based on whether they delivered between 07:00-19:00 (Day), or 19:00-07:00 (Night). Rates of early initiation of HME (<6 hours postpartum) were compared between Pre-I and Post-I groups, and between Day and Night groups, using Chi square tests in SPSS.
Summary of Results
Interviews were conducted with 62 mothers of NICU-hospitalized infants. Of 28 Pre-I, 18.5% (5/27) of mothers received lactation assistance within 6 hours of delivery, while of the 34 Post-I, 36.3% (12/33) received appropriate assistance. There was significant improvement in early initiation of HME in Day mothers, from 7.1% (1/14) to 42.9% (6/14) Post-I (p=0.03). There was no improvement in the rate of early initiation of HME among Night mothers (30.8% [4/13] to 31.6% [6/19], p=0.961).
Conclusions
Standardized documentation of whether lactation assistance is offered can improve rates of early initiation of HME in mothers of NICU-hospitalized infants. Next steps include developing additional interventions to improve nighttime education in order to achieve an 80% rate of early HME initiation.
#63 The burden of prior authorizations in a pediatric endocrinology outpatient practice
J Samuels*
M Yau
CJ Romero
Icahn School of Medicine at Mount Sinai, New York, NY
Purpose of Study
Insurers have placed selective and restrictive criteria for specialty medication and approval often requires prior authorizations (PA), despite needed on-going care for chronic conditions. Furthermore, many insurance organizations require reauthorizations for continued treatment, and the interruption or discontinuation of therapy poses a risk for worsened health outcomes and added expenses. PA also requires additional administrative support. Thus, providers are further burdened by extra efforts to maintain appropriate medical care. This burden has been previously reported; therefore, we chose to better quantify the burden in our practice.
Methods Used
An anonymous 11 question online survey was designed using RedCap and completed by all of our providers. Data from responses were then tabulated and graphed to review distribution of responses.
Summary of Results
Providers included 9 (64.3%) faculty, 3 (21.4%) post-doctorate fellows and 2 (14.3%) nurse practitioners. 30.8% have been in practice >10 years and 38.5%, <3 years; 23.1% 4-7 years and 7.7% 8-10 years. 100% of providers did have a designated employee to handle PA. The communication of PA requests was most commonly a pharmacy fax (84.6%). However, providers report PA were delayed sometimes (38.5%) and often (30.8%), while fewer replied always (7.7%) and rarely (7.7%). 15.4% were unsure. Providers endorsed that utilization of evidence based medicine and/or published guidelines to process PA occurred sometimes (46.2%) and 30.8% thought often; 23.1% did not know. 69.2% stated they receive 1-2 PA weekly, while15.8% responded 3-5 or 5-10. A comparison with trainees showed that fellows received 1-2 PA, while 37.5% faculty received >2/week. 58.3% spent <1 hour each week on PA; 38.5% 1-3 hours and 7.7% 3-5 hours. Amongst specialty medication, 100% stated growth hormone therapy as the most common. Ultimately, 92.3% of providers felt they had a negative experience with PA.
Conclusions
Despite a small cohort, our data shows how the PA burden has a direct impact on daily work and patient care. All providers have a designated employee for PA, but this means additional financial resources for personnel. Communication for PA requests is most commonly faxes, yet a majority felt PA delay patient care. Interestingly, the burder of PA also extends to trainees and not just faculty. The majority of providers are not confident if evidence based medicine is used for requests, thus, decision making by insurers to approve PA is not clear. Consistent with literature, we demonstrate that the PA process overall has a negative impact. There is increased national awareness of PA burden. Our next step is to extend this survey to other endocrine practices in our city to better validate findings and begin to explore solutions to decrease the burden of PA.
#64 Continuous positive airway pressure weaning guidelines in preterm infants: a quality improvement project
S Mattikalli1*
S Amatya1
K Weller2
H Stephens2
J Erkinger2
K Wisecup1
1Penn State College of Medicine, Hershey, PA
2Penn State Health, Hershey, PA
Purpose of Study
Continuous positive airway pressure (CPAP) has many benefits in managing preterm infants with respiratory distress. It is associated with less surfactant use, decreased extubation failure, and increased alveolar recruitment. Introduction of CPAP bundles has been shown to decrease bronchopulmonary dysplasia (BPD). Successful weaning from CPAP facilitates oral feeding and developmentally appropriate activities. There have been two randomized controlled trials and one systemic review investigating weaning methods; however, no consensus has been reached about the optimal timing. This study aims to increase compliance to new weaning guidelines to 100% and increase successful weaning to room air to 95% in a level-IV neonatal intensive care unit (NICU) over 2 years.
Methods Used
Bubble CPAP was initiated in our NICU in 2020. Guidelines were created, including weaning criteria, and education was provided. This ongoing quality improvement (QI) initiative used the Institution of Healthcare model for improvement with 3 plan-do-study-act cycles to date. Primary outcomes include compliance with guidelines and successful transition to room air on the first attempt. Secondary outcomes include the presence and grade of BPD. Process measures included managing variation with the creation of bedside cards, changing the work environment with the introduction of multidisciplinary rounds, and avoiding mistakes using reminders. Balancing measures included total days on respiratory support and length of hospital stay. Trends were observed using a run chart, and process changes were studied using control p charts. This project was reviewed by the institutional review board and deemed exempt.
Summary of Results
Between March 2020 and December 2021, 109 neonates with an average gestational age of 29 3/7 weeks and birth weight of 1.22 kilograms were studied. The majority of these infants were inborn; approximately half required surfactant and one-third intubation. Concept changes included managing variation (standardization), changing the work environment (developing alliances and providing access to information), and designing a system to avoid mistakes (use of reminders). Practice changes resulted in an increase in compliance (figure 1a) and overall improvement. In addition, there were no noted special-cause variations (figure 2).
Conclusions
Implementation of process measures leads to greater compliance to weaning guidelines. Trends showed that as compliance improved, so did successful weaning to room air. Areas where this did not track occurred in the extremely low gestational age and birth weight infants. It is important to determine which weaning criteria lead to success, as well as increasing the compliance to criteria as opposed to an ad hoc method of weaning.
3B: Education
#65 Developing, implementing, and assessing an ethics and professionalism curriculum for neonatal clinicians utilizing flipped classroom technology: an international pilot study
G Geis1*
D Williams2
C Cummings2
1Albany Medical Center, Albany, NY
2Boston Children’s Hospital, Boston, MA
Purpose of Study
Clinicians in the NICU face ethical dilemmas daily in their care of sick newborns and their families. Despite requirements to establish trainee competency in ethics and professionalism, there is little evidence to suggest whether current attempts advance knowledge and skills or alter attitudes and behaviors or if these competencies are assessed across interprofessional members of the healthcare team. In an attempt to close this gap, our regional pilot data demonstrated efficacy and feasibility of this curriculum across various academic health systems, demonstrated by knowledge acquisition and improved confidence among neonatal-perinatal medicine fellows.
Our objective was to:
To implement a digitally innovative curriculum in ethics and professionalism in neonatology on an international level;
To evaluate the effects of the curriculum on clinician knowledge and confidence during an international pilot.
Methods Used
We made our previously developed 12 module curriculum in neonatal ethics available to healthcare clinicians around the world via an online platform. Data collection began in July 2017 and is ongoing. Multi-media content was constructed by experts in neonatal ethics, peer-reviewed, and uploaded onto a digital platform. Participants reviewed content online and then participated in live sessions at their home institutions to further solidify knowledge and skills. We contrasted paired pre-and post-test scores for each lesson to date to assess knowledge acquisition. The Wilcoxon signed-rank test for paired data was used
Summary of Results
We developed a process map to illustrate the development and implementation of our curriculum (figure 1). Preliminary data were obtained for 789 participants in the international pilot. Pre/post comparisons of median differences in test scores were significant <0.001 in all modules (table 1).
Median difference in pre/post test score by lesson
Educational Process Map. TEK-Neo= Test of Ethics Knowledge for Neonatal-Perinatal Physicians; BCH=Boston Children’s Hospital; TMC=Tufts Medical Center; AMC = Albany Medical Center; AAP = American Academy of Pediatrics.
Conclusions
Our curriculum has been supported by the Organization of Neonatal-Perinatal Medicine Training Program Directors of the American Academy of Pediatrics as the standard curriculum for neonatal ethics and successfully implemented internationally on an online platform. Preliminary data demonstrates that for each lesson, participants’ knowledge levels of approaching ethical challenges significantly improved. Ongoing steps include assessing the effects of this curriculum on overall knowledge and confidence levels across various educational levels as well as utilizing an ethics behavioral assessment tool to better quantify clinician performance when leading clinical discussions.
References
Cummings, Geis, Kesselheim, Sayeed. Journal of Perinatology 2015, PMID: 26110498.
Cummings, Geis, Feldman, Berson, Kesselheim. Journal of Pediatrics 2018, PMID: 29754867.
Geis, G, Cummings, C. ‘Ethics and Professionalism in Neonatology Year 1 Curriculum’. 2017, July. Online curriculum. OPENPediatrics TM.
Geis, G, Cummings, C. ‘Ethics and Professionalism in Neonatology Year 2 Curriculum’. 2018, Aug. Online curriculum. OPENPediatrics TM.
Geis, G, Cummings, C. ‘Ethics and Professionalism in Neonatology Year 3 Curriculum’. 2019, Oct. Online curriculum. OPENPediatrics TM.
Geis, Feldman, Berson, Cummings. Journal of Perinatology 2021, PMID: 34504300.
#66 Can education lead to a sustained improvement in neonatology clinical documentation integrity?
AO Gupta1,2*
1Nemours Childrens Health, Wilmington, DE
2Inspira Health Network, Vineland, NJ
Purpose of Study
The current medical education curriculum does not include a formal education on clinical documentation strategies, even though the physician documentation directly impacts the medical decision making, and ultimately the revenues. In an external audit, we identified a substantial gap in the clinical documentation for medical decision making, diagnosis selection and risk stratification, which is an essential requirement for optimal billing or DRG code identification. Physician education and an effective strategy to improve documentation is paramount to bridge this gap.
The AIM of the study is to increase the accuracy of clinical documentation for common Neonatology diagnoses by 80% within 1 year.
Methods Used
A quality improvement project was performed at a 20-bed level III NICU from May 2020-Dec 2021. Retrospective data was collected over 6 months from May-Oct 2020 for infants born at <34 weeks of gestational age- clinical documentation and diagnosis accuracy for 5 common neonatology diagnoses: respiratory distress, apnea of prematurity, neonatal sepsis, jaundice and feeding immaturity. A scoring tool was developed and% accuracy was collected for clinical documentation and diagnosis selection for each of the five diagnoses. An educational tool was developed for providers, EMR optimization (key documentation phrases and reorganizing the preferred diagnosis list) performed, and education provided to billing and coding team. A periodic review performed by coding integrity team (2-3 times/week) and project champion (weekly)- queries generated in EMR and feedback provided to clinicians.
Summary of Results
A total of 150 patient charts were reviewed during the study period. Retrospective data collection revealed the average accuracy of clinical documentation ~42%, accuracy for selection of correct diagnosis was 27% and overall accuracy was ~36%. Among individual diagnoses, accuracy of documentation and diagnosis code selection was worse for respiratory distress (<20%), and best for jaundice (~50%) (table 1). After educational intervention, accuracy of clinical documentation and diagnosis selection both improved for all 5 categories significantly and sustained for more than one year (figure 1). A slight dip in accuracy noted in July-Aug 2021, which was most likely secondary to addition of new providers.
Monthly overall accuracy of clinical documentation and diagnosis for each of the five categories
Monthy run charts
Conclusions
A multidisciplinary comprehensive educational approach could lead to significant improvement in clinical documentation and selection of billing codes for common neonatology diagnoses. Our future plan is to review the financial impact of improved clinical documentation and medical decision making.
#67 Use of practice based learning modules to teach primary care preventative measures in pediatric residency
V Wang1*
R Carter1
K Donohue1
N Davis1
E Wisniewski2
M Mehta1
1Pediatrics, University of Maryland Medical Center, Baltimore, MD, United States
2Pediatrics, Mercy Medical Center, Baltimore, MD, United States
Purpose of Study
Identifying age-appropriate developmental milestones, vaccine schedules, and preventive screenings is a critical cornerstone of Pediatric residency training, and ultimately primary care practice. A prior study performed by our residents demonstrated that the implementation of practice based learning modules (PBLs) improved residents’ comfort with routine and special vaccine schedules, as well as routine lab screenings. However, the sample size was small and the data collection period was short. The aim of this study was to extend the understanding of knowledge and comfort level of these topics at health supervision visits before and after participating in the PBLs, and their influence on the annual Pediatric In-Training Exam (ITE) scores.
Methods Used
Pediatric residents participated in PBLs during their continuity clinics, utilizing modules to guide their practice and reflect on their ability to assess developmental milestones, vaccine schedules, and preventive care screenings. ITE data, including the total score and Preventive Care/Well Child sub-score (PC/WC), was analyzed to determine changes pre- and post-PBL implementation. In addition, residents completed pre- and post-intervention surveys to assess comfort with preventive care components.
Summary of Results
There was a statistically significant increase in overall ITE scores pre- and post-PBL implementation (n=45, p<0.0001), but this did not extend to overall scores when comparing across training levels. When comparing PC/WC sub-scores within training levels pre- and post-PBL, there was a statistically significant improvement (p<0.001, p=0.011). Survey analysis demonstrated improvement in residents’ comfort in their ability to identify age-appropriate developmental milestones (n=9, p=0.0081).
Overall ITE scores pre- and post-PBL implementation
PC/WC sub-scores pre- and post-PBL implementation
Conclusions
Pre- and post-intervention analysis demonstrated improvement in the overall scores, as well as PC/WC sub-scores, suggesting that PBLs are an effective teaching tool for Pediatric primary care interventions. The post-PBL survey demonstrated improved resident comfort with developmental milestones but not with vaccine schedules or routine lab screenings, and the survey was limited by small sample size and inability to match pre- and post-data. Future studies should increase sample size of resident surveys and match ITE scores with survey data. Additionally, multi-institution data will reinforce the role of PBLs on ITE scores as well as resident comfort and understanding of preventive care measures.
#68 Implementation of a longitudinal outpatient curriculum to enhance education for our modern pediatric residents
S Ishkin1*
A Halpern1
J Singh2
A Cornish1
EH Romanos-Sirakis1
1Staten Island University Hospital – Northwell Health, Staten Island, NY
2Maimonides Infants and Children’s Hospital of Brooklyn, Brooklyn, NY
Purpose of Study
Data on the implementation of successful pediatric ambulatory curricula in residency are limited. Although the majority (63%) of pediatric residents pursue a career in primary care, the educational focus in residency training sways towards inpatient medicine. In addition, barriers exist to standardized and consistent teaching in the outpatient clinic. We created a novel longitudinal ambulatory curriculum focusing on high-yield topics delivered over short sessions during weekly resident continuity clinic to meet the needs of modern learners.
Methods Used
Over two academic years, 32 pediatric residents were exposed to an 18-month curriculum, consisting of 62 high-yield ambulatory topics. A brief topic guide was created by content experts to standardize teaching across preceptors and was taught in 10-15 minutes during weekly continuity clinic. Pre and post-tests were used to assess knowledge. Topic guides were emailed to the residents for self-study. Cumulative exams were given after each half (Part A and B) of the curriculum to assess knowledge retention. A one-year follow-up exam was given to assess long-term knowledge retention. A Likert scale (1=not at all, 5=very much) was used to assess satisfaction and use of the curriculum in clinical practice. Continuous variables were described by mean and standard deviations. Categorical data were summarized as frequency counts and percentages. Paired t-test compared continuous variables between pre and post-intervention. Analysis of variance method compared mean differences between PGY years.
Summary of Results
Mean weekly evaluation pre-test scores increased from 69.95% to post-test scores of 94.4% (p<0.0001). The mean final exam score was 84.15%. The one-year follow-up mean test score for Part A was 85.23%. Mean knowledge scores increased from pre-test to post-test (p<0.0001) and from pre-test to final exam foreach half curriculum (p<0.0001). The mean test score one year later was sustained at over 85%. Mean scores for overall satisfaction and effectiveness after Part A were 4.6 and 4.5, respectively. When asked how much the curriculum was used in clinical practice, the average score was 4.45.
Cumulative mean test scores for all pediatric residents at Staten Island University Hospital separated by Curriculum A, Curriculum B, and the entire combined curriculum. The mean test scores included pre-test, post-test, final exam, and one-year post-test scores.
Conclusions
Ambulatory education in residency is often inconsistent and varies across preceptors and programs. We created a new approach that provided consistent pediatric outpatient education of high-yield topics, was well-received, and led to a sustained knowledge increase. This curriculum can be utilized in busy clinic settings by other institutions to improve resident knowledge and enhance patient care, with minimal interruption to clinical sessions.
#69 A pilot multimodal structured communication curriculum for neonatology fellows utilizing simulation in the delivery of difficult news
J Erickson*
Quinones Cardona
S Joshi
K Lewis
O Menkiti
St. Christopher’s Hospital for Children, Philadelphia, PA
Purpose of Study
Educational curricula centered on communication skills in the delivery of difficult news within neonatology is lacking. Traditionally, these skills are acquired by observing encounters during training in an apprenticeship model, which may vary within and between institutions. Simulation has been shown to be an effective tool in teaching communication strategies for the delivery of difficult news in several settings.
Methods Used
A single-center prospective pilot study including 16 neonatal-perinatal medicine fellows was conducted from March 2020 and is ongoing through May 2022. Baseline and ongoing evaluations of subjects include pre- and post-standardized patient (SP) encounter surveys to assess perceived comfort in delivering difficult news as well as objective evaluation of video recordings by a blinded simulation specialist utilizing the Kalamazoo Communication Effectiveness Tool (KCET). A multimodal curriculum consisting of four didactic sessions, two simulation sessions, and two video-recorded SP encounters was implemented and continued annually. Baseline data and yearly performance were compared between post-graduate year levels using one-way ANOVA. Individual comfort data and KCET performance were also analyzed longitudinally with paired Student’s t-test.
Summary of Results
Baseline assessments were completed on 12 fellows prior to implementation of the study curriculum with post-intervention data collected on seven thus far. Despite varying years of training, perceived comfort and KCET performance was comparable between training levels at baseline except for ‘understanding family perspective’ (higher among 1st year fellows). There was statistically significant improvement in average total scores relating to comfort in delivering difficult news after 1 year of curriculum exposure (table 1). There was statistically significant improvement in only one of the variables, ‘reaching agreement’, of KCET performance thus far (table 2).
Conclusions
A pilot multimodal communication curriculum has the potential to improve perceived comfort among neonatology fellows in delivering difficult news. Continued assessments are needed to determine the effectiveness of this curriculum in improving objective communication skills.
#70 Impact of a pediatric resident-led integrated quality improvement curriculum
A Abdelhafiz*
A Ahmed
R Bisarini
M Abuali
Einstein Medical Center Philadelphia, Philadelphia, PA
Purpose of Study
Background: A resident needs assessment identified Quality Improvement (QI) knowledge gaps. Studies have shown successful QI curriculums allow residents to improve patient care processes, however little is known about resident-led QI curriculums in Pediatrics programs.
Aim: Within 12 months, develop an effective resident-led QI curriculum for the Pediatrics program with the end goal of integrating QI into improving patient care.
Objectives
At the end of the curriculum, participating residents will be able to:
Define the Model for Improvement.
Identify patient care processes in need of improvement.
Formulate a SMART(IE) AIM and develop measures (outcome, process, balancing).
Design QI projects and implement PDSA cycles addressing patient safety and healthcare disparities.
Methods Used
Methods: Launch date 7/1/2021 with target of 30 residents.
Planning:
Prelaunch, trained three QI resident champions through small group faculty led sessions, online Institute for Healthcare Improvement (IHI) modules, and Academic Pediatric Association QI conference attendance.
Obtained an educational innovation grant.
Teaching:
Small group resident sessions facilitated by QI expert faculty.
Flipped classroom utilizing IHI modules, followed by resident–led discussions with faculty coaching.
Learner Assessment:
Pre/Post curriculum resident self–assessments of comfort level/self–efficacy and perceptions of value (1–5).
QIKAT–R validated tool (3 points each for AIM, Measure, Change) to evaluate resident skills on three simulated clinical scenarios.
Program Evaluation:
a. Change in clinical processes based on successful resident-led PDSA cycles.
Summary of Results
Results: In the initial five months, 20 residents participated. On post curriculum self-assessments, comfort constructing an AIM statement increased from 18% to 65% at highest levels (4-5) of proficiency. Ability to develop measures increased from 18 to 30% (figure 1). Resident participation in PDSA cycle remained stable at 30%. Most residents continued to strongly agree on the high value of QI. QIKAT scoring showed variable proficiency levels (figure 2). A resident-led project improved timely follow up of urgent ambulatory lab results from 60% to 78% in 3 months (ongoing).
Conclusions
Conclusion: A resident-led QI curriculum utilizing peer education shows promise in enhancing fundamental QI skills and improving patient care. Next steps include integration of QI into daily workflow and developing longitudinal projects linked to patient outcomes.
#71 Facilitating QI activities globally through digital technology: decreasing severe neonatal hyperbilirubinemia
I Narayanan1*
A Bakari2
J Arhin3
N Crowell4
J Ramasethu1
1Georgetown University Medical Center, Washington
2Suntreso Hospital, Ashanti Region, Ghana
3University of Maastricht, Maastricht, Netherlands
4Georgetown University, Washington
Purpose of Study
Severe Neonatal Hyperbilirubinemia (SNH) is a major cause of neonatal mortality in Sub-Saharan Africa and can cause neurodevelopmental disability in survivors. Exchange transfusions (ET) to reduce high bilirubin levels are common in low/middle income countries (LMIC) due to late detection of jaundice. Mothers are often discharged from hospital < 24 hours after delivery. A Blended Learning Quality Improvement (QI) Program using digital technology (the in- country workshop was cancelled due to COVID 19 pandemic) was developed between Georgetown University (GU) and district hospitals in Ghana to improve quality of neonatal care (funded by GU Global Health Initiative).
The objective of this program was to facilitate QI activity at a Ghana District Hospital (GDH) promoting early care seeking in mothers for neonatal jaundice so that phototherapy may be used to decrease SNH and ET.
Methods Used
GU faculty used Zoom and WhatsApp platforms to work with GDH staff to facilitate formation of a QI team, implement interactive health education with videos by trained midwives for antenatal/post-partum mothers, initiate daily rounds by physicians in postnatal wards, promote community health nurses to call/visit mothers postnatally at home, and maintain data on pre-defined key outcome indicators. The goal was to reduce the proportion of inborn infants ≥ 34 weeks gestational age being brought to the neonatal unit with SNH (serum bilirubin levels ≥ 340umol/L or 20 mg/dL) by 15% within 3 months. The program was exempted from review by the GU IRB. Statistical analysis: Chi- square; Fisher exact test.
Summary of Results
From Oct 2019 to Jan 2020, 14 (28%) of 50 discharged infants were readmitted with SNH and 7 (14%) received ET. Figure 1 shows the trend graph of infants admitted with SNH and ET each month after the initiation of the QI project in Jan 2020. Table 1 shows the decline in SNH and ET in the 3 months post intervention as well as a significant sustained decline for 16 months. There was a significant increase in infants being brought in for bilirubin levels < 255umol/L after the intervention.
Severe neonatal hyperbilirubinemia and exchange transfusions in infants pre- and post-intervention
Pre- and Post-intervention Bilirubin Levels and Exchange Transfusions Rates
Conclusions
Despite internet connectivity problems, this digitally mediated QI project demonstrated success in reduction of SNH and ET in a district hospital in a LMIC. Regular review of trend graphs and repeated facilitation, implemented through low-cost digital technology, are effective in promoting QI activities and can be applied regionally and globally. The increase in infants being brought in for mild jaundice points to the need for objective methods of determining bilirubin levels in the community.
#72 Implementation of a small baby bundle in a level IV NICU
H Jolley*
G DeAbreu
E Konieczny
K Bailey
D Pena
C Macioch
Z Ibrahim
B Weinberger
V Boyar
Division of Neonatal-Perinatal Medicine, Cohen Children’s Medical Center, Northwell Health and Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY
Purpose of Study
Preterm infants are exposed to iatrogenic stressors that may contribute to adverse outcomes. For example, weighing infants, performing cuff blood pressures, and prolonged line placement can cause hypothermia and blood pressure fluctuations. Intraventricular hemorrhage can be reduced by small baby care bundles that decrease stimulation in the first week.
To facilitate care and minimize nonessential interventions for preterm infants (<30 wks and/or < 1500 g) during the first week. The SMART aims were to: 1) decrease weight measurements to only days 1, 4, and 7 for > 80% of infants, 2) decrease performance of cuff blood pressure (BP) measurements to < 10% of infants with arterial lines, and 3) decrease times to start and completion of umbilical line placement by 20%, by December 1, 2021.
Methods Used
A multidisciplinary team implemented an evidence-based practice bundle for minimal stimulation. Several PDSA cycles were performed to accomplish targeted bundle elements, including: 1) conferences and nurse educator sessions, with laminated bedside cards, 2) just-in-time coaching for bedside nurses, 3) interval reminders to on-service teams, and 4) departmental presentations and posters. Balancing measures were changes in total fluid intake and frequency of treatment for hypotension.
Summary of Results
Weight measurements decreased quickly after nursing education to a median of 80% bundle compliance (figure 1). Similarly, the number of cuff BP measurements decreased by 84%, from a mean of 17.1 to 2.7 per infant with umbilical line (figure 1). Mean time to start umbilical line placement decreased by 11% after bundle roll-out and decreased further after specific interventions targeting the medical team (figure 2). Times to complete umbilical line placement remained unchanged at 111 minutes (figure 2). Total fluid intakes and the incidence of hypotension were not affected.
Blood pressure measurements and weights
Timing of umbilical line placement
Conclusions
Alterations in nursing practices to decrease agitation of preterm infants (fewer weights and cuff BPs) are readily acceptable and easily adopted. Our experience suggests that minimal intervention has intuitive appeal and that decreasing tasks is easier than increasing them. In contrast, time to starting umbilical lines improved only after programs targeting both nurses and medical providers, which underscores the requirement for interdisciplinary coordination. To improve time to line completion, training for medical providers will be modified to emphasize efficiency and better utilization of team resources.
3C: AFMR case reports
#73 Management of diabetic ketoacidosis on medical floors in a coronavirus disease 2019 (COVID-19) patient
RN Tiperneni*
R Padappayil
A Chandini
Monmouth medical center, Long Branch, NJ
Case Report
Introduction
Patients with mild to moderate diabetic ketoacidosis (DKA) can be safely treated with subcutaneous, rapid-acting insulin analogs on the medical floor or in the emergency department. Here we describe a case of COVID pneumonia with DKA, effectively treated with a subcutaneous insulin regimen with anion gap closure in 4 hours since the presentation on medical floors.
Case
The patient is a 64-year-old male with no medical history, has not been in follow-up with a primary care physician for the past 20 years presents to the emergency department [ED] with a 2-week history of generalized weakness and fatigue. Reports feeling very thirsty and dehydrated with increased frequency of urination. On arrival he was noted to be saturating at 88 to 89% on room air, was switched to non 2 Litres nasal cannula with improvement in saturation to 94%, sinus tachycardia at 110 beats per minute, blood pressure 110/72 mmHg. Blood glucose was noted to be at 486 mg/dL with anion gap greater than 24 mEq/L, bicarbonate less than 10 mEq/L, creatinine at 1.62 mg/dL. Arterial blood gas analysis showed pH of 7.39, partial pressure of carbon dioxide at 16, partial pressure of oxygen at 61, bicarbonate of 10 suggestive of metabolic acidosis with respiratory compensation. He received a bolus of 0.3 units/kg [21 units] of subcutaneous insulin lispro (rapid-acting). Then was switched to 0.2 units/kg [14 units] subcutaneous insulin every 2 hours, the basic metabolic panel was done every 2 hours. Anion gap was closed in 4 hours. For transition, we calculated 0.5 units/kg [35 units] which was divided into basal – insulin glargine 17 units and bolus – sliding scale insulin lispro before meals and bedtime (insulin naive patient). His anion gap remained closed thereafter. He was treated with remdesivir and dexamethasone for COVID pneumonia. He was discharged after 5 days with improvement in his respiratory status from COVID pneumonia with outpatient follow-up.
Discussion
Subcutaneous insulin protocols are being used with increasing frequency to treat selected patients with mild to moderate DKA. Especially during this COVID pandemic, this helps to decrease the exposure frequency of staff (health care workers especially doctors and nursing staff) to patients given insulin dosing and lab frequency of 2-4 hours (compared with hourly checks for insulin intravenous drip), decreases the use of personal protective equipment (PPE), decreases the upgrade to intensive care units (ICU) that in turn helps with effective resources management in ICU for more critical patients. This protocol has not been studied in severe DKA yet but has similar efficacy and safety in mild or moderate DKA patients when compared to IV insulin therapy.
#74 A case of FSGS in a previously healthy male after the second dose of COVID-19 mRNA vaccine
V Sirpal*
H Fichadiya
A Al-Alwan
M Ashok
Monmouth Medical Center, Long branch, NJ
Case Report
Background
COVID-19 infection and COVID-19 mRNA vaccines have been associated with the occurrence of de-novo and relapsing glomerulopathies. Although, Focal Segmental Glomerulosclerosis (FSGS) similar HIV associated Nephropathy (HIVAN) has been reported with COVID-19 infection in African American population with Apolipoprotein L1 gene mutation, amongst the few reported cases post-vaccine, Minimal change disease (MCD), IgA nephropathy (IgAN), Anti-Glomerular basement membrane glomerulonephritis (Anti GBM GN), and membranous glomerulonephritis (MGN) have been reported.
Case
A 26-year-old Caucasian male with a history of tobacco use complained of Frothy urine and edema for 3 weeks post second dose of Moderna COVID-19 vaccine on 06/01/21. He received the first dose on 5/04/21. On his annual wellness visit on 5/18/21, he had no complaints, normal physical examination with serum albumin 5g/dl, and urinalysis significant for trace proteinuria. A repeat urinalysis post-onset of symptoms on 7/18/21 revealed 3+ proteinuria, no RBCs, 24-hour urine revealed 3.2g proteinuria. Further investigations revealed Hypoalbuminemia (2g/dl), persistent proteinuria, and an unremarkable renal ultrasound, ANA, ANCA, Anti-dsDNA, Anti-PLA2R, anti-streptolysin, RF, HIV, hepatitis panel, and serum complement levels. Renal biopsy revealed Tip lesion variant of FSGS with 100% effacement of podocyte foot process. Therapy with Prednisone 60 mg daily was initiated, following which an improvement in edema and serum albumin levels (2.7 g/dl) were noted.
Discussion
A few de-novo cases of anti-GBM GN, ANCA positive vasculitis, MCD and IgAN, and relapsing cases of IgAN, MCD, MGN, and Thrombotic microangiopathy have been reported post-COVID 19 mRNA vaccination. Most reported cases of MCD occurred after the first dose whereas IgAN flare-up occurred after the second dose. Our case is unique as our Caucasian patient developed FSGS post-second dose of Moderna vaccine. Although the pathogenesis is unclear, it is thought to be related to an acute T-cell immune response involving cytokine production to COVID 19 spike protein which is responsible for inducing or worsening existing podocytopathies. Interestingly fewer cases have been reported following adenovirus vector or inactivated virus vaccination. Most of the reported cases of IgAN flare-up have been mild and a small number of MCN cases required ICU admission for management of fluid overload. As observed in a few prior case reports our patient had a slow response to steroid therapy. Although guidelines on COVID 19 vaccination in patients with existing glomerulopathies remain unclear and are based on case-by-case scenarios, the benefit of COVID 19 vaccination, may in general, outweighs the risk of glomerular diseases. We encourage further studies on this topic, especially in the era of booster doses with ongoing discussion about mixing two types of vaccines.
#75 A complementary case of abdominal pain
VD Williams1*
LN Hodo1
H Hotchkiss2
1Pediatric Hospital Medicine, Mount Sinai Hospital, New York, NY, United States
2Pediatric Nephrology, Mount Sinai Hospital, New York, NY, United States
Case Report
History: An 11-year-old male with a history of hypothyroidism presented with fever, abdominal pain, and vomiting. The day prior to admission, he complained of nausea, had three episodes of non-bloody, non-bilious emesis and two episodes of non-bloody diarrhea along with mild RLQ pain and tactile fevers. Upon further questioning, he endorsed intermittent eyelid and lower extremity swelling for several months prior to admission, as well as several episodes of dark urine and fatigue during this time. He was seen by his pediatrician, who attributed the eyelid and lower extremity edema to allergies, and started him on allergy medications. He described a history of intermittent episodes of RLQ pain x 1 year, but no fevers, vomiting, diarrhea, sick contacts, or recent travel. He denied URI symptoms, rash, urinary urgency/increased frequency, or dysuria.
Physical Exam: Vitals were significant for a fever of 101.3°F but otherwise normal. He was ill-appearing, very thin, with sallow skin. His abdominal exam was notable for tenderness at McBurney’s point, along with tenderness in the LLQ; Rovsing, psoas, and obturator signs were negative. Right CVA tenderness was also elicited. Skin exam was notable for dry erythematous macular patches surrounding his eyes bilaterally.
Diagnostic Evaluation: CBC showed WBC count of 15K, Hgb 12.7. Lipase was normal. CMP was notable for an albumin of 1.5. Urinalysis showed specific gravity 1.033, protein >500, moderate leukocyte esterase, and microscopy demonstrated 113 WBCs/hpf and 42 RBCs/hpf. Urine and blood cultures were sent and showed no growth. Two abdominal ultrasounds could not visualize the appendix; however, they did show mildly increased echogenicity throughout the right kidney with accentuation of corticomedullary differentiation, suggestive of an evolving right pyelonephritis. Additional labs were obtained including an ANA, anti-dsDNA, ANCA, urine protein/creatinine ratio, C3 and C4 levels. ANA, anti-dsDNA, ANCA were negative. The urine protein/creatinine ratio was elevated to 8.67. C3 was low at 17 but C4 was normal at 23.
