The Epigenetic Link of Perinatal BMI to Maternal Phenotype and Fetal Heart Rate

Abstract

Obesity is a metabolic stressor associated with a suboptimal physiological milieu including an inflammatory state and a dysregulated stress axis. Perinatal maternal BMI impacts pregnancy and birth outcomes along with child metabolic and neurodevelopmental health that are believed to be mediated by epigenetic mechanisms. Our research examines the impacts of pre-pregnancy BMI in a cohort of healthy pregnancies (n=187); first, by characterizing maternal phenotype throughout pregnancy, including her stress physiology (diurnal salivary cortisol), inflammatory status (blood cytokine levels), perinatal depression (EPDS scores), and the underlying epigenetic signature (DNA methylation) in blood that could mediate these effects. Second, we examine the effects of pre-pregnancy BMI on fetal heart rate measurements as an early marker of programming effects of altered autonomic nervous system and the associated placental DNA methylation with a focus on sex-dimorphic effects. Finally, we explore the impact of increasing the allostatic load of high BMI with stress, which was phenotyped in women early in pregnancy driven by data with 27 variables assessing psychological and physical health, on differential placental DNA methylation. To date: regional analysis revealed about 4500 differentially methylated regions (DMR) overall in response to high BMI. Gene ontology enrichment analysis revealed that DM genes annotated to these DMRs were enriched for biological processes involving inflammation in males and RNA silencing in females. This work highlights that the metabolic stress associated with BMI could leave a molecular fingerprint that mediate other maternal physiological and psychological outcomes, which in turn program the fetal neurodevelopmental outcomes.