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Effects of Antenatal Betamethasone on Maternal and Fetoplacental Matrix Metalloproteinases 2 and 9 Activities in Human Singleton Pregnancies
  1. Zahra Gharraee,
  2. Kay D.A. Beharry,
  3. Arwin M. Valencia,
  4. Steve Cho,
  5. Leonel Guajardo,
  6. Michael P. Nageotte,
  7. Houchang D. Modanlou
  1. 1From the Department of Pediatrics (Z.G., K.D.A.B., H.D.M.), Division of Neonatal-Perinatal Medicine, University of California, Irvine, Orange, CA; Division of Neonatal-Perinatal Medicine (Z.G., A.M.V., S.C., L.G.), Miller Children's Hospital, Long Beach, CA; Division of Maternal-Fetal Medicine (M.P.N.), Women's Pavilion, Miller Children's Hospital, Long Beach, CA
  1. This work was made possible through a grant from the Long Beach Memorial Medical Center Foundation, Long Beach, CA.
  2. This article was presented in part at the 2005 Western Society for Pediatric Research Annual meeting in Carmel, CA, and at the 2005 American Pediatric Society-Society for Pediatric Research annual meeting in Washington, DC.
  3. Address correspondence to: Dr. Houchang D. Modanlou, Division of Neonatology, University of California, Irvine Medical Center, 101 The City Drive South, Route 81, Building 56, Suite 600, Orange, CA 92868; tel: 714-456-6933; fax: 714-456-7658; e-mail: modanlou{at}


Background A single course of antenatal betamethasone is administered to women at risk of preterm labor to advance fetal lung maturation. Matrix metalloproteinases (MMPs) are collagen-degrading enzymes that remodel extracellular matrix components during lung development. We tested the hypothesis that the effects of betamethasone on fetal lung maturation involve changes in MMP activity.

Methods We conducted a prospective, observational pilot study of three groups of singleton pregnancies. Group 1 (n = 21) was composed of women who were antenatally treated with a single course of betamethasone and who delivered < 37 weeks of gestation, group 2 (n = 7) was composed of matched untreated women who delivered < 37 weeks of gestation, and group 3 (n = 15) was composed of untreated women who delivered > 37 weeks of gestation. Maternal blood, mixed cord blood, and placental samples were collected at the time of delivery for MMP-2 and MMP-9 activity and tissue inhibitor of metalloproteinases (TIMP)-1 and -2 levels.

Results MMP-2 activity was significantly higher in the maternal, placental, and fetal compartments in group 1 compared with group 2 (p < .05). TIMP-2 levels were lower in groups 1 and 2 compared with group 3. Maternal TIMP-2 levels were higher (p < 0.003), whereas fetal TIMP-1 (p < .01) and MMP-9 to TIMP-1 ratios (p < .05) were lower when delivery was delayed more than 2 weeks following betamethasone treatment.

Conclusion We conclude that elevated MMP-2 activity in the maternal and fetoplacental compartments may suggest a mechanism, in part, for betamethasone-induced fetal lung maturation.

Key Words
  • betamethasone
  • matrix metalloproteinases
  • tissue inhibitor of metalloproteinases

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