Chaiworapongsa Tinnakorn, Romero Roberto, Kusanovic Juan P, Savasan Zeynep A, Kim Sun Kwon, Mazaki-Tovi Shali, Vaisbuch Edi, Ogge Giovanna, Madan Ichchha, Dong Zhong, Yeo Lami, Mittal Pooja, Hassan Sonia S
Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, MI 48201, USA.
J Matern Fetal Neonatal Med. 2010 Aug;23(8):794-805. doi: 10.3109/14767050903443467.
Angiogenesis is critical for successful pregnancy. An anti-angiogenic state has been implicated in preeclampsia, fetal growth restriction and fetal death. Increased maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, have been reported in women with preeclampsia and in those with fetal death. Recent observations indicate that an excess of sVEGFR-1 and soluble endoglin (sEng) is also present in the amniotic fluid of patients with preeclampsia. The aim of this study was to determine whether fetal death is associated with changes in amniotic fluid concentrations of sVEGFR-1 and sEng, two powerful anti-angiogenic factors. Study design. This cross-sectional study included patients with fetal death (n = 35) and controls (n = 129). Fetal death was subdivided according to clinical circumstances into: (1) unexplained (n = 25); (2) preeclampsia and/or placental abruption (n = 5); and (3) chromosomal/congenital anomalies (n = 5). The control group consisted of patients with preterm labor (PTL) who delivered at term (n = 92) and women at term not in labor (n = 37). AF concentrations of sVEGFR-1 and sEng were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had higher median amniotic fluid concentrations of sVEGFR-1 and sEng than women in the control group (p < 0.001 for each); (2) these results remained significant among different subgroups of stillbirth (p < 0.05 for each); and (3) amniotic fluid concentrations of sVEGFR-1 and those of sEng above the third quartile were associated with a significant risk of unexplained preterm fetal death (adjusted OR = 10.8; 95%CI 1.3-89.2 and adjusted OR 87; 95% CI 2.3-3323, respectively). Conclusion. Patients with an unexplained fetal death at diagnosis are characterized by an increase in the amniotic fluid concentrations of sVEGFR-1 and sEng. These observations indicate that an excess of anti-angiogenic factors in the amniotic cavity is associated with unexplained fetal death especially in preterm gestations.
血管生成对于成功妊娠至关重要。抗血管生成状态与子痫前期、胎儿生长受限及胎儿死亡有关。据报道，子痫前期患者及胎儿死亡患者的母体血浆中抗血管生成因子可溶性血管内皮生长因子受体（sVEGFR）-1的浓度升高。最近的观察表明，子痫前期患者的羊水中也存在过量的sVEGFR-1和可溶性内皮糖蛋白（sEng）。本研究的目的是确定胎儿死亡是否与羊水中两种强大的抗血管生成因子sVEGFR-1和sEng的浓度变化有关。研究设计。这项横断面研究纳入了胎儿死亡患者（n = 35）和对照组（n = 129）。胎儿死亡根据临床情况分为：（1）原因不明（n = 25）；（2）子痫前期和/或胎盘早剥（n = 5）；（3）染色体/先天性异常（n = 5）。对照组由足月分娩的早产（PTL）患者（n = 92）和足月未分娩的女性（n = 37）组成。通过酶联免疫吸附测定法（ELISA）测定羊水中sVEGFR-1和sEng的浓度。应用非参数统计和逻辑回归分析。结果。（1）胎儿死亡患者羊水中sVEGFR-1和sEng的中位数浓度高于对照组女性（每项p < 0.001）；（2）这些结果在死产的不同亚组中仍然显著（每项p < 0.05）；（3）羊水中sVEGFR-1和sEng浓度高于第三四分位数与原因不明的早产胎儿死亡风险显著相关（调整后的比值比分别为10.8；95%可信区间1.3 - 89.2和调整后的比值比87；95%可信区间2.3 - 3323）。结论。诊断为原因不明的胎儿死亡的患者，其特征是羊水中sVEGFR-1和sEng的浓度升高。这些观察结果表明，羊膜腔内抗血管生成因子过量与原因不明的胎儿死亡有关，尤其是在早产妊娠中。
