Evidence in support of a role for anti-angiogenic factors in preterm prelabor rupture of membranes

J Matern Fetal Neonatal Med. 2010 Aug;23(8):828-41. doi: 10.3109/14767050903440471.

Abstract

Objective: Vaginal bleeding, placental abruption, and defective placentation are frequently observed in patients with preterm prelabor rupture of membranes (PROM). Recently, a role of vascular endothelial growth factor (VEGF) and its receptor, VEGF receptor (VEGFR)- 1 has been implicated in the mechanisms of membrane rupture. The purpose of this study was to determine whether the soluble form of VEGFR-1 and -2 concentrations in amniotic fluid (AF) change with preterm PROM, intra-amniotic infection/inflammation (IAI), or parturition.

Study design: This cross-sectional study included 544 patients in the following groups: (1) midtrimester (MT) (n = 48); (2) preterm labor (PTL) leading to term delivery (n = 143); (3) PTL resulting in preterm delivery with (n = 72) and without IAI (n = 100); (4) preterm PROM with (n = 46) and without IAI (n = 42); (5) term in labor (n = 48); and (6) term not in labor (n = 45). The concentrations of sVEGFR-1 and sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied.

Results: (1) Preterm PROM (with and without IAI) had a lower median AF concentration of sVEGFR-1 than patients with PTL who delivered at term (p < 0.001 for each comparison); (2) A decrease in AFsVEGFR-1 concentrations per each quartile was associated with PROM after adjusting for confounders (OR 1.8; 95%CI 1.4-2.3); (3) IAI, regardless of the membrane status, was not associated with a change in the median AF concentrations of sVEGFR-1 and sVEGFR-2 (p > 0.05 for each comparison); and (4) Spontaneous term and PTL did not change the median sVEGFR-1 and sVEGFR-2 concentrations (p > 0.05 for each comparison).

Conclusion: (1) This is the first evidence that preterm PROM is associated with a lower AF concentration of sVEGFR-1 than patients with PTL intact membranes. These findings cannot be attributed to gestational age, labor, or IAI; and (2) AF concentrations of sVEGFR-2 did not change with preterm PROM, IAI, or labor at term and preterm.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Amniotic Fluid / metabolism*
  • Cross-Sectional Studies
  • Female
  • Fetal Membranes, Premature Rupture / metabolism*
  • Gestational Age
  • Humans
  • Pregnancy
  • Premature Birth / metabolism
  • Term Birth / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • Young Adult

Substances

  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2