Final Diagnosis: Since the protein/creatinine ratio demonstrated nephrotic-range proteinuria, a nephrology consult was obtained. A renal biopsy was obtained and confirmed a diagnosis of C3 glomerulopathy (C3GN).
Discussion
The patient was admitted for acute fever and abdominal pain and underwent an infectious workup, which was non-focal. However, his general appearance, history, and labs were suggestive of a chronic renal disease process. In this case, C3GN is a rare kidney disorder which often progresses to end stage renal disease. It is difficult to treat, as available therapies are often not successful. He was started on tacrolimus but failed due to an increase in his serum creatinine. He was subsequently switched to combination therapy with an ACE inhibitor and mycophenolate mofetil, which has kept his renal function stable.
#76 Vulvar carcinoma, a rare complication of solid organ transplant
JE Smith*
University of South Florida, Tampa, FL
Case Report
A 73-year-old female presented with an inguinal rash and right lower extremity swelling. Her past medical history was significant for Autosomal Polycystic Kidney Disease status post two deceased donor kidney transplants on mycophenolic acid, prednisone, and tacrolimus, now with chronic kidney disease stage IV. Social history delineated a twenty-pack year smoking history with cessation thirty years ago. Physical exam demonstrated a hemodynamically stable, obese female with pitting right lower extremity edema and a right inguinal rash that extended into the groin and vaginal mucosa. The rash was described as: scattered, erythematous, macerated nodules – some verrucous appearing with ulcerations and erosions, some appearing punched out. Labs were relatively unremarkable for acute pathology. Infectious workup (Bacterial and Fungal Cultures, Cytomegalovirus, Epstein-Barr Virus, BK Virus, Herpes Simplex Virus, Varicella Zoster Virus) was negative. Lower extremity dopplers did not reveal deep vein thrombosis. Abdominal and Pelvic CT pictured para-aortic and bilateral inguinal lymphadenopathy with the largest node measuring approximately eight centimeters in length. Skin biopsy revealed squamous cell carcinoma (SCC). Inguinal lymph node biopsy also showed SCC with extensive necrosis. Immunohistochemistry stains were positive for CK5/6 and p40, which are highly sensitive and specific for SCC. Stains were also p16 positive, a marker which is commonly correlated with HPV infection. The final diagnosis for this patient was metastatic squamous cell carcinoma of vulvar origin.
Discussion
Literature review shows that infections are one of the most common complications following solid organ transplants. In the described patient, infection was listed as the first several suspected diagnosis on the differential, and the patient was intially treated accordingly. However, a less commonly recognized but increasingly evident complication of solid organ transplants is malignancy, especially those related to viral infections. The complications are largely due to chronic immunosuppression which is prudent to prevent organ rejection.
Squamous cell carcinoma is an invasive malignancy that arises from keratinocytes of skin and mucosa. Risk factors for SCC include sun exposure, actinic keratosis or cheilitis, arsenic exposure, scars, burns, xeroderma pigmentosa, ionizing radiation, human papilloma virus (HPV) and immunosuppression. Vulvar cancer accounts for four percent of gynecological malignancies with SCC being the most common subtype. One study demonstrated a 100-fold increase in incidence of vulvar and anal carcinomas in renal transplant patients when compared to the general population. The above case of metastatic vulvar SCC demonstrates the need to maintain a broad differential when evaluating pathology in post-transplant patients.
#77 Vertebral artery dissections leading to cerebellar infarct due to chiropractor manipulation
A Chandini Arjun*
S Shenouda
H Fichadiya
R Tiperneni
Monmouth Medical Center, Long Branch, NJ
Case Report
History
The patient is a 29 year old female who presented to the emergency room with chief complaints of new sudden- onset dizziness, nausea and vomiting for one day after manipulation of her neck by a chiropractor. The patient was seeing the chiropractor for the sensation of having a ‘pinched’ nerve in her neck. Immediately after the manipulation, the patient vomited, felt extremely dizzy, and nauseated and presented to us for evaluation.
Physical Examination: On arrival, the patient‘s vital signs included a blood pressure of 196/119 and a heart rate of 109. She was afebrile and saturating 97% on room air. On physical examination, the patient was alert and oriented to time, place and person although she was visibly dizzy on ambulation. Her chest was clear to auscultation and heart sounds were present with no murmurs. Her neurological exan was normal : Cranial nerves intact, reflexes present, motor and sensory function intact bilaterally. Cerebellar function was intact on finger-finger test and finger-nose test; and no ataxia or dysmetria was noted on ambulation.
Laboratory and Diagnostic Imaging:
Complete blood count was normal except for an elevated white count of 20.6. Comprehensive metabolic panel and urinalysis were normal. The patient underwent a Computed Tomography Angiography (CTA) of the neck with contrast along with Magnetic Resonance Imaging (MRI) of the brain with contrast. On the CTA, two left vertebral artery dissections were demonstrated at the level of C3- C4 and at C6, along with stenosis and severe irregularity of the V3 segment of the left vertebral artery with pseudoaneursym as seen in the image. Focus of diffusion restriction in the region of the left inferior cerebellar vermis was seen in the Magnetic Resonance Imaging (MRI) of the brain, consistent with an acute infarct.
Final Diagnosis
Vascular sugery, neurology and interventional radiology were consulted. Since both the dissections were extracranial, the decision was made for no acute intervention. The patient was started on aspirin and clopidogrel for the left cerebellar stroke and was set up for outpatient follow up. Physical therapy and rehabilitation was started as an in-patient, and were continued after discharge. Patient‘s high blood pressure was treated with intravenous labetalol and hydralazine. Her symptoms improved and and she was discharged on amlodipine.
Computed Tomography Angiography of the Neck: Left Image- Vertebral Artery Dissection at the C3-C4 Level as shown by the black arrow. Right Image- Vertebral Artery Dissection at the C6 level as shown by the black arrow.
Magnetic Resonance Image (MRI) of the Brain: Left Image – Left Cerebellar Vermis diffusion restriction on Diffusion Weighted Imaging (DWI) sequence as shown by the black arrow. Right Image- Left Cerebellar Vermis hypointensity on Apparent Diffusion Coefficient (ADC) sequence as shown by the black arrow. These findings are indicative of acute stroke of the left cerebellar vermis.
Discussion
This patient suffering a potentially devastating vertebral artery dissection and subsequent left cerebellar stroke as a direct result of chiropractor manipulation underlines the dangers of physical manipulation of sensitive areas in the head and neck. Careful and judicious use of such manoevers is wise. Although there are published case reports of cervical and vertebral artery dissections frollowing manipulaton, this is a rare instance of two vertebral artery dissections and a following cerebellar stroke.
#78 A rare microthrombi disease: catastrophic antiphospholipid antibody syndrome
B Mohanakrishnan1*
M Nandar1
K Holder2
W Rasheed1
N Ranasinghe3
1TexasTech University Health Sciences, Amarillo, TX
2Texas Tech School of Medicine, Amarillo, TX
3Allergy ARTS, Amarillo, TX
Case Report
A 23-year-old female with a past medical history of antiphospholipid syndrome, C-ANCA vasculitis, polyangiitis with granulomatosis, CKD stage III, hypertension, seizure disorder presented with headache, nausea, and vomiting over the past 2-week with poor oral intake and low BP 80/50. She was admitted for E. coli urosepsis and work-up for intractable nausea and vomiting, showing adrenal suppression by syntropic stimulation likely secondary to exogenous steroid and MRI brain showing few punctate foci of chronic microhemorrhage, most notably in the left frontal and right parietal lobes. The patient reported having painful cutaneous vasculitis rash on both palms in the hospital with Hgb and platelet trending down to 6.7 and 47k, respectively. Her C3 and C4 were trending down with worsening of prolonged PTT in the absence of any anticoagulation. Her recent three months prior renal biopsy showed a combination of findings, including microthrombi and possible posse immune glomerulonephritis. However, repeat PR-3 was negative, and no evidence of active ANCA-associated vasculitis. Work up for TTP, DIC, HIT, and new sepsis were negative. Her kidney functions worsened, needing hemodialysis, dropping in Hb, and platelets with microthrombi formation affecting more than three organ systems. She was suspected of having Catastrophic antiphospholipid antibody syndrome. Initially, she received five courses of plasmapheresis, IVIG, and high-dose steroids. However, Thrombocytopenia has not consistently improved despite treatment. Her Hgb continued to drop with some degree of hemolysis, and low haptoglobin accompanied by severe Thrombocytopenia was noted. She was considered for Rituximab treatment and anticoagulation with the possibility of resistant CAPS. After completing the treatment course, her white blood cell count, platelets, and PTT and C3/C4 levels have been stable, with an overall improvement in clinical condition.
Discussion
In a rare and small subset of patients with APS has a widespread thrombotic disease with multiorgan failure called ‘catastrophic APS.’ Thromboses in this setting typically involve multiple small blood vessels in various organs rather than an extensive vessel deep vein thrombosis. This patient met all CAPS criteria that include a history of APS, three or more new organ thromboses, biopsy confirmation of a microthrombus with the exclusion of other causes of multiple organs thromboses.
Conclusion
This case is a rare presentation of a rheumatological emergency with a high mortality rate of 50%, Early diagnosis and aggressive therapy are essential. The medical management includes full dose anticoagulation, systemic steroids, intravenous immune globulin, plasma exchange, and in resistant disease Anti CD 20 monoclonal antibody may be beneficial.
#79 Duodenal adenocarcinoma causing a small bowel obstruction in a patient with pancreatic cancer: a case of two primary tumors
V Sumbly*
I Landry
V Rizzo
Icahn School of Medicine at Mount Sinai | NYCHHC Queens, Jamaica, NY
Case Report
A 66-year-old male with a past medical history of hypertension and type 2 diabetes presented with worsening abdominal pain, anorexia, and an unintentional 15 lbs weight loss over the course of one month. On admission, the patients vital signs were BP: 144/80, HR: 102, T: 99.4F and O2 saturation: 98% on room air. Physical examination was significant for cachexia and a tender, distended abdomen. Initial work-up returned significant for an elevated ALP of 146 U/L and CEA of 4.3U/L. A computed tomography (CT) scan of the abdomen and pelvis revealed a mass in the head of the pancreas and mid jejunal wall edema associated with mesenteric vascular narrowing (figure 1). CT chest resulted negative for metastatic lesions. IR-guided biopsy of the pancreas and jejunal wall confirmed a final diagnosis of primary pancreatic carcinoma and duodenal carcinoma, respectively. The patient rapidly developed a small bowel obstruction, which was temporarily managed by nasogastric (NG) tube decompression. The patient was deemed to be an extremely poor surgical candidate. The patient’s complete blood count (CBC) showed leukocytosis of 22.3 x109/L. Chest x-ray (CXR), blood cultures and urine cultures were negative. The patient was empirically started on vancomycin and piperacillin-tazobactam. Several days into the patient’s admission he developed altered mental status worrisome for metabolic encephalopathy and was transferred to the step-down unit for closer monitoring. During his course, he developed worsening hypotension refractory to fluid administration and required peripheral norepinephrine and albumin infusions. Shortly thereafter, the patient expired.
A CT abdomen pelvis revealing bowel wall edema, increase in the size of the pancreatic duct and narrow of the mesenteric vasculature due to mass effect
Discussion
Primary DA associated with concurrent pancreatic adenocarcinoma is a rare phenomenon. Tumors detected at an early stage can often be treated by surgical resection and adjuvant chemotherapy. Tumors which arise from the second portion of the duodenum can be managed via pancreaticoduodenectomy (PD), whereas cancers confined to the first, third, or fourth part of the duodenum can be treated with segmental resection (SR) or PD. At this time, there is no standard-of-care adjuvant chemotherapy for DAs that have been surgically resected. The ESPAC-3 clinical studied patients with an R0/R1 resection for pancreatic ductal adenocarcinoma who were randomized to either 5-fluorouracil plus folinic acid (FU/FA) or gemcitabine for 6 months. This trial did not find any significant differences between adjuvant gemcitabine, adjuvant fluorouracil or simple observation. Conversely, a phase II clinical trial led by Overman et al . revealed that patients with metastatic/unresectable small bowel or ampullary cancers who received oxaliplatin and capecitabine (CAPOX) benefited from a 50% overall response rate and 10% complete response. Median overall survival was 20.4 months and median time to progression was 11.3 months.
#80 Management of hypercalcemic crisis in the setting of malignancy: a case of necrotic hepatocellular carcinoma
V Sumbly*
I Landry
V Rizzo
Icahn School of Medicine at Mount Sinai | NYCHHC Queens, Jamaica, NY
Case Report
A 70-year-old male with a past medical history of hypertension, controlled HIV and treated hepatitis C was admitted to the hospital for generalized malaise and unintentional weight loss for the past four months. Intial vital signs were BP: 124/86, HR: 98, T: 99.9F and O2 saturation: 98% on room air. Physical examination was significant for diffuse abdominal tenderness. A computed tomography (CT) scan of the abdomen revealed a 17.7x8.5x10.1 cm mass in the left hepatic lobe (figure 1). An initial basic metabolic panel (BMP) revealed a creatinine of 2.34 mg/dL and calcium of 17.3 mg/dL (corrected calcium: 18.3 mg/dL; albumin: 2.7). Parathyroid hormone level (PTH) was 4 pg/mL and parathyroid related protein level (PTHrP) was 15 pmol/L. Vitamin D 1,25 OH level was 22.7 pg/ml and vitamin D 25 OH level was 14.0 ng/ml. Alpha fetoprotein marker (AFP) was 500,080 ng/ml, CA 19-9 was 131 U/ml, CA 125 was 80 U/ml and CEA was 17.6 ng/ml. Liver function testing (LFT) showed an ALP of 142 U/L and an AST of 80 U/L. The patient was started on normal saline (NS) at 150 cc/hr, which then increased to 250 cc/hr with improvement in calcium from 17.3 mg/dL to 15.7 mg/dL. Endocrinology recommended calcitonin 4 units/kg every twelve hours for 4 doses with one dose of zoledronic acid 4mg IVPB. The calcium level normalized to 9.9 mg/dL over the next 48 hours. IR-guided biopsy of the hepatic mass was consistent with poorly differentiated carcinoma of the liver with extensive necrosis.
CT abdomen/pelvis, coronal view, showing a 17.7x8.5x10.1 cm left lobe hepatic mass
Discussion
Hypercalcemic crisis is an oncologic emergency requiring prompt medical intervention. Management involves treatment of the underlying malignancy and administration of medications that promote renal calcium excretion and reduce bone resorption. Hypercalcemic patients tend to be extremely volume depleted, frequently presenting with a pre-renal acute kidney injury (AKI). These patients should receive immediate fluid management with NS boluses (at least 2L) and maintenance fluid (100-300 cc/hr) for 24-72 hours. Bisphosphonate therapy should be administered within 48h of diagnosis as these medications have peak onset between 48-96h. Although zoledronic acid and pamidronate are both available in the United States of America, a study by Goldner suggested that zoledronic acid was a more potent bisphosphonate. Denosumab, an anti-RANKL monocloncal antibody, may be used for bisphosphonate-resistant hypercalcemia as it has been proven to be more efficacious in reducing serum calcium levels than zoledronic acid. Calcitonin may be used to acutely reduce serum calcium levels in hypercalcemic crisis. It is initially administered as 4-8 IU/kg subcutaneously every 6-12 hours for up to a maximum of 48 hours, due to risk of tachyphylaxis. Glucocorticoids may be given with calcitonin to potentiate its effect. Cincalcet helps to prevent hypercalcemia by inhibiting parathyroid hormone (PTH) but has not been extensively studied in hypercalcemic crisis.
#81 A fulminant case of microscopic polyangitis leading to rapid demise
A Chandini Arjun*
G Mohan
J Ravilla
S Shenouda
S Yarrarapu
RN Tiperneni
Rutgers-Monmouth Medical Center, Long Branch, NJ
Case Report
History and physical
The patient is a 71-year-old female with a history of heart failure, atrial fibrillation(AFib), hemorrhagic stroke, myocardial infarction, hypertension and chronic kidney disease who was in her usual state of health until she developed sudden – onset dysuria, frequency, and mild vaginal spotting which was diagnosed as a urinary tract infection and treated with trimethoprim-sulfamethoxazole. Her initial symptoms improved but she went on to develop generalized arthralgia, for which she presented to our hospital, and was admitted for evaluation. Gynecology recommended an outpatient biopsy to evaluate her vaginal spotting as it improved. She was noted to have acute kidney injury on admission, and was managed with intravenous fluids. Within 5 days from the day of her initial symptom, she had an episode of desaturation with atrial fibrillation requiring BiPAP. Physical exam was significant for crepitations and decreased breath sounds, no dermatological findings seen.
Lab work and imaging
Chest X-ray showed bilateral pleural effusions with pulmonary vascular congestion and telemetry showed AFib with a rapid ventricular response. Her BUN was 104 and Creatinine 5.75 up from her baseline of 2.5; Proteinuria and hematuria with casts were noted. She was started on anti-arrhythmic medications, anti-coagulation, and hemodialysis.She eventually went into septic shock requiring pressor support with a WBC count as high as 26,000 with bandemia for which she was placed on broad-spectrum antibiotics. Eventually, her respiratory status and mentation declined to the point where she required intubation. Meanwhile, her MPO-ANCA test came back positive suggesting a diagnosis of Microscopic Polyangiitis/Granulomatosis with Polyangiitis(MPA/GPA) given the findings of kidney and lung involvement with initial findings of arthralgia. We began treating her with steroids after which she was extubated and started on rituximab. She was then sent to the general medical floors where she was improving. However, her hemoglobin eventually began dropping and she was found to be septic with blood cultures growing Klebsiella pneumonia. Plans to start cyclophosphamide were deferred due to the active infection. She required intubation again following which she was terminally extubated by her family after a long and hard fight.
CT chest showed septal thickening with ground glass opacities
Discussion
To our knowledge, this is a unique instance of such rapidly progressing MPA/GPA. This case highlights the importance of early initiation of steroids or monoclonal antibodies. Multi-system involvement may be confused for other individual diagnoses such as chronic kidney disease, heart failure exacerbation, or AFib. In our patient, we were unable to confirm the diagnosis with a kidney biopsy as the patient was extremely unstable through most of her hospital course. Early ANCA testing with prompt initiation of medications may be life-saving.
#82 A complex relationship between brain and heart – ictal asystole
RN Tiperneni*
A Chandini
R Padappayil
A Al-Alwan
Monmouth medical center, Long Branch, NJ
Case Report
Introduction
Epileptic seizures can cause cardiac arrhythmias. The most common arrhythmia seen is tachycardia, bradycardia, atrioventricular block. If bradycardia is severe enough it can lead to ictal asystole. It is usually associated with left temporal seizures with longstanding epilepsy, but it can also occur early in the course of epilepsy and can be caused by right temporal, frontal, and insular seizures. This is a case of a patient with ictal asystole twice a few hours apart, with the return of spontaneous circulation (ROSC) in 4-6 minutes each time.
Case
The patient is a 69-year-old male with a medical history of metastatic melanoma to the brain (reported remission) presents to the emergency department (ED) for an episode of unresponsiveness and spacing out. He was in the hospital a week ago for dehydration given poor oral intake and was discharged home after treating electrolyte imbalances. Since then he was noted to have staring episodes with near syncope and unresponsiveness at home. In the ED, he was noted to be gazing to the right side and became unresponsive a couple of minutes after arrival with stable vitals. After 10 minutes, he woke up but was lethargic and confused. After 15-20 minutes, he went to bradycardia with evidence of recurrent seizure activity – starring episode, with subsequent asystole arrest. ROSC was achieved in 4 minutes, intubated to maintain the airway, was started on Keppra intravenously, norepinephrine for low blood pressure with mean arterial pressure (MAP) less than 65, and transferred to the intensive care unit. Lab work showed blood glucose at 60 mg/dL, lactic acid at 6.9 mmol/L, troponin <0.010 ng/mL, arterial blood gas analysis – pH of 7.36, partial pressure of carbon dioxide at 29, partial pressure of oxygen at 67, bicarbonate at 19. An electrocardiogram (EKG) on arrival showed sinus tachycardia at 128 with left axis deviation [similar to previous]. EKG post-cardiac arrest showed atrial fibrillation with competing junctional pacemaker, left axis deviation, right bundle branch block, the ventricular rate of 62. After 2 hours he had another asystole arrest with ROSC achieved in 6 minutes. An echocardiogram done the next day was within normal limits, electroencephalography was suggestive of partial complex seizures due to metastatic disease. MRI of the brain is suggestive of metastatic disease (as shown in the attached image). He was downgraded to floors when he was clinically stable and eventually discharged home on Keppra with outpatient follow-up.
An ovoid 1.7 X 1.5cm lesion with T1 hyperintensity in the posteromedial aspect of the right temporal lobe
Discussion
Ictal bradycardia and even asystole can be seen in some patients with epilepsy, with sudden unexpected death in epilepsy. However, the association or increased risk is not well established. The recurrence risk of ictal asystole is around 30-40%. This case is a diagnostic challenge and needs effective communication between subspecialties.
#83 Thyrotoxic periodic paralysis in a Caucasian adolescent male
L Ejaz*
K Rush
SUNY Upstate Medical University, Syracuse, NY
Case Report
History: A 19-year-old Caucasian male with a history of depression presented to the pediatric emergency department with acute onset of bilateral lower extremity weakness. Symptoms began one day prior with difficulty moving his legs or standing after waking from sleep. He denied recent fevers, respiratory symptoms, numbness, paresthesia or myalgia but had emesis and transient dyspnea before coming to the emergency department.
Physical examination: On arrival he was found to be hypertensive and tachycardic. Physical examination revealed 1/5 strength in bilateral lower extremities but full strength in upper extremities. His sensation was intact throughout. The remainder of the exam was within normal limits.
Diagnostic work-up: Labs showed hypokalemia of 1.9 mmol/L, mild metabolic acidosis of 18 mmol/L and mildly elevated creatinine kinase of 247 U/L. Cardiac and infectious labs were otherwise negative. His electrocardiogram showed prolonged PR intervals with flattening of the T waves and U waves most notable in the lateral precordial leads and V3. He received parenteral potassium chloride and anti-emetics. Neurology was consulted and deferred imaging given his hypokalemia. He was admitted to the PICU for cardiac monitoring. His neurologic symptoms resolved after potassium administration and intravenous fluid therapy. Thyroid function tests revealed hyperthyroidism (FT4 3.87 ng/dl and TSH less than 0.03 IU/ml). Endocrinology recommended obtaining Thyroid Stimulating Immunoglobulins and receptor antibodies, which were later found to be elevated at 14.40 IU/L. Thyroid ultrasound during admission showed an enlarged heterogeneous thyroid gland without any nodules.
Final diagnosis: The patient was diagnosed with thyrotoxic periodic paralysis due to Graves’ Disease. Metoprolol was initially recommended for acute thyrotoxicosis management. He was later switched to propranolol and started on daily methimazole prior to discharge. At the time of discharge, he had full strength in all four extremities. He is awaiting treatment for radioiodine ablation.
Prolonged PR intervals with flattening of the T waves and U waves most notable in the lateral precordial leads and V3
Discussion
Thyrotoxic periodic paralysis is characterized by hypokalemia, acute onset of lower extremity weakness and hyperthyroidism. It is mostly found in adult Asian males and is often overlooked in Western countries and the pediatric population. In the past two decades, less than 20 cases in adolescents have been reported. The pathophysiology is unclear; however the theory is hyperthyroidism increases tissue responsiveness to beta-adrenergic stimulation which increases sodium-potassium ATPase activity on the skeletal muscle membrane, leading to an intracellular potassium shift resulting in hypokalemia, muscle weakness and potential cardiac arrhythmias. Acute treatment involves potassium replacement with cardiac monitoring given the risks of hyperkalemia. A beta-blocker may reverse adrenergic hyperstimulation but treating hyperthyroidism is the most definitive management.
#84 Snare assisted valve-in-valve transcatheter aortic valve implantation
V Maddali1*
B Dave2
D Godkar2
1Rutgers Robert Wood Johnson Medical School, Piscataway, NJ
2St. Barnabas Medical Center, Livingston, NJ
Case Report
Endovascular snare has been used for foreign body retrieval procedures like retrieval of inferior vena cava filters and repositioning indwelling venous catheters. We present a case where endovascular snare was used to assist a valve in valve Transcatheter Aortic Valve Implantation (TAVI).
Valve in valve TAVI is now frequently used to treat patients with symptomatic aortic valve disease secondary to degeneration of previously implanted surgical aortic valves. Although knowledge of previously implanted valve along with fluoroscopy markers make it easier to plan a valve in valve procedure in terms of valve sizing and placement, the presence of a rigid valve prosthesis poses its own set of challenges.
We present the case of a 70-year-old male with previous SAVR for native bicuspid aortic valve stenosis complicated by ascending aortic aneurysm requiring 23 mm Edwards Perimount 2800 bioprosthetic valve and aortic aneurysm repair at age 57 presenting with heart failure requiring Snare-assisted valve-in-valve TAVR. Echocardiographic evaluation revealed degeneration of the bioprosthetic valve with severe bioprosthetic aortic valve stenosis and insufficiency. Analysis of computerized tomography (CT) scan qualified this patient for a 26 mm Evolut Medtronic valve with suggested transfemoral approach.
Intraoperatively, despite the wire crossing the left ventricle easily and excellent support from a double curve Lunderquist wire, we were unable to cross the valve with the Evolut valve delivery system despite multiple manipulations. We decided to use a 25 mm Merit Endovascular EN snare (through the contralateral femoral access) to assist us in delivering the valve. The entire valve crossing process with stiff Amplatz wire-Amplatz catheter-Glide wire-double curve Lunderquist wire was repeated but from within the snare. In the final exchange as the valve delivery system was introduced in the patient’s vascular system the distal tip of the nosecone was snared as it passed the descending thoracic aorta (figure 1). The snare was then allowed to ride with the nosecone across the arch and then the ascending aorta. As soon as the valve delivery system hit resistance (figure 2) the snare was used to pull the nosecone and the valve delivery system away from the bioprosthetic valve scaffolding into the valve lumen (figure 3). The snare was then released, withdrawn, and pulled back into the descending thoracic aorta. The valve in valve deployment was then completed (figure 4). Previous valve scaffolding was used to guide accurate valve deployment and pigtail assisted aortography was not performed.
As the indications for percutaneous valve procedures increase, this technique may assist in smoother delivery of these bulky valve delivery systems across resistance encountered by heavy native aortic/aortic valve calcification or previously placed bioprosthetic valves.
4A: Neonatal nutrition/breast milk
#85 Associations of human milk oligosaccharides with brain development in very preterm infants
M Ong1*
S Cherkerzian2
K Bell2
A Furst3
T Inder2
L Bode3
M Belfort2
1Boston Children’s Hospital, Boston, MA
2Brigham and Women’s Hospital, Boston, MA
3University of California, San Diego, San Diego, CA
Purpose of Study
Among very preterm infants, human milk feeding is associated with improved brain growth and neurodevelopmental outcomes. Mechanisms of neuroprotection are poorly understood but may involve non-nutrient bioactive factors such as human milk oligosaccharides (HMOs). Currently, little is known about relationships between HMO intake and brain injury, growth, and maturation during the critical developmental period in the neonatal intensive care unit (NICU). The objective of this study is to investigate associations between HMO composition of maternal milk and brain injury, size, and maturity at term-corrected age in very preterm infants. We hypothesized that higher concentration of specific HMOs would be associated with less brain injury, larger brain volume, and more mature white matter microstructure.
Methods Used
We studied 51 infants <32 weeks’ gestational age (GA) fed primarily maternal milk (≥75% at day 28). We measured HMO composition with high performance liquid chromatography on milk collected at 2 time points while the infant was in the NICU (T1, 13.0±7.7 days; T2, 66.4±24.8 days) and defined HMO exposure as mean area under the curve between measurements for: 1) concentration (µg/mL) of five specific HMOs; 2) HMO-bound sialic acid (nmol/mL); 3) total HMO (µg/mL). From brain MRI at term (post-menstrual age [PMA], 38.8±1.4 weeks), we quantified: 1) global brain abnormality score; 2) total and regional brain volumes; 3) white matter microstructure (fractional anisotropy [FA] in the posterior limbs of the internal capsule [PLIC] and corpus callosum [CC]). We used linear mixed effects models to estimate associations between HMO exposure (>75th vs ≤75th percentile) and each outcome, adjusting for GA, sex, birth weight z-score, PMA at MRI, and intrafamilial correlation among twins.
Summary of Results
Mean birth weight was 1026±378g; GA, 28.1±2.4 weeks [table 1]. Specific HMO concentrations were positively correlated with each other. Higher 3’SL, DSLNT, and total HMO were associated with higher FA-CC (1.0% higher mean FA in >75th vs ≤75th percentile, 95% CI (0.1, 2.0) for 3’SL; 0.8%, 95% CI (0.03, 1.5) for DSLNT; 0.8%, 95% CI (0.03, 1.6) for total HMO). Higher 6’SL exposure was associated with smaller hippocampus volume (0.4cc lower in >75th vs ≤75th percentile, 95% CI (-0.6, -0.3)) [table 2].
Participant characteristics (n=15)
Adjusted associations between HMO exposure from maternal milk and brain MRI outcomes at term-corrected age among very preterm infants (n=51) fed predominantly maternal milk
Conclusions
Exposure to higher concentrations of specific (3’SL, DSLNT) and total HMOs may benefit white matter development in very preterm infants. However, exposure to higher 6’SL concentration was associated with smaller hippocampus volume, suggesting heterogeneity among HMO effects.
#86 Nutritional outcomes after introducing human-milk-based human-milk fortifier for preterm infants in an urban level IV NICU
S Patel*
N Mangalapally
A Vlk
C Capriolo
E Schofield
NL Davis
University of Maryland School of Medicine, Baltimore, MD
Purpose of Study
Preterm infants fed breast milk in comparison to bovine-based infant formula have lower incidence of morbidities such as necrotizing enterocolitis (NEC), late onset sepsis, and bronchopulmonary dysplasia (BPD). Our urban level IV NICU therefore introduced human-milk-based human-milk fortifiers (HMBHMF) in November 2018 for neonates born <1250g who were being fed maternal breast milk (MBM) or donor breast milk (DBM) to meet nutritional goals while providing an early exclusive human milk diet. However, HMBHMF is significantly more expensive than bovine-based fortifiers and concern exists about poorer somatic growth. The objective of this study was to evaluate the effect of HMBHMF introduction on feeding characteristics, growth, and incidence of morbidities during NICU admission.
Methods Used
Retrospective medical record review of infants born <1250g in 2 cohorts: 1) prior to introduction of HMBHMF with bovine-based HMF only (9/2015 – 10/2018) and 2) after introduction of HMBHMF (11/2018 – 12/2020). We compared clinical and demographic characteristics between those who received only bovine-based HMF vs. those receiving HMBHMF. We performed multivariable logistic regression to assess the association between HMBHMF use and NEC stage 2/3, controlling for changes in feeding protocols over time.
Summary of Results
We identified 419 subjects, of whom 121 (29%) received HMBHMF. Infants completed HMBHMF by median day of life 43 [IQR 31-56]. Neonatal characteristics were similar over time in regards to sex, birth weight, race, and small for GA (SGA) status. [Table 1] Feeding with HMBHMF was not associated with lower incidence of NEC, BPD, retinopathy of prematurity requiring treatment, periventricular leukomalacia, intraventricular hemorrhages, late onset sepsis, or death. Introduction of HMBHMF did not affect time to full enteral feeds, time to completion of TPN, need for central access, or duration of central access. Infants fed HMBHMF had a slower average weight gain (g/kg/day) at 4 weeks (p=0.0008) and 6 weeks (p=0.0493) of age compared to those prior to introduction of HMBHMF. Using a multivariable logistic regression model for predictors of stage 2 or 3 NEC, we found that HMBHMF did not significantly decrease the adjusted odds of NEC (p=0.9730). [Table 2] Lower birth GA and premature prolonged rupture of membranes (PPROM) were significantly associated with NEC.
Comparison of neonates based on human-milk-based human milk fortifier feeding status
Multivariable logistic regression model of predictors of stage 2/3 NEC
Conclusions
Infants fed HMBHMF had slower growth rates without improvement in feeding characteristics such as timing of full feeds and reduction in central line days. Despite the presumed potential for lowering the incidence of NEC with an early exclusive human milk diet, our study found no association between introduction of HMBHMF and reduction in rates of NEC or other common comorbidities of prematurity.
#87 Changes to NICU feeding protocols improved provision of human milk to early preterm infants
N Mangalapally*
S Patel
A Vlk
E Schofield
C Capriolo
NL Davis
University of Maryland School of Medicine, Baltimore, MD
Purpose of Study
We modified our NICU’s feeding protocol over time to improve rates of early exclusive human milk diet via maternal breast milk (MBM), donor breast milk (DBM), human-milk-based human milk fortifier (HMBHMF), and to stop routine gastric aspirate monitoring, in an attempt to optimize nutrition and reduce rates of necrotizing enterocolitis (NEC). However, concern exists for poor somatic growth and decreased provision of MBM with the introduction of DMB and HMBHMF. Our objective was to assess the effect of these feeding protocol changes on growth, characteristics of feeds during NICU admission, and incidence of comorbidities such as NEC.
