Effects of antenatal betamethasone on maternal and fetoplacental matrix metalloproteinases 2 and 9 activities in human singleton pregnancies.
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.


CONCLUSIONS
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.
Gharraee
Zahra
Z
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California, Irvine, Orange, CA 92868, USA.
Beharry
Kay D A
KD
Valencia
Arwin M
AM
Cho
Steve
S
Guajardo
Leonel
L
Nageotte
Michael P
MP
Modanlou
Houchang D
HD
D000328:Adult; D001623:Betamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology; D011247:Pregnancy / Q000378:metabolism*; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D019715:Tissue Inhibitor of Metalloproteinase-1; D001623:Betamethasone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9