Maternal Obesity and the Risk of Congenital Heart Defects: the Mediation Effect of Pregestational Diabetes

Abstract Background Congenital heart defects (CHDs) are the most common birth defects worldwide. Maternal obesity has been proposed as a risk factor for CHDs, but the results are controversial and inconclusive. Pregestational diabetes (PGDM) is well known as a risk factor for CHDs and is closely related to obesity. However, the effect of PGDM on the association between maternal obesity and CHDs has not been investigated.Objectives We aimed to explore the association between maternal obesity and CHDs and to further evaluate the mediation effect of PGDM on this association.Methods We involved 53708 mother-infant pairs with deliveries between 2017 and 2019 from the Birth Cohort in Shenzhen (BiCoS). Mothers were categorized into four groups: the underweight group (BMI < 18.5), normal weight group (18.5 ≤ BMI < 24), overweight group (24 ≤ BMI < 28) and obesity group (BMI ≥ 28). To evaluate the association between BMI and CHDs, we fit multivariable logistic regression models, adjusting for maternal age, maternal education level, mode of conception, parity, GDM and offspring sex. Mediation analysis was used to confirm the mediation effect of PGDM on the association between maternal obesity and CHDs.Results The proportion of obese individuals in the BiCoS was 2.11%. Overall, 372 (0.69%) infants were diagnosed with CHDs. The prevalence of CHDs in underweight, normal weight, overweight and obese individuals was 0.64%, 0.68%, 0.72% and 1.24%, respectively. Maternal obesity was associated with an increased risk of CHDs (OR=1.97, 95% CI 1.14–3.41). The offspring of women with PGDM were 6.88 times (95% CI 4.11–11.53) more likely to have CHDs than the offspring of mothers without PGDM. The mediation effect of PGDM on the association between maternal obesity and CHDs was significant (OR=1.18, 95% CI 1.06–1.32). The estimated mediation proportion was 24.83%.Conclusion Our findings suggested that maternal obesity was associated with CHDs and that PGDM partially mediated the association between maternal obesity and CHDs.