Maternal diabetes and overweight as risk factors for congenital heart defects in offspring - A nationwide register study from Finland

Importance Congenital heart defects (CHDs) affect 1–2% of newborns and are associated with significant mortality and morbidity. Understanding risk factors underlying CHDs is essential for prevention. Objective To determine the association between maternal diabetes and overweight/obesity and CHDs among offspring. Design Nationwide population-based register study. Setting Finland Participants All children born between 2006–2016 (N=620 751), and their mothers. Exposures Maternal pre-pregnancy body mass index (BMI) categorized as underweight (<18.5 kg/m 2 ), normal (18.5–24.9 kg/m 2 ), overweight (25.0–29.9 kg/m 2 ), and obese (≥30 kg/m 2 ). Maternal diabetes classified as no diabetes, type 1 (T1DM), type 2/other (T2DM), and gestational diabetes (GDM). Main Outcomes and Measures Odds ratio (OR) of isolated CHD in the child. In addition, nine anatomical CHD subgroups were studied. Results Of the 620 751 children born in Finland during the study period, 10 254 (1.65%) had an isolated CHD. T1DM was associated with an increased risk of having a child with any CHD (OR 3.71 (95% CI 3.16–4.35)), whereas maternal overweight (OR 0.98 (95% CI 0.98–1.04)) and obesity (OR 1.00 (95% CI 0.93–1.07)) were not. When analyzing anatomical subgroups, T1DM was associated with an increased risk in six subgroups. Maternal overweight was associated with complex defects (OR 2.24 (95% CI 1.01–4.94)), left ventricular outflow tract obstruction (OR 1.26, (95% CI 1.07–1.49), maternal obesity with complex defects (OR 3.22 (95% CI 1.31–7.92)), and right ventricular outflow tract obstruction (OR 1.26, (95% CI 1.01–1.55)). At the population level, maternal diabetes was responsible for 3.0% and maternal overweight and obesity for 0.7% of offspring’s CHD. Conclusions and Relevance This study indicated a less profound association between maternal overweight and obesity and CHD in the offspring than previously reported. The different risk profiles of T1DM and overweight/obesity may suggest distinct underlying teratogenic mechanisms.