Placental epigenetic age and adolescent blood pressure: the Extremely Low Gestational Age Newborn cohort.

Abstract

We examined the association between placental epigenetic gestational age (eGA) acceleration and adolescent systolic blood pressure (SBP) in a cohort born extremely preterm. Study participants were a subset of the Extremely Low Gestational Age Newborn cohort (born <28 weeks' gestation) who had placental DNA methylation quantified and had SBP measured during adolescent follow-up. eGA acceleration was calculated as the residual from the regression of predicted placental eGA (using the Robust Placental Clock) onto chronological gestational age. Unadjusted and adjusted mixed effects models were used to test the association between eGA acceleration and adolescent SBP. We also tested the interaction of eGA acceleration and sex on SBP. In the overall sample (N = 193), we found no association between placental eGA acceleration and adolescent SBP. When interaction between eGA acceleration and sex was tested, males had a 3.6 mmHg increase in SBP (95% CI 0.9, 6.4; p = 0.01) for every 1-week acceleration in eGA after adjusting for confounders. Placental eGA acceleration is associated with SBP increase in adolescent males but not females born extremely preterm, supporting the hypothesis that placental eGA could be evaluated as a risk biomarker for childhood cardiovascular outcomes. This study examines the association between placental epigenetic gestational age (eGA) and adolescent blood pressure. For every 1-week acceleration in placental eGA, adolescent males born extremely preterm had a 3.6 mmHg increase in systolic blood pressure (95% CI 0.9, 6.4; p = 0.01) after adjusting for confounders. The same association was not seen in females or the overall cohort. Our sex-specific finding supports the hypothesis that differences in placental eGA are associated with childhood health. Placental eGA estimation as a tool for identifying children who are at risk for developing elevated blood pressure should be further evaluated in other cohorts.