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


METHODS
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).


CONCLUSIONS
(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.
Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, Michigan, USA.
Zeynep Alpay
ZA
Savasan
Roberto
R
Romero
Tinnakorn
T
Chaiworapongsa
Juan Pedro
JP
Kusanovic
Sun Kwon
SK
Kim
Shali
S
Mazaki-Tovi
Edi
E
Vaisbuch
Pooja
P
Mittal
Giovanna
G
Ogge
Ichchha
I
Madan
Zhong
Z
Dong
Lami
L
Yeo
Sonia S
SS
Hassan
D000293:Adolescent; D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism; D047929:Term Birth / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D055815:Young Adult
D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2