Methods Used
Retrospective medical record review of neonates born <1250g admitted to an urban Level IV NICU. Compared neonatal characteristics in 4 nutritional time-epochs: 1) Baseline (9/2015-4/2016), 2) after DBM introduction (5/2016–6/2018), 3) after discontinuing routine gastric aspirate monitoring (7/2018-10/2018), and 4) after introduction of HMBHMF (11/2018–12/2020).
Summary of Results
Baseline demographics were similar for our 422 subjects over the 4 epochs including sex, birth gestational age (GA), birth weight, race, and small for GA (SGA) status. [Table 1] The later epochs were associated with significant reduction in time to first feed (p<0.0001), time to first MBM feed (p<0.0001), time to full feeds (p=0.0003), need for peripherally inserted or surgical central lines (p=0.0080), and central line duration (p<0.0001). [Figure 1] Although DBM and HMBHMF use increased over time, we found no decrease in MBM use with changes in protocols. The incidence of morbidities including NEC, intraventricular hemorrhage, retinopathy of prematurity (ROP) requiring treatment, and late onset sepsis did not differ between the epochs. There was a significant decrease in bronchopulmonary dysplasia (BPD) over time (p=0.0427) and a significant improvement in rates of exclusive MBM feeds at time of discharge (p=0.0322). We did not find a significant reduction in average daily weight gain over time.
Patient characteristics during feeding protocol changes
Changes in nutritional characteristics over time
Conclusions
Our study found that feeding protocol changes (discontinuing routine gastric aspirate monitoring and the introduction of DBM and HMBHMF) were associated with more rapid feed advancement and fewer central line days without significantly slowing average daily weight gain for the first 6 weeks of life. MBM use did not decrease with introduction of DBM and HMBHMF, and more neonates were feeding exclusive MBM at discharge. These changes were found to be safe without increased morbidities such as NEC, ROP, and sepsis, and were associated with lower rates of BPD. Identifying risks and benefits of feeding protocol changes for early preterm infants will allow researchers and clinicians to allocate funding and resources appropriately.
#88 Longitudinal changes of macronutrients in preterm milk through 40 weeks corrected gestational age (CGA)
D Merzel1*
J Gross2
T Roeder3
C Giblin1
B Parvez1
1Maria Fareri Children’s Hospital at Westchester Medical Center, Valhalla, NY
2New York Medical College, Valhalla, NY
3Westchester Medical Center, Valhalla, NY
Purpose of Study
Human breastmilk is fortified to provide complete nutrition for preterm infants. Most commonly, fortification adds a set amount of a standardized fortifier to the human milk to achieve a specified caloric and macronutrient content. Less commonly, individualized fortification adjusts fortification based on the infant’s metabolic response or the measurement of the macronutrients using a human milk analyzer. There is a paucity of data on the longitudinal changes in macronutrient content of preterm breastmilk. The objective is to identify patterns of gestational age specific macronutrient content that will guide individualized fortification.
Methods Used
This IRB study enrolled mothers of neonates less than 37 weeks gestation admitted to Maria Fareri Children’s Hospital. Expressed breastmilk samples were collected weekly from birth until 40 weeks CGA. Analysis of milk samples was performed using an FDA-approved human milk analyzer measuring fat, protein, carbohydrate and energy content using near-infrared spectroscopy.
Summary of Results
When analyzing by CGA, protein content ranged from 1.5g/100ml to 0.7g/100ml at a CGA of 24 and 40 weeks respectively. There was a protein and caloric content of 1.2 ± 0.4 g/100ml and 20.5 ± 4 cal/oz prior to 35 weeks, and a protein and caloric content of 1.0 ± 0.4 g/100ml and 20.8 ± 4.5 cal/oz after 35 weeks (mean ± standard deviation) (table 1). The starting protein content of the breastmilk differs based on gestational age, thus protein content during the same CGA varies. Longitudinally, there is a decrease in protein content over time, a relatively stable carbohydrate level, and variable fat and energy levels (figure 1).
Macronutrient content in preterm milk through 40 weeks gestational age
Protein content of preterm breastmilkLongitudinal changes of protein content in preterm breastmilk, measured in grams per 100 milliliters, as represented by 3 individual mothers; the first mother delivered at 23 weeks gestation, the second delivered at 26 weeks gestation, and the third delivered at 30 weeks gestation.
Conclusions
Maternal contribution towards the macronutrient content of breastmilk accounts for variability within samples of the same CGA. The earlier preterm the delivery, the higher the protein content at birth. Based on a 150ml/kg diet, preterm breastmilk alone is not meeting the recommended protein intake of 4g/kg/day nor the recommended caloric intake of 120kcal/kg/day. Individualized fortification with predominant protein fortification based on gestational age should be used considering the steady decrease in protein content. Further, calories can be provided with a high-fat maternal diet and utilization of hindmilk, accounting for variability both within a single mother as well as between mothers.
#89 Helping babies grow- are we setting babies up for success post discharge?
G Kennady*
A Ivashchuk
B Storm
T Headley
A Mackley
C Duran
D Tuttle
ChristianCare, Newark, DE
Purpose of Study
Preterm infants have higher nutritional requirements. Fortified breastmilk (BM) and preterm formulas may not meet the recommended daily intake (RDI) of nutrients. In addition, fortified BM are stopped prior to discharge, placing infants at risk for growth restriction and nutritional deficiencies. The aim of this study is to determine the differences between RDI and actual nutrients in discharge feeds of very low birthweight (VLBW) infants using nutrition gap analysis.
Methods Used
Retrospective chart analysis on 105 infants who were discharged from a tertiary NICU between 2017 and 2019. Nutritional gap analysis was completed at 1 week prior and at the time of discharge by the NICU nutritional specialists. Growth parameters, type of feeds, volume of feeds and nutrients including supplements were collected. The amount of energy, protein, calcium, phosphorus, and vitamins in the infants’ diet was calculated using this data.
Summary of Results
The goal RDI was not met for energy in 32% vs 42%, protein in 30% vs 37%, calcium in 38% vs 35%, phosphorus in 26% vs 29% and vitamin D in 28% versus 24% infants at the time of discharge and 1 week prior to discharge. This was despite only 20% of infants were receiving >75% of their diet as maternal breast milk feedings. At the time of discharge, 19% of the infant’s born small for gestational age (SGA) remained SGA and 32% of appropriate for gestational age (AGA) infants were SGA.
Nutritional gaps at 1 week prior to discharge and at discharge
Prevalence of maternal breast milk (MBM) feeds
Conclusions
The discharge diet in VLBW infants was insufficient to meet the RDI in more than 30% of babies. Extrauterine growth restriction is a major problem in VLBW infants despite fortification of feeds. Optimizing discharge nutrition is important to achieve optimal growth, bone mineralization and developmental outcomes. Measures to support maternal BM feeds, balancing with nutritional needs must be strengthened.
#90 Feeding choices amongst mothers of babies in the neonatal intensive care unit
D Abramova*
K Hunter
A Kushnir
Cooper University Hospital, Camden, NJ
Purpose of Study
National studies have shown that neonatal intensive care units (NICU) with a greater proportion of underserved populations have lower rates of breastfeeding and use of mother’s own milk (MOM). Despite the evidence that the use of MOM during the NICU stay is protective against associated comorbidities related to prematurity, Cooper University Hospital’s NICU has a low initiation and continuation rate of feeding MOM. Our aim is to determine the challenges for women of preterm neonates admitted to the NICU in initiating breastfeeding and the reasons for choosing not to express milk for their infant.
Methods Used
In this mixed-methods study, mothers with pre-term deliveries participated in telephone in-depth interviews answering a series of questions related to their feeding choices, as well as other factors that influenced their decisions to breastfeed or not. The primary outcome was to identify any maternal obstacles to the initiation of breastfeeding during the NICU stay of the baby. Questions evaluating deterrents to breastfeeding included family and cultural beliefs, as well as previous experience with breastfeeding and certain aspects of socio-economic status.
Summary of Results
Out of 30 mother’s post pre-term deliveries interviewed, 24 were able to provide their infants with breastmilk (maternal or donor), and 6 babies received exclusive formula. There was no association between maternal age and the choice to breastfeed a preterm neonate. Gestational age (GA) of the neonate was significantly related to maternal choice in initiating breastfeeding. Neonates who received some or exclusive breastmilk had a mean GA of 31 weeks, whereas those receiving formula had a mean GA of 35 weeks (p<0.04). Neonates receiving maternal breast milk (MOM) were significantly older compared to neonates who received donor milk (34 weeks vs 27 weeks, p<0.001). Mothers who denied using any substances, including tobacco or alcohol, had a higher rate of providing some or all MOM. Factors such as breastfeeding education, past experiences, socioeconomic status, or knowledge of the benefits of breastfeeding for preterm infants did not have an effect on the initiation of breastfeeding. There was a trend for decreased rate of MOM for preterm neonates in mothers on Medicaid, with 100% receiving formula, and with 62.5% of those with private insurance receiving partial or exclusive MOM.
Conclusions
Based on our study, gestational age of the neonate had an impact on whether or not mothers initiated breastfeeding and if baby received any breastmilk. In addition, mothers who were substance abuse free were more likely to breastfeed.
#91 Efficacy of milk expression in the first week predicts lactation success for mothers of preterm infants
C Gomez-Juge*
V Scarpelli
D Yellayi
B Weinberger
M Brewer
D Maffei
Pediatrics, Northwell Cohen Children’s Medical Center, Queens, NY, United States
Purpose of Study
The provision of mother’s-own-milk is critical for short and long-term health outcomes among preterm infants, but medical and social barriers often interfere with the initiation or maintenance of milk expression. Moreover, many mothers who deliver prematurely are subsequently unable to provide adequate milk for their infant throughout the hospitalization. The effects of time to first milk expression, frequency of milk expression, and volume of milk production in the first week on volumes of milk produced in the following 4 weeks are not well established. We hypothesize that earlier initiation, increased frequency of milk expression, and increased milk volume in the first week will be associated with higher milk volume on day 28.
Methods Used
Mothers of preterm infants (< 32 weeks gestation and birth weight < 1500 grams, n = 49) were recruited within 48 hours of delivery. Mothers maintained a pumping log (record of each pumping session including date/time and volumes produced) and this data was shared with the study team. Standard lactation consultation and education was provided as per the institutional standard of care.
Summary of Results
Time to first milk expression and frequency of milk expression in the first week were not associated with milk volume on day 28 (R2 = 0.08, p = 0.22 and R2 = -0.08, p = 0.33, respectively). In contrast, milk volumes produced on day 7 correlated with those on days 14, 21 and 28 (R2 = 0.84, 0.71, 0.45 respectively; p < 0.004).
Conclusions
Efficacy of milk production in the first week, as indicated by milk volumes, is a strong predictor of later success. This finding highlights the importance of lactation support for mothers of preterm infants in the first week. Although timing and frequency of milk expression in the first week do not directly predict milk volumes at 28 days, further studies are being conducted to establish the strength of their impact on milk production in the first week.
#92 Human milk-derived fortifier versus bovine milk-derived fortifier use in very low birth weight infants: impact on growth and vitamin D status
E Lavassani*
K Tauber
J Cerone
J Ludke
U Munshi
Albany Medical Center, Albany, NY
Purpose of Study
Bovine milk-derived fortifier (BMDF) has been the standard of care for human milk fortification in premature infants, but the introduction of human milk-derived fortifier (HMDF) provides the opportunity for an exclusive human milk diet, which reduces the risk of adverse outcomes but may not provide enough protein for adequate growth compared to BMDF. There is insufficient data in current literature comparing the effects of BMDF and HMDF on growth and serum 25 hydroxy vitamin D (25OHD) levels in preterm very low birth weight (VLBW) infants. The purpose of this study is to investigate the effects of BMDF versus HMDF on growth and vitamin D levels in premature VLBW infants in the first two months of life.
Methods Used
IRB-approved retrospective chart review of VLBW infants admitted to the Neonatal Intensive Care Unit (NICU) within 24 hours of birth, defined as weight < 1500 g and gestational age ≤ 32 + 6/7 weeks at birth. Only infants receiving exclusively human milk (mother’s milk and/or donor milk) were analyzed after being separated into those fortified with BMDF and those fortified with HMDF. Analysis of growth parameters and vitamin D status was done at 4 and 8 weeks postnatal age.
Summary of Results
517 infants were eligible but only 139 received exclusive human milk from birth to 4 weeks of age and were enrolled. Of the 139 infants, 44 continued to receive exclusively human milk between 4 and 8 weeks of age. Birth demographic characteristics are shown in table 1. There was no statistically significant difference between BMDF and HMDF groups in growth parameters, including weight, head circumference, or length gain, at 4 and 8 weeks post-birth. Serum 25OHD levels in the HMDF group were significantly increased in comparison to the BMDF group, 30.6 ± 9.0 ng/mL vs 28.2 ± 10.9 ng/mL (P=0.02), at 4 weeks post-birth despite receiving less vitamin D supplementation than the BMDF group, 13.7 ± 3.3 μg/day vs 18.3 ± 3.7 μg/day (P=0.0001) (figure 1). Differences in vitamin D status and supplementation were not significant at 8 weeks of age. NEC rates were low and not statistically different between the groups.
Demographics of the HMDF and BMDF groups
Comparison of growth parameters, vitamin D status, and vitamin D supplementation of HMDF and BMDF groups at 4-and 8-weeks of age. HMDF = human milk-derived fortifier; BMDF = bovine milk-derived fortifier; 25OHD = serum 25 hydroxy vitamin D; Supp = supplementation. (* P < 0.05)
Conclusions
Growth parameters were similar between the HMDF and BMDF groups suggesting that HMDF provides adequate nutrients for growth. The HMDF group had significantly increased serum vitamin D levels at 4 weeks compared to the BMDF group. A difference was not seen at 8 weeks likely due to low numbers of infants in that cohort. Infants who received HMDF required lower vitamin D supplementation to achieve higher serum levels than infants that received BMDF. Further studies with larger numbers are needed to confirm these results.
4B: COVID-19/infectious disease
#93 Detection of SARS-CoV-2 in stool but not nares of newborns of mothers with COVID-19 during pregnancy
JC Jin1,2*
A Ananthanarayanan2
JA Brown2
SL Rager2
Y Bram1,2
KZ Sanidad2
M Amir2
R Baergen1
H Stuhlmann2
RE Schwartz1,2
J Perlman1
M Zeng2
1New York Presbyterian Weill Cornell Medicine, New York, NY
2Weill Cornell Medicine, New York, NY
Purpose of Study
To investigate potential evidence of in utero transmission of SARS-CoV-2 in the stool of newborns born to mothers with COVID-19 infection during pregnancy.
Methods Used
We investigated stool from 1 day to 2 months of age from 14 newborns born at 25-41 weeks whose mothers had COVID-19 during pregnancy. Newborns were admitted at delivery to the NICU or newborn nursery of our urban academic hospital from July 2020 to May 2021. A comparison group of 30 newborns had similar GAs and were born to mothers without COVID-19 during pregnancy. SARS-CoV-2 RNA was quantified with quantitative PCR using primers against SARS-CoV-2 envelope protein and non-structural protein 14 (NSP-14), spike protein with enzyme-linked immunosorbent assay (ELISA), and inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ) elicited by stool homogenates in mouse bone marrow macrophages. This study was IRB approved with parental consent.
Summary of Results
Despite negative nasal PCRs from all newborns, viral RNAs and spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life (range 0-2 months, figure 2A and 2B). Stool RNA and spike protein levels increased over time in 2 and 4 newborns, respectively. Stool homogenates from all newborns elicited elevated inflammatory cytokines, IL-6 and IFN-γ, from mouse macrophages (figure 1). Most newborns were clinically well except for one death from gestational autoimmune liver disease and one with necrotizing enterocolitis.
Increased proinflammatory components in the stool specimens from the COVID-19 cohortExpression of IL-6, IFN-γ, and IL-1β by mouse macrophages after co-culture with heat-inactivated stool specimen for 18 hours. Stool specimens from earliest time points (1-2 time points) from COVID-19 and GA-matched non-COVID-19 groups were used. > 1 time point were analyzed for some of the infants that had multiple samples collected. *p<0.05; 2-way ANOVA.
Detection of SARS-CoV-2 viral RNA and spike protein in stool specimensA. Delta Delta Ct (levels quantified by qPCR) values of stool specimens collected from COVID-19 (n=14) and non-COVID-19 (n=11) groups using the primers for NSP 14. **p<0.001; unpaired t test. Positive controls were kidney organoids infected with SARS-CoV-2. B. Detection of the spike protein in the stool samples of COVID-19 (n=14) and non-COVID-19 (n=30) neonates by enzyme-linked immunosorbent assay (ELISA). Relative amounts of spike in all stool specimens were shown as absorbance at O.D. 450 after subtracting background levels. **p<0.001; unpaired t test. The stool specimens with the highest viral or spike protein were included for each neonate; GA-matched samples from neonates without maternal COVID-19 history were used for comparison.
Conclusions
These novel findings suggest risk of in utero SARS-CoV-2 transmission to the premature and term fetal intestine during gestation despite negative postnatal nasal PCRs. It is unclear if the presence of viral RNA and protein within the gut microbiome represents active virus in newborns with clinical hospital courses typical of their gestational age in 12 out of 14 cases. However, increasing levels of viral RNA and protein over time suggest replication in some infants, and their gut microbiome induced inflammation in mouse models. The presence of SARS-CoV-2 RNA and spike protein in the intestines of newborns may potentially impact development of the gut microbiome and the immune system and should be further investigated.
#94 Characteristics of post-acute sequelae of Covid-19 (PASC) in pediatrics
T Fashina1*
E Paintsil2,3
CR Oliveira2
1Department of Global Health & Health Policy, Yale University School of Public, New Haven, CT
2Department of Pediatrics, Section of Infectious Diseases and Global Health, Yale University School of Medicine, New Haven, CT
3Department of Pharmacology, Yale University School of Medicine, New Haven, CT
Purpose of Study
A subset of children and adolescents who have been infected with SARS-CoV-2 can experience recurrent or persistent symptoms beyond the typical recovery period. The constellation of findings that occur post-infection is known Post-Acute Sequelae of Covid-19 (PASC). Relatively little is known about this condition in the pediatric population. This study aimed to explore the clinical spectrum and outcomes of children and adolescents diagnosed with PASC within a large healthcare system.
Methods Used
In this cross-sectional study, encounter- and patient-level data were extracted from the electronic health records (EHR) of patients <21 years who had at least one health care visit between 5/1/21 and 9/30/21 in an ambulatory site affiliated with the Yale-New Haven Health System. Individuals with a PASC-associated encounter were identified using Systematized Nomenclature of Medicine (SNOMED) codes, the standard for encoding patient conditions in the EHR. Free-text data fields denoting the ‘reason for visit’ were also queried to optimize case-finding. Descriptive statistics were used to summarize demographics, clinical characteristics, and management of pediatric patients with PASC.
Summary of Results
During the study period, there were 66,590 pediatric patients with an encounter in the health system, of which 1,520 had a Covid-19-related encounter diagnosis, and 37 had PASC. The mean age for PASC was 16 years (± 4), and 65% were female. Most identified their race/ethnicity as either White (59%), Black (5%), or Hispanic (32%). The most common comorbidities included atopy (32%), asthma (22%), and obesity (12%). Approximately 28% of children diagnosed with PASC had no prior medical history, and 30% were previously active in sports before Covid-19. In the acute phase of the disease, most (88%) had a mild illness, and only 12% required hospitalization. The median time between acute Covid-19 and their PASC encounter was 3 weeks (IQR 1-5). The most prevalent symptoms are shown in figure 1. Patients with PASC had a mean follow-up of 2.6 months. Medical utilization was high, with an average of 3 medical encounters per patient (range 1-12). Most (75%) had minimal to no limitations in daily functioning, though at least 5% experienced severe limitations and reported high rates of school absenteeism. Out of the 31 patients screened for depression, 8 (26%) tested positive. Cardiology and pulmonology evaluated 72% and 48% of PASC cases, respectively, yet only 8% found abnormalities in their work-up.
Conclusions
This study highlights the wide range of clinical symptoms children and adolescents can experience post-Covid-19. PASC can occur even after mild SARS-COV-2 infections and may lead to severe limitations. To better understand the true risk SARS-CoV-2 poses to children, more research is needed to quantify the long-term outcomes of infection and the impact PASC has on quality of life.
#95 Host maturity and microbial factors regulate the anti-inflammatory effects of adjunctive pentoxifylline in murine neonatal sepsis
EM Speer*
AA Adedeji
Stony Brook Children’s, Stony Brook, NY
Purpose of Study
Neonatal sepsis triggers an inflammatory response that contributes to increased mortality and brain injury. The phosphodiesterase inhibitor pentoxifylline (PTX), which suppresses pro-inflammatory and enhances anti-inflammatory cytokines, is a candidate adjunctive therapy for newborn sepsis. The effects of PTX on sepsis-induced cerebral inflammation in the newborn and its interaction with microbial and host factors remain however poorly understood. We therefore aimed to determine the role of postnatal age and microbial agents on the anti-inflammatory effects of PTX in an antibiotic-treated murine neonatal sepsis model.
Methods Used
Newborn (<24 hours (h)) or infant (7 days old) C57BL/6J mice (n=209), corresponding immunologically to preterm and term human neonates, were injected intraperitoneally with live Escherichia coli K1 (105colony forming units (CFU)/g weight) or Staphylococcus epidermidis (107 CFU/g). 1.5 h after sepsis initiation, pups were randomly assigned to saline, antibiotic (gentamicin or vancomycin), antibiotic with PTX, or PTX alone, and were euthanized after an additional 4 h. CFUs, cytokines and chemokines were measured in homogenized brain tissue and compared with 1-way ANOVA and Kruskal-Wallis tests, corrected by false discovery rate.
Summary of Results
Cerebral cytokine and chemokine concentrations were significantly lower in newborn vs infant mice with E. coli sepsis, and were lowest in S. epidermidis-infected pups. PTX did not suppress pro-inflammatory cytokines (IL-1, IL-2, IL-12, TNF, interferon-γ) except for IL-12p40 in E. coli septic newborn mice. Whereas adjunctive PTX augmented the anti-inflammatory and pro-resolution cytokines IL-10, IL-6 and G-CSF in E. coli septic infant mice, IL-6 and G-CSF were diminished and IL-10 unchanged in E. coli-infected newborn mice, without any changes in S. epidermidis septic infant mice (Abstract #95 figure 1). Addition of PTX to antibiotics decreased cerebral expression of keratinocyte-derived chemokine (CXCL1), chemokine ligand 2 (CCL2), CCL3 and CCL4 in E. coli septic newborn, however showed blunted chemokine suppression in E. coli septic infant mice, without any changes in S. epidermidis septic infant mice (Abstract #95 figure 2). Cerebral tissue CFUs remained low in saline- and antibiotic-treated mice, and addition of PTX did not augment bacterial growth.
Adjunctive PTX differentially modifies anti-inflammatory and pro-resolutin cytokines in newborn and infant mice with E. coli sepsis a) Newborn mice (< 24 hours old), b) Infant mice (7 days old).SAL (saline), GENT (gentamicin), G+P (gentamicin and pentoxifylline), PTX (pentoxifylline alone).Significance: *p<0.05, **p<0.01, ***p<0.001.
Adjunctive PTX inhibits cerebral chemokine responses in murine neonantal E. coli sepsis a) Newborn mice (< 24 hours old), b) Infant mice (7 days old).SAL (saline), GENT (gentamicin), G+P (gentamicin and pentoxifylline), PTX (pentoxifylline alone).Significance: *p<0.05, **p<0.01, ***p<0.001.
Conclusions
Postnatal age and microorganisms differentially modify the anti-inflammatory profile of adjunctive PTX in antibiotic-treated neonatal septic mice, with prominent chemokine suppression in newborn and enhanced anti-inflammatory cytokine expression in infant mice with E. coli sepsis, without changing S. epidermidis-induced cerebral inflammation. These findings may have implications for individualized therapy of newborn sepsis.
#96 Provision of human milk at NICU discharge for preterm infants during the COVID-19 pandemic
L Boudreau1*
B Vohr1,2
R Tucker1
E McGowan1
1Women and Infants Hospital of Rhode Island, Providence, RI
2Alpert Medical School of Brown University, Providence, RI
Purpose of Study
To investigate the impact of the COVID-19 pandemic on provision of human milk (HM) at the time of discharge (DC) home from the NICU in a cohort of survivors born < 34 weeks gestational age.
Methods Used
Retrospective analysis of prospectively collected data from the Women & Infants Follow-up Clinic database. 532 preterm (PT) infants born between 1/1/2019 and 3/30/2021 who survived to DC are included. Infants born during the COVID-19 period (defined as 3/1/20 to 4/30/21) were compared to infants born pre-COVID (defined as 1/1/19 to 2/29/20), and the primary outcome was the provision of any HM at NICU DC. Secondary analyses were performed by public and private insurance. Multivariable regression analyses were run for the total cohort and by health insurance, adjusting for socio-economic demographics and medical risks. An interaction term for public insurance and COVID-19 period was also tested.
Summary of Results
Infants born during COVID-19 pandemic were larger than infants born pre-COVID (table 1). There were more mothers who identified as single prior to pandemic onset, and more cases of chorioamnionitis after pandemic onset (table 1). Rates of public insurance were similar between groups (55% pre-COVID and 50% COVID). There was no change in provision of any HM at DC between time periods, 63% to 71%; p=0.08 (table 1). Provision of any HM at DC increased from 77% to 88%; p=0.02 for those on private insurance and remained unchanged for infants on public insurance; 52% to 53%; p=0.92 (table 1). In regression analyses, mothers with private insurance were twice as likely to provide HM at DC during the COVID period compared to pre-COVID. OR; CI (2.07; 1.06-4.03); p=0.03 (table 2). For those on public insurance, the odds for HM provision during COVID versus pre-COVID were 0.95; 0.55-1.66; p=0.85 NS, with a 2% decrease in odds for each day in the NICU (table 2). The interaction term showed lower odds of HM for public vs private insurance during the COVID-19 period (OR 0.41; 0.17-0.98; p=0.05).
Conclusions
Mothers with private insurance were twice as likely to provide HM at DC during the COVID-19 pandemic, whereas there was no change in provision among families with public insurance. We speculate that both the dedication of our lactation support team and health care disparities contributed to this difference in outcomes by insurance status.
#97 Patient characteristics and outcomes of staphylococcus aureus bacteremia in a quaternary neonatal intensive care unit
AJ Patel*
K Gibbs
MC Harris
L Srinivasan
Children’s Hospital of Philadelphia, Philadelphia, PA
Purpose of Study
Despite progress in infection prevention, Staphylococcus aureus (SA) remains a leading cause of infections in NICUs. Invasive infections secondary to both methicillin sensitive (MSSA) and methicillin resistant SA (MRSA) contribute significantly to morbidity and mortality, especially among critically ill premature and low birth weight infants who require complex interventions for survival. Hence, the objective of this study is to identify risk factors for SA bacteremia in a level IV NICU and to compare outcomes between MSSA and MRSA infected infants.
Methods Used
We reviewed medical records of patients in the Children’s Hospital of Philadelphia NICU who underwent sepsis evaluations from January 2017 – November 2021. Statistical analysis included summary statistics, Chi-square tests, Fisher’s exact tests, Wilcoxon rank-sum, Kruskal Wallis tests, and a statistical process control P chart to measure variation in SA infection over time.
Summary of Results
Among 3297 sepsis evaluations from 2017-2021, 177 (4%) had bacteremia. SA accounted for 33% (n=59) of all bacteremia cases, the majority caused by MSSA (n=49, 83%). There was no statistically significant change in the percent of SA isolates over time (figure 1). Patients with SA bacteremia were more likely to be preterm (p 0.001) and have lower birth weight (p 0.006) compared to patients without bacteremia (table 1). Compared to infants with non-SA infections, SA bacteremia patients were more likely to require oscillator support (36% vs. 19%, p<0.001), steroids (32% vs. 20%, p 0.02), and central lines (73% vs. 59%, p 0.02) (table 1). SA bacteremia was also associated with longer length of stay among survivors compared to non-SA infections (median 142 days vs. 125 days, p 0.02). All-cause mortality was similar in patients with MRSA bacteremia (30%) compared to MSSA (29%). Non-survivors with SA infections were more likely than survivors to require ventilatory support (100% vs. 58%, p 0.001), vasoactive medications (53% vs. 16%, p 0.004), and steroids (59% vs. 18%, p 0.003).
Demographics and risk factors for S. aureus invasive blood infections bacteremia
% Blood cultures isolated S. aureus over time
Conclusions
In our level 4 NICU, SA bacteremia is associated with prematurity, low birthweight, and frequent use of complex medical interventions, devices, and cardiorespiratory support. While MSSA infections are more common, both MSSA and MRSA bacteremia are associated with considerable mortality. There is urgent need for efforts targeted towards prevention of SA in critically ill infants. Next steps include investigating and mitigating SA colonization in our NICU and monitoring the impact of interventions on rates of invasive infection.
#98 Utility of the neonatal sequential organ failure assessment (nSOFA) score in predicting morbidity and mortality in infants with early-onset sepsis (EOS)
M Daniele*
R Sahni
R Polin
Pediatrics, New York Presbyterian Morgan Stanley Children’s Hospital, New York, NY, United States
Purpose of Study
Sepsis is a major cause of morbidity and mortality in neonates. In adults and older pediatric patients, the Sequential Organ Failure Assessment (SOFA) score enables quantification of life-threatening organ dysfunction. However, the SOFA score is not applicable to neonates because the clinical variables used in the SOFA score are not developmentally appropriate. In order to derive a similar operationalization method in neonates with sepsis, the neonatal SOFA (nSOFA) was developed and validated. The absolute and change in nSOFA is associated with mortality in neonatal late-onset sepsis. However, the nSOFA score has yet to be validated in neonates with EOS. This study aims to assess the utility of the nSOFA score in predicting morbidity and mortality in neonates with EOS.
Methods Used
Retrospective, single-center study of infants admitted to a Level IV NICU between 2013-2020. Neonates with early-onset (< 72 hours of life) infection as defined by bacteremia, or fungemia were included. Physiologic data were collected every 6 hours for the first 36 hours of life to derive nSOFA scores using the nSOFA scoring system. nSOFA scores were compared in survivors and non-survivors and in infants with or without major morbidities. A single composite ‘morbidity score’ was calculated which included the following outcomes: bronchopulmonary dysplasia, periventricular leukomalacia, intraventricular hemorrhage (grade II or higher), retinopathy of prematurity (stage III or higher), necrotizing enterocolitis (Bells stage II or higher) and spontaneous intestinal perforation.
Summary of Results nSOFA scores were determined for 20 neonates with documented infection at 0, 6, 12, 18, 24, 30, and 36 hours of life (HOL). Compared to neonates who did not survive (n=2), neonates who survived (n=18) had significantly lower nSOFA scores (figure 1) The peak nSOFA score was significantly higher in non-survivors vs. survivors (12.5 vs. 2.2, p < 0.001) (figure 2). The peak nSOFA trended lower in neonates without major morbidity vs. those with major morbidity at discharge (0.6 vs. 3.3, p=0.09).
Highest nSOFA and outcomes
Average nSOFA scores in survivors vs. non-survivors
Conclusions
The nSOFA provides an objective score to help provide prognostic information in infants with early-onset sepsis. The nSOFA score may provide a basis for risk-stratifying neonates with EOS to determine therapeutic interventions and antibiotic stewardship.
#99 Early-onset sepsis and antibiotic exposure among infants with congenital anomalies
LM Finnegan*
A Ades
N Rintoul
L Srinivasan
Children’s Hospital of Philadelphia, Philadelphia, PA
Purpose of Study
Early-onset sepsis (EOS) is associated with significant morbidity and mortality. However, in the current era EOS rates are low, and neonatal antibiotic exposure is known to be associated with adverse outcomes. Rates of EOS for infants with complex congenital anomalies are unknown. Cardiorespiratory instability due to underlying condition may be clinically indistinguishable from sepsis, leading to antibiotic initiation. We aimed to measure rates of EOS and early antibiotic exposure (< 72 hours of life) among infants with congenital anomalies born in the Special Delivery Unit (SDU) at the Children’s Hospital of Philadelphia and admitted to the Neonatal Intensive Care Unit (NICU).
Methods Used
Retrospective study of infants born in the SDU between 2011 and 2020 and admitted to the NICU. EOS was defined as a positive blood culture within 7 days of life associated with antibiotic treatment for >5 days. We analyzed EOS and early antibiotic initiation rates by year. We further categorized the early antibiotic initiation group into those who received short courses (1-3 days of antibiotic exposure within the first week) and long courses (4-7 days). Analysis included summary statistics, Chi-squared analysis, Kruskal-Wallis and Wilcoxon rank sum testing, and Pearson’s linear regression.
Summary of Results
From 2011-2020, 2513 patients were born in the SDU and admitted to the NICU. There were 10 cases of EOS (0.40%). Rates of early antibiotic exposure decreased (p< 0.01), while rates of prematurity, birth weight < 1500g, and pressor, steroid, and ventilator use within the first week did not significantly change (figure 1). Those with early antibiotic exposure were more likely to be initiated on steroids, pressors, and invasive ventilation during the first week, and were also more likely to be preterm and weigh < 1500g at birth (figure 2), suggesting more severe illness. Early antibiotic exposure was associated with increased 28-day mortality and length of hospital stay (figure 2), as was increased severity of illness (p< 0.01).
