Placental hypoxia-regulating network in relation to birth weight and ponderal index: the ENVIRONAGE Birth Cohort Study

Background: HIF1 alpha, miR-210 and its downstream targets ISCU, COX-10, RAD52 and PTEN are all part of the placental hypoxia-responsive network. Tight regulation of this network is reguired to prevent development of maternal-fetal complications such as fetal growth restriction. HIF1 alpha expression is increased in preeclamptic placentae, but little is known about its association with birth weight in normal pregnancies. Methods: We measured placental levels of HIF1 alpha, miR-20a, miR-210, ISCU, COX-10, RAD52 and PTEN in 206 mother-newborn pairs of the ENVIRONAGE birth cohort. Results: Placental HIF1 alpha gene expression was inversely associated with the ponderal index (PI): for a doubling in placental HIF1 alpha expression, PI decreased by 6.7% (95% confidence interval [Cl] 1.3 to 12.0%, p = 0.01). Placental RAD52 expression also displayed an inverse association with PI, a doubling in gene expression was associated with a 6.2% (Cl 0.2 to 12.1% p = 0.04) decrease in PI. As for birth weight, we observed a significant association with placental miR-20a expression only in boys, where a doubling in miR-20a expression is associated with a 54.2 g (Cl 0.6 to 108 g, p = 0.05) increase in birth weight. Conclusions: The decrease in fetal growth associated with expression of hypoxia-network members HIF1 alpha, RAD52 and miR-20a indicates that this network is important in potential intrauterine insults.