Pre-pregnancy BMI Association with Maternal Phenotype and Offspring Neurobehavioral Outcomes

Allostatic load due to chronic exposure to physiological or psychological stressors lead to compromised capacity of the body to maintain homeostasis. Obesity as a metabolic stressor is associated with a suboptimal physiological milieu including an inflammatory state and a dysregulated stress axis. Perinatal maternal body mass index (BMI) impacts pregnancy, birth outcomes, and child metabolic and neurodevelopmental health. We examine the impacts of pre-pregnancy BMI on maternal phenotype characteristics throughout pregnancy and fetal heart rate measurements as an early marker of programming effects of altered autonomic nervous system and infant neurobehavioral outcomes with a focus on sex-dimorphic effects. Pregnant women (n=176) attended sessions at gestation weeks 12-22, 23-28, and 34-36, where blood was collected for cytokine analysis and DNA methylation, and Edinburgh post-partum depression scale was administered. On the latter two visits, heart rate assessment was carried out for mothers and fetuses. Maternal high BMI was associated with higher perinatal depression, increased inflammation, and reduced heart rate variability. DNA methylation of maternal blood indicated enrichment in immune related biological processes. Moreover, we observed a decrease in fetal heart rate variability in female fetuses of women of high BMI, indicating alteration in the neurobehavioral development of the fetus. In infancy, female infants of high BMI mothers had reduced behavioral regulation and orientation to stimulus. This work highlights that the metabolic stress associated with BMI could leave a molecular fingerprint that could explain other maternal physiological and psychological outcomes, which in turn program the fetal neurodevelopmental outcomes.