Espinoza Jimmy, Chaiworapongsa Tinnakorn, Romero Roberto, Kim Yeon Mee, Kim Gi Jin, Nien Jyh Kae, Kusanovic Juan Pedro, Erez Offer, Bujold Emmanuel, Gonçalves Luis F, Gomez Ricardo, Edwin Samuel
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, USA.
J Matern Fetal Neonatal Med. 2007 Jul;20(7):495-507. doi: 10.1080/14767050701413022.
Pregnancy creates a unique situation in which both vasculogenesis and extensive angiogenesis are required for successful fetal and placental development. Recently, the soluble form of vascular endothelial growth factor (VEGF) receptor-1 (sVEGFR-1), an antagonist to VEGF and placental growth factor (PlGF) (two important angiogenic factors), has been implicated in the pathophysiology of preeclampsia and small for gestational age (SGA) without preeclampsia. There is, however, a paucity of information concerning plasma sVEGFR-1 concentrations in other obstetrical disorders. The purpose of this study was to determine plasma sVEGFR-1 concentrations in normal pregnancy, term gestation in labor, and in patients with pregnancy complications including spontaneous preterm labor, preterm premature rupture of the membranes (PROM), fetal death, and acute pyelonephritis.
A cross-sectional study was conducted to determine the concentrations of sVEGFR-1 in plasma obtained from 499 women in the following groups: (1) non-pregnant women (n = 40); (2) pregnant women (n = 135); (3) normal pregnant women at term in labor (n = 60); (4) fetal death (n = 60); (5) spontaneous preterm labor with intact membranes (n = 102); (6) preterm PROM (n = 64); and (7) pregnancy with acute pyelonephritis (n = 38). Since plasma sVEGFR-1 concentration changes with gestational age, the difference between the actual and the expected plasma sVEGFR-1 concentration (derived from regression equation of normal pregnancy) for each patient (delta value) was calculated and used to examine the differences of plasma sVEGFR-1 concentrations among various groups. Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay. Regression analysis and non-parametric statistics were used for analysis.
(1) Normal pregnant women before term had a median plasma sVEGFR-1 concentration significantly higher than non-pregnant women (p < 0.001); (2) plasma sVEGFR-1 concentration increased with advancing gestational age in normal pregnancy (r = 0.5; p < 0.001); (3) there was no significant difference in the median delta plasma concentration of sVEGFR-1 between normal pregnant women at term with and without labor (p = 0.09); (4) patients with fetal death had a median delta plasma concentration of sVEGFR-1 significantly higher than normal pregnant women (p = 0.001). Among patients with fetal death, those with unexplained causes (p = 0.04) and those with preeclampsia (p < 0.001) had a significantly higher delta plasma sVEGFR-1 concentration than normal pregnant women; and (5) there was no significant difference in the median delta plasma sVEGFR-1 concentration between normal pregnancy and preterm labor with intact membranes, preterm PROM (regardless of the presence or absence of microbial invasion of the amniotic cavity), or acute pyelonephritis (all p > 0.05).
Plasma sVEGFR-1 concentration is increased in a subset of patients with fetal death, but does not change in term and preterm parturition, rupture of fetal membranes, or acute pyelonephritis.
妊娠创造了一种独特的情况，即成功的胎儿和胎盘发育需要血管生成和广泛的血管新生。最近，血管内皮生长因子（VEGF）受体-1（sVEGFR-1）的可溶性形式，一种VEGF和胎盘生长因子（PlGF）（两种重要的血管生成因子）的拮抗剂，已被认为与子痫前期和小于胎龄儿（SGA）但无子痫前期的病理生理学有关。然而，关于其他产科疾病中血浆sVEGFR-1浓度的信息却很少。本研究的目的是确定正常妊娠、足月分娩以及患有包括自发性早产、胎膜早破（PROM）、胎儿死亡和急性肾盂肾炎在内的妊娠并发症患者的血浆sVEGFR-1浓度。
进行了一项横断面研究，以确定从以下几组499名女性获得的血浆中sVEGFR-1的浓度：（1）非妊娠女性（n = 40）；（2）妊娠女性（n = 135）；（3）足月正常妊娠分娩女性（n = 60）；（4）胎儿死亡患者（n = 60）；（5）胎膜完整的自发性早产患者（n = 102）；（6）早产胎膜早破患者（n = 64）；以及（7）合并急性肾盂肾炎的妊娠患者（n = 38）。由于血浆sVEGFR-1浓度随孕周变化，计算了每位患者实际血浆sVEGFR-1浓度与预期血浆sVEGFR-1浓度（源自正常妊娠回归方程）之间的差异（差值），并用于检验各组间血浆sVEGFR-1浓度的差异。采用酶联免疫吸附测定法测定血浆sVEGFR-1浓度。采用回归分析和非参数统计进行分析。
（1）足月前正常妊娠女性的血浆sVEGFR-1浓度中位数显著高于非妊娠女性（p < 0.001）；（2）正常妊娠中血浆sVEGFR-1浓度随孕周增加而升高（r = 0.5；p < 0.001）；（3）足月正常妊娠分娩和未分娩女性的血浆sVEGFR-1浓度差值中位数无显著差异（p = 0.09）；（4）胎儿死亡患者的血浆sVEGFR-1浓度差值中位数显著高于正常妊娠女性（p = 0.001）。在胎儿死亡患者中，原因不明者（p = 0.04）和子痫前期患者（p < 0.001）的血浆sVEGFR-1浓度差值显著高于正常妊娠女性；并且（5）正常妊娠与胎膜完整的早产、早产胎膜早破（无论羊膜腔是否存在微生物入侵）或急性肾盂肾炎患者的血浆sVEGFR-1浓度差值中位数无显著差异（所有p > 0.05）。
胎儿死亡患者亚组中的血浆sVEGFR-1浓度升高，但足月和早产分娩、胎膜破裂或急性肾盂肾炎时其浓度无变化。
