Longitudinal maternal glycemia during pregnancy and placental epigenetic age acceleration

Abstract

Background: Dysregulation of maternal glucose homeostasis has been related to an increased risk of morbidity and mortality in mothers and fetuses, yet the mechanism remains unclear. This study investigated the association between maternal glycemic levels and placental epigenetic age acceleration (PAA) in a multiethnic cohort. Methods: In a sample of 301 pregnant women (102 Hispanic, 77 White, 72 Black, and 50 Asian/Pacific Islander), the association of glycemic markers cumulative exposure with PAA was tested using linear regression adjusting for fetal sex, maternal age, educational status, and health insurance status. Models were applied in the full cohort and stratified by race/ethnicity. Further, sensitivity analyses were performed after excluding women with GDM or preeclampsia. Results: Among Black women, high glucose, HbA1c, and insulin cumulative exposure levels were associated with lower PAA compared to low cumulative exposure levels (β = − 0.75 weeks, 95% CI = − 1.41 to − 0.08); β = − 0.86, 95% CI = − 1.51 to − 0.21; and β = − 0.76, 95% CI = − 1.49 to − 0.03, respectively). Among Asian/Pacific Islander women, medium insulin cumulative exposure level was associated with lower PAA (β = − 0.94 weeks, 95% CI = − 1.74 to − 0.14). No significant association was observed among White and Hispanic women as well as in the full cohort. Conclusions: Elevated glucose, HbA1c, and insulin cumulative levels throughout pregnancy were associated with lower PAA in Black and Asian/Pacific Islander women. Placental epigenetic aging may be altered by maternal elevated glycemia and may in part underlie early programming of health outcomes in pregnancy and childhood health outcomes.