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

Zeynep Alpay Savasan, Roberto Romero, Tinnakorn Chaiworapongsa, Juan Pedro Kusanovic, Sun Kwon Kim, Shali Mazaki-Tovi, Edi Vaisbuch, Pooja Mittal, Giovanna Ogge, Ichchha Madan, Zhong Dong, Lami Yeo, Sonia S. Hassan

Research output: Contribution to journalArticlepeer-review

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 (n48); 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.

Original languageEnglish
Pages (from-to)828-841
Number of pages14
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume23
Issue number8
DOIs
StatePublished - Aug 2010
Externally publishedYes

Keywords

  • MIAC
  • SKDR
  • SVEGFR-1
  • SVEGFR-2
  • amniotic fluid
  • angiogenesis
  • chorioamnionitis
  • intraamniotic infection
  • intraamniotic inflammation
  • microbial invasion of the amniotic cavity
  • parturition
  • prematurity
  • preterm PROM
  • preterm labor
  • sflt-1
  • term labor

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