Rates of early antibiotic exposure, prematurity, and illness severity markers by year. rates of early antibiotic initiation (initiation of antibiotics within the first 72 hours of life) decreased over the study period, while rates of prematurity, birth weight <1500g, and pressor, steroid, and antibiotic use within the first week of life did not significantly change
Characteristics of patients with and without early antibiotic exposureP-values calculated based on Chi-squared testing for categorical variables, and Kruskal-Wallis and Wilcoxon rank-sum testing for continuous variables.1: Differences between all groups and all pairs significant (p<0.05)2: Differences between no exposure group and each of short and long course groups significant (p<0.05); No difference between short and long course groups (p>0.05)3: Differences between no exposure group and long course group significant (p<0.05); No difference between no exposure and short course groups, or between short and long course groups (p>0.05)
Conclusions
Despite low rates of EOS, early antibiotic exposure remains high among newborns with complex congenital anomalies. Prematurity and severity of illness are associated with antibiotic initiation as well as prolonged antibiotic exposure. While rates of prematurity and illness severity remain stable, rates of antibiotic initiation are decreasing. Additional multivariate analyses will further define associations with prematurity, specific diagnoses, and severity of illness, and facilitate development of targeted strategies to decrease unnecessary antibiotic exposure.
#100 Neonatal antimicrobial stewardship: discontinuing therapy at 36 hours
T Borja*
P Giri
J Blau
B Vomero
Pediatrics, Northwell- Staten Island, Staten island, NY, United States
Purpose of Study
Frequent and prolonged use of antibiotics is well-established treatment for term and preterm neonates in the NICU. However, broad-spectrum antibiotics are associated with an increasing risk of NEC, late onset sepsis, neurodevelopmental impairment and even death. Growing evidence also suggests adverse effects of asthma, allergies, obesity and type 1 DM in childhood. Antibiotic use disrupts the developing microbiome and results in less variation in microbial diversity and the emergence of multidrug resistant bacteria. Antibiotics reduced expression of immune-related genes resulting in an impaired immune system which further increases risk of infection. Hospitalization costs also increase, in addition to interference with maternal bonding and breastfeeding.
While antibiotics are typically stopped at 48 hours if cultures are negative, empiric treatment of presumed sepsis is increasingly discontinued at 36 hours in term neonates, after multiple reports that 89% – 96% of blood cultures grow the most common pathogenic microorganisms by 36 hours. Mukhopadhyay et al reported similar findings in VLBW infants with time to positivity of EOS blood cultures of 88% at 36 hours. Limiting antibiotic use in term and preterm neonates to 36 hours may decrease risk of prolonged exposure without adverse events of sepsis.
Objective
To decrease empiric antibiotic utilization by 20% through discontinuation of antibiotics at 36 hours in both term and preterm neonates. The primary outcome will be antibiotic duration and total number of doses.
Methods Used
Providers were educated on discontinuing antibiotics at 36 hours if blood culture is negative, but will continue antibiotics if clinically indicated. Previous term and preterm neonates with antibiotics discontinued at 48 hours serve as matched historical controls. Demographic, clinical, and laboratory data will be collected for control (April 2018-March 2020) and post-intervention groups (April 2020-March 2022). Preliminary data was analyzed by Chi-Squared test and Fischer’s test.
Summary of Results
There were no significant differences in demographic characteristics between control and post-intervention groups. For both term and preterm groups, p-value was < 0.05 for number of ampicillin doses given comparing historical controls and post-intervention groups. There was no statistically significant increase in LOS cases or blood culture positivity. Control group for neonates < 34 weeks had mortality of ~12%, compared to 2% in experimental group.
Clinical data
Demographic characteristics
Conclusions
Antibiotics are commonly used in NICU for presumed sepsis, despite risks associated with long-term use. Through antimicrobial stewardship, we hope to continue to decrease number of doses and duration of antibiotics during NICU stay. Preliminary results suggest that neonates receiving only 36 hours of antibiotics have a significantly decrease in antibiotic doses with no cases of missed sepsis.
4C: Hospital medicine
#101 Care quality differs for moderate and late preterm infants by NICU level
EG Salazar1*
S Handley1
LT Greenberg2
E Edwards2
S Lorch1
1Children’s Hospital of Philadelphia, Philadelphia, PA
2Vermont Oxford Network, Burlington, VT
Purpose of Study
Representing 80% of preterm births, moderate and late preterm (MLP) infants (30-36 weeks gestational age [GA]) are at risk for prematurity-associated outcomes. A higher level of care improves outcomes in very low birthweight (VLBW) infants; however, the impact of NICU level on MLP and VLBW care quality is unknown. This study examined the association between NICU level and care quality in MLP and VLBW infants.
Methods Used
Using the Vermont Oxford Network all NICU admissions database, we examined quality scores of MLP and extremely/very preterm (25-29 weeks GA) infants from 2016-2020. Included infants survived >12 hours, were transferred ≤1 time, and were without congenital anomalies. An established VLBW composite quality score (Baby-MONITOR) and an adapted composite MLP quality measure (MLP-QM) score defined care quality. Component measures were adjusted for infant characteristics (GA, sex, 5-minute Apgar, prenatal care, inborn, small for GA, multiple birth, cesarean birth), standardized using the Draper-Gittoes method, and averaged to derive the composite score. We compared composite and component scores in each population by NICU level using Kruskal-Wallis tests. NICU levels were defined as NICUs with ventilation restrictions without surgery (type A with restrictions), similar to AAP level II NICUs; without surgery (type A), and with surgery not requiring cardiac bypass (type B), similar to AAP level III NICUs; and with all surgery (type C), similar to AAP level IV NICUs.
Summary of Results
We studied 376,219 MLP and 57,595 extremely/very preterm infants from 465 US hospitals with a mean GA of 34.2 (SD 1.7) and 27.7 (SD 1.4) weeks respectively. In the study cohort 6.6% received care in type A NICUs with ventilation restrictions, 29.3% in type A NICUs without ventilation restrictions, 39.7% in type B NICUs, and 24.4% in type C NICUs. Compared to extremely/very preterm infants, MLP infants had lower rates of Cesarean birth (60% vs. 73%), ventilation after initial resuscitation (12% vs. 68%), and any respiratory support after resuscitation (59% vs. 99%). Among MLP infants, MLP-QM scores decreased with increasing NICU level (figure 1A, p<0.001). There was no difference in extremely/very preterm Baby-MONITOR scores by NICU level (figure 1B, p=0.34). MLP infants in type C NICUs had lower scores in ‘no extreme length of stay’ (p<0.001) and ‘greater than median change in weight z score’ (p<0.01) (figure 2A). Extremely/very preterm infants in type C NICUs had higher scores in antenatal steroids (p<0.001) and ROP exam (p<0.001) but lower scores in growth velocity (p=0.001) (figure 2B).
MLP-QM in MLP infants (panel A) and baby-MONITOR in extremely and very preterm infants (panel B) by NICU type
Box and whisker plots of components of the moderate and late preterm-quality measure (panel A) and of the extremely and very preterm quality measure, baby-MONITOR, (panel B) by NICU type
Conclusions
While MLP composite quality scores were lower for MLP infants in type C NICUs, extremely/very preterm composite quality scores were similar across NICU levels. Further studies should assess whether MLP infants receive higher quality care in lower level NICUs.
#102 Skin and soft tissue infections and associated complications in children aged 0–3 years in two urban multiethnic community hospitals
M Ruiz Holgado*
AS Youssef
L Rahman
R Maddali
T McGrath-Blagrove
L Kc
T Wajih
B Malla
L Pedraza Gonzalez
L Lew
E Fakioglu
Flushing Hospital Medical Center, Flushing, NY
Purpose of Study
Skin and soft tissue infections (SSTI) include cellulitis and abscess. Cellulitis is an infection of the deep dermis and abscess is collection of pus within the dermis and subcutaneous space. Complications of SSTI include bacteremia, lymphadenitis, endocarditis, septic arthritis or osteomyelitis, metastatic infection sepsis and toxic shock syndrome. There are no studies evaluating SSTI and complications and outcomes in children aged 0-3 years.
Objective
To determine the prevalence of positive and false-positive blood cultures and complications of SSTI.
Methods Used
This was a retrospective chart review of SSTI in children aged 0-3 years in Flushing Hospital Medical Center and Jamaica Hospital Medical Center between Jan 2015 and Oct 2021. Data extracted from EHR included demographics (age, gender, ethnicity), clinical presentation, laboratory studies, imaging studies, antibiotic used, treatment course, complications and length of stay (LOS). Data were analyzed using percentages.
Summary of Results
Of 206 patients admitted for SSTI, about a half (48%) were abscesses, less than half (44%) cellulitis, few impetigo (6%) and staphylococcal scalded skin syndrome (2%). Most were male (52%), Hispanic (70%) and Asian (26%). A fifth (18%) had previous SSTI and a tenth (8%) had a positive family history. Of a third (36%) who had imaging studies, three quarters (76%) had an ultrasound, less than a half (44%) confirmed an abscess and less than a third (29%) soft tissue infection. Almost all (94%) had a blood culture and most a wound culture (59%). Of the positive blood cultures (4%), majority (78%) were contaminants or normal skin flora and remainder (22%) Staphylococcus aureus. Of the positive wound cultures, most (86%) were Staphylococcus aureus. Methicillin-sensitive (MSSA) was equal to methicillin-resistant (MRSA) (44% vs 43%). Of the 11% having complications, the most common was lymphadenitis (6%). Clindamycin was the antibiotic of choice in most (70%) and 14% required a change in antibiotic due to susceptibility pattern. The median LOS was 3 days.
Conclusions
The most common SSTI in children aged 0-3 years is abscess and cellulitis. The yield of blood cultures is low. Prevalence of MRSA was equal to MSSA. Knowing the low prevalence of complications in children with SSTI, healthcare providers can provide appropriate antibiotic coverage and disposition for SSTI in our community.
#103 Post-traumatic wound infections following pediatric non-lethal, firearm extremity injuries
S Induru*
A Shah
R Hamdy
M Petrosyan
K Parikh
SJ Patel
Children’s National Hospital, Washington
Purpose of Study
Background: Firearm injuries are a significant cause of morbidity and mortality among US children. Extremities are the most common location of non-lethal firearm injury and wound infection can lead to extended hospitalization. Little evidence exists on the incidence or associated risk factors of post-traumatic infections in non-lethal extremity firearm injury in children.
Objective: To describe factors associated with post-traumatic wound infection among US children with firearm-related penetrating trauma
Methods Used
Methods: The Kids Inpatient Database (2000-2016), which yields national estimates of pediatric admissions for those age < 21 years, was queried for survivors of firearm-related extremity injuries. Children with extremity injuries who also had a major bodily injury (abbreviated injury scale >2) were excluded. We performed an unadjusted, bivariate analysis to determine the strength of association between potential risk factors that could influence access to care and the development of post-traumatic wound infection. Next steps include multivariable logistic regression analysis.
Summary of Results
Results: A total of 18,864 weighted visits of children with non-lethal firearm extremity injuries were identified, of which 292 (1.6%) developed a post-traumatic wound infection. We found an increased likelihood of developing a wound infection amongst White (OR 1.98, 95% CI 1.1-3.55) and Hispanic (OR 2.72, 95% CI 1.57-4.71) patients compared to Black patients. Public insurance (OR 1.56, 95% CI 1.03-2.36), as compared to private insurance, was also associated with a higher likelihood of developing a wound infection. Higher income was associated with a lower likelihood (OR 0.13, 95% CI 0.05-0.34) of developing a wound infection. Hospital volume, and teaching status were not associated with post-traumatic wound infection (see table 1).
Conclusions
Conclusion: Wound infection following non-lethal firearm extremity injury is an uncommon occurrence and associated with White and Hispanic race/ethnicity and public insurance. Further study is needed to better understand the reasons behind these associations.
#104 Cardiac recovery in children admitted to the pediatric intensive care unit with multisystem inflammatory syndrome in children
Z Ghersin1
A Corson1
S Galeotti1*
S Chin1,2
H Kim3
S Agarwal3
1Hackensack Meridian K. Hovnanian Children’s Hospital at the Jersey Shore University Medical Center, Neptune, NJ
2Alpert Zales and Castro Pediatric Cardiology, Brick, NJ
3Joseph M Sanzari Children’s Hospital, Hackensack, NJ
Purpose of Study
Objective: To evaluate the short and midterm cardiac outcomes in children hospitalized with MIS-C in two pediatric intensive care units (PICU) in New Jersey.
Methods Used
Design/Methods: We conducted a retrospective review of children admitted to the PICU with a diagnosis of MIS-C between April 2020 through March 2021. Cardiac biomarkers and echocardiograms performed during hospitalization were analyzed. Follow-up echocardiograms were performed two to eight weeks post-discharge, with interval follow-up of up to one year. Shortening fraction (SF) was used to assess left ventricular systolic function using standard M-mode (SF < 28% considered abnormal).
Summary of Results
Results: Twenty-seven patients (18 male; median age 11 years) were included. The mean peak Troponin I in 25 patients was 2.10 +/- 5.0 ng/dL, and mean peak NT-ProBNP level in 26 patients was 1,606 +/- 1293 pg/dL. Most patients had normalization of cardiac biomarkers by time of discharge (table 1). Seven of the 23 patients who had an echocardiogram on admission had a SF less than 28%. Lowest SF and SF at the time of discharge were compared in 21 patients with a median improvement of 6% (p <0.001) (table 2). Nineteen patients had a follow-up echocardiogram two to ten weeks post discharge and 18 of those had normal left ventricular systolic function (p < 0.001). No patient had evidence of diastolic dysfunction at follow-up. Eight patients had midterm follow-up five to seven months post-discharge; one patient was followed for one-year post-discharge. Abnormalities that persist in these patients include low normal left ventricular systolic function. Three subjects had evidence of left coronary artery dilation (z score >2) during hospitalization and continued to have diffuse dilation at follow up, with one developing right coronary artery dilation.
Results for shortening fraction by echocardiography
Conclusions
Conclusion: In this cohort of patients, most children admitted to the PICU with MIS-C had abnormal cardiac biomarkers with normal to mildly decreased left ventricular systolic function that improved by time of discharge and continued to improve with midterm (5-7 months) follow-up. A very small subset of patients, however, continue to have cardiac complications including diffuse coronary artery dilation.
#105 Consistency of interpretation of ischemic changes on pediatric exercise stress tests between cardiologists
S Sanker1*
BW Goudie1
PH Stockwell2,3
JW Ziegler1
1Hasbro Children’s Hospital, Providence, RI
2Lifespan Cardiovascular Institute, Providence, RI
3Rhode Island Hospital, Providence, RI
Purpose of Study
In contrast to the adult population, ischemic heart disease in pediatric patients is rare, and pediatric exercise stress tests are infrequently performed specifically to provoke ischemic changes. In addition, there are no generally established criteria for defining ischemic changes on pediatric exercise stress tests or published reports regarding the degree of concordance between pediatric cardiologists’ interpretations. Given the relative unfamiliarity with ischemic heart disease among pediatric cardiologists along with the lack of specific diagnostic guidelines, we examined the consistency in interpreting ischemic changes on pediatric exercise stress tests between cardiologists.
Methods Used
After receiving IRB approval, we retrospectively reviewed 2668 pediatric exercise stress tests done over 18 years at a single institution in patients between 4 and 20 years of age. Any study that documented ‘ST segment depression’ or ‘ischemic ECG changes’ on the stress ECG report was pulled for review. If a patient had more than one abnormal study, only the first one was included. Fifty-four studies (2% of total) met inclusion criteria; all were blindly interpreted by two pediatric cardiologists and one adult cardiologist. One of three possible readings was assigned: ischemic changes present, no ischemic changes present, or non-diagnostic. An unweighted Fleiss’ kappa test of agreement was utilized to assess for inter-observer variability in interpretation.
Summary of Results
Overall, there was only fair agreement in interpretation of ischemic ECG changes among all three cardiologists [Kappa=0.25 (95% CI: 0.10-0.40), P-value = 0.001]. There was no significant agreement between the two pediatric cardiologists’ readings [Kappa=0.10 (95% CI: -0.05-0.36), P-value = 0.129]. When each pediatric cardiologist’s interpretations were compared to that of the adult cardiologist’s interpretations, the degree of agreement ranged from none to moderate, [Kappa = 0.02 (95% CI: -0.17-0.22), P-value = 0.805] versus [Kappa = 0.56 (95% CI: 0.37-0.75), P-value < 0.001].
Conclusions
These results suggest that interpretation of ischemic changes on pediatric exercise stress tests is inconsistent between pediatric cardiologists and also between pediatric and adult cardiologists. The reasons for inconsistency require further investigation. In addition, criteria for diagnosing ischemic changes in pediatric patients undergoing exercise stress testing need to be standardized and prospectively assessed for consistency of interpretation within and between laboratories.
#106 The value of DNR orders in the NICU: the medical staff perspective
K Redford*
R Li
A Malfa
B Lechner
Women and Infants Hospital, Providence, RI
Purpose of Study
In adults, code status and DNR orders have been established as an explicit guideline and are considered a component of the standard of care in the provision of quality end-of-life care. As most neonatal deaths occur after withdrawal of life-sustaining technology, DNR orders might not be as useful in the NICU population. It is unclear whether the presence of a DNR order impacts the quality of care provided at the end of life in the NICU and whether it impacts the experience of provision of care for NICU staff.
The aim of this study was to elucidate NICU staff perceptions of the value of the DNR order and their perception of the quality of care provided at the end of life.
Methods Used
This study employed an online survey completed by neonatologists, neonatology fellows, and bedside nurses who cared for infants who died during their admission to the NICU at our single center. Results were analyzed using either the two-tailed t-test (when comparing continuous variables between two groups) or one-way ANOVA (when comparing continuous variables between three or more groups).
Summary of Results
27 infants died during the study period. 85 participants who cared for these infants at the end of their life responded to the survey. Bedside nurses were significantly more likely than neonatologists or fellows to think that families would benefit from a DNR order (table 1). Whether or not a provider believed the family would benefit from a DNR order was unrelated to their age or years in practice (table 1). For infants who died with a DNR order versus those who died without a DNR order, there was no difference in staff perception of parent understanding of the clinical situation, of the medical staff’s understanding of the parents’ wishes, the level of burden unto the patient, or the sense of ‘giving up’ on the patient too soon (table 2). When caring for an infant with a DNR order, staff were more likely to state that there was sufficient discussion of the ethics surrounding the case (table 2).
Staff perceptions of benefit of DNR Order
Staff perceptions of care provided
Conclusions
Our results suggest that the presence of a DNR order does not affect the perception of quality of care an infant receives at the end of life in the NICU and that the perceived benefit of a DNR order varies based on role in the NICU.
#107 Rates of firearm-related injuries in children during COVID
S Swan1*
A Hunter2
M Nowobilski1
J Knod1
S Smith1
1CCMC, Hartford, CT
2UCONN, Hartford, CT
Purpose of Study
Firearm violence comprises a large percentage of pediatric injuries within the United States. Among all high-income countries, 91% of childhood firearm deaths occur in US children younger than 14 years. Coronavirus-19 Pandemic is associated with increased firearm violence, but little is known about the impact on children. Our objective is to evaluate the pediatric rates of firearm-related injuries within the state of Connecticut (CT) before- and during-COVID.
Methods Used
Data was abstracted from the Connecticut Health Information Management Exchange (CHIME) datasets from 2016-2020. All cases of firearm related injuries were identified by ICD -10 codes. Two study groups were created using events occurring in 2018 and 2019 (before-COVID) and events occurring in 2020 (during COVID). Before and during COVID groups were compared to assess differences in rates of injuries and any associations by age, sex, race, cause of injury, bodily location of injury, and geographic location of event.
Summary of Results
A total of 188 encounters were identified. The mean age was 14 years (SD+/- 3.5), 20% girls, 80% boys, 43% White, 37% Black, and 12% Hispanic. The overall rate of firearm injuries before COVID was 1.6 per 100,000 and during COIVD was 2.1/100,000 (p<0.01). Adjusting for population changes, the incidence of firearm injuries in CT increased by 33%. White and Black children accounted for similar proportion of injuries in all time periods. In all years, about 80% were unintentional while half were injured in suburban areas compared to urban and rural (p=0.97). Almost half of all injuries involved an extremity.
Demographic comparison
Conclusions
The proportion of children with firearm related injuries significantly increased during COVID compared to the preceding two years. The age, sex and race/ethnicity of injured children was similar before and during the COVID-19 pandemic. Unintentional injury accounted for the majority of injuries. Overall the proportion of White and Black children injured by firearms was similar, and children living in suburban areas were injured more than other areas.
#108 Infant developmental screening at 16 to 18 months of age after in-utero exposure to maternal SARS-CoV-2 infection
A Shah*
S Verma
S Kazmi
P Martindale
T Groth
M Zaccario
F Sklamberg
H Howell
NYU, New York, NY
Purpose of Study
Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in pregnant women is associated with increased maternal and neonatal morbidities. The impact of in-utero exposure to maternal SARS-CoV-2 infection on long-term infant neurodevelopment is currently unknown.
Objective: The objective of the study was to undertake developmental screening in infants aged 16-18 months born to mothers with confirmed SARS-CoV-2 during pregnancy.
Methods Used
This was a descriptive prospective cohort study of full-term infants who had in-utero exposure to maternal SARS-CoV-2 infection as assessed by the Ages and Stages Questionnaire- 3rd edition® (ASQ-3®) at 16 to 18 months of life. Subjects were identified via electronic medical record search of full-term infants delivered to mothers with SARS-CoV-2 positive test during hospitalization between 3/1/2020 to 12/31/2020. The families of eligible subjects were contacted via telephone and if they agreed to participate an informed consent was obtained. Infants with prematurity (<37 weeks gestational age), major congenital anomalies or genetic diagnoses were excluded. Data on maternal and neonatal characteristics were extracted from the charts.
Summary of Results
A total of 31 children were enrolled in the study till date. Seven (23%) were below cutoff in at least one domain of development. Two subjects (6.5%) were below cutoff in more than one domain. Fine motor was identified as delayed among 3 children (10%). While communication, gross motor and problem solving was identified below cutoff in 2 children (6.5%). One child (3%) had delay in personal social domain.
Conclusions
About one-quarter of children with history of in-utero exposure to maternal SARS-CoV-2 infection were below cutoff in at least one domain of development on (ASQ-3®) at 16-18 months. In this currently ongoing study, we intend to enroll larger group of children with in-utero exposure with maternal SARS-CoV-2.
5A: GI/nutrition
#109 The effect of in utero polycyclic aromatic hydrocarbon exposure on the neonatal meconium microbiome
D Keerthy*
L Wen
D Seeram
H Park
L Calero
H Hu
A Uhlemann
J Herbstman
Columbia University, New York, NY
Purpose of Study
In utero exposure to environmental polycyclic aromatic hydrocarbon (PAH) is associated with neurodevelopmental impairments, prematurity and low birth weight. It may also lead to dysbiosis given that the gut microbiome serves as an intermediary between self and external environment. Exploring the impact of PAH on microbiota may help elucidate their role in disease. The objective of this study is to evaluate the effect of in utero PAH exposure on meconium microbiome.
Methods Used
We evaluated 49 mother-child dyads within Fair Start Birth Cohort with adequate meconium samples who had normal spontaneous vaginal delivery after 37-week gestation. Exclusion criteria included maternal infection, perinatal antibiotics, GBS positive status, prolonged rupture of membranes or neonatal intensive care admission. Prenatal PAH was measured using personal active samplers housed in backpacks worn for 48 hours during third trimester. In first 48 hours of life, meconium was collected and frozen at -80°C. DNA extraction, sequencing V3-V4 region of the 16S rRNA gene, Amplicon Sequence Variant analysis using DADA2 pipeline and taxonomy assignment against Silva were performed.
Summary of Results
Categorical exposure groups (high (H), medium (M), low (L)), were based on total PAH exposure tertile. Low read counts or sequencing failure occurred in 14 samples. Remaining 35 samples were analyzed. No significant difference in bacterial alpha diversity (richness or evenness) was observed between groups for Chao1 nor Shannon index. Within H subset (n=12), there were significant linear relationships between Chao1 (richness) index and log benzo-a-anthracene and log chrysene (figure 1). In terms of beta diversity, no significant difference was observed across groups using UniFrac, weighted UniFrac, or Bray method. Using differential abundance testing, significantly differentially abundant taxa were observed for all comparisons among treatment groups H, M, and L (figure 2).
Linear regression plots of alpha diversity. Fit linear regression models of alpha diversity (Chao1) with log PAH exposure, within H subsets
Volcano plots of DESeq2. Differential abundance testing (DESeq2, an R package) was carried out to determine taxa differences between groups. Here, we identified a small number of bacterial ASVs that differed between the baseline and the other group(s). Bacterial taxa in red and blue are significantly different at p < 0.05 and absolute fold change > 0
Conclusions
Meconium microbiome showed presence of detectable bacterial organisms. In utero PAH exposure may alter bacterial communities. Mechanism of specific PAHs (benzo-a-anthracene and chrysene) having differential effects will need further evaluation. A possible mechanism explaining the differences in species abundance between exposure groups includes activation of inflammatory pathways through the PAH activated aryl hydrocarbon receptor altering gut habitability. These findings are limited by small sample size but demonstrate the feasibility of performing this study on a larger scale. Our next steps include using mixture models to evaluate these diversity metrics.
#110 Epinephrine responses to hypoglycemia on the first postnatal day: keep testing serum glucose!
FL Peña-Cruz1*
B Nankova2
A Zhang3
E La Gamma1,2
1Maria Fareri Children’s Hospital at Westchester Medical Center, Valhalla, NY
2New York Medical College, BCHP, Valhalla, NY
3New York Medical College, Valhalla, NY
Purpose of Study
Catecholamines are rapid responding neurohumoral signals that provide a survival advantage aiding in adaptation to common postnatal stressors such as hypoglycemia. Our previous preclinical studies showed that antibiotic-induced gut dysbiosis results in prolonged sympathoadrenal hyporesponsiveness (LaGamma, Neurobio Stress;2021, doi.org/10.1016/j.ynstr.2021.100376). To characterize this phenomenon in humans, we sought to identify a metric for baseline responsiveness before gut colonization. Epinephrine responses to hypoglycemia on the first postnatal day would fulfill this goal.
Methods Used
All urine samples (cumulative index of interval Epi release) were obtained in our regional level IV NICU within 24h after birth. Samples were collected in cotton sponges, acidified with 0.01 M HCL (1:1 v/v) and stored at -80°C until analyzed. Samples were run in duplicate batches of 16 to minimize variability (Rocky Mountain Dx, CO). Spot urine measurements were normalized to urine creatinine [Epi/Cr (ng/ml) ratio]. The protocol was approved by our NYMC IRB.
Summary of Results
Samples from 21 patients at gestational age median= 27wks (25%-75%’ile: 24,32) and weight of 780g (620, 1475) were analyzed. We defined abnormal urinary Epi/cr ratio values as exceeding 3 SEM for the entire patient population (2.1 ± 0.5; or ≤ 0. 6 ng/ml ratio). Hypoglycemia < 55 mg/dl was detected in 12 patients, where 42% (5/12) failed to respond by increasing Epi levels into the normal range. In contrast, 58% (7/12) responded with a 383% increase in Epi/cr to 2.9 (0.7- 3.4; p=0.003) consistent with a responsive sympathoadrenal axis. Cumulative risk (CR) (i.,e. ≥1 recognized risk factors for hypoglycemia: preterm, SGA, PEC, low APGARs) was identified in 46% (22/48) of all hypoglycemic patients but, did not differ from the euglycemic cohort: 44% (16/36). Non-responders were more likely to have CR exposure when compared to responders [65% (13/20) vs 32% (9/28), p= 0.04]. Unexpectedly, presence of ≥1 recognized risk factors correlated with an inability to respond to hypoglycemia.
Conclusions
Clinicians cannot determine at-risk newborns by physical or perinatal history alone. As the brain is dependent on this substrate, our results underscore the need for early and frequent measures of serum glucose to ensure adequate supply. Factors (e.g. fermentation products of gut flora; Giri, Ped Res 85:57, 2019) that determines early functional maturation of the sympathoadrenal system remain to be further elucidated.
#111 A randomized controlled trial (RCT) investigating the effect of L-carnitine supplementation on growth parameters in preterm infants
I Avulakunta1,2*
M Clarke3
EJ Silver2
R Stein2
N Esteban-Cruciani2
M Fuloria1,2
1Children’s Hospital at Montefiore, Bronx, NY
2Albert Einstein College of Medicine, Bronx, NY
3Case Western Reserve University School of Medicine, Cleveland, OH
Purpose of Study
Background: Carnitine facilitates beta-oxidation of mitochondrial fatty acids providing acetyl moieties for metabolic pathways and protecting cells from toxic metabolites. It is unclear if carnitine supplementation improves growth in preterm infants born at <32 weeks gestation.
Objective: To assess the effect of early L-carnitine supplementation on growth parameters in preterm infants born at <32 weeks gestation. We hypothesized that preterm infants on parenteral nutrition supplemented early with physiologic doses of L-carnitine have improved short-term growth compared to control infants.
Methods Used
Infants born at <32 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) were randomized to receive either L-carnitine, 50 µmol/kg/day, or an equivalent volume of 5% dextrose (placebo) for a minimum of 2 weeks or until enteral intake of 100 ml/kg/day was achieved. Primary outcomes included time to regain birth weight (BW), food efficiency, and percent weight loss in the first 2 weeks of life. Differences between groups in continuous and categorical variables were compared using ANOVA and either Chi-square test or Fisher’s exact test, respectively. A p-value <0.05 was considered statistically significant.
Summary of Results
144 infants were enrolled in the study, 72 in each study group. One infant from carnitine and three from the placebo group withdrew from the study. Four infants died before reaching the primary study endpoint, leaving 136 infants (97.15% survival) for analysis. Mothers of infants in the control group were more likely to be older in age (p<0.01), have received antenatal magnesium sulfate (p=0.01), antibiotics (p=0.008), and were more likely to have chorioamnionitis (p=0.041). Infants randomized to the carnitine group were more likely to require intubation at delivery (p<0.01) (table 1). There were no significant differences in the time to regain BW, percent weight loss, food efficiency at 2 weeks, or weight and head circumference at 36 weeks post-menstrual age (table 2). There were no differences in the rates of bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, intraventricular hemorrhage, sepsis, necrotizing enterocolitis, and death (table 3).
Baseline maternal and infant characteristics
Primary study outcomes
Morbidity outcomes
Conclusions
Early supplementation with physiologic dose of carnitine did not improve growth parameters in preterm infants <32 weeks gestation. There were no differences in prematurity-related morbidities between the study groups.
#112 Evaluation of dextrose gel use in neonatal hypoglycemia- a single center study
S Abuso1*
JJ Choi1
M Akerman1
R El-Khawam1
R Kamity1
C Clauss2
N Hanna1
V Dumpa1
1NYU Langone Long Island School of Medicine, Mineola, NY
2NYU Langone Long Island, Mineola, NY
Purpose of Study
The incidence of neonatal hypoglycemia (NH) is higher in infants with certain risk factors such as prematurity, small for gestational age, large for gestational age, maternal diabetes, and perinatal asphyxia. The use of oral dextrose gel in NH has been proven to reduce the need for intravenous dextrose and NICU admissions. However, it is not clear if dextrose gel treatment is associated with a successful response among the various at-risk groups. Also, there are no clear guidelines on the use of dextrose gel in symptomatic NH. The primary objective is to identify the risk factors associated with unsuccessful response to dextrose gel treatment, i.e. admission to NICU in NH. The secondary objective is to evaluate the effectiveness of dextrose gel in mild to moderate NH with symptoms.
Methods Used
We analyzed a retrospective cohort of 969 healthy newborns in well baby nursery diagnosed with NH in first 24 hours of life, from 10/1 to 9/21. Individual chart review was performed for data extraction. Infants were excluded if they had no known risk factor for NH, had severe hypoglycemia (<25 mg/dl) or if they were admitted to NICU for any reason other than NH. Jitteriness or mild hypothermia are the signs noted in symptomatic NH in this study. Chi-square test or Fisher’s exact test, as deemed appropriate, for categorical variables and the two sample t-test or Mann-whitney test for continuous data are used to compare those who had a successful or unsuccessful response to dextrose gel.
Summary of Results
Of the 969 included infants with NH, 143 (14.8%) failed dextrose gel treatment and were admitted to NICU. Male gender and cesarean section are associated with a higher risk of dextrose gel failure (table 1). Maternal gestational diabetes was the highest predictor of of dextrose gel failure (p=0.04). Use of dextrose gel in symptomatic NH resulted in avoidance of NICU admission in majority of infants (77.5% vs. 22.5%) but these infants are still at higher risk of dextrose gel failure (table 2).
Demographics of infants with neonatal hypoglycemia
Risk factors for hypoglycemia and their association with dextrose gel treatment
Conclusions
Infants of gestational diabetic mothers (IDM) and symptomatic NH infants are at higher risk of dextrose gel treatment failure needing admission to NICU. If larger studies prove this association, strategies aimed at increasing glucose homeostasis such as early skin-to-skin, early supplementation and frequent breast-feeding can be promoted in IDM receiving dextrose gel. Further studies are needed to evaluate role of dextrose gel in mild to moderate symptomatic NH that will enable avoiding NICU admission and promoting mother-baby bonding.
#113 Identification and testing in infants with perinatal hepatitis C exposure
N Morris*
K Hunter
V Bhat
A Kushnir
Cooper Medical School of Rowan University, Camden, NJ
Purpose of Study
The incidence of hepatitis C virus (HCV) infection has seen a rising trend in recent years, primarily driven by injection drug use. In women of childbearing age, infection rates doubled from 2006 to 2014. As a blood-borne disease, HCV carries a risk for vertical transmission. Infants born to women infected with HCV tend to be smaller for their gestational age and require Neonatal Intensive Care Unit (NICU) admission and ventilation more often than their counterparts. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) recommends testing children born to HCV infected mothers at 18 months with anti-HCV antibody testing or serum HCV RNA after two months of age. Studies suggest that exposed infants are not being adequately tested for HCV. The purpose of this study is to determine whether infants exposed to HCV in utero had prenatal HCV exposure documented in electronic health records (EHR) and if they were adequately tested for HCV after birth.
