Epigenome-wide association study of maternal hemoglobin A1c in pregnancy and cord blood DNA methylation

Background: Gestational hyperglycemia is associated with adverse perinatal outcomes and long-term offspring metabolic programming, likely through dysregulation of DNA methylation (DNAm). Materials & methods: We tested associations between maternal HbA1c and cord blood DNAm among 412 mother-child pairs in the genetics of glucose regulation in gestation and growth (Gen3G) and implemented Mendelian randomization to infer causality. We sought replication in an independent sample from Healthy Start. Results: Higher second trimester HbA1c levels were associated with lower DNAm at cg21645848 (p = 3.9 x 10(-11)) near URGCP. Mendelian randomization and replication analyses showed same direction of effect between HbA1c and DNAm at cg21645848, but did not reach statistical significance. Conclusion: We found that higher maternal glycemia reflected by HbA1c is associated with cord blood DNAm at URGCP, a gene related with inflammatory pathways. Lay abstract An adverse metabolic environment in utero, such as elevated maternal blood glucose levels, may have long-lasting impacts on child development. Studies show that maternal glucose can cross the placenta and may impact regulatory markers acting upon genes through epigenetics. We investigated associations between 3 month maternal glucose levels, reflected by HbA1c, during pregnancy and cord blood DNA methylation (one type of epigenetic marker) in two prospective cohorts of mother-child pairs. We found that higher maternal blood glucose levels were associated with lower cord blood DNA methylation near a gene called URGCP, suggesting potential influence of elevated maternal glucose on inflammatory pathways in the newborn.

Automated summary

The study found an association between maternal hyperglycemia and cord blood DNA methylation levels, potentially influencing inflammatory pathways in newborns.