Maternal Diabetes and Risk of Offspring Congenital Heart Diseases: the Japan Environment and Children's Study

Background: Few prospective cohort studies have examined the association between maternal diabetes, including pre-pregnancy and gestational diabetes, and the risk of congenital heart disease (CHD) in Asian offspring.

Methods: We examined the association between maternal diabetes and offspring CHD among 97,094 mother-singleton infant pairs in the Japan Environment and Children's Study (JECS) between January 2011 and March 2014. Odds ratios (OR) and 95% confidence intervals (CI) of offspring CHD based on maternal diabetes (pre-pregnancy diabetes and gestational diabetes) were estimated using logistic regression after adjusting for maternal age at delivery, pre-pregnancy body mass index (BMI), maternal smoking habits, alcohol consumption, annual household income, and maternal education. The diagnosis of CHD in the offspring was ascertained from the transcript of medical records.

Results: The incidence of CHD in the offspring was 1,132. Maternal diabetes, including both pre-pregnancy diabetes and gestational diabetes, was associated with a higher risk of offspring CHD: multivariable OR (95%CI) = 1.81 (1.40-2.33) for maternal diabetes, 2.39 (1.05-5.42) for pre-pregnancy diabetes and 1.77 (1.36-2.30) for gestational diabetes. A higher risk of offspring CHD was observed in pre-pregnancy BMI ≥25.0 kg/m (OR = 2.55, 95% CI: 1.74-3.75) than in pre-pregnancy BMI <25.0 kg/m (OR = 1.49, 95% CI: 1.05-2.10, p for interaction = 0.04).

Conclusions: Maternal diabetes, including both pre-pregnancy and gestational, was associated with an increased risk of CHD in offspring.