Methods Used
A retrospective review of infants born in a tertiary urban hospital in NJ from 1/1/2011 to 1/1/2021. Records of infants born to mothers with prenatal diagnosis of HCV were examined to determine whether they were documented to have HCV exposure in EHR. Infants with perinatal HCV exposure were evaluated to determine if anti-HCV antibody testing at 18 months or serum HCV RNA after two months of age was performed. Infants who received the exposure in EHR but were lost to follow-up prior to two years of age and not tested in that time period were excluded. General maternal and neonatal clinical and demographic data was analyzed.
Summary of Results
Of the 142 mothers with prenatal diagnosis of HCV, 114 (80%) infants had a diagnosis of HCV exposure in EHR. Of the 77 infants with follow up data available by 24 months of age, 60 (78%) were tested with 41 out of 77 (53%) receiving adequate testing. Of infants documented as HCV exposed, 94.5% of mothers were Caucasian, 98% of mothers had a history of opioid use, 90.3% had opioid use during pregnancy, and 3.5% of mothers were diagnosed at delivery.
Infants born to HCV positive mothers
Percent of infants born to hepatitis C mothers with adequate testing by 2 years of infants tested
Conclusions
A significant proportion of infants born to HCV-infected mothers were either not identified at birth (20%) or did not receive appropriate testing on follow-up (47%). Further work needs to be done to improve documentation of HCV exposure at birth and follow-up testing in order to avoid missing congenitally acquired HCV.
#114 Transitional neonatal hypoglycemia- how low is too low?
R El-Khawam1
V Dumpa1*
B Kohn2
N Hanna1
1NYU Long Island School of Medicine, Mineola, NY
2NYU Grossman School of Medicine, New York, NY
Purpose of Study
The brain in a newborn utilizes up to 90% of the total glucose produced in the body, making it highly dependent upon glucose. Alternate fuels such as ketones are produced in very low quantities in the first few hours of life and are unlikely to provide neuroprotection during early hypoglycemia (GLOW study J Pediatr 2021). Hypoglycemia at birth has been associated with long-term brain damage, making it important to detect and treat this problem promptly. The AAP recommends feeding newborns within 1 hour and screening blood glucose (BG) 30 minutes after this initial feeding. This will practically result in the first BG level to be checked around the 1-2 hours mark. Based on a quality improvement initiative at our institution, the practice of screening at-risk newborns includes checking an initial pre-prandial point-of-care (POC) BG level within 30 minutes of birth.
The primary aim of this study is to establish the incidence of severe early pre-prandial hypoglycemia, defined as a BG level ≤ 25 mg/dL, in asymptomatic infants who are at-risk for hypoglycemia. The secondary aim is to identify the specific risk factors associated with severe early neonatal hypoglycemia in this population.
Methods Used
Pre-prandial POC BG levels within 30 minutes of birth were performed on all asymptomatic babies at risk for developing neonatal hypoglycemia (defined as late prematurity at 35 0/7-36 6/7 weeks gestation, SGA, LGA, and IDM) in the calendar years 2020 and 2021. Individual chart review was performed for data extraction. The incidence of severe hypoglycemia was calculated in the different at-risk groups.
Summary of Results
Of the total 9919 births in the study period, 1684 (17%) infants had risk factors for neonatal hypoglycemia, prompting screening at 30 minutes after birth. As demonstrated in table 1, the incidence of hypoglycemia (BG≤25 mg/dl) was 3% (50/1684); however 0.5% (9/1684) of these at-risk infants had undetectable BG levels (BG≤10 mg/dl). A breakdown of the number of infants with BG levels ≤ 25 mg/dl, ≤15 mg/dl and ≤10 mg/dl among the different risk factors is presented in table 2.
Table showing births and number of infants with severe hypoglycemia from 1/2020 to 12/2021
Number of infants with severe hypoglycemia among various risk factor groups in 2020-2021
Conclusions
Severe early hypoglycemia is not uncommon among asymptomatic neonates at risk of hypoglycemia, especially in infants with multiple risk factors. While glucose nadir is physiological and helps promote gluconeogenesis, our data demonstrate that some extremely low glucose levels can be detrimental. Appropriate measures should be taken to detect and treat severe hypoglycemia. We propose earlier screening for hypoglycemia within 1 hour of age in infants at risk for neonatal hypoglycemia.
#115 The relationship between early protein intake and changes to weight Z-score in very low birth weight neonates
N Asif*
S Sridhar
H Alcala
S Mathieson
J Pynn
Stony Brook University Hospital, Stony Brook, NY
Purpose of Study
Practice variations exist in optimizing post-natal nutrition in the Very Low Birth Weight (VLBW) population. Despite the NASPGHAN recommendations for protein intake, ambiguity and controversies exist with the VLBW, SGA, and IUGR populations. Early amino acid administration in the first 24 hours of life has been shown to decrease rates of growth failure in pre-term infants at discharge, defined as growth below the 10th percentile. However, growth failure as defined by weight percentiles does not accurately predict neurodevelopmental outcomes as well as a change in Z-score. The purpose of this study is to identify the relationship between earlier attainment of protein intake of 4 g/kg/day and a weight for age Z-score difference of no more than 0.8 SD below birth weight at 36 weeks post-menstrual age (PMA) and discharge.
Methods Used
This is a retrospective chart review of 370 VLBW neonates admitted to the Stony Brook Children’s Hospital NICU from 2014 to 2019. Data collected included growth parameters at birth, 36 weeks PMA, and discharge, Z-scores calculated using the 2013 Fenton Growth Curve, weight Z-score change from birth to 36 weeks PMA and discharge, and protein intake on days 4, 7, 14, and 21 of life. Adjusted odds ratios with 95% confidence intervals (CI) were calculated (table 1) to assess the association of protein intake with changes in z-scores of more than 0.8 SD below weight Z-score from birth to 36 weeks PMA and discharge. Scores for Neonatal Acute Physiology with Perinatal Extension-II (SNAPPE-II) were included in the regression analysis to control for severity of illness.
Summary of Results
Neonates included in the study had a mean GA 29 ± 2weeks and BW 1089 ± 266grams with a mean BW Z-score -0.43 SD. Mean Z-score difference from birth at 36 weeks PMA and at discharge were -0.79 ± 0.93 and -0.74 ± 0.7 respectively. Forty-two percent lost more than 0.8 SD from birth. Protein intake of 4 g/kg/day was reached at a mean of 9 ± 7days. Regression analysis revealed an adjusted odds ratio of 1.04 (95% CI 1.01, 1.08) between days to protein goal of 4 g/kg/day and dropping ≥0.8 SD in weight Z-score from birth to 36 weeks. SNAPPE-II had a significant association with weight Z-score change from birth to 36 weeks PMA and discharge.
Adjusted odds ratio (AOR) and confidence intervals (CI)
Conclusions
In our study cohort, earlier achievement of 4 g/kg/day protein intake was predictive of a change in weight Z-score from birth to 36 weeks PMA in the VLBW population. Optimizing protein intake in the first two weeks of life is associated with improved z-scores at 36 weeks PMA.
#116 Incidence and predictors of post-necrotizing enterocolitis stricture formation in preterm neonates
T Tran1*
M Gray2
NL Davis1
1University of Maryland School of Medicine, Baltimore, MD
2Columbia, New York, NY
Purpose of Study
Necrotizing enterocolitis (NEC) is devastating disease for preterm infants and survivors have an added risk of stricture formation following ischemic injury to the intestine, leading to feeding intolerance and often requiring surgical interventions. Little is known about risk factors for stricture formation in these patients, but factors such as NEC stage, small for gestational age (SGA) status, type of treatment/intervention, and laboratory values have been hypothesized as predictors. Interestingly, no studies have focused on the effect of feeding characteristics on stricture development. We hypothesize that exposure to breast milk (BM) before or after NEC diagnosis will be protective against stricture formation. The objective of our study was to identify incidence and risk factors for stricture formation in neonates diagnosed with NEC and to evaluate for associations between BM vs. formula exposure on post-NEC stricture incidence.
Methods Used
Retrospective medical record review of neonates born 2007-2018 diagnosed with NEC (Bell’s Stage 1-3) evaluating incidence of stricture formation and comparing clinical and demographic predictors between those with or without stricture formation using SAS 9.4.
Summary of Results
We identified 118 neonates diagnosed with NEC, of whom 15 (13%) were diagnosed with stricture(s) at a median day of life (DOL)=56 [IQR 42-78]. We found no difference between those with or without stricture development in terms of birth weight, birth gestational age (GA), race, SGA status, respiratory support requirements, DOL or post-menstrual age at NEC diagnosis. [Table 1] We found no difference in type of initial feed, DOL at first feed, fortification timing, DOL at full feeds, or type of feed at time of NEC. We also found no differences in stricture incidence based on NEC Bell’s Staging or type of feed restarted after NEC. We did find that treatment method (medical vs surgical) was significantly associated with stricture formation; those with strictures were more likely treated via exploratory laparotomy (p=0.0001) and had an ostomy (p<0.0001). After NEC diagnosis, those who developed strictures were NPO significantly longer than those who did not develop strictures (p=0.0255). Those who developed strictures also had significantly lower values for serum sodium, white blood cells (WBCs), and platelet counts, and significantly higher serum potassium values within the week after NEC diagnosis.
Clinical and demographics risk factors for post-NEC stricture formation
Conclusions
Although BM is protective against NEC development, we did not find the same protective factors against subsequent stricture formation. Neither type of feed nor NEC stage were associated with strictures, but longer NPO duration after NEC was significantly associated with stricture formation. In addition, neonates with post-NEC strictures had higher potassium levels and lower sodium, WBC, and platelet counts in the week after NEC diagnosis.
5B: Neonatology general
#117 Association between neonatal abstinence syndrome and congenital anomalies in the United States
I Oredein1*
C Ampem-Darko2
J Umscheid3
GA Cudjoe4
AO Asiama5
N Parmar6
R Vasudeva7
P Bhatt8
K Donda9
K Patel10
S Saloni11
H Doshi12
F Dapaah-Siakwan7
1Hurley Medical Center, Flint, MI
2Tema General Hospital, Tema, Ghana
3University of Kansas School of Medicine Wichita, Wichita, KS
4Korle Bu Teaching Hospital, Accra, Ghana
5Pantang Hospital, Accra, Ghana
6Brookdale University Medical Center, New York City, NY
7Valley Children’s Hospital, Madera, CA
8United Hospital Center, Bridgeport, WV
9University of South Florida, Tampa, FL
10Sheth Vadilal Sarabhai General Hospital, Ahmedabad, India
11GMERS Medical College, Surat, India
12Children’s Hospital of Southwest Florida, Fort Myers, FL
Purpose of Study
Previous studies that examined the relations between Neonatal Abstinence Syndrome (NAS) and congenital anomalies (CAs) in the United States (US) preceded the current opioid epidemic or were small studies limited to specific states. Our aim was to determine if NAS increases the odds of CAs among newborn hospitalizations in the US in a nationally representative cohort.
Methods Used
This was a cross-sectional analysis of NAS-related hospitalizations among newborns within the Healthcare Cost and Utilization Project’s 2016 edition of the Kids Inpatient Database. International Classification of Diseases (ICD-10) diagnostic codes were used to identify NAS hospitalizations. ICD-10 codes were used to identify congenital anomalies in newborn hospitalizations with and without NAS. The primary outcome was the odds of CAs in NAS hospitalizations. The exposure variable was NAS. Multivariable survey logistic regression adjusted for demographic, hospital characteristics and complications of pregnancy was used to analyze the relationship between NAS and congenital anomalies. P-value <0.05 was considered significant.
Summary of Results
Among 3.7 million newborn hospitalizations, 25,394 were hospitalized for NAS (6.7 per 1000). The characteristics of the NAS hospitalizations with congenital anomalies were: 56.8% were male, 67.1% were White, 85% had Medicaid, 77.6% were in urban teaching hospitals, and 74.3% were born at term. As shown in table 1, the unadjusted prevalence rate (per 10,000) of any CA was higher in those with NAS when compared to non-NAS hospitalizations (1055 and 492; Odds ratio (OR) 2.27; 95% confidence interval (CI), 2.13-2.43). Similarly, when compared to hospitalizations without NAS, those with NAS had a higher unadjusted prevalence rate of CAs in the central nervous system (CNS) [118 vs 31; OR 3.84, 95% CI: 3.26-4.52), sense organs (74 vs 43; OR 1.7, 95% CI: 1.41-2.04), cardiac system (566 vs 197; OR 2.94, 95% CI: 2.68-3.22), respiratory, digestive, urogenital, and musculoskeletal systems. In adjusted analysis controlling for demographic and pregnancy complications (table 2), NAS hospitalizations had increased odds of any CA (OR 1.84, CI: 1.72-1.96) as well as increased odds of central nervous system (CNS) anomalies (non-neural tube defects and microcephaly), sense organs anomalies, oral clefts, cardiac anomalies (non-critical, septal, and non-septal), digestive and musculoskeletal anomalies.
Prevalence of CAs in neonatal hospitalizations with and without NAS in the United States
Association of NAS with odds of congenital anomalies
Conclusions
Our nationwide study shows that NAS may be associated with increased odds of CAs, particularly CNS and heart defects, suggesting that NAS may be a risk factor for increased morbidity in the newborn period.
#118 Do small for gestational age infants experience less severe neonatal abstinence syndrome?
D Friedman1*
N Zubair2
Z Aghai2
1Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA
2Thomas Jefferson University, Philadelphia, PA
Purpose of Study
Small for gestational age (SGA) infants are likely to have lower amounts of fat deposition of opioids and other substances, hence less severe neonatal abstinence syndrome (NAS). Literature is sparse to demonstrate the existence of a relationship between weight restriction at birth and the severity of NAS. The goal of this study is to correlate SGA status and severity of NAS in infants admitted to the neonatal intensive care unit (NICU).
Methods Used
This is a retrospective analysis of term and late-preterm infants (≥35 weeks gestation) exposed to in utero substances, born between September 2006 and May 2021, and admitted to an inner-city NICU for medical therapy for NAS. Indicators of the severity of NAS (duration of medical treatment, duration of hospitalization, use of phenobarbital, and use of clonidine) were compared between infants characterized as SGA (birth weight < 10th percentile for gestational age) to those not categorized as SGA (non-SGA). Infants who did not require medical therapy or transferred to another facility were excluded from the analysis. The groups were compared using the Student t-test, Mann-Whitney U test, Chi-square, and Fisher exact test as appropriate.
Summary of Results
A total of 992 infants met the study criteria; 205 (20.7%) in the SGA group and 787 (79.3%) in the No SGA group. There was no significant difference in baseline characteristics including use of cocaine, marijuana, benzodiazepine, selective serotonin reuptake inhibitors (SSRI), methadone dose, neonatal sex, or neonatal race between the groups. There was a higher proportion of exposure to smoking in the SGA group. The median duration of medical treatment was significantly lower in infants in the SGA group (22 days vs. 26 days, p= 0.04). Infants in the SGA group were also less likely to be treated with phenobarbital than the No SGA group (19% vs. 26.8%, p= 0.02). There was a trend toward a shorter duration of hospitalization for infants in the SGA group (27 days vs. 32 days, p= 0.07) and less frequent treatment with clonidine for infants in the SGA group (0.97% vs. 3.4%, p=0.06).
Demographics and clinical characteristics. Data presented as, median (interquartile range), or N (%)
Comparison of outcomes in SGA and no-SGA neonates. Data presented as median (IQR) or N (%)
Conclusions
Infants characterized as SGA displayed less severe NAS as indicated by shorter duration of medical treatment and decreased treatment with phenobarbital. Additionally, trends demonstrated a shorter duration of hospitalization and treatment with clonidine for infants with SGA. Based on these findings, infants characterized as SGA at birth may have less severe symptoms of NAS and may require less escalated medical treatment with phenobarbital and clonidine. Our findings may impact decisions around identifying the optimum treatment protocols catered to SGA infants with NAS.
#119 The effect of high protein intake on insulin-like growth factor – 1 and retinopathy of prematurity in very low birth weight neonates
D Keerthy*
A Holuba
D Bateman
S Kashyap
Columbia University, New York, NY
Purpose of Study
Insulin-like growth factor 1 (IGF-1) has been implicated in fetal and neonatal growth, glucose metabolism, and maturation of neural and retinal cells. Optimizing IGF1 may improve neonatal growth and prevent morbidities, such as retinopathy of prematurity (ROP). The objective of this study was to determine effects of early higher protein (P) intake in parenteral nutrition regimens of very low birth weight (VLBW) infants on IGF-1 levels and ROP.
Methods Used
This was a post-hoc analysis of a prospective, double blind randomized control trial of appropriate for gestational age, VLBW infants (BW < 1250 g) randomized to either early high P intake (n = 52) or conventional P intake (n = 48). In the high P intake group, infants received 18% of gross energy intake as P (protein to energy ratio: 4.5g:100kcal) versus 12.5% in the conventional group (protein to energy ratio: 3.1g:100 kcal). Enteral feeds occurred at discretion of healthcare team. Serum levels of IGF1 were obtained on average weekly while receiving parenteral nutrition. Severe ROP was defined as greater than stage 2.
Summary of Results
IGF-1 levels were significantly associated with protein group when controlling for week of postnatal age, week of gestational age (WGA) and sex with levels increasing by 21.9 (1.71,46.0)% (p=0.03) with high P regimen. For a 1 gram increase in mean daily P intake, IGF-1 increased by 89.0 (70.8,109.3)% (p<0.001). Incidence of any ROP or severe ROP was not significantly different between the two groups, nor was it related to actual daily protein intake or IGF-1 levels. Higher protein intake was associated with a lower risk of plus disease (OR 0.17 (0.02,0.88), p=0.02). No plus disease occurred in patients born after 26 WGA. Mean IGF level was 25 (0.19,43.8)% lower in infants with plus disease.
Conclusions
Early high P intake regimen was associated with higher IGF-1 levels; both were associated with a lower incidence of plus disease. Optimizing P intake may decrease risk of plus disease, especially in infants born at less than 27 WGA.
#120 Respiratory dysfunction and newborn screen acylcarnitine profiles predict growth failure in extremely low gestational age newborns
I Khodak*
ED Cohen
G Pryhuber
L Scholer
J Holden-Wiltse
A Mcdavid
MA O’Reilly
A Dylag
University of Rochester Medical Center, Rochester, NY
Purpose of Study
Extremely Low Gestational Age Newborns (ELGANs, <29weeks gestation) experience respiratory failure and nutritional deficiencies that are both associated with growth failure. Newborn screen (NBS) metabolites (e.g. acylcarnitine (AC) profiles) have emerged as predictors of important neonatal morbidities, but their associations with neonatal intensive care unit (NICU) exposures and growth rates are not yet established. The objective of this study was to correlate respiratory dysfunction, nutritional intake, and NBS AC profiles over the first 28 days of life (DOL) to growth failure at 36 weeks corrected gestational age (CGA).
Methods Used
Two ELGAN cohorts (n = 125 across 2 centers) had daily recording of nutritional intake and respiratory exposures. Plasma AC profiles (22 compounds) were obtained from New York State (NYS) NBS at approximately DOL 3 and 28. The primary outcome measure (deemed Zchange) was defined as the change in weight Z score from birth to hospital discharge or 36 weeks CGA (Zchange = ZCGA36 – ZDOL0). Three multivariate regression analysis models using robust standard errors were developed looking at various NICU exposures including nutritional intake/route, respiratory dysfunction (cumulative oxygen (O2) exposure, OxygenAUC28), and AC level univariates and their individual effects on average daily caloric intake and growth failure (expressed as Zchange) in this ELGAN cohort. Some variables were log transformed before analysis.
Summary of Results
When modeling for total caloric intake, infants of younger gestational age, those with higher OxygenAUC28, and those fed a smaller proportion of enteral calories were found to have received less total calories over the first 28 days of life. Higher OxygenAUC28 also had negative impacts on Zchange, while higher DOL 0 weight Z score and increased delivery of enteral fat calories predicted better Zchange, and average 28 day total calories did not impact growth. Of the 22 ACs added to the Zchange model, C14 was independently associated with decreased Zchange.
Conclusions
Elevated cumulative neonatal O2 exposure and a lower percentage of enteral feeding are each individually associated with fewer total calories received over the first 28 postnatal days, suggesting that O2 requirements and route of feeding have impacts on total calories delivered, which may reflect clinician hesitancy to enterally feed babies in respiratory distress. Higher C14 and oxygen exposure have independent negative impacts on growth (Zchange) through unclear mechanisms. This study is the first, to our knowledge, to use NBS results to link oxygen exposure with growth failure, thus providing intriguing preliminary data to further interrogate this underutilized clinical information to predict neonatal morbidities.
#121 Oral prednisolone in infants with bronchopulmonary dysplasia: is there a subset that responds?
N Mehandi*
D Handa
G Perez
J Nair
University at Buffalo, (SUNY), Buffalo, NY
Purpose of Study
Systemic steroids are used to prevent Bronchopulmonary dysplasia (BPD) and facilitate extubation in premature infants. There is limited data on the use of steroids in infants with established BPD. In a single-center study on infants with BPD on nasal cannula, oral prednisolone (Pred) therapy for 2 weeks succeeded in weaning 63% of infants off oxygen, lowering capillary CO2 and Pulmonary Acuity Scores (PAS). In infants with severe BPD, a long prednisolone course was associated with moderate short-term improvement in PAS but decreased linear growth. Currently, there is no consensus on the timing or duration of Pred therapy or the specific patient population that benefits most from treatment. The objective of our study is to determine the short-term respiratory outcomes with Pred therapy in infants over 36 weeks corrected gestational age with established BPD
Methods Used
Retrospective chart review of infants with BPD who received Pred in the neonatal intensive care unit between 2017 and 2021. Infants were excluded if they received Pred for 1) less than 7 days or 2) indications other than BPD. Baseline demographic parameters and PAS were documented before the Pred course. PAS is calculated using FiO2, respiratory support and BPD medications. Infants with a 20% or higher reduction in PAS after the end of the prednisolone course were defined as responders. Characteristics of responders (Pred-R) and non-responders (Pred-NR) were compared. Outcome measures included post-Pred PAS, need for tracheostomy, length of stay and duration of mechanical ventilation. GraphPad PRISM software was used for statistical analysis using appropriate statistical tests.
Summary of Results
Out of 55 infants with BPD who received Pred, 21 were excluded based on criteria, yielding 34 subjects. There was a reduction in PAS after Pred in the whole cohort (figure A). Demographic characteristics of Pred-R (n=14) and Pred-NR (n=20) at baseline were similar between groups (table 1a) though the Pred-NR group had more ventilated infants. Pred-R had a longer Pred course, received fewer post-Pred steroid courses, had a shorter overall duration of ventilation and length of stay (table 1b).
PAS before (pre) and after (post) PRED
Characteristics of pred-R pred-NR
Conclusions
Overall, infants with established BPD who received Pred had improvement in PAS. Pred-R had significantly improved respiratory outcomes with a shorter duration of mechanical ventilation and reduced need for tracheostomy. It is feasible that Pred-NR were sicker at baseline with more ventilated infants and prior steroid courses, though these baseline differences did not reach statistical significance. While Pred is promising in a subset of infants with BPD, which is yet to be defined, variations in practice continue to exist without definite treatment guidelines. Larger multicenter studies are needed to identify optimal dose, the timing of Pred, and patient characteristics that could predict response.
#122 Cerebral palsy and persistent motor impairment in extremely low gestational age newborns: associating risk factors with diagnoses at age 2 and 10 years
TP Marinelli1,2*
Yi JX2
M O’Shea2
R Joseph3
S Hooper2
K Kuban3
C Sakai1
M Msall4
R Fry2
R Singh1
1Tufts Children’s Hospital, Boston, MA
2University of North Carolina School of Medicine, Chapel Hill, NC
3Boston University School of Medicine, Boston, MA
4University of Chicago Pritzker School of Medicine, Chicago, IL
Purpose of Study
Cerebral palsy (CP) and motor impairment (MI) remain the most prevalent neuro-motor disabilities of childhood, with up to 50% of affected individuals born extremely preterm (EP). Despite the well-described relationship between preterm birth and CP/MI, there remains an unstudied interplay of additional risk factors and comorbidities that complicate the clinical prediction of CP/MI in infants born EP. Our objective is to identify perinatal factors in infants born EP that are associated with diagnosis of CP/MI at 2 and 10 years of age to inform the design of a predictive algorithm to estimate the risk, at NICU discharge, of receiving a diagnosis of CP/MI during childhood.
Methods Used
Participants were enrolled at birth in the Extremely Low Gestational Age Newborn (ELGAN) Study between 2002 and 2004. Based on a standard neurological examination at 2 and the Gross Motor Function Classification System at 10 years of age, 849 participants (71% of survivors) were classified as follows: No CP/MI, CP only at 2 years, MI only at 10 years and CP/MI at both 2 and 10 years. To describe associations, between risk factors and CP/M, odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression, with no CP/MI at age 2 and age 10 as the referent group.
Summary of Results
Overall, 849 study participants underwent evaluation for CP/MI at 2 and 10 years of age. Of these, 64 (7.5%) had a diagnosis at both 2 and 10 years, while an additional 63 (7.4%) participants had a diagnosis of CP/MI at one visit but not the other (table 1). Of 22 total risk factors queried, the strongest association with diagnosis of CP/MI at 2 and 10 years of age was seen with ventriculomegaly (OR 22.2, CI 12.0-41.2), periventricular leukomalacia (PVL), (OR 14.1, CI 7.7 – 25.8) and echogenicity on head ultrasound (OR 8.1, CI 4.5 – 14.5.) (table 2).
Baseline prenatal, perinatal and postnatal factors for CP/MI diagnosis at 2 and/or 10 years of age
Associated odds ratio for diagnosis of CP/MI by subgroups
Conclusions
In the ELGAN cohort, the diagnosis of CP at 2 years did not always predict a diagnosis of MI at 10 years. We identified multiple clinical risk factors predictive of CP/MI, that are currently being used to compare individuals with a persistent diagnoses of CP/MI and those whose MI resolved, as well as to construct a predictive algorithm to estimate the risk.
#123 Sodium supplementation and hypertension in preterm infants: a retrospective study
D Clermont*
R Petersen
N Hillman
H Williams
SSM Health Hospitals, St. Louis, MO
Purpose of Study
To determine if oral sodium supplementation is associated with HTN in preterm infants less than 32 weeks.
Methods Used
This was a retrospective study of infants admitted to the SSM Health Cardinal Glennon Children’s Hospital and the SSM Health St. Mary’s Hospital Neonatal Intensive Care Units from 12/01/2015-12/01/2020. Using the electronic medical record, we collected data for each subject as shown in table 1. Inclusion criteria included infants born 22-32 weeks and weighing 450-1500 grams. Exclusion criteria included infants with major congenital malformations deemed incompatible with life, chromosomal disorders, renal insufficiency, short gut, disease states characterized by edema (i.e. hydrops fetalis), and infants who did not survive beyond 7 days of life. We then determined the association between sodium supplementation and HTN in the entire cohort (N=874) and in babies weighing less than 1000 grams (n=434).
Summary of Results
Infants receiving sodium supplementation were smaller and less mature (table 1). Fifty percent of infant <32 weeks received sodium supplementation, and 76% of infants <1000 g. Infants receiving sodium were more likely to have HTN in total cohort (27% vs 6%), and in infants less than 1000 grams (29% vs 9%). Unadjusted Odds of HTN with sodium supplementation were OR 5.6 (95% CI 3.6, 8.7) for total cohort and OR 4.5 (95% CI 2.2, 9.3) for infants < 1000 g.
Descritive analysis and association between sodium supplementation and hypertension in infants <32 weeks gestation and Infants <1000 grams
Conclusions
These findings suggest that sodium supplementation contributes to the development of HTN in preterm infants, with increasing odds with lower birth weights. Logistic regression with common neonatal morbidities are underway to determine the causative effect of sodium supplementation.
#124 Screening and management practices of osteopenia of prematurity at a level IV NICU
L Cromwell*
A Kasanagottu
Quinones Cardona
FI Kehinde
St. Christopher’s hospital for children, Philadelphia, PA
Purpose of Study
Osteopenia of prematurity (OOP) is a prevalent but silent disease in the NICU, occurring in about 40% of infants <1500g and 50% of those <2500g. Delays in the diagnosis of OOP can result in fractures and poor postnatal growth. Radiologic findings of bone demineralization are late findings. Timely screening and diagnoses may be beneficial in preventing disease progression and complications. While laboratory monitoring of alkaline phosphatase (ALP), phosphorous (Phos), calcium (Ca), and vitamin D levels are performed in the NICU, there is no consensus on screening and management protocols.
The main objective is to review current practices for the screening, diagnosis, and management of OOP among at-risk infants in a level IV NICU.
Methods Used
Retrospective chart review of infants born at ≤ 32 weeks gestation admitted to a referral level IV NICU from 12/2019 to 6/2021. De-identified data including demographics, co-morbidities, medications, timing and frequency of OOP laboratories, OOP diagnosis (defined as ALP>500), management and consultations were collected. At risk infants were divided into OOP or no OOP. Groups were compared using student t-test for continuous data and chi square test for nominal data.
Summary of Results
A total of 107 infants were included. Of these, 19 (17.7%) met the diagnosis of OOP and 89 (82.2%) did not. Overall, 38/107 (35.5%) infants had documented OOP screening laboratories at 4 weeks of life. There was wide variation in the frequency of these laboratories ranging from every 2 weeks to 2 months. Infants with OOP compared to those without OOP had a lower mean gestational age (26.8+/-2.2 weeks vs 29 +/-3.3 weeks, p=0.008), mean birth weight (865+/-402g vs 1269+/-559g), and more likely to have bronchopulmonary dysplasia (84.3% vs 56.8%, p=0.036) (table 1).
Among infants with OOP, the majority were on Vitamin D supplementation (89%) and received physical/occupational therapy (100%) as well as nutritional consultation (94.7%). Only 26% had endocrinology consultation with 52.6% receiving calcium supplementation (figure 1). Two of these patients had fractures and orthopedics involvement. None had endocrine follow-up at discharge specifically for OOP.
Patient characteristics
OOP screening and management practices
Conclusions
Clinical practice variation exists within a level IV NICU in the screening and management of infants with OOP. Failure of timely detection and management of OOP can lead to unnecessary morbidity. Next steps include a quality improvement initiative to standardize OOP screening and management practices in the NICU to prevent morbidity in this fragile population.
#125 Non-pharmacological management of neonatal abstinence syndrome (NAS) success and risk factors for failure
K Tauber1*
LK Stanfel2
U Munshi1
1Albany Medical Center, Albany, NY
2Nemours Children’s Hospital, Delaware, DE
Purpose of Study
Opioid use in pregnancy is rising mirroring the opioid epidemic that has been observed in the general population. The management of infants born to mothers with an opioid use disorder (OUD) has been evolving to optimize the care provided. Currently, symptoms in these infants are managed with non-pharmacological measures (NPMs) as a first line of treatment. When these fail, medication (commonly morphine) is given to control withdrawal symptoms. We aimed to study how well NPMs alone control symptoms in infants born to mothers with OUD and identify risk factors associated with failure of NPMs leading to morphine administration in our institution.
Methods Used
IRB approved retrospective study of infants >35 weeks gestation at birth with maternal OUD born at our hospital between 1/1/16 to 12/31/21. NPMs (swaddling, low light, breastfeeding, low stim environment) were used as first line treatment. From 2016-2019 the modified Finnigan scoring system was used; a score >8 x3 resulted in scheduled morphine administration. The Eat, Sleep, Console (ESC) protocol was implemented on 1/1/19. NPMs were continued but morphine was given every 3 hours as needed when infants failed ESC protocol. If > 2 prn doses were given, then it was scheduled every 3 hours and dosage adjusted until infant captured. Infants were divided into 2 groups, those managed with only NPMs and those who failed NPMs and required morphine. Demographic data, exposure to multiple drugs, length of stay (LOS), and discharge status were collected. Continuous variables were analyzed with t-test and nominal data with Fisher Exact test.
Summary of Results
165 charts were reviewed. There were 140 opioid exposed infants managed with NPMs alone vs 25 infants who required morphine treatment. Demographics and maternal risk factors are shown in table 1. All infants requiring morphine were exposed to multiple drugs vs 75% of infants in the NPM only group (p< 0.0001). Infants treated with morphine had a significantly longer LOS and were more likely not to be discharged with their mother. Implementation of ESC since 2019 significantly decreased the average LOS as well as the number infants needing medication (p< 0.007) (figure 1).
Demographic and maternal characteristics of opioid exposed infants. Length of stay (LOS)
Average length of stay (LOS) by year. *p<0.05
Conclusions
NPMs as part of the ESC protocol are an important first line management of opioid exposed infants which results in a significantly decreased LOS and decreased medication administration. Failure of NPMs was more likely in infants with multiple drug exposure who had a higher rate of needing morphine, longer LOS, and were less likely to be discharged with their mother. Early initiation of treatment programs in pregnancy may help reduce these outcomes.
5C: Hematology/immunology
#126 Adjunctive pentoxifylline suppresses chemokine and enhances interleukin 10 expression in renal tissue of cefotaxime-treated neonatal mice with escherichia coli peritonitis
AA Adedeji*
RP Woroniecki
EM Speer
Stony Brook Children’s Hospital, Stony Brook, NY
Purpose of Study
Neonatal systemic infection triggers an intense host inflammatory response that contributes to increased mortality and acute kidney injury (AKI) in term and preterm neonates. The phosphodiesterase inhibitor pentoxifylline (PTX) has demonstrated renal protection from ischemia and inflammation in adult rodents. We hypothesized that addition of PTX to cephalosporines may decrease renal inflammation and biomarkers of kidney injury in a murine neonatal bacterial sepsis model. We therefore aimed to determine the effects of PTX when added to cefotaxime (CEF) on markers of renal tissue injury and inflammation in murine neonatal E. coli peritonitis.
