Fetal death: A condition with a dissociation in the concentrations of soluble vascular endothelial growth factor receptor-2 between the maternal and fetal compartments
Fetal death: A condition with a dissociation in the concentrations of soluble vascular endothelial growth factor receptor-2 between the maternal and fetal compartments
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DOI：
10.3109/14767050903410664
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发表时间：
2010-09-01
影响因子：
1.8
通讯作者：
Romero, Roberto
中科院分区：
文献类型：
--
作者：
Chaiworapongsa, Tinnakorn;Kusanovic, Juan Pedro;Romero, Roberto
目标。抗血管生成状态被认为与子痫前期、胎儿生长受限和胎儿死亡的病理生理学有关。血管内皮生长因子(VEGF)是胚胎和胎盘发育所必需的血管生成因子，通过其受体(VEGFR)-2发挥其血管生成作用。最近在母体血液中检测到这种蛋白质的一种可溶性形式(sVEGFR-2)。这项研究的目的是确定胎儿死亡是否与孕妇血浆和羊水中sVEGFR-2浓度的变化有关。研究设计。孕妇血浆取自死胎患者59例和正常孕妇134例。收集36例死胎患者的羊水，160例足月分娩的羊水作为对照组。死胎按临床情况分为：(1)原因不明；(2)先兆子痫和/或胎盘早剥；(3)染色体和/或先天异常。用双抗体夹心法测定血浆和羊水中sVEGFR-2的浓度。应用非参数统计和Logistic回归分析。(1)胎死组血浆sVEGFR-2浓度中位数显著低于正常妊娠组(p<；0.001)。不明原因死亡组和子痫前期/早剥组的血浆sVEGFR-2浓度中位数低于正常孕妇(p=0.006，p=0.001和p=0.2)，而先兆子痫/早剥组的血浆sVEGFR-2浓度不低于正常孕妇(p=0.20)；(3)胎死组各亚组羊水sVEGFR-2浓度中位数均高于对照组(P50.001)；(4)调整潜在混杂因素后，羊水sVEGFR-2浓度与早产不明原因死亡的相关性仍显著(OR：15.6；95%CI：羊水sVEGFR-2浓度每四分位数增加1.5~164.2)；(5)在胎死组中，母体血浆和羊水sVEGFR-2浓度之间无相关性(P=0.90)。胎儿死亡的孕妇，在诊断时，其特征是孕妇血浆中sVEGFR-2浓度降低，但羊水中该蛋白浓度升高。虽然孕妇外周血中sVEGFR-2浓度的降低取决于胎儿死亡的临床情况，但羊水中sVEGFR-2浓度的升高似乎是胎儿死亡的共同特征。本文中观察到的母体和胎儿体内sVEGFR-2浓度的扰动是否发生在胎儿死亡之前仍有待确定。
Objective. An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid.Study Design. Maternal plasma was obtained from patients with fetal death (n = 59) and normal pregnant women (n 134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term (n 160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Nonparametric statistics and logistic regression analysis were applied.Results. (1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women (p < 0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women (p = 0.006, p < 0.001 and p = 0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95% CI: 1.4-7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group (p50.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95% CI: 1.5-164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p = 0.9).Conclusion. Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus.