Accelerated Biological Aging As An Early Pregnancy Predictor Of Preeclampsia

Introduction: Inability to predict risk for preeclampsia represents a major limitation in prenatal care. Hypothesis: We expect that accelerated biological aging in early pregnancy is an important predictor of preeclampsia. Aim: The aim of this study was to determine the clinical relevance of maternal characteristics and a blood-based biomarker of accelerated biological aging in early pregnancy as a predictor of preeclampsia. Methods: In the discovery phase, we analyzed data from a prospective cohort of pregnant, nulliparous women (n=54). Maternal peripheral blood (MPB) was collected during the first trimester and DNA methylation was quantified using the Illumina Infinium 450K array. Six women developed preeclampsia during the assessed pregnancy and 48 women served as controls. In the validation phase, we analyzed publicly available data from the Prenatal Exposures & Preeclampsia Prevention Project (PEPP3) cohort study. MPB was collected during the first trimester with DNA methylation quantified using the Illumina Infinium 850K array among 28 cases and 28 controls matched for race, pre-pregnancy BMI, smoking history, and gestational age at sampling. For both phases, biological aging was estimated using established epigenetic clocks. Predictors of preeclampsia were identified using lasso regularization and random forest, with final models produced using logistic regression. Results: In the discovery cohort, accelerated biological aging, as well higher chronological age and greater gestational weight gain, were identified as important predictors of preeclampsia. Interestingly, only Hannum’s epigenetic clock (and not Horvath nor Levine’s epigenetic clocks) showed predictive power for preeclampsia. In the validation cohort, accelerated biological aging per Hannum’s epigenetic clock and chronological age also arose as important predictors of preeclampsia. Though weight gain data was not available for further analysis. Conclusions: Among women who developed preeclampsia, accelerated biological aging during early pregnancy may represent a risk biomarker that can be leveraged in clinical care. Findings represent the potential for a key clinical indicator for preeclampsia risk, addressing an important gap in screening and early diagnosis.