Methods Used
Newborn C57BL/6J mice (<24 hours (h) old) were injected intraperitoneally with E. coli K1 at 105colony forming units (CFU)/g weight. Pups (N=68; mean weight 1.4 g) were randomly assigned to intraperitoneal saline, CEF, or CEF with PTX (CEF+PTX) at 1.5 h after sepsis initiation, and euthanized after an additional 4 h. CFUs, inflammatory and kidney injury biomarkers were measured from homogenized renal tissue and results were compared with 1-way ANOVA or Kruskal-Wallis tests corrected by false discovery rate.
Summary of Results
Median CFUs/g tissue from saline control septic pups were 1455 (IQR 348-4583), whereas CFUs were mostly undetectable after CEF or (CEF+PTX) treatment. Tissue inflammatory cytokine and chemokine concentrations were higher in untreated septic animals compared to non-septic controls (p<0.05). Neither CEF nor (CEF+PTX) inhibited any of the tested pro-inflammatory cytokines (TNF, IL-1α, IL-1β, IL-2, IL-12, IL-17, interferon-γ) except for IL-6 after (CEF+PTX). CEF significantly decreased the chemokines CXCL-1 (keratinocyte-derived chemokine) and chemokine ligand 3 (CCL3). Addition of PTX to CEF significantly diminished tissue expression of CCL2, CCL3, and CXCL-1 compared to untreated (p<0.001), and CCL2 and CCL3 compared to CEF alone-treated (p<0.01) mice (figure 1). Furthermore, (PTX+CEF) markedly increased renal tissue expression of the anti-inflammatory IL-10 compared to saline or CEF alone (> 3-fold increase, p<0.01). The renal injury markers neutrophil gelatinase-associated lipocalin, osteopontin and cystatin C showed however only a non-significant trend towards diminished renal tissue expression.
Effect of adjunctive PTX on Escherichia coli-induced renal tissue cytokines, chemokines and kidney injury markers in cefotaxime-treated septic newborn mice
Conclusions
Addition of PTX to CEF in newborn mice with E. coli peritonitis suppresses the expression of several chemokines and augments IL-10 production without promoting bacterial growth, suggesting potential protection from sepsis-induced AKI.
#127 Iron deficiency at the time of discharge in very low birth weight infants (VLBW): impact of delayed cord clamping
G Kennady1*
F Afridi2
D Neumann1
B Amendolia2
N Kilic2
V Bhat2
V Bhandari2
Z Aghai1
1Thomas Jefferson University/Nemours, Philadelphia, PA
2Cooper University Hospital, Camden, NJ
Purpose of Study
Iron deficiency, even in the absence of anemia, is associated with neurocognitive impairment. It is crucial to identify infants who are iron deficient. Preterm infants are at high risk for iron deficiency due to low iron stores at birth, high growth velocity in the first few months of life, low levels of erythropoietin and small circulating blood volume relative to iatrogenic blood loss. Reticulocyte hemoglobin content (CHr) is a reliable early indicator of iron deficiency. Delayed cord clamping (DCC) can improve iron status at discharge in VLBW infants. This study is aimed at utilizing CHr to evaluate the iron status at discharge in VLBW preterm infants from two tertiary care NICUs. We also evaluated the impact of DCC on CHr at discharge.
Methods Used
Retrospective analysis on all VLBW infants from two tertiary NICUs born between 04/2017- 05/2020 who survived and had CHr performed close to discharge. In preterm infants, the cut off value for a low CHr is < 29 pg. The CHr at discharge and number of infants with low CHr were compared to infants who received DCC and those who did not. Infants with a positive newborn screen for Barts hemoglobin (Hb Barts) were excluded.
Summary of Results
A total of 315 VLBW infants met the inclusion criteria (table 1). The median (IQR) hemoglobin and hematocrit prior to discharge were 10 gm/dl (9-11.3) and 29.7% (27.1-33.3), respectively. The median (IQR) CHr prior to discharge was 30.8 pg (28.4-39). In 99 infants (31.4%), the CHr was low prior to discharge. DCC was performed in 46.7% of infants. Hemoglobin at birth, discharge and CHr at discharge were significantly higher in infants who received DCC (table 2). DCC also reduced the need for blood transfusion and the number of infants with low CHr at discharge. Fifteen infants were Hb Bart positive (4.8%), with a median CHr of 23.9 pg (22.7 to 29.7). In infants with Hb Barts, 14 infants (93.3%) had CHr <29 pg and only one infant had CHr above 29 pg (i.e, 29.7 pg).
Hematological parameters at discharge
Comparison of infants who received delayed cord clamping (DCC) and no DCC.
Conclusions
Approximately 31.4% VLBW infants had lower CHr near the time of discharge suggesting they were iron deficient. DCC improved iron status at discharge in VLBW infants. CHr content can be used to direct iron supplementation in VLBW infants to potentially improve their iron status and long-term neurocognitive outcomes. Quality improvement projects to increase DCC in VLBW infants can also improve their iron status at discharge.
#128 Elliptocytosis in newborn secondary to novel heterozygous mutation
D Varadi1
B Caplan1*
M Scarano2
R Ahmed2
1Cooper Medical School of Rowan University, Camden, NJ
2Cooper University Hospital, Camden, NJ
Purpose of Study
To describe a novel mutation of the SPTB gene as a potential pathogenic cause of elliptocytosis in a newborn with hemolytic anemia (HA).
Methods Used
Single subject case report.
Summary of Results
HA is attributable to the erythrocyte’s intrinsic characteristics or extrinsic processes affecting the erythrocyte. Serology is significant for reticulocytosis, hyperbilirubinemia, anemia, and abnormal peripheral blood smear. Pallor and jaundice are indicative of an intrinsic cause. Further information is necessary to elucidate the specific etiology, including family history, MCHC, direct antiglobulin, enzyme function, and genetic testing. Hereditary elliptocytosis is caused by genetic variations in proteins that disrupt the erythrocyte membrane and cytoskeleton, such as spectrin, ankyrin, band 3, and band 4.2.
The patient is a 3-week-old male born full-term via NSVD with a history of an 8-day NICU stay due to significant hyperbilirubinemia requiring phototherapy for 5 days. His labs were significant for anemia, reticulocytosis, negative Coombs test, and no ABO or Rh incompatibility. Peripheral smear was significant for polychromasia with microcytes, normocytes, and burr cells in the absence of nucleated cells. G6PD and Pyruvate Kinase levels were within normal limits. Both parents are of African American heritage, and family history was negative for hemoglobinopathies and HA. Initial HA screening panel on day 6 revealed increased osmotic fragility, decreased Eosin 5-Maleimide binding, and decreased Protein band 3, which suggests hereditary HA. His persistent symptomatic anemia with reticulocytosis and elevated MCHC initiated evaluation of next-generation sequencing (NGS). Hereditary Hemolytic Anemia Panel revealed a heterozygous out-of-frame deletion in Exon 2-3 of the SPTB gene, resulting in an abnormal and non-functioning protein product. Loss-of-function mutations of the SPTB gene are known to cause abnormally shaped erythrocytes. However, the specific deletion present in this patient has not been reported in literature and is thus potentially pathogenic.
Conclusions
Elliptocytosis commonly presents in the neonatal period with jaundice secondary to HA. This case presents an example of elliptocytosis in the setting of a heterozygous SPTB loss-of-function mutation not previously reported in the literature. Evaluation of the patient‘s clinical course and treatment strategies can elucidate future management recommendations to treat patients with this mutation. Parental blood NGS is pending to discover if this is a de novo or inherited mutation.
#129 Obesity and adipose distribution impact genetically determined blood traits
CS Thom1,2*
MB Wilken1
ST Chou1
BF Voight2
1Children’s Hospital of Philadelphia, Philadelphia, PA
2University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
Purpose of Study
Obesity afflicts a growing number of children and adults. Related comorbidities are incompletely understood. For example, clinical observations link obesity (body mass index, BMI, >30 kg/m2) with anemia, but it is unclear if these 1) reflect direct causal effects and/or 2) extend to other blood cell traits. We hypothesized that adipose tissue type and location may explain these findings. Increased BMI or truncal adiposity (waist-hip ratio, WHR) raise cardiovascular disease risk (Fig). Here, we aimed to define causal genetic effects of BMI and WHR on blood traits and reveal related mechanisms.
Methods Used
Mendelian randomization (MR), akin to a ‘genetic randomized controlled trial’, uses variants linked to an exposure trait to estimate causal effects on a given outcome. Random variant allocation at meiosis enables MR to address confounding and reverse causality that otherwise preclude causal inference from observational studies. Multivariable MR and mediation analyses can reveal traits using common genetic mechanisms. Our study used gender- and age-adjusted genome wide association study summary statistics from European individuals.
Summary of Results
We hypothesized that increased BMI would decrease HGB. Indeed, we found that per 5 kg/m2 increased BMI, HGB decreased by 0.06±0.01 g/dL (p=1x10-5, Abstract #129 figure 1). Increased BMI also decreased erythrocyte, platelet and white blood cell counts (all with p<5x10-3). Coordinate effects across lineages suggested BMI effects on hematopoietic progenitor cells (HPCs) that spawn mature blood cells (Abstract #129 figure 1).
We thought altered adipose distribution (WHR) may help explain BMI-related effects. Certain adipose tissues (e.g., bone marrow adipocytes) regulate HPCs and hematopoiesis. In surprising contrast to BMI, increased WHR increased HGB (0.08±0.02 g/dL, p=9x10-6) as well as erythrocyte, platelet, and white cell counts (all with p<4x10-3, Abstract #129 figure 1). Multivariable experiments confirmed that WHR effects functioned through common pathways with BMI, and helped identify putatively responsible genes (e.g., LepR and RAPGEF3), pathways, and tissue types (e.g., bone marrow).
Effects of obesity and adipose distribution on blood traitsIncreased genetically determined body mass index (BMI) decreases hemoglobin (HGB), red blood cell (RBC), platelet (PLT) and white blood cell (WBC) counts, suggesting effects on hematopoietic progenitor cells (HPCs) common to these mature cell types. Like BMI, increased waist-hip ratio (WHR) increases cardiovascular disease risk. However, increased WHR has opposite effects on blood traits, increasing HGB and cell counts. Created with BioRender.com.
Conclusions
Higher BMI causally decreases hemoglobin, confirming related anemia risk, and affects multilineage blood traits. These effects are mediated by genetic predisposition to low WHR (peripheral or bone marrow adipose tissue accumulation). Future work will examine how adipose location and type impacts hematopoiesis, and explore genes and mechanisms driving profound effects of obesity on pediatric health and maternal-infant dyads, including novel BMI-related effects on hematopoiesis.
#130 Decreasing formula use for initial enteral feeds in very low birth weight babies at a tertiary care neonatal intensive care unit: quality improvement project
V Hamilton1*
C McLaughlin2
V Agrawal3
A Mari1
C DeMarco2
D Handa1
1University at Buffalo, Buffalo, NY
2John R. Oishei Children’s Hospital, Buffalo, NY
3Linda Loma University Children’s Hospital, San Bernardino, CA
Purpose of Study
AAP recommends mother’s own milk (MOM) as the primary enteral diet for premature infants and pasteurized donor human milk (PDHM) as an effective alternative. Use of exclusive human milk diet in premature infants has been shown to decrease the rate of Necrotizing enterocolitis compared to formula (FORM). In our Regional Perinatal Center level 4 Neonatal Intensive Care Unit (NICU), PDHM was available, but FORM continued to be used for initiation of enteral feeds (IEF) if MOM was unavailable or insufficient. From our initial data collection, we identified knowledge gaps and practice deficiencies in offering and using PDHM in Very Low Birth Weight (VLBW) infants in our NICU leading to high FORM use and delayed timeline for IEF.
Objectives
1. To decrease FORM usage for IEF in VLBW infants from 46% to 10% and 2. To decrease average time for IEF by 20%, from 70 hours to 48 hours by Dec 2020.
Methods Used
After IRB approval, baseline data was collected through retrospective chart review of all VLBW infants born at the center in 2018. We excluded infants with surgical diagnosis, hemodynamic instability requiring pressers, and those who expired during NICU stay. Multidisciplinary team created a Driver diagram to identify primary and secondary drivers, and interventions were planned based on that (figure 1). Baseline survey was sent to all Neonatal providers to identify knowledge gap followed by multiple education sessions to increase maternal and staff awareness. Didactic presentations and discussions were given separately to all the neonatal provider groups, and changes were made to standardize the maternal consent process. Data was collected post intervention to evaluate for PDSA (Plan-Do-Study-Act) cycles.
Summary of Results
Knowledge gap regarding PDHM use was noted on baseline survey of NICU providers. Only 34% of providers routinely discussed PDHM with mothers in the NICU and 77% providers knew which infants qualified for PDHM. There was a reduction in FORM use for IEF in VLBW infants from 46% to <10% (p<0.001) after the QI project was initiated (figure 2). The average time for IEF decreased from 70 to <43 hours (p<0.001) in the same time frame (figure 2). The number of days TPN was used reduce from 18.2 to 14.9 days (p=0.02). The number of infants receiving PDHM increased from 25% to 83%(p<0.001) and the number of infants receiving MOM at discharge increased from 31% to 42%. There was no significant difference with growth, NEC rates, or use of MOM during NICU stay in this study.
Conclusions
Educational strategies and standardizing provider practices helped to increase utilization of PDHM for early feeds while awaiting MOM supply to increase. This helped decrease FORM use and improved time to introduce IEF in VLBW infants.
#131 Association of platelet transfusion and severe intraventricular hemorrhage in very low birth weight infants
KM Raja1*
B Hussey-Gardner1
M Gopalakrishnan2
S Sundararajan1
1University of Maryland School of Medicine, Baltimore, MD
2University of Maryland School of Pharmacy, Baltimore, MD
Purpose of Study
Very low birth weight (VLBW) infants with moderate to severe thrombocytopenia receive platelet transfusions to minimize the risk of intraventricular hemorrhage (IVH). While a lower platelet threshold (25,000/µL) is associated with lower rates of IVH compared to a higher threshold (50,000/µL), platelet transfusion practices are variable in the newborn intensive care unit (NICU). The objective of this study was to determine the platelet transfusion threshold in VLBW infants and examine the association of platelet transfusion and the risk of severe IVH (Grade III/IV) in week one of life.
Methods Used
A retrospective chart review of 782 VLBW infants was performed at the University of Maryland Medical Center (UMMC) NICU between 2016 and 2020. Demographic information, delayed cord clamping (DCC) status, platelet transfusion characteristics, and severity of IVH were collected. A multivariable logistic regression analysis was performed for IVH status adjusting for gestational age (GA), body weight, small for gestational age (SGA) status, gender, and red blood cell (RBC) transfusion status.
Summary of Results
Of the 540 infants that met inclusion criteria, 105 (19.4%) received a platelet transfusion during their NICU stay. The mean threshold for platelet transfusions was 62,190/µL (SD: 27,100/µL, figure 1). Infants that received platelet transfusion were of lower birth weight (760g), lower gestational age (26.4wks), and had a longer hospital stay (p<0.001). Infants that had DCC received fewer platelet transfusions (p<0.001). In subjects that received platelet transfusion, median time to first IVH diagnosis was 4 days of life. 119 (22.0%) infants developed IVH (all grades) during week 1 of life. Of the 35 (6.5%) infants that developed severe IVH in week 1 of life, 28 (80.0%) received a platelet transfusion (table 1) and 14 (50.0%) had severe IVH at the time of platelet transfusion. In multivariable logistic regression analysis of severe IVH status, platelet transfusion was a significant predictor of IVH (p<0.001) after adjusting for GA, birth weight, SGA status, gender, and RBC transfusion status. Platelet transfusion increased the odds of developing IVH (all grades) (OR: 4.3, 95% CI: 2.3-8.2) and severe IVH (OR: 41, 95% CI: 14.0-146.6) compared to infants that did not receive platelet transfusions keeping all other predictors constant.
Association of platelet transfusion and intraventricular hemorrhage in the first week of life in VLBW infants.
Distribution of the platelet threshold at which transfusions were performed in VLBW infants at the UMMC NICU between 2016 and 2020
Conclusions
Mean platelet transfusion threshold in VLBW infants was higher compared to published guidelines. The significant effect of platelet transfusion on severe IVH in week one of life could be minimized with a renewed focus on restrictive platelet transfusion practices.
#132 Impact of hydroxyurea use on the clinical expression of sickle cell disease in a community hospital in Brooklyn
A Agdamag*
bogdan m
M Habibi
S Keller
T Orisamolu
A McKechnie
O Nulman
R Sundaram
New York Presbyterian Brooklyn Methodist Hosptial, Brooklyn, NY
Purpose of Study
Sickle cell disease (SCD) is an inherited disorder that affects 1 in 365 African American births in the US. The most common challenge is excruciating pain. Hydroxyurea reduces pain crises by 50% and is recommended in infants (6 and 9 months) with symptomatic disease and all older patients. In our practice, we have met with significant resistance to the use of hydroxyurea. Our aim is to assess the impact of hydroxyurea use on reduction of pain crisis, and other parameters in our hospital.
Methods Used
A retrospective review of EMR over a 4-year period was done. Inclusion criteria were SCD patients between the age of 0 to 21 years, followed at our hematology clinic and on hydroxyurea for at least 6 months. Noncompliant or transfusion program patients within the previous six months of hydroxyurea use were excluded. Information up to 2-year pre and 2-year post initiation of hydroxyurea therapy were assessed. Data collection included frequency of hospital admissions, Length of Stay (LOS), visits to the Emergency Department (ED) for pain, narcotic use and acute chest syndrome (ACS).
Summary of Results
Out of 233 patients 44 had been prescribed hydroxyurea. 21 patients had complete data for the analysis: SCD type (19 SS, 1 SC and 1 SO Arab type), Age (Mean 12.05 [range 3, 20] ± 5.73 SD), Gender (11 (52%) Males and 10 (48%) Females). Results were analyzed using a t-test with a test level of 0.05 and linear regression to account for differences in age, sex, body weight, etc. Hydroxyurea use decreased the average number of admissions from 2.67 to 1.33 (p= 0.04). There was no difference between males and females. Admissions decreased in the 3–5-year age group from 4.33 to 1 (p= 0.03). Admissions decreased in the treated 17+ age group from 2.67 to 1.33 (p=0.03). The overall average LOS, days on narcotics during admission, and fetal hemoglobin percentage were not statically significant.
There was a significant drop in ED visits for pain in the treated group from 2.15 to 1 (p<0.01). Males showed the greatest difference, 2.8 to 1.3 (p=0.01) Females were affected in the 13+ group 1.57 to 0.57(p=0.04) as were males in the 17+ age group 2.2 to 0.4 (p=0.01). The incidence of ACS decreased from 0.43 to 0.33 (p<0.01) mostly in females in the 13+ age group (p< 0.01).
Admissions for VOC decreased with hydroxyurea especially in older children. There was a decrease in ED visits for pain and the incidence of ACS decreased with hydroxyurea use. Overall LOS, fetal hemoglobin, and days on narcotics were not affected.
Conclusions
We present our pilot study of the impact of hydroxyurea use on severity of SCD in a population of a small community hospital clinic. Even though the sample size was small, the data showed benefit. We plan to continue to identify barriers to hydroxyurea use and improve outcomes.
#133 Urinary epinephrine measurements in the NICU and their correlation with severity of illness: optimizing reporting methodology
FL Peña-Cruz1*
B Nankova2
A Zhang2
E La Gamma1,2
1Maria Fareri Children’s Hospital at Westchester Medical Center, Valhalla, NY
2New York Medical College, Valhalla, NY
Purpose of Study
There is no established reliable method for reporting normalized urine epinephrine concentrations – particularly in the neonate. Urinary creatinine (Ucr) is often used to standardize urinary analyte concentrations but is influenced by clinical status, muscle mass and renal blood flow. In pheochromocytoma patients, 24h collection & normalization to urinary output are used. However, this may not be suitable for critically ill VLBWs due to the variable range of homeostatic imbalances. We sought to determine the preferred normalization tool by comparing 2 approaches after spot collection: i) to creatinine in the same sample (Epi/Cr ratio) or ii) extrapolated to 24h urinary output (ng/ml/kg/day).
Methods Used
46 samples were collected from 33 VLBWs on cotton sponges, acidified with 0.01 M HCL (1:1) and stored at -80°C before assay of duplicate samples (Rocky Mountain Dx kit; CO); batched to minimize variability. Protocol approved by NYMC IRB.
Summary of Results
Average time of collection was 31 weeks postmenstrual age, average gestational age was 28 ± 3/7 and average weight at time collection was 1.4 kg. When using Epi/Cr (ng/ml) ratio we found that higher Epi/Cr values [4.2 ± 0.5 vs 1.6 ± 0.3; 3.0 ± 0.4; x ± sem p< 0.0002] were associated with antibiotics exposure [72% (n= 18/25) vs 33% (n= 7/21); p< 0.01] and higher white blood cell counts [median 12 (min-max: 9.2, 19.5) vs 8.2 k/mm3 (5.1, 12.2); p< 0.04]. Patients receiving antibiotics had: higher white blood cell counts [13.5 (9.3, 19.8) vs 7.5 k/mm3 (4.4, 11); p< 0.0009]; lower lymphocyte counts [29% ± 2.5 vs 44% ± 3; p< 0.0006]; higher absolute neutrophilic counts [7.3 (3.85, 11.1) vs 2.94 k/mm3 (2, 4.5); p< 0.0004]; higher FiO2 requirements [0.37 (0.27, 0.58) vs 0.21% (0.21, 0.25); p< 0.0001]; higher heart rates (174 ± 4 vs 163 bpm ± 4; p< 0.03); lower mean arterial pressures [31 ± 2 vs 38 mmHg ± 2; p< 0.02) and lower pulse oximeter saturations [84% (79%, 90%) vs 91% (84%, 96%); p< 0.02].
Conclusions
Spot measurements of absolute epinephrine concentration normalized to 24h urine output showed no significant clinical correlates; presumably due to diminution of any individual stressor event distributed over 24h. In contrast, spot measurements obtained closer to the inciting event and normalized to Ucr correlated well with other indices of severity of illness, suggesting the Cr method is preferred for comparing rapid responses to stressors and interventions of short duration.
6A: Cardiopulmonary
#134 Rapid bicarbonate bolus post extensive neonatal resuscitation leads to increased perfusion to the heart and brain
M Bawa*
S Gugino
J Helman
N Bradley
A Mari
A Prasath
C Blanco
M Rawat
P Chandrasekharan
SUNY Buffalo, Buffalo, NY
Purpose of Study
Sodium bicarbonate (NaHCO3) is not routinely recommended in neonates with metabolic acidosis. However, post-resuscitation and in infants with perinatal metabolic acidosis and hypoxic-ischemic encephalopathy (HIE), NaHCO3 continues to be used to correct acidosis. Rapid infusion of NaHCO3 can lead to carbon dioxide (CO2) formation, myocardial injury, and fluctuations of cerebral blood flow. The acute effects of rapid infusion of NaHCO3 on cerebral and coronary perfusion especially post extensive neonatal resuscitation remains unknown. We wanted to study the effect of rapid infusion of 2meq/kg of NaHCO3 in an ovine model on 1) gas exchange 2) coronary and cerebral perfusion in the immediate post-resuscitation phase.
Methods Used
Twelve near-term lambs (138-140d) at 1 hour post resuscitation for severe asphyxia were given 2meq/kg bicarb followed by 2ml flush via a central line. Blood gas parameters (pH), arterial carbon dioxide (PaCO2), arterial oxygenation (PaO2), base excess (BE), coronary blood flow (ml/kg/min), carotid blood flow (ml/kg/min) were recorded for 15 minutes before and after administration of NaHCO3. We further delineated the lambs who received NaHCO3 to pH < 7.1 and pH ≥ 7.1. The effect of NaHCO3 with arterial carbon dioxide of < 35mmHg and >35mmHg was also analyzed.
Summary of Results
Eight lambs had pH < 7.1 and four had a pH ≥ 7.1 before administering NaHCO3 (figure 1A). The gas exchange based on pH before and after NaHCO3 is represented in figure 1B. There was a significant rise in exhaled CO2 levels (figure 1C) after NaHCO3 administration in all lambs and a significant change in PaCO2 in lambs with pH ≥7.1. Coronary and carotid blood flows after NaHCO3 (figure 1C) administration were significantly higher. When comparing the impact of NaHCO3 in animals with PaCO2 < 35 or >35mmHg, we found that coronary, carotid and pulmonary flows were significantly higher. (Figure 2).
Conclusions
Following extensive resucitation, rapid NaHCO3 administration led to a significant rise in myocardial and cerebral perfusion along with higher levels of exhaled carbon dioxide. The effect of increased flow appears to be primarily due to changes in CO2 levels. These acute changes could be detrimental especially during the reperfusion phase of ischemic injury post neonatal resuscitation.
#135 Comparison of echocardiographic indices of ventricular function and pulmonary hypertension in premature infants after transcatheter vs. surgical closure of the patent ductus arteriosus
C Sommer*
S Mahajan
J Fishbein
D Kholwadwala
S Epstein
H Heiman
R Koppel
L McPhillips
DA Hayes
Cohen Children’s Medical Center, Queens, NY
Purpose of Study
A hemodynamically significant patent ductus arteriosus (PDA) is a common comorbidity in premature infants. Previously, surgical ligation was the only option for those who had contraindications for or had previously failed medical therapy, however surgical complications were common. Use of the less invasive transcatheter PDA closure (TCPC) in low weight infants has increased in the years since FDA approval of the Amplatzer™ Piccolo Occluder in 2019.
Well-described complications of PDA closure include left ventricular (LV) and pulmonary vascular dysfunction. We sought to compare post-procedural echocardiographic indices of ventricular function and pulmonary hypertension in premature infants after TCPC vs. surgical ligation.
Methods Used
Premature infants born at <28 weeks gestation who underwent TCPC or surgical ligation at <6 months old were retrospectively analyzed. Transthoracic echocardiograms performed within 48 hours post-procedure were interpreted by a pediatric cardiologist, blinded to the type of PDA closure. Measurements were compared between groups by independent t tests and Fisher’s exact tests.
Summary of Results
Twenty-one subjects were identified (11 TCPC, 10 surgical ligation). Median procedure age and weight were 45 days (interquartile range 23-84), 1.37kg (1.06-1.82) for surgical ligation and 44 days (32-61), 1.39kg (1.15-1.82) for TCPC. Only 1 subject, in the surgical group, had a trivial residual PDA. Four subjects (all in the surgical group) were receiving inotropic medications at the time of the echocardiogram. Mean LV cardiac index calculated by velocity time integrals was significantly lower in the surgical group (2.3 ± 0.5 L/min/m2) vs. TCPC group (3.8 ± 1.2 L/min/m2), p=0.002. Right ventricular (RV) function as measured by tricuspid annular plane systolic excursion indexed to body surface area was significantly lower in the surgical (5.6 ± 1.5 cm/m2) vs. TCPC group (7.1 ± 1.1 cm/m2), p=0.016. Higher pulmonary vascular resistance was suggested by significantly shorter mean pulmonary artery acceleration time (PAAT) in the surgical (42.0 ± 15.7 msec) vs. TCPC group (65.2 ± 13.4 msec), p=0.002. There were no significant differences between groups in RV fractional area change, LV shortening or ejection fractions, PAAT/RV ejection time ratio, or estimation of pulmonary artery pressure (see table 1).
Conclusions
Certain indices of ventricular function and pulmonary vascular resistance on post-procedural echocardiograms suggest more favorable hemodynamics in premature infants after TCPC compared to surgical ligation of the PDA. Larger studies are needed to further assess these measurements and their relation to clinical outcomes.
#136 Initial elevated midline head position reduces hemodynamic fluctuation with subsequent position change
A Mari*
M Bawa
S Gugino
J Helman
N Bradley
C Koenigsknecht
A Prasath
P Chandrasekharan
M Rawat
J Nair
University at Buffalo, Buffalo, NY
Purpose of Study
ELBW infants have limited ability to autoregulate cerebral blood flow (CBF) placing them at high risk for brain injury and intraventricular hemorrhage (IVH) due to systemic hemodynamic instability (Perlman, 2009). Routine head position changes may affect cerebral hemodynamics by affecting venous drainage (Liao 2015) and increased cerebral blood volume is noted with lateral head turning. We hypothesized that maintaining a 150 EMHP in the post-resuscitation period would reduce hemodynamic fluctuations and improve cerebral oxygen delivery (DO2) during subsequent position changes.
Objective
To evaluate the effect of an initial EMHP on subsequent position changes in periviable lambs.
Methods Used
120d gestation beta mature lambs, partially exteriorized and instrumented in utero, were randomized into the elevated midline group (ELEV: 15 deg elevation) or standard group (FLAT) from 3 min after birth. Lambs were resuscitated per NRP guidelines. 60 min after birth, each lamb was placed in the alternate position (e.g. FLAT to ELEV) for 30 min. Carotid (CBF) and pulmonary (PBF) blood flows as well as blood pressure (BP) were monitored continuously using Biopac systems. Blood gases were collected before and after position changes at 15 min intervals. GraphPad PRISM software was used for statistical analysis using appropriate statistical tests.
Summary of Results
Baseline hemodynamics were similar between groups (table 1). Lambs that were in the ELEV position for the first hour after birth maintained stable, higher CBF and PBF (figure 1a and 1b) during and after position change at 60 min. Systolic, diastolic, and mean BP were similar. DO2 was significantly higher and stable after position change in the initial ELEV group. pCO2 and inspired oxygen requirement did not show any significant differences before and after position change between groups.
Demographic table
Hemodynamics and oxygen delivery before and after position change in each lamb. Blue bar represents timing of position change. 1a) Cerebral blood flow (CBF) and 1b) Pulmonary blood flow (PBF) higher and stable in ELEV to FLAT change 1c) DBP was similar 1d) Higher and stable oxygen delivery after position change in ELEV to FLAT change
Conclusions
In this periviable model, we observed hemodynamic benefits of initial MEHP. Subsequent position changes led to fluctuation and decrease in CBF as well as PBF in the FLAT to ELEV group, but not in the ELEV to FLAT group. Oxygen delivery was also increased in the initial ELEV lambs. We speculate that EMHP immediately after birth improves lower segment lung recruitment leading to clinical stability and improved oxygen delivery, reducing hemodynamic fluctuations during subsequent position changes. Clinical studies are needed to evaluate benefits and outcomes of EMHP in ELBW infants.
#137 Is NIPPV superior to CPAP in maintaining targeted oxygen saturation ranges in preterm infants on moderate non-invasive respiratory support?
C Hegedus*
W Bucher
D Carola
Z Aghai
Nemours/Thomas Jefferson University Hospital, Philadelphia, PA
Purpose of Study
The objective of this study was to determine if oxygen saturation is more within the target range on NIPPV compared to CPAP using the data from histograms.
Methods Used
Retrospective analysis of premature neonates (birth weight <1500 grams, gestational age <30 weeks) admitted to the NICU between 11/2014 and 06/2021, for which oxygen saturation histogram data was available one day before and after the transition between NIPPV and CPAP. FiO2 at the time of data collection was greater than 21 percent. This histogram data, the percentage of time spent in certain SpO2 ranges, was compared before and after the de-escalation from NIPPV to CPAP, or escalation from CPAP to NIPPV. FiO2 was additionally compared between the two modes of respiratory support.
Summary of Results
A total of 26 infants met inclusion criteria. The median gestational age was 25.5 weeks and the median weight of the infants was 792 grams. Among the 26 infants, there were 34 episodes of transition between NIPPV and CPAP, 19 switches from NIPPV to CPAP, and 15 from CPAP to NIPPV. The percentage of time that oxygen saturation was within the target range (89-94 %) was not statistically significant between the two modes of respiratory support (CPAP 39.9% vs. NIPPV 43.9%, p=0.09) (table 1). The percentage of time that oxygen saturation was between 86-88% was higher on NIPPV and the percentage of time that oxygen saturation was >94% was higher on CPAP. There was a trend towards lower FiO2 on NIPPV compared to CPAP. When switched from NIPPV to CPAP, there was a higher percentage of time spent above the target range (>94%) while on CPAP (56% vs 49%, p=0.001), and below the target range (86-88%) while on NIPPV (5.0% vs 1.4%, p=0.02) (table 2). When switched from CPAP to NIPPV, there was no difference in oxygen saturation ranges.
Conclusions
Target oxygen saturation ranges on histogram data were similar in premature infants when supported on CPAP and NIPPV. However, oxygen saturation below the target range was more frequent on NIPPV compared to CPAP. NIPPV is not superior to CPAP in maintaining oxygen saturation within the target range in premature infants on moderate non-invasive respiratory support. The potential risk of low oxygen saturation range while supported on NIPPV in preterm infants requires further research.
Respiratory support and oxygen saturation (Med, IQR)
Respiratory support and oxygen saturation (Med, IQR) switching from NIPPV to CPAP (n=19)
#138 Blood sugar levels and its association with neonatal resuscitation using an ovine cardiac arrest model
A Prasath*
S Gugino
J Helman
N Bradley
L Nielsen
A Gupta
C Blanco
A Mari
J Nair
VH Kumar
M Rawat
P Chandrasekharan
Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, NY
Purpose of Study
In neonates, glucose consumption increases during anaerobic metabolism. Hypoglycemia could occur because of the rapid depletion of glucose stores during perinatal stress. Glucose is an essential fuel for brain function in newborns and prolonged hypoglycemia could contribute to brain injury after resuscitation. It remains unknown if neonates who are subjected to extensive resuscitation with low blood sugars have similar rates and time to establish return of spontaneous circulation (ROSC) compared to those who have higher blood sugar levels.
