Altered angiogenesis as a common mechanism underlying preterm birth, small for gestational age, and stillbirth in women living with HIV.
Altered angiogenesis as a common mechanism underlying preterm birth, small for gestational age, and stillbirth in women living with HIV.
复制标题
DOI：
10.1016/j.ajog.2017.10.003
复制
发表时间：
2017-12
影响因子：
9.8
通讯作者：
Kain KC
中科院分区：
文献类型：
--
作者：
Conroy AL;McDonald CR;Gamble JL;Olwoch P;Natureeba P;Cohan D;Kamya MR;Havlir DV;Dorsey G;Kain KC
胎盘中的血管生成过程是胎儿生长的关键调节因子，并影响出生结果，但在艾滋病毒感染妇女或低资源环境中的妇女中记录这些过程的数据有限。我们试图确定血管生成因子是否与开始抗逆转录病毒治疗的HIV感染孕妇的不良出生结局相关。这是对在乌干达托罗罗（Tororo）进行的一项临床试验中收集的样本进行的二次分析，该临床试验将感染艾滋病毒的孕妇和青少年随机分为基于洛匹那韦/利托那韦（n = 166）或基于依法韦仑（n = 160）的抗逆转录病毒治疗组。感染艾滋病毒的孕妇在妊娠12-28周之间登记。通过酶联免疫吸附测定法评价妊娠16-<20、20-<24、24-<28、28-<32、32-<36、36-<37周之间血浆样品的血管生成生物标志物（血管生成素-1、血管生成素-2、血管内皮生长因子、可溶性fms样酪氨酸激酶-1、胎盘生长因子和可溶性内皮糖蛋白）。主要结局为早产。总共评价了来自326名孕妇和青少年的1115份血浆样本。抗逆转录病毒治疗组的血管生成因子无差异（P > 0.05）。自然早产的不良出生结局发生率为16.9%，小于胎龄儿为25.6%，死产为2.8%。我们使用线性混合效应模型来评估出生结局组之间血管生成因子浓度的纵向变化，调整静脉穿刺时的胎龄、母亲年龄、体重指数、妊娠以及治疗组与胎龄之间的相互作用。两种血管生成因子可溶性内皮素和胎盘生长因子与不良的出生结局有关。在整个妊娠期间，在注定早产的研究参与者[似然比检验，χ2（1）= 12.28，P <0.0005]和那些注定死产的研究参与者[χ2（1）= 5.67，P <0.02]中发现可溶性内皮素浓度显著较高。相比之下，小于胎龄儿和死产儿在整个妊娠期胎盘生长因子浓度显著降低[χ2（1）= 7.89，P <0.005]和[χ2（1）= 21.59，P <0.0001]。妊娠中期或妊娠晚期的抗血管生成状态与不良的分娩结果有关，包括感染艾滋病毒并接受抗逆转录病毒治疗的妇女和青少年的死产。
Angiogenic processes in the placenta are critical regulators of fetal growth and impact birth outcomes, but there are limited data documenting these processes in HIV-infected women or women from low-resource settings. We sought to determine whether angiogenic factors are associated with adverse birth outcomes in HIV-infected pregnant women started on antiretroviral therapy. This is a secondary analysis of samples collected as part of a clinical trial randomizing pregnant women and adolescents infected with HIV to lopinavir/ritonavir-based (n = 166) or efavirenz-based (n = 160) antiretroviral therapy in Tororo, Uganda. Pregnant women living with HIV were enrolled between 12-28 weeks of gestation. Plasma samples were evaluated for angiogenic biomarkers (angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin) by enzyme-linked immunosorbent assay between: 16-<20, 20-<24, 24-<28, 28-<32, 32-<36, 36-<37 weeks of gestation. The primary outcome was preterm birth. In all, 1115 plasma samples from 326 pregnant women and adolescents were evaluated. There were no differences in angiogenic factors according to antiretroviral therapy group (P > .05 for all). The incidence of adverse birth outcomes was 16.9% for spontaneous preterm births, 25.6% for small-for-gestational-age births, and 2.8% for stillbirth. We used linear mixed effect modelling to evaluate longitudinal changes in angiogenic factor concentrations between birth outcome groups adjusting for gestational age at venipuncture, maternal age, body mass index, gravidity, and the interaction between treatment arm and gestational age. Two angiogenic factors–soluble endoglin and placental growth factor–were associated with adverse birth outcomes. Significantly higher concentrations of soluble endoglin throughout gestation were found in study participants destined to deliver preterm [likelihood ratio test, χ2(1) = 12.28, P < .0005] and in those destined to have stillbirths [χ2(1) = 5.67, P < .02]. By contrast, significantly lower concentrations of placental growth factor throughout gestation were found in those destined to have small-for-gestational-age births [χ2(1) = 7.89, P < .005] and in those destined to have stillbirths [χ2(1) = 21.59, P < .0001]. An antiangiogenic state in the second or third trimester is associated with adverse birth outcomes, including stillbirth in women and adolescents living with HIV and receiving antiretroviral therapy.
登录
查看更多内容
影响因子：
9.8
作者：
Darling, Anne Marie;McDonald, Chloe R.;Conroy, Andrea L.;Hayford, Kyla T.;Liles, W. Conrad;Wang, Molin;Aboud, Said;Urassa, Willy S.;Kain, Kevin C.;Fawzi, Wafaie W.
通讯作者：
Fawzi, Wafaie W.
DOI：
10.1016/s0002-9378(98)70210-8
发表时间：
1998-10-01
影响因子：
9.8
作者：
Joffe, GM;Esterlitz, JR;Catalano, PM
通讯作者：
Catalano, PM
影响因子：
9.8
作者：
Easter, Sarah Rae;Cantonwine, David E.;McElrath, Thomas F.
通讯作者：
McElrath, Thomas F.
影响因子：
9.8
作者：
Baltajian, Kedak;Bajracharya, Surichhya;Rana, Sarosh
通讯作者：
Rana, Sarosh
影响因子：
2.3
作者：
Gavard, Jeffrey A.
通讯作者：
Gavard, Jeffrey A.