4 years ago

Altered angiogenesis as a common mechanism underlying preterm birth, small-for-gestational age and stillbirth in women living with HIV

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. Objective To determine whether angiogenic factors are associated with adverse birth outcomes in HIV-infected pregnant women started on antiretroviral therapy. Study Design This is a secondary analysis of samples collected as part of a clinical trial randomizing pregnant women infected with HIV to lopinavir/ritonavir (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 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng)) by enzyme linked immunosorbent assay between: 16–20, >20–24, >24–28, >28–32, >32–36, and >36 –<37 weeks of gestation. The primary outcome was preterm birth. Results 1115 plasma samples from 326 pregnant women were evaluated. There were no differences in angiogenic factors according to antiretroviral therapy group (p>0.05 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— sEng and PlGF— were associated with adverse birth outcomes. Significantly higher concentrations of sEng throughout gestation were found in those women destined to deliver preterm (LR test, χ2(1)=12.28, p<0.0005) and in those destined to have stillbirths (χ2(1)=5.67, p<0.02). By contrast, significantly lower concentrations of PlGF throughout gestation were found in those destined to have small-for-gestational age births (χ2(1)=7.89, p<0.005) and in those destined to have stillbirths (χ2(1)=21.59, p<0.0001). Conclusions An anti-angiogenic state in the second or third trimester is associated with adverse birth outcomes, including stillbirth in women living with HIV and receiving antiretroviral therapy.

Publisher URL: www.sciencedirect.com/science

DOI: S0002937817311857

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