We seek to understand the association between the effect of blood sugar levels on extensive neonatal resuscitation using a near-term ovine model on, a) times and rates of ROSC, b) blood sugars during resuscitation and at ROSC and, c) the difference between the blood sugar levels between lambs that did and did not achieve ROSC.
Methods Used
Near-term lambs 139 – 141 days were instrumented and cardiac arrest was induced by umbilical cord occlusion. These ovine models required extensive resuscitation and blood sugars were collected as part of blood gas analysis before, at cardiac arrest, and every minute during resuscitation until ROSC or 20 min of resuscitation. The baseline blood sugars were consistently 20±5mg/dl. For this study, we defined hypoglycemia as ≤ 20 mg/dl and normoglycemia as >20 mg/dl at the start of the resuscitation.
Summary of Results
We included a historical data from a total of 85 lambs with 47 having hypoglycemia and 38 having normoglycemia (figure 1). The blood sugars were significantly lower in the hypoglycemia group at the start of resuscitation (figure 1). The time to ROSC was faster in the normoglycemia group, however, this was not significant (figure 1). The comparison of blood sugar during arrest, resuscitation, and at ROSC or at 20 min if the lambs did not achieve ROSC is shown in figure 2 (a & b). Interestingly we observed significantly higher blood sugar levels during resuscitation in lambs that did not achieve ROSC compared to those that achieved ROSC (figure 2C).
Conclusions
Lambs that achieved ROSC had lower blood sugars during resuscitation. We speculate that this could be secondary to the increased energy need during resuscitation. Future studies comparing the effect of a dextrose bolus when extensive neonatal resuscitation is needed may help us further understand the role of blood sugar levels.
#139 Work of breathing indices and oxygen saturation at discharge in premature infants with history of respiratory insufficiency
KZ Kovatis1*
R Locke1
A Mackley1
TH Shaffer2
1Christiana Care, Newark, DE
2A.I Dupont Hospital for Children, Wilmington, DE
Purpose of Study
Premature infants commonly demonstrate Thoracoabdominal asynchrony (TAA) secondary to highly compliant rib cage and poor compensation by immature respiratory muscles. Increased TAA signifies increased work of breathing (WOB). Respiratory inductive plethysmography (RIP) is a noninvasive way to objectively assess TAA and quantify WOB. Normative WOB data for premature infants at discharge has not been established. The purpose of this study is to establish normal WOB indices [phase angle(PA), labor breathing index (LBI), HR, Saturations) at discharge for premature infants in the supine position (S) and in the car seat test (CST).
Methods Used
This is a prospective observational study of infants born with a birth weight of <1500 grams and at >26-week gestation at a single center NICU. Infants had RIP and pulse oximetry measurements (mean +/- SEM) in the S position and during the CST within 7 days of discharge. PneuRIP, a portable, bedside software provided real time clinical data. Diagnosis of BPD was based on the 2018 NICHD criteria. PA>40 and LBI> 1.15 suggests respiratory distress in pediatric populations.
Summary of Results
Preliminary data includes 30 of the anticipated 62 infants. The PA in the S position is 720±5. There is no difference in WOB indices in the S position for infants with BPD vs Control. Infants with BPD had lower HR [150±4 vs 161±2; p <0.01] and saturations [95%±1 vs 99%±0.3; p<0.01]. We observed Increased WOB indices in the S position compared to the CST [PA: 750±6 vs 490±5; p <0.001]. Infants in the CST had statistically but not clinically lower saturations [96%±1 vs 97%±0.4; p <0.01] (table 1). Infants with PA >900 (70th percentile), demonstrated significantly improved WOB indices during the CST [PA:1080±2 vs 570±15, p=0.02) (figure 1). Infants with BPD have increased WOB indices in the CST compared to controls [PA: 680±14 vs 420±3.3; p<0.01] and LBI: [1.4±0.2 vs 1.2±0.1; p<0.05].
Comparison of work of breathing indices in supine (S) and CST position
Comparison of phase angle in the supine (S) and car seat position
Conclusions
Premature infants at discharge have increased WOB indices relative to the older pediatric population. Position (S vs CST) at discharge affects WOB indices. BPD and/or increased WOB indices at discharge may impact guidelines for patient position, discharge criteria and respiratory support.
#140 Cyclophilin D inhibition rescues cardiac function in neonatal hypoxia
JR Burris*
G Beutner
M Yee
MA O’Reilly
GA Porter
University of Rochester, Rochester, NY
Purpose of Study
Congenital heart disease (CHD) affects 40,000 newborns yearly and is the leading cause of birth defect related mortality. The heart develops in utero under hypoxic conditions. At birth ambient oxygen levels rise, activating changes in cardiac bioenergetics to allow survival ex-utero. This transition to normoxia does not occur in infants with CHD. Mitochondria are critical in terminal cardiac myocyte differentiation after birth, and inhibition of the mitochondrial chaperone protein cyclophilin D (CypD) enhances this process by regulating the function of the electron transport chain (ETC) to meet metabolic demands of the beating heart. In CHD and cardiomyopathies, oxidative phosphorylation and cardiac function are impaired due to mitochondrial abnormalities and/or hypoxia. This work seeks to understand the bioenergetic pathways in the normoxic and hypoxic neonatal heart and how intervention on CypD may recover the detrimental effects of hypoxia.
Hypothesis: Inhibition of CypD with cyclosporin A (CsA) or N-methyl-4-isoleucine cyclosporin (NIM811) will rescue the effects of hypoxia on cardiac function and on ETC activity.
Methods Used
Mice were exposed to continuous hypoxia (12% oxygen) immediately before birth (gestational age E19.5) to postnatal day 7 (P7). Hypoxic mice received no treatment (NoTx) or intraperitoneal injections 10mg/kg of vehicle (VEH), CsA, or NIM811 from P1 to P6. Room air neonates served as controls. On P7, mice underwent echocardiography and hearts were harvested for mitochondrial isolation. Enzymatic activity of ETC complexes, mitochondrial oxygen consumption, and tissue histology were analyzed.
Summary of Results
Overall survival decreased in the hypoxic mice. Neonatal hypoxia caused decreased body weight, cardiomegaly, and markedly decreased cardiac function in the NoTx and VEH groups when compared to room air controls (P<0.0001). The enzymatic function of ETC complexes I and III (P<0.01) and complex I-mediated respiration (P<0.0001) was decreased in the untreated hypoxic groups. Histology revealed decreased cellular organization and increased nuclear size of hypoxic myocytes. Treatment of hypoxic neonates with CsA and NIM811 normalized cardiomegaly, cardiac function, ETC activity of complexes I and III and the mitochondrial respiratory capacity for complex I. Histology showed a return to mature cellular structure and decreased nuclear size.
Conclusions
Pharmacologic inhibition of CypD reversed the effects of hypoxia on ETC activity and overall cardiac function in the neonatal heart. Our study may help develop therapies to treat cardiomyopathies and the effects of hypoxia on the neonatal heart.
#141 The relationship between coronary sinus diameter and severity of pulmonary hypertension in preterm infants
E Capossela*
R Koppel
DA Hayes
A Siegel
I Gershkovich
Cohen Children’s Medical Center, Queens, NY
Purpose of Study
Pulmonary hypertension (PH) is associated with increased morbidity and mortality in preterm infants. Screening typically includes B-type natriuretic peptide (BNP) measurement and echo. In adults, increased coronary sinus diameter (CSD) has been shown to correlate with elevated right atrial and pulmonary artery (PA) systolic pressures and severity of PH. There are no published studies examining the relationship between CSD and PH in neonates. The aim of this study was to investigate if such a relationship exists.
Methods Used
This was a single center, retrospective chart review of 38 preterm infants < 30 weeks with PH on echo defined by PA pressure >1/3 systemic blood pressure. Infants were excluded if they had congenital heart disease other than a small atrial septal defect/ventricular septal defect/patent ductus arteriosus (PDA) or bicuspid aortic valve. Coronary sinus (CS) dimensions examined included CSD at the os and mid-portion (MP) with body surface area (BSA) correction. Echo indices included degree of PH (none/mild vs moderate/severe), tricuspid regurgitation (trivial/mild vs moderate/severe), right ventricular function (normal vs mildly decreased/moderately decreased/severely decreased), and presence of a PDA (yes/no). Statistical analyses included Spearman correlation and exact Wilcoxon rank sum tests to look for associations between each CS dimension and degree of PH and presence of a PDA. A P-value < 0.05 was considered statistically significant. All analyses were conducted using SAS version 9,4. Records from 34 subjects were included in all final analyses.
Summary of Results
No statistically significant association was observed between os or MP CSD and degree of PH or PDA presence. However, there was a positive trend observed as babies with moderate/severe PH had higher os CSD (2.70-3.50 mm lower/upper quartiles) compared to those with mild PH (2.30-3.05mm lower/upper quartiles). Similarly, MP CSD was higher in babies with moderate/severe PH (2.50-3.10, lower/upper quartiles) compared to babies with mild PH (2.30-3.0, lower/upper quartiles). No statistically significant association was observed between os or MP CSD and other echo indices. Interestingly, BNP was significantly negatively correlated with os CSD (rs=-0.41, p=0.015) but not with MP CSD (rs=-0.34, p=0.015).
Conclusions
We observed larger os and MP CSD in babies with moderate/severe PH compared to those with mild PH. It is likely that the small sample size may have resulted in reduced power to detect statistically significant associations. The reason for the negative correlation between CSD and BNP is unclear. We speculate that CS enlargement may reflect increased intracardiac metabolism of BNP prior to secretion. Future studies may demonstrate the utility of CSD as an additional marker for PH severity in preterm infants.
6B: Potpourri
#142 Cessation of routine gastric aspirate monitoring improves nutritional outcomes in early preterm infants without increasing comorbidities
S Patel*
N Mangalapally
A Vlk
C Capriolo
E Schofield
NL Davis
University of Maryland School of Medicine, Baltimore, MD
Purpose of Study
Routine gastric aspirate (RGA) monitoring is a common practice used to guide initiation and advancement of gavage feeds while monitoring for early signs of necrotizing enterocolitis (). NEC Since limited data are available to prove whether this practice actually identifies infants at risk of NEC or simply delays enteral feeds, our level IV neonatal intensive care unit (NICU) stopped this practice in June 2018. Our study objective was to evaluate the effect of ceasing RGA monitoring on nutritional outcomes as well as incidence of NEC.
Methods Used
Retrospective medical record review of infants <1250g in 2 cohorts: 1) RGA monitoring (9/2015 – 6/2018) and 2) non-RGA monitoring (7/2018 – 12/2020). We compared clinical, demographic, nutritional characteristics between the cohorts using bivariate analyses. We used multivariable modelling to assess the impact of RGA monitoring on incidence of NEC while controlling for changes in feeding protocols over time.
Summary of Results
We identified 230 subjects (55%) in the RGA and 192 (45%) in the non-RGA cohorts. We found no significant differences in baseline characteristics [table 1]. The non-RGA cohort had significant improvement in time to first feed (p<0.0001), time to first mother’s breast milk (p<0.0001), time to full feeds (p=0.0002), and completed parenteral nutrition significantly sooner (p<0.0001). We found that after ceasing RGA, significantly fewer neonates required peripherally inserted central catheters or surgical central lines (p=0.0019) and the non-RGA cohort had fewer overall central line days (p<0.0001). While the differences did not reach statistical significance, we found lower incidence of all stage NEC (16% vs 11% p=0.16) and Stage 2/3 NEC (8.3% vs 5% p=0.14) after cessation of RGA. There were no differences in rates of spontaneous intestinal perforations (SIP), retinopathy of prematurity (ROP), periventricular leukomalacia, or death. We performed multivariable logistic regression to evaluate associations between RGA status and stage 2/3 NEC diagnosis [table 2]. We included use of donor human milk and human-milk-based fortifiers in the model to account for changes in our feeding protocols over time as well as known risk factors of formula exposure and birth gestational age (GA). We found the only significant predictor of NEC was birth GA and that RGA monitoring did not impact NEC rates.
Comparing cohorts pre- and post-RGA cessation
Multivariable Logistic Regression for Predictors of NEC Stage 2/3
Conclusions
Cessation of routine gastric aspirate monitoring was associated with improved timing of enteral feeds, fewer central line days, and fewer days of parenteral nutrition. We found no impact of RGA on risk of SIP, ROP, or death, and no impact on NEC incidence even when accounting for changes in our feeding protocol over time. Our data support the cessation of routine gastric aspirate monitoring for infants born <1250g.
#143 Car seat screening in infants with cyanotic congenital heart disease
E Sangillo*
NL Davis
University of Maryland Children’s Hospital, Baltimore, MD
Purpose of Study
Certain patient populations are at increased risk for cardiorespiratory instability when placed in the semi-upright car seat position, including premature and low birth weight infants, which led to the AAP recommendation for pre-discharge car seat tolerance screening (CSTS) in all infants born < 37 weeks gestation. In their most recent clinical report, the AAP acknowledged varied hospital practices for inclusion of other ‘at risk’ infants, including those with congenital heart disease (CHD), though formal recommendations for testing these at-risk populations do not exist. Additional epidemiologic data on CSTS outcomes for CHD patients will help guide evidence-based recommendations.
Methods Used
We performed a retrospective medical record review of neonates with cyanotic CHD admitted to the University of Maryland neonatal intensive care unit (NICU), pediatric intensive care unit (PICU), or newborn nursery (NBN) between 2016-2020 to identify incidence and risk factors for CSTS failure in this population. Infants were excluded if they died prior to CSTS, were discharged in a car bed due to medical necessity, were discharged or transferred on positive pressure ventilation (PPV), or if parents declined CSTS. Bivariate analysis was used to identify predictors of CSTS failure using SAS 9.4.
Summary of Results
Fifty-three infants with cyanotic heart disease met inclusion criteria, and of those, 5 (9.4%) failed initial CSTS with reasons for failure including: desaturation (N=2), bradycardia (N=1), both (N=1), or other (N=1). All infants passed a repeat CSTS. Subjects who failed CSTS had smaller birth head circumference, and were more likely exposed to stadol perinatally and caffeine postnatally. [Table 1] Other statistically significant factors associated with CSTS failure include aortic stenosis, seizures, hypotonia, and periventricular leukomalacia (PVL). The incidence of CSTS failure by cyanotic heart lesion is shown in table 2. The incidence of CSTS failure was highest among infants with diagnoses of aortic stenosis (50%), total anomalous pulmonary venous return (TAPVR) (33%), pulmonary valve stenosis (25%), and hypoplastic left heart syndrome (HLHS) (17%).
Characteristics of Study Population
CSTS Failure by Cyanotic Heart Lesion
Conclusions
This is the largest study to date focusing on CSTS exclusively in cyanotic CHD and we identified a 9.4% CSTS failure rate. The incidence of CSTS failure was highest among infants with diagnoses of aortic stenosis, TAPVR, pulmonary valve stenosis, and HLHS. Those with neurologic abnormalities including seizures, hypotonia, and PVL were also more likely to fail a CSTS. More studies are needed, but these data can help guide recommendations for CSTS testing in this population.
#145 Spatial patterns of spontaneous and medically indicated preterm birth in philadelphia
N Yang1*
H Quick2
S Melly2
A Mullin3
LH Schinasi2,3
H Burris1,4
1Children’s Hospital of Philadelphia, Philadelphia, PA
2Drexel University Dornsife School of Public Health, Philadelphia, PA
3Tufts University School of Medicine, Boston, MA
4University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
Purpose of Study
Understanding area-level patterns of preterm birth (PTB) may inform social and environmental determinants of PTB and PTB disparities. Because spontaneous preterm birth (sPTB) and medically indicated preterm birth (mPTB) may have different underlying causes, reliable estimates of small-scale geographic variations in PTB, sPTB, and mPTB rates are needed.
Thus, we aim (1) to detect and compare neighborhood spatial patterns of PTB, sPTB, and mPTB across block groups in Philadelphia using spatial methods that account for sparse numbers and allow derivation of more reliable small area estimates and (2) to determine whether spatial patterns differed between Black and non-Black patients.
Methods Used
We used a pregnancy cohort of singleton births at two Penn Medicine hospitals in 2008-2020. Each PTB (<37 wks’ gestation) was manually classified by two independent, blinded reviewers as sPTB (e.g., preterm labor, spontaneous rupture of membranes) or mPTB (e.g., clinician initiated due to maternal or fetal health condition). Addresses at birth were geocoded, and residential block groups were included in the analysis if they were contained within census tracts where ≥25% of births occurred at Penn Medicine. We applied a Bayesian model that accounts for spatial dependence structures and smooths estimates of PTB rates by borrowing information from neighboring block groups to obtain more reliable estimates than one would by simply calculating percent of births that are preterm in each block group. We used Global Moran’s I to test whether PTB was spatially autocorrelated.
Summary of Results
65,715 births were included in this analysis. There were 6670 (10.1%) PTBs, of which 3787 (56.8%) were sPTB, 2276 (34.1%) were mPTB, and 626 (9.1%) could not be adjudicated. Bayesian small area estimates revealed clustering of rates of PTB across different areas of Philadelphia, with PTB hot spots differing by race (figure 1). For example, southwest Philadelphia is a hot spot for non-Black patients whereas South Philadelphia is a hot spot for Black patients. In addition, there were different spatial patterns of clustering of sPTB and mPTB (figure 2). Moran’s I was significant for PTB overall and by race (p < 0.05), suggesting that PTB is not randomly distributed across the city.
Spatial patterns of PTB rate among the overall population, Black patients, and non-Black patients.
Spatial patterns of sPTB and mPTB rates among the overall population, Black patients, and non-Black patterns
Conclusions
In Philadelphia, geographic patterns of PTB differ for Black vs. non-Black patients, and according to PTB phenotypes (sPTB vs. mPTB). Further analysis of spatial patterns and social and environmental exposures that may explain these geographic patterns may provide evidence needed to improve birth outcomes.
#146 Pilot study of transcriptomic evidence of the effects of prenatal opioids in preterm neonates
J Baik1*
J Maron2
E Yen3,4
1Tufts University, Medford, MA
2Women and Infants Hospital of Rhode Island, Providence, RI
3Tufts University School of Medicine, Boston, MA
4Tufts Medical Center, Boston, MA
Purpose of Study
The impact of prenatal opioid exposure on the preterm neonate is poorly understood. Previously, our laboratory performed comparative salivary gene expression analyses between neonates who were and were not exposed to opioids in utero to further our understanding of the sex-specific impact of prenatal opioids on the expression of hypothalamic and reward genes that regulate feeding behavior. The current objective was to analyze the data exclusively derived from premature neonates to further our understanding of the effects of opioids on the developing preterm brain.
Methods Used
A pre-existing, salivary transcriptomic database was curated to include gene expression data derived from preterm neonates (gestational ages: 34 to 37 week). Select hypothalamic and reward genes analyzed included: neuropeptide Y2 receptor (NPY2R), leptin receptor (LEPR), proopiomelanocortin (POMC), and dopamine receptor type 2 (DRD2). Gene expression levels were expressed as normalized delta threshold cycle (ΔCt) values. Gene expression of each gene was compared between the opioid-exposed and non-exposed preterm neonates and further stratified by sex. Continuous data were analyzed using a student’s t test; categorical data analyzed using Chi-square test. Two-factor ANOVA was used to explore interactions between study group and sex.
Summary of Results
There were 17 preterm neonates: 8 opioid-exposed neonates and 9 non-exposed neonates (table 1). Two opioid-exposed neonates (a male and a female) required pharmacotherapy. While the expression of all genes did not differ significantly between the two cohorts, there was a trend toward higher expression of LEPR in opioid-exposed compared to non-exposed neonates (6.24±0.99 vs. 8.49±3.87, p=0.13). No significant gene expression difference was seen across sex, however, similar to our prior study, opioid-exposed males had greater DRD2 expression compared to their female counterparts (8.28±1.35 vs. 11.48±4.79, p=0.28). Similarly, there was a significant interaction between sex and prenatal opioid exposure for DRD2 (p<0.01) in this premature group (figure).
Demographic data of premature neonates enrolled in the study
Abstract #146 Figure Two-way analysis of variance looking at DRD2 expression in opioid exposed neonates and interaction with sex (p=0.0012) ΔCt values are inversely proportional to the level of gene expression
Conclusions
Despite the lack of opioid withdrawal signs in the premature neonate, these data suggest that prenatal opioid exposure directly impacts the developing preterm neonate at the molecular level. While limited by the small sample size and retrospective nature of this study, our study aligns with some findings previously seen in the term neonate and supports the need to further investigate the molecular impact of prenatal opioids in preterm neonates.
#147 Theme-coded qualitative analysis to understand parental perceived stress and depression in the neonatal intensive care unit
C Ressel*
JA Wolfe
D Perry
L Rubin
Georgetown School of Medicine, Washington DC
Purpose of Study
Parents of infants admitted to NICUs often experience significant psychosocial stress and have higher risks for depression, anxiety, and disturbed parent-child bonding. Analyses of parental stress often use either a predominantly biomedical or qualitative approach. The current study integrates these domains, using parental demographic and psychosocial assessments, stress-related salivary biomarkers, measures of illness severity, and open-ended question interviews for a more complete assessment of parental NICU experience and stressors.
We detail a novel use of theme-coded qualitative analysis of open-ended interviews to explore parents’ perceptions of the NICU experience, sources of stress and well-being, and associations with stress/depression measurements.
Methods Used
Inclusion criteria: parents of infants admitted to a Level IV NICU born ≤34 weeks gestation or having a predicted length of stay >2 weeks. At weeks 1 and 6 and before discharge, we collected parental salivary cortisol and α-amylase (AM, PM) and the Edinburgh Postpartum Depression Scale, Perceived Stress Scale, and Social Provisions Scale. Infant data and the Neonatal Acute Physiology Perinatal Extension-II and Neonatal therapeutic Intervention Scoring System were recorded. Parents individually participated in recorded open-ended question interviews. Interviews were transcribed and annotated using qualitative content analysis based on a grounded theory approach. Investigators affixed codes (with inter-rater checks) to transcripts using an iterative approach, highlighting common phrasing and themes. Transcripts were entered into NVivo qualitative data analysis software to sort and label categories and themes.
Summary of Results
Results are available for 15 interviews. We identified patterns, themes, subgroup differences, and common phrasing to develop an interactive model of the complex interplay among social supports, NICU environment, COVID-19-related stressors, and parental experience [figure]. The model facilitates evaluating multiple components which influence parental experience and clarifies parental-perceived barriers and facilitators. Voiced resiliency was compared to subjects’ stress and depression salivary biomarkers and the validated scales.
Conclusions
Parent interviews revealed feelings of isolation, fear, and resilience among NICU parents. Textual analysis of open-ended interviews informed construction of a conceptual model describing the NICU experience. Integration of biomedical and qualitative methods more comprehensively reveals experiences of parents and points to strategies for fostering support and resilience.
#148 Evaluating the effect of infant sex on a standardized cue-based feeding protocol in preterm infants
IM Moore1
M Walker1*
N Hussain2
TS Rosenkrantz2
L Eisenfeld3
M Pappagallo2
1University of Connecticut School of Medicine, Farmington, CT
2Connecticut Children’s NICU at UConn Health, Farmington, CT
3Connecticute Children’s Medical Center, Hartford, CT
Purpose of Study
The achievement of sufficient oral feeds is a competency that determines the timing of preterm infants discharge from the NICU. Cue-based feeding (CBF) focuses on developmental cues and feeding quality rather than quantity. Evidence shows that infants achieve full oral feeding earlier with CBF than those fed with volume driven methods, but few studies have evaluated oral feeding outcomes using this protocol. Sex is a major predictor of NICU outcomes. Thus we have hypothesized that infant sex will affect time to full oral feeds in premature infants. To determine the impact of sex on the achievement of full oral feeds in premature infants born at 26-29 wks. gestational age (GA), using a standardized CBF protocol.
Methods Used
A retrospective study was conducted at Connecticut Children’s NICU at UConn Health in Farmington, CT from the time of CBF implementation in Jan 2017 to Mar 2021. Feeding data was collected through chart review. Inclusion criteria consisted of infants between 26 wks. and 29 wks. and 6 days GA at birth. This GA distribution centers around the border between extremely and moderately premature infants, 28 wks. GA. Infants transferred out of the NICU before reaching full oral feeds (140cc/k/day), transferred in after starting a non-CBF protocol, or with genetic, GI, congenital heart or neurological abnormalities as well as infants with NEC were excluded due to impact on feeding velocity. Potential confounders, including BPD, RDS, PDA, IVH, ROP, and GERD, were included in the analysis. Two-tailed unpaired Student’s t-tests, Chi-squared test and multiple linear regression (MLR) were used for data analysis.
Summary of Results
(See table 1.) Data from 50 infants (male (M) n=27 and female (F) n=23) were included. F attained first and full oral feeds and were discharged one week earlier than M (P <0.05). Despite F attaining earlier oral feeds, M weighed significantly more at their first and full oral feeds and at discharge. There were no significant sex differences in GA at birth, race, ethnicity, birth weight, length, head circumference, and z scores. A MLR confirmed the lack of effect of any of the studied confounders on the sex differences in attainment of earlier full oral feeds in F compared to M.
Sex Comparison of Feeding Outcomes using CBF
Conclusions
Use of a standardized CBF protocol in the NICU demonstrated earlier achievement of feeding milestones (PMA at first and full oral feeds) in F compared to M. Weight differences of F vs M are likely due to PMA differences. F infants reached physiological criteria for discharge at earlier PMA. We plan to conduct further analysis to include infants ranging from 23 wks. to 31 wks., to further validate our findings.
#149 Outcomes and resource use for surgical versus transcatheter patent ductus arteriosus closure in preterm infants in the United States
H Doshi1*
P Bhatt2
C Ampem-Darko3
GA Cudjoe4
AO Asiama5
T Parekh6
F Dapaah-Siakwan7
K Donda8
1Pediatrix Medical Group, Sunrise, FL
2United Health Center, Bridgeport, WV
3N/A, N/A, Ghana
4Korle Bu Teaching Hospital, Accra, Ghana
5Pantang Hospital, Accra, Ghana
6George mason university, Faifax, VA
7Valley Children Hospital, Madera, CA
8Tampa General Hospital, Tampa, FL
Purpose of Study
Hemodynamically significant patent ductus arteriosus (PDA) is associated with significant morbidity in preterm infants. Preterm infants with PDAs refractory to pharmacologic closure undergo either surgical closure (SC) or transcatheter closure (TC). However, the outcomes of these two methods of PDA closure have not been well-studied.
To compare the in-hospital outcomes and resource use among preterm infants ≤32 weeks gestational age (GA) undergoing SC versus TC of PDAs. We hypothesized that infants with SC of PDAs will have worse outcomes compared to those with TC.
Methods Used
This was a retrospective cross-sectional analysis of preterm newborn hospitalizations ≤32 weeks GA within the Healthcare Cost and Utilization Project’s (HCUP) National Inpatient Sample from 2016-2018. ICD-10 diagnostic and procedure codes were used to identify SC and TC of PDA. The outcomes of interest were mortality before discharge, BPD or death, resource use (LOS and hospital cost) between the two groups. Chi-square test and Kruskal-Wallis test were used for categorical and continuous variables, respectively. Multivariable logistic and linear regression was performed for categorical and continuous variables respectively to control for demographic and perinatal characteristics to ascertain the outcome of interest. P-value <0.05 was considered significant.
Summary of Results
Total 3,765 preterm newborns ≤32 weeks GA had either SC (n=3,275) or TC (n=490) of PDA. Newborns with SC were more likely to be ≤24 weeks GA (19.7% vs 6.1%), less likely to be of GA 27-28 weeks (12.4% vs 25.5%), and less likely to be at large bed size hospitals (66.3% vs 77.6%) than TC. In bivariate analysis, no significant differences were found among both groups for gender, mode of delivery, race, insurance status, hospital teaching status, RDS, pulmonary hypertension, BPD or death, severe ROP, and severe IVH. However, newborns with SC were more likely to receive invasive mechanical ventilation for ≥96 hours (82.6% vs 67.3%; P<0.001), and noted higher mortality (10.2% vs 3.1%; P=0.02). After controlling for demographic characteristics and complications of prematurity, newborns with SC of PDA did not have increased odds of BPD or death [OR 1.04; 95% CI: 0.43-2.51], prolonged LOS (β = -4.9 days; 95% CI: -14.5 – 4.8; P=0.32) or increased hospital cost (β=132,932; 95% CI: -128,052 – 393,916; P=0.32) when compared to TC.
Conclusions
SC of PDA is associated with higher mortality but not BPD or death or increased resource use when compared to TC. A clinical trial is warranted to confirm these findings and optimize outcomes for preterm infants with PDAs.
#150 Does normothermia in the delivery room predict neonatal intensive care unit admission normothermia?
GM Asefa*
D D’Alleva-Byrne
K Bailey
M Duran
M O’Connell
J Fishbein
B Weinberger
V Boyar
Cohen Children Medical center, Queens, NY
Purpose of Study
Our objective was to determine whether standard early diagnosis and treatment of hypothermia in the Delivery Room/Operating Room (DR/OR) decreases NICU admission hypothermia. We hypothesize that 1) infant’s post-stabilization temperature in the delivery room is an accurate predictor of NICU admission temperature, and 2) axillary temperatures agree with rectal measurements.
Methods Used
Newborn axillary temperatures were obtained in the DR/OR (a 2–3-minute walk from the NICU) from March 2020-September 2021. Medical teams were instructed to perform standard interventions based on the unit’s ‘hypothermia prevention bundle’ and to achieve and document normothermia before departure from the DR/OR if possible. Temperatures were then also obtained by both axillary and rectal measurements on admission to the NICU within 1 hour of birth (n=445, including 331 with DR/OR measurements).
Summary of Results
DR/OR axillary temperature moderately correlated with NICU admission temperature (Pearson coefficient 0.40, p < 0.0001). After adjusting for delivery mode, respiratory support, gestational age, and time between measurements, DR/OR axillary temperature remained significantly associated with NICU admission temperature (p<0.0001). Axillary temperatures were, on average, 0.13 ± 0.35°C lower than rectal measurements (Bland Altman limits of agreement -0.57 to 0.83) (figure 1).
Conclusions
Our findings suggest that achievement of normothermia in the DR/OR immediately after initial resuscitation is feasible and may decrease NICU admission hypothermia and its sequelae. Quality improvement interventions to decrease NICU hypothermia should include practices to decrease or eliminate DR/OR hypothermia. Axillary temperatures are a good approximation of rectal temperatures, enabling repeated non-invasive measurements to facilitate normothermia in the DR/OR and on admission to NICU.
6C: AFMR abstracts
#151 Ontogenetic oxycodone exposure demonstrates sex-dependent alterations in sensory processing, opioid reward preference, and weight trajectory in adult mice
E Minakova*
MO Mikati
RG Swift
KB McCullough
JD Dougherty
S Maloney
R Al-Hasani
Washington University in Saint Louis, Saint Louis, MO
Purpose of Study
The national prevalence of opioid use disorder among pregnant women quadrupled from 1999 to 2016. Consequently, there has been a significant increase in neonatal hospitalizations for Neonatal Abstinence Syndrome (NAS), a constellation of withdrawal symptoms affecting the nervous system, gastrointestinal tract, and respiratory systems. Moderate-severe NAS is managed by opioid replacement therapy to alleviate withdrawal symptomatology. In utero opioid exposure is associated with lower birth weight, adverse neurodevelopmental outcomes in childhood, and mood disorders. However, clinical studies have not addressed if long-term neurobehavioral outcomes are worsened with continued postnatal exposure to opioids. In addition, clinical studies comparing in utero opioid only exposure to continued post-natal opioid administration for withdrawal mitigation are lacking. To address these concerns, we implemented a rodent perinatal opioid exposure model of Oxycodone (Oxy) exposure for comparison of long-term consequences of prenatal Oxy exposure until birth (short Oxy) to the impact of continued postnatal opioid exposure (long Oxy) spanning gestation through birth and lactation.
Methods Used
Dams were anesthetized and an Alzet pump model 2004 (short Oxy) or 2006 (long Oxy) was subcutaneously implanted and continuously infused 10 mg/kg/day Oxy or sterile 0.9% NaCl. Utilization of the subcutaneous pump allowed for adequate post-surgical recovery time, breeding, and administration of desired treatment duration of Oxy. Juvenile behavioral testing was performed between P35-52 with evaluation of social interactions, sensorimotor abilities, learning and memory. Adult behavioral testing occurred after P56 and evaluated social dominance behavior, social motivation, anxiety-related behaviors, operant-based feeding behaviors, morphine conditioned place preference, and nociceptive responses using hot and cold plate assays.
Summary of Results
Short Oxy exposure was associated with a sex-specific increase in weight gain trajectory in adult male mice. Pups with long Oxy exposure demonstrated increased weight gain trajectory in adult males, sex-specific alterations in nociceptive processing, and preference towards morphine reward reinforcement behavior in females. There was no evidence of long-term social behavioral deficits, anxiety, hyperactivity, or memory deficits following short or long Oxy exposure.
Conclusions
Our findings suggest that offspring with prolonged opioid exposure experienced long-term sequelae affecting weight trajectory, sensory processing, and drug-reward responses compared to pups with opioid cessation at birth.These results raise concern regarding the safety of opioid administration as a mitigation strategy for clinical NAS symptomology.
#152 Inappropriate use of antinuclear antibody testing in the inpatient and outpatient settings at a community-based healthcare institution
MA McGill*
F Vastola
J Ambut
M Trotter
J Alvarez
M Pagacz
Mount Sinai Medical Center, Miami Beach, FL
Purpose of Study
The commercial availability of the antinuclear antibody (ANA) test has led to unnecessary ordering when there is a low pretest probability for a connective tissue disease (CTD). The purpose of the study aims to assess the inappropriate use of ANA testing in inpatient and outpatient settings at our institution.
