Maternal T1D Associated With Risk of Congenital Heart Defects in Offspring

A nationwide study conducted in Finland found that maternal type 1 diabetes (T1D) was associated with a significantly higher risk of any congenital heart defect (CHD) in offspring, and that maternal overweight or obesity was associated with certain CHDs in offspring. The findings were published in JAMA Network Open.

While diabetes and overweight or obesity during pregnancy are known to increase the risk of CHDs in offspring, study authors explained that no large studies have assessed these outcomes in a single model. In a nationwide, population-based register study of all infants born in Finland between January 2006 and November 2023, the investigators analyzed the association of maternal diabetes and overweight or obesity with CHD incidence in offspring.

“While there clearly is a hereditary component associated with CHD, potentially modifiable maternal factors, such as maternal overweight, obesity, and pregestational and gestational diabetes (PGD and GD) have been associated with increased risk for CHD in offspring,” the authors wrote. “The role of maternal T1D as a significant risk factor has been well documented, but the significance of GD and maternal obesity and overweight is less clear, especially for specific CHD subgroups.”

A total of 620,751 children born to 573,259 mothers aged 20 to 40 years in Finland were included in the analysis, and 10,254 of those children (1.7%) had an isolated CHD.