Epigenetic mediation may explain intergenerational associations between maternal lifestyle and children’s birth weight - Findings from the NorthPop prospective birth cohort
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Background
Epigenetic alterations during fetal development have been proposed as key factors explaining associations between maternal lifestyle during pregnancy and later health outcomes in the offspring, pertaining to the developmental origin of health and disease (DOHAD) hypothesis.
Objectives
To assess the association of maternal lifestyle with offsprings’ birth weight and underlying epigenetic mediatory mechanisms in the NorthPop prospective birth cohort.
Methods
A three-step analytic pipeline was applied. In 722 mother-child pairs, overall associations between 10 maternal lifestyle factors and the offspring’s standardized birth weight were first evaluated by multiple linear regression. Three high dimensional mediation methods (HDMA, HIMA, and HIMA2) were then applied on the beta methylation matrix to identify candidate CpG mediators in cord blood driving the significant overall associations. Finally, robust- and ordinary least squares-regression-based classical mediation, including single- and multiple-(parallel and serial) mediator models were assessed.
Results
Gestational weight gain (GWG) (β-adj = 0.03; p = 2×10 -5 ) and maternal BMI at the beginning of pregnancy (β-adj = 0.036; p = 1×10 -4 ) were significantly associated with the offspring’s standardized birth weight. High dimensional mediation analyses identified pooled sets of four (cg19242268; cg08461903; cg14798382; cg21516291) and five (cg17040807; cg19242268; cg26552621; cg04457572; cg06457011) candidate CpG mediators related to GWG and BMI at the beginning of pregnancy, respectively. For both exposures, classical mediation analyses revealed a range of significant single- and multiple (both serial and parallel) mediator models via both robust- and OLS-regression based approaches. These indicated the likely presence of individual-, causally linked multiple-, and causally independent multiple mediatory pathways underlying the two significant overall associations.
Conclusions
Our findings support the hypothesis that neonatal health effects related to maternal lifestyle may be partly mediated by epigenetic alterations. Findings also suggest the possible involvement of multiple DNA methylation sites via various mediatory pathways.