Methods Used
In this retrospective study, we reviewed charts from 99 patients with ordered ANA in inpatient and outpatient settings at our institution. Variables included age, sex, ethnicity, specialty of the ordering physician, setting of the ordering physician, test indication, and ANA result. Inclusion criteria were patients ≥18 years old and had an ANA billing code in August 2019. Exclusion criteria included a previous ANA positivity, history of CTD, and rule-outs for non-CTD. The primary outcome was appropriateness for ordering ANA against clinical and laboratory parameters included in the 2000 College of American Pathologists (CAP) Guidelines for Clinical Use of the Antinuclear Antibody Test.
Summary of Results
For the total sample (n = 99), the mean age was 54 ±17.9 years old, with the majority consisting of females (n = 61). Hispanic ethnicity accounted for 47.47% (n = 47), 51.51% (n=51) were non-Hispanic, and 1.01% (n = 1) did not answer. 15.15% (n = 15) records were not accessible, 4.04% (n = 4) had a prior history of CTD, 3.03% (n = 3) had a previous ANA positivity, and 2.02% (n = 2) were rule outs for autoimmune hepatitis. In the remaining 75 patients, 57.33% (n = 43) of ANA tests were ordered in the outpatient setting, and 42.67% (n = 32) were ordered in the inpatient setting. ANA was positive (titer >1:80) in 8% (n = 6) where 2.67% accounted for inpatient setting and 5.33% accounted for the outpatient setting. Internal medicine ordered the majority of the ANA tests (53.33%) followed by hematology (24%). The most frequent indications included thrombocytopenia (13.33%), arthralgia (10.67%), leukopenia (6.67%), rash (4%), back pain (2.67%), and pancytopenia (1.33%). Remaining indications (61.33%) was combined into ‘another’ category. Only 8% (n = 6) of ANA testing ordered was considered appropriate based on the 2000 CAP Guidelines for Clinical Use of ANA Test parameters. Of the 8%, the inpatient setting accounted for 5.33% (n = 4), and the outpatient setting accounted for 2.6 (n = 2) (figure 1). No patients were diagnosed with a CTD.
Appropriate vs inappropriate ANA testing in the inpatient and outpatient setting
Conclusions
ANA testing in inpatient and outpatient settings appears to be overutilized by healthcare providers at our institution. None of the ordered ANAs resulted in a diagnosis of a CTD. ANA testing without high pretest probability is inappropriate and can result in false positives leading to patient and physician confusion. Physicians need more education on guidelines and physical features regarding CTDs.
#153 Diagnosing bone fractures using imaging and deep learning
JH Miao1*
KH Miao1,2
1Cornell University, New York, NY
2NYU School of Medicine, New York, NY
Purpose of Study
Millions of people are impacted by bone fractures every year. With earlier diagnosis, patients’ bone fractures can be better managed with improved outcomes. Thus, detecting bone fractures in patients early and accurately is important for improving quality of life. Deep learning and imaging, especially in underserved communities, can increase fracture diagnosis rate and accuracy by helping medical professionals.
Methods Used
In this research project, a deep learning model is created using artificial intelligence, imaging, and patient data to diagnose bone fractures and increase detection accuracy. Clinical data from over 2,100 patients was used to develop the model. To train, 60% of the clinical data was randomly utilized with the other 40% being utilized to test its diagnosis capabilities in bone fractures.
Summary of Results
In detecting bone fractures in patients, the deep learning model was able to accurately diagnose an overall 86% of bone fractures in patients compared to previously published works ranging from 58% – 82% in accuracy.
Conclusions
Thus, deep learning algorithms and imaging can be applied to aid healthcare professionals globally for detecting bone fractures in patients, such as in underserved communities, and improving patients’ quality of life.
#154 Deconstructing work engagement’s relationship to student and employee turnover
RN Steiner*
AF Snell
J Elicker
University of Akron, Akron, OH
Purpose of Study
Work engagement is measured by organizations to assess employee wellbeing, performance, and turnover. However, scholars have lamented the broad conceptualization of engagement and its overlap with other popular job attitudes, such as organizational commitment and job satisfaction. Thus there is a need to clarify the construct. This study sought to better understand how engagement’s theorized, but less explored, task versus social-based facets work to uniquely predict traditional outcomes of employee motivation and turnover moderated by trait-based differences in growth mindset. Cross-sectional survey data was collected from a sample of students at a university and a snowball sample of employees from LinkedIn.
Methods Used
265 students and 85 employees were administered a Likert-based survey. The survey was composed of measures assessing social and task-based work engagement, job embeddedness, affective organizational commitment, growth mindset, and turnover intentions. Students were primarily recruited from introduction to psychology classes; employees were recruited via LinkedIn. Multiple regression analyses were conducted using IBM SPSS Statistics, along with conditional mediation analyses using the Hayes (2017) PROCESS macro. Statistical significance for hypothesis testing was based on confidence intervals that did not include zero. All primary measures were reliable (α ≥ 0.80).
Summary of Results
Student task (CI95 [.346, 0.585]) and social-based engagement (CI95 [.288, 0.766]) demonstrate unique effects above and beyond each other predicting affective organizational commitment (ΔR 2 = 0.048). Employee task (CI95 [.515, 1.034]) and social-based engagement (CI95 [.192, 1.113]) also demonstrate unique effects above and beyond each other predicting affective organizational commitment. Student social-based engagement has a significant conditional indirect effect on turnover intentions through job embeddedness and affective commitment at various levels of fixed-growth mindset for talent based on the index of moderated mediation (CI95 [-0.1164, -0.0028]). Although they did not exhibit a conditional indirect effect, employees showed the same serial mediation of social-based engagement predicting turnover intentions through job embeddedness and affective organizational commitment (CI95 [-1.040,- 0.34]).
Hierarchical regression results for task engagement and social engagement predicting student affective organizational commitment.
Results of the indirect effect tests for social-based engagement predicting employee turnover intentions
Conclusions
Work engagement includes unique task and social facets that help to account for the likelihood of turnover among students and employees. Job embeddedness and affective organizational commitment are explanatory mechanisms for the relationship between social-based engagement and turnover intentions among students and employees. Students higher in their growth mindset towards their own and others’ talent are more likely to be socially engaged, committed, and satisfied, and less likely to turnover from their universities.
#155 Early screening for gestational diabetes – experience of a community health center
G Asefi1
I Pourshams1*
H Arreaza1
A Arreaza1
M Najafi2
C Stewart1
1Rio Bravo Family Medicine Residency Program, Bakersfield, CA
2Columbia University, New York, NY
Purpose of Study
Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Pregnancy complications include infant macrosomia and primary cesarean section, preeclampsia, as well as impaired glucose metabolism in the newborn and cardiovascular disease in both mother and infant. Therefore, increased feto-maternal morbidity calls for further research into how we can diagnose and treat GDM in a timely and appropriate manner. The United States Preventive Services Task Force (USPSTF) has concluded there is insufficient evidence to screen pregnant persons earlier than 24 weeks of gestational. Given the high-risk population we serve, we universally screen all pregnant women for gestational diabetes at the initial visit regardless of gestational age. Our study aim is to analyze the data of our institution to show possible benefit of early screening, detection, and management of hyperglycemia in pregnancy.
Methods Used
We performed a retrospective analysis of all pregnant patients seen at Clinica Sierra Vista in Kern and Fresno counties from April 1, 2019 through November 10, 2021. We compared the patients being screened before 24 weeks and patients screened between 24-28 weeks of gestation. Patients who were screened before 24 weeks were labeled abnormal if the plasma glucose was above 140 mg/dL one hour after taking 50 grams of oral glucose. Patients who underwent diagnostic test before 24 weeks were labeled as abnormal if their fasting was >95 mg/dL, 1 hour >180 mg/dL, 2 hours >155 mg/dL, 3 hours > 140 mg/dL. The percentage of abnormal results before 24 weeks was compared with the percentage of abnormal results after 24 weeks.
Summary of Results
A total of 1505 patients who fit the criteria and had sufficient data were included in the study. Out of our patients screened with non-fasting 1-hour 50-G GCT, fifty six percent (56%) had abnormally high glucose before 24 weeks of gestation, which suggests value in early screening to identify patients who may require dietary and activity modification to prevent subsequent complications associated with uncontrolled hyperglycemia. Additionally, forty three percent (43%) of our patients who underwent the fasting 100-G OGTT diagnostic test were positive before 24 weeks gestation, which again supports early detection of diabetes is possible and potentially benefit from early intervention to prevent potential complications.
Conclusions
Screening for hyperglycemia before 24 weeks shows a significant proportion of elevated glucose. Further research is needed to confirm our suggestion to screen patients for GDM earlier than 24 weeks of gestation, especially in high-risk groups. While our patient demographics may not fully represent the total population, our findings suggest that early detection of uncontrolled glucose may help identify at-risk patients and allow treatment.
#156 Radial styloid approach for unstable distal radius fracture open reduction and internal fixation
M Porter1*
MG Johnston1
M Rusev1
M Schmitz1,2
1Elson S. Floyd College of Medicine, Spokane, WA
2Alpine Orthopaedics and Spine P.C., Spokane, WA
Purpose of Study
Distal radius fractures are one of the most common fractures with a significant variability of severity, and as such, requires a comprehensive understanding of indications for surgical and nonsurgical approaches to manage the problem.
Methods Used
A case series of patients treated for distal radius fractures using the radial styloid approach.
Summary of Results
This case series identifies effectiveness of open reduction and internal fixation of distal radius fractures via a radial approach and the dorsal approach to allow bone augmentation of the distal radius with allograft bone while maintaining radial and volar inclination. The range of motion and recovery of strength are acceptable and there is a low incidence of a need for hardware removal. The approach has been demonstrated to avoid concerns for tendon rupture while avoiding manipulation of the median nerve and allowing a radial volar approach to the distal radius as necessary.
Conclusions
This series identifies that the radial styloid approach is a viable surgical intervention for the management of certain distal radius fractures while preserving the pronator quadratus, brachioradialis tendon, and other structures of the wrist.
#157 The consequences of special operations occupational stressors on androgen levels and fertility in military males: a review of the literature
MG Johnston1*
K Schuppe1
G Britt1
C Lyons2
1College of Medicine, Washington State University, Spokane, WA, United States
2Urology, Naval Medical Center San Diego, San Diego, CA, United States
Purpose of Study
The effects of prolonged stress and long-term physiologic strain on endocrine function in adult males has been studied extensively with particular focus on androgens due to their essential role in the proper homeostasis of the musculoskeletal system, sexual function and cognitive well-being. This topic has garnered a high level of attention within the US Military and specifically within its Special Operations Communities. Due to the demanding nature of special operations, there is strong evidence to suggest that androgen levels, specifically testosterone, are acutely reduced in response to elevated levels of cortisol during high stress training, prolonged operations, and modern combat deployments. It is hypothesized that long-term exposure to this type of high stress lifestyle can lead to chronic and potentially irretractable hypogonadism, yielding a variety of secondary health problems.
Methods Used
This review seeks to examine, compare, and contrast current literature pertaining to androgen deficiencies and hypogonadism within military personnel, with particular focus on special operations where there is a significantly high operational pace, deployment tempo, and high prevalence of other compounding stressors. Additionally, it seeks to investigate the potential for proactive treatment plans to address deficiencies before they lead to long-term negative health problems. In this review, we utilized Pubmed and Google Scholar searches of the following key terms: Testosterone, Androgen, Hypogonadism, Military, Special Operations, Special Forces.
Summary of Results
This review found 28 of 31 pertinent and relevant sources relating to androgen deficiencies and hypogonadism within military personnel. We isolated our search to articles published between 2000 and 2021 in order to best capture the operational tempo and demand throughout our most recent armed conflicts in Iraq and Afghanistan, attempting to focus on special operations individuals who were subject to a high number of combat focused deployments
Conclusions
Results showed numerous studies focused on the effects of hypogonadism in this population, often focusing on the short-term effect of training on testosterone level. Numerous studies show both increased cortisol and subsequent decreased testosterone. The summarized results indicate the serum values; however, most of these sources pertain to relatively short duration training, ranging from hours to weeks. The idea that short term exposure to high intensity training with an energy deficit leads to increased cortisol and decreased testosterone is an important concept that has a fair amount of published data; however, there is a lack of literature and/or data surrounding the idea that continuous exposure to this type of lifestyle and chronic stress leads to chronic hypogonadism and possibly infertility.
#158 Association between fruit and vegetable fiber consumption and panic disorder and anxiety in national health and nutrition examination surveys 1999–2004
J Choompoo*
AB Reiss
A Pinkhasov
L Kasselman
NYU Long Island School of Medicine, Mineola, NY
Purpose of Study
Diets rich in fruits and vegetables have naturally high fiber content. The fiber in these foods has been repeatedly associated with improved mental health outcomes. While the current research is robust in showing the inverse association between fiber intake and depression, the link between fiber intake and panic disorder and anxiety is less clear. We used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 cohorts to determine if there is a relationship between daily dietary intake of fruit/vegetable fiber and panic and anxiety disorder in US adults.
Methods Used
Using R version 4.0.4, NHANES consumption behavior data for fiber intake were merged with data on the presence of panic disorder or anxiety. Dietary intake data were obtained through 24-hour dietary recall interviews, and fiber intake was calculated using the US Department of Agriculture (USDA) food and nutrient databases, with the sources of dietary fiber identified by USDA food codes. Fiber consumption from fruits and vegetables was calculated as a percent of total fiber intake. Outcome variables were whether study participants met diagnostic criteria for panic disorder and/or anxiety, determined by modules from the automated version of the World Health Organization Composite International Diagnostic Interview, Version 2.1. Logistic regressions were used to quantify associations between fruit/vegetable fiber consumption for each of the outcomes. After removing missing data, the NHANES 1999-2004 dataset contained 2,158 participants. Statistical significance was set at p ≤ 0.05.
Summary of Results
Most participants did not meet minimum USDA daily fiber intake goals (31g/day for males; 25g/day for females), with mean fiber intake at 16.0 ± 10.6g/day. Fruit/vegetable fiber intake was not associated with a diagnosis of panic disorder (p=0.80; n=44) or anxiety (p=0.63; n=48).
Conclusions
This study did not identify an association between fruit/vegetable fiber consumption and meeting diagnostic criteria for panic disorder or anxiety. The discrepancy between earlier studies of depression and fiber consumption and the current study could be due to the strict diagnostic definitions present for mental health disorders in the NHANES 1999-2004 cohorts. Other years relied on different questionnaires to assess mental health. Participants were also deficient in total fiber consumption, potentially masking fiber’s previously shown role in mental health. Currently, statistical models are being built which incorporate demographic and other important covariates in the relationship between fruit/vegetable fiber and panic disorder and anxiety. There were very few participants diagnosed with panic and anxiety disorder, which limits interpretation and indicates a need for more data availability on panic and anxiety disorders.
Plenary session II
#159 Association of surfactant protein gene variants with respiratory syncytial virus (RSV) infection in children
LC Depicolzuane1,2*
C Gandhi1,2
C Roberts2
N Thomas1,2
KN Anderson-Fears2
D Liu2
R Wu2
J Floros1,2,3
1Penn State Health Children’s Hospital, Hershey, PA
2Pennsylvania State University College of Medicine, Hershey, PA
3Penn State Health Hershey Medical Center, Hershey, PA
Purpose of Study
Respiratory syncytial virus (RSV) is the leading cause of hospitalization in the first year of life in developed countries. The clinical presentation of RSV infection is heterogeneous and complex interactions between genetic and environmental factors may explain this phenomenon. Surfactant dysfunction and dysregulation of host defense and inflammatory processes are central to pathophysiologic mechanisms of various pulmonary diseases. We hypothesized that single nucleotide polymorphisms (SNPs) of surfactant protein (SP) genes are associated with RSV severity.
Methods Used
We prospectively enrolled 405 children with RSV and divided them into two groups, mild and severe RSV. DNA was extracted and genotyped for 16 specific SP gene SNPs and SP-A1 and A2 haplotypes were assigned. We used the multivariate logistic regression to study association of SP gene SNPs with disease severity. A likelihood ratio test was done to test goodness of fit between two models (one with clinical and demographic data only and another that included gene variants). We also used the Wang’s-SNP interaction approach to study the genetic effects of each SNP on RSV severity with Bonferroni correction. p ≤ 0.05 was considered statistically significant.
Summary of Results
Demographic data are summarized in table 1. The rs17886395_C allele of SFTPA2 is associated with decreased risk of severe RSV (p=0.002) as well as the rs2243639_A allele of SFTPD (p=0.045). An increased risk of severe RSV was found with the rs1059047_C allele of SFTPA1 (p=0.032).The 1A0 haplotype of SFTPA2 was associated with increased risk of severe RSV in its homozygous (OR (Odds Ratio)=5, p=0.009) and heterozygous form with 1A3 (OR =7.2, p=0.04). We also found associations of increased risk of severe RSV compared to mild RSV with pet exposure, co-infection, and younger age. The likelihood ratio test showed the model with the gene variants along with clinical and demographic data was a better fit (p=0.03 and Chi sq of 57). The Wang’s SNP-SNP interaction approach revealed, in the two-SNP model, two interactions to associate with increased risk of severe RSV and in the three-SNP model, a total of 29 interactions associated with RSV severity (table 2).
Demographics of the cohort stratified by mild and severe RSV disease
Association of SNP-SNP interactions with severe RSV in a two-SNP and three-SNP model
Conclusions
The model that included gene variants along with clinical and demographic data was better in predicting RSV severity and showed that 1A0, and SP-A1, SP-A2 and SP-D gene variants are associated with RSV severity. In SNP-SNP interactions, SNPs of SP genes, involved in innate immunity and host defense (SFTPA1, SFTPA2, and SFTPD), were overwhelmingly represented. We postulate that these genes play a role in RSV infection and for its prognostication and may serve as modifiers in RSV severity.
#160 Intravitreal bevacizumab for retinopathy of prematurity and exacerbation of pulmonary hypertension
L Park1*
L Donohue1
S Lakshminrusimha1
D Sankaran1,2
1University of California, Davis Medical Center, Sacramento, CA
2Adventist Health and Rideout Hospital, Marysville, CA
Purpose of Study
Background
Bevacizumab is a recombinant antibody against vascular endothelial growth factor (VEGF) that is increasingly used in the neonatal intensive care unit (NICU) to treat retinopathy of prematurity (ROP), instead of or prior to laser ablation. Animal studies suggest systemic absorption following intravitreal bevacizumab (Hard et al, Acta Paediatr 2011) and effects on the systemic vasculature including pulmonary hypertension (PH) (Le Cras et al, Am J Physiol Lung Cell Mol Physiol 2002).
Objectives
To compare the echocardiographic findings of PH, need for pulmonary vasodilator therapy, and respiratory support before and after bevacizumab and laser ablation, respectively, for severe ROP.
Methods Used
We performed a retrospective chart review of preterm infants admitted in the University of California, Davis NICU over a 10-year period from August 2011 to July 2021, who received either bevacizumab or laser therapy for severe ROP during their NICU course. We collected data including gestational age at birth, sex, stage of ROP before and after bevacizumab administration, presence of bronchopulmonary dysplasia (BPD), and respiratory support, echocardiographic findings of PH, and need for pulmonary vasodilator therapy before and after bevacizumab administration.
Summary of Results
13 infants who received bevacizumab and 18 infants who received laser ablation were analyzed. Mean (SD) gestational age at birth was 24.1 (1.4) weeks and 25.2 (1.8) weeks for infants treated with bevacizumab and laser ablation, respectively. At the time of treatment, mean (SD) corrected gestational age was 33.5 (2.6) weeks and 38.8 (3.3) weeks for infants treated with bevacizumab and laser ablation, respectively (p <0.05). Number of patients who had concurrent BPD were similar. Four out of 13 (31%) infants who received intravitreal bevacizumab had signs of worsening PH on echocardiogram after bevacizumab therapy (table 1), and all 4 (31%) infants required pulmonary vasodilator therapy. In contrast, 3 out of 18 (16.7%) infants had worsened PH on echocardiogram (p = 0.41) after laser ablation (table 2), and required pulmonary vasodilator therapy (p = 0.41). Interestingly, 3 out of 4 (75%) infants who received multiple doses of bevacizumab required pulmonary vasodilator therapy. Two infants had an increase in respiratory support after intravitreal bevacizumab and needed home oxygen therapy upon discharge, whereas none of the infants treated with laser had an increase in respiratory support after treatment.
Echocardiographic findings, respiratory support and pulmonary vasodilator therapy among infants treated with intravitreal bevacizumab
Echocardiographic findings, respiratory support and pulmonary vasodilator therapy among infants treated with laser ablation
Conclusions
Intravitreal bevacizumab administration for ROP may be associated with increased risk of PH and warrants larger preclinical and clinical studies with different doses. Periodic echocardiographic monitoring after intravitreal bevacizumab might be warranted to look for this complication.
#161 Decreased heart rate variability and elevated inflammatory cytokines in preterm neonates with late-onset infection
J Wardinger*
D Thompson
F Gardner
B Fronheiser
L Sanchez Pena
K Doheny
Division of Neonatal-Perinatal Medicine, Penn State College of Medicine, Hershey, PA, United States
Purpose of Study
Late-onset infection contributes to significant morbidity and mortality for preterm infants. Heart rate variability (HRV) which reflects counterbalancing of parasympathetic and sympathetic inputs shown in beat-to-beat interval variance has been demonstrated as a useful index for predicting neonatal morbidity. However, less is known on the predictive utility of HRV in inflammatory mediated pathways.
We aimed to test that diminished parasympathetic tone measured by the high frequency (HF) component of HRV (HF-HRV) and elevated levels of inflammatory cytokines would have utility in predicting neonatal late-onset infection.
Methods Used
In this multi-site prospective cohort/comparison study, we enrolled 250 preterm (26-34 weeks’ PMA) neonates. Post-prandial ECG was obtained in the afternoon on day 5-8 of life and weekly thereafter until 35weeks’ PMA and processed using frequency domain analysis. Blood cytokines were measured at 1 and 3 weeks of life and at the time of sepsis workup. The electronic medical record was used to calculate the score for neonatal acute physiology (SNAP), and to confirm evidence of late-onset infection defined as a neonatal infection that occurred after day 7 of life. Neonates with positive meconium toxicology for opioids (n=2) were excluded as they are known to have autonomic dysregulation. In addition, neonates with gastrointestinal pathology (n=32) were excluded from this analysis as those results have been reported previously.
Summary of Results
HF-HRV was decreased at weeks 1 and 2 of life in neonates who developed a late-onset infection (n=10) vs controls (n=206) at p=0.01 for both. There were no differences in mean cytokine levels between cases and controls. However, Low HF-HRV was associated with elevated TNF-α (p=0.03) and IL-8 (p=0.01) at week one of life. Logistic regression with SNAP and HF-HRV as predictors indicated that only HF-HRV at day 5-8 days of life was a significant predictor of late-onset infection with an odds ratio of 0.43; 95% CI: 0.21-0.88; p=0.02.
Conclusions
The association of low HF-HRV with elevated inflammatory cytokines in evolving infection provides evidence for the putative role of the vagal cholinergic pathway in sepsis pathogenesis. HRV is a useful modality for the identification of those neonates at risk for late-onset infection.
Funding
NIH-DK09935 and Penn State Department of Pediatrics.
#162 Endothelial expansion contributes to enhanced blood cell production from Tropomyosin 1 deficient induced pluripotent stem cells
MB Wilken1*
BF Voight2
ST Chou1
DL French1
CS Thom1
1Children’s Hospital of Philadelphia, Philadelphia, PA
2Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Purpose of Study
Donor-derived blood products do not currently meet the needs of all patients, including preterm infants who suffer increased morbidity and mortality from allogeneic platelet transfusions. In vitro-derived ‘embryonic’ or ‘fetal’ type blood cells from induced pluripotent stem cells (iPSCs) could address these issues, but current production strategies are inefficient.
We previously found that Tropomyosin 1 (TPM1) inhibits in vitro hematopoiesis (Thom et al, BMC Biol 2020). Genome-edited TPM1 knockout (TPM1KO) iPSCs produced 2-fold more hematopoietic progenitor cells (HPCs) than controls, thereby increasing functionally normal mature blood cell yields. Here, we aimed to i) define related mechanisms and ii) reveal pharmacologically manipulable targets to enhance blood cell production without need for genomic manipulation.
Methods Used
We used cell and molecular biology techniques to interrogate wild type and isogenic TPM1KO iPSCs during primitive (embryonic) hematopoietic differentiation. In this in vitro differentiation system, iPSCs sequentially adopt mesoderm, endothelial, and hematopoietic identities through epithelial-to-mesenchymal transitions (EMTs). Distinct surface markers allow identification and isolation of each cell type.
Summary of Results
We used cell counting and flow cytometry to determine if TPM1KO enhanced cell proliferation and/or survival at each developmental stage. TPM1KO cells were not hyperproliferative as iPSCs or at any differentiation stage. Instead, TPM1KO enhanced survival during mesoderm-to-endothelial and endothelial-to-hematopoietic transitions. This quantitatively increased total endothelial cell production, and ‘hemogenic’ endothelial cells within this expanded population were responsible for increased HPC yields.
To define molecular mechanisms by which TPM1 regulates EMTs during in vitro hematopoiesis, we analyzed RNA expression in sorted iPSCs, endothelial cells, and HPCs from TPM1KO and control cultures. TPM1KO altered expression of genes and pathways known to promote EMT, including cell adhesion, integrin, and integrin-signaling gene expression (p<0.05). For example, TPM1KO endothelial cells had increased N-cadherin and RAP1-activating gene expression, which promote EMT in other cellular and biological contexts.
Conclusions
TPM1KO cells undergo more efficient differentiation, increasing in vitro endothelial cell and ultimately blood cell production. Exploiting TPM1-mediated EMT regulation, through RAP1 or other pharmacologically modifiable pathways, represents a novel strategy to boost in vitro blood cell production toward clinically relevant scales.
#163 Evidence for the role of heme oxygenase-1 on cortical mononuclear cell gene expressions and T helper cell prominent neuroinflammation after intrauterine exposure to chorioamnionitis
M Ozen*
A Gall
S Robinson
LL Jantzie
Johns Hopkins University School of Medicine, Baltimore, MD
Purpose of Study
We previously showed that elevation in Heme-oxygenase-1 (HO-1) mRNA expression in utero and in the early perinatal period resulted in sustained increase in HO-1/Transferrin Receptor1 (TfR1), increased neuroinflammation (CD45+CD11b/c+ mononuclear cells (M)) at term equivalent age and increase in peripheral double negative T cells at P21. Dysregulation of HO-1 favors pro-inflammatory signals while TfR1 regulates anti-inflammatory signal transduction. Here, we hypothesized that altered HO-1/TfR1 timeline would correlate with inflammatory/immune signal changes in brain. Our objective was to define chorioamnionitis (CHORIO)-induced inflammatory signatures in brain mononuclear and T cell subsets, during a critical developmental window and its correlation with sustained increase in HO-1/TfR1 timeline.
Methods Used
Pregnant Sprague-Dawley rats were stratified to Sham or CHORIO groups and underwent laparotomy on embryonic day 18 (E18). CHORIO was induced by transient occlusion of the uterine arteries followed by intra-amniotic injection of lipopolysaccharide. Shams received laparotomy with equivalent duration of anesthesia. Brains from male and female pups were collected at E18.5, E19, P2 and P7 for TNFα, CD86 (M1, inflammatory) and Arg1 (M2, anti-inflammatory) mRNA expression. Brain T cell subsets were studied at P21 by flow cytometry. n=7 at E18.5-P2, n=3-6 at P7 and 21. Data are represented as mean±SEM. For statistical comparisons t-test, Mann-Whitney U, ANOVA were used with p<0.05 considered significant.
Summary of Results
Our results show that Arg1 is significantly decreased at E18.5, in CHORIO cortex compared to Sham (p=0.007) consistent with decreased M2 macrophages. At P2, there is a significant increase in CD86 in CHORIO compared to Sham (p=0.042) which suggests an increased M1. Importantly, CHORIO has a significant injury effect on cortical Arg1 expression. We did not see a significant timepoint effect on TNFα, CD86 and Arg1 expression between E18.5 and P7. At P21, CD3+CD4+ T helper (Th) cells are significantly increased in CHORIO brains compared to Sham (p=0.019) concomitant with an increase in peripheral double negative T cells.
Conclusions
An acute decrease in anti-inflammatory M2 mononuclear signature in cortex at E18.5 precedes the increased proinflammatory signature at P2. The timing of M2 and M1 changes correlate with our previously reported sustained HO-1/TfR1 dysregulation at E18.5-P2, leading to neuroinflammation. Prominence of Th cells at P21 may suggest evidence of emerging chronic neuroinflammation and neural injury. Further studies will define how these inflammatory/immune signatures contribute to white matter injury in CHORIO.
#164 Impact of maternal diabetes on early weight loss and other health outcomes in moderate preterm infants in the neonatal intensive care unit
CO Buck1*
V Shabanova1
RH Clark2
SN Taylor1
1Yale School of Medicine, New Haven, CT
2MEDNAX, Sunrise, FL
Purpose of Study
Diabetes in pregnancy is associated with adverse maternal and infant health outcomes, including preterm birth. Neonatal morbidities are higher in infants born moderately preterm compared with infants born at term. It is unknown how diabetes in pregnancy affects health outcomes in moderate preterm infants. The objective of this study was to examine the influence of diabetes in pregnancy on short term neonatal morbidities and early growth trajectories in moderate preterm infants.
Methods Used
This is a retrospective study from the MEDNAX Clinical Data Warehouse of moderate preterm infants (32 0/7 to 36 6/7 weeks gestational age [GA]) discharged from neonatal intensive care units (NICU) 2008-2019. Infants who died, had major congenital anomalies, or were discharged after 40 weeks post-menstrual age were excluded. Maternal and infant health characteristics and average percent weight loss were compared between maternal diabetes (DM) exposure groups. Change in growth parameters (weight, length, weight change per day) during the delivery hospitalization were compared between groups using linear mixed effects modeling.
Summary of Results
Of the 301,499 moderate preterm infants included in the analysis, 14% (N = 42,512) were born to mothers with DM in pregnancy (DM group). DM-group had higher incidence of hypoglycemia (33% vs 17%, p < 0.001), hyperbilirubinemia (68% vs 65%, p < 0.001), patent ductus arteriosus (5% vs 3%, p < 0.001), and need for some respiratory support (56% vs 54%, p = 0.02) than non-DM infants. DM-group had faster weight loss in the first postnatal week when stratified by GA at birth (table 1). The adjusted difference in weight (g/day) from days 0 to 3 was -7.2 (95% CI: -8.2, -6.2), -6.5 (95% CI: -7.4, -5.7), and -4.5 (95% CI: -5.1, -3.9) for infants born 36-, 35-, and 34-weeks GA, respectively. Patterns of weight change from birth weight also differed by GA and DM-group status, such that 36-week DM-group infants remained on average 2% (± 0.4) below birthweight on day 14, while 32-week DM-group infants were on average 2% (± 0.4) above birthweight on day 14 (figure 1). Differences in other growth parameters from birth to hospital discharge were statistically significant, but small in magnitude (table 1).
Regression estimates of infant growth changes by exposure to diabetes in pregnancy
Percent weight change from birth weight among moderate preterm infants by exposure to diabetes in pregnancy and birth gestational ageLegend: DM (diabetes group); non-DM (non-diabetes group)
Conclusions
In this large study of moderate preterm infants, diabetes in pregnancy was associated with common neonatal morbidities, including need for respiratory support in the first postnatal days. Weight loss patterns in the first postnatal weeks among infants with exposure to diabetes differed by gestational age at birth and could be related to feeding maturity and nutritional management. Future studies should focus on long term risk associated with these outcomes in this vulnerable group of preterm infants.
#165 A randomized control trial comparing the current recommendations of ventilation and chest compression vs. ventilation during neonatal resuscitation using an ovine model of bradycardia
M Bawa*
S Gugino
J Helman
N Bradley
A Mari
A Prasath
C Blanco
M Rawat
P Chandrasekharan
University at Buffalo, Buffalo, NY
Purpose of Study
Current guidelines recommend initiating chest compressions (CC) when heart rate (HR) is < 60bpm after 30s of effective ventilation. Neonates receiving CC are at high risk for mortality and poor neurodevelopmental outcome. While CC provides circulatory support, its efficacy in neonatal bradycardia secondary to its asynchronous nature to the existing cardiac rhythm remains unknown and could be deleterious. Addressing neonatal asphyxia with adequate ventilation (PPV) could reduce the need for CC and improve overall outcomes.
We wanted to evaluate the effect of current neonatal resuscitation program guidelines (CONTROL) i.e. PPV for 30s followed by CC, endotracheal epinephrine (ETTEPI), and intravenous epinephrine (IVEPI) vs (STUDY) continuing PPV with ETTEPI and IVEPI; initiate CC only if bradycardia continues to full arrest (HR 0) with resuscitation until return of spontaneous circulation (ROSC) or until 20 min. Our objectives were to evaluate the effect of these interventions between the groups on i) timing of ROSC ii) frequency of requiring CC iii) gas exchange and hemodynamics using a neonatal bradycardia ovine model.
Methods Used
Thirty near-term lambs (138-140d) were randomized to control or study groups after instrumentation (fig 1A). Data from 6 lambs in each group was included based on criteria (fig 1A).The timing and incidence of ROSC, need for CC, blood gas parameters, peak coronary (CoBF), peak left carotid (CaBF), peak left pulmonary blood flow (PBF) were recorded.
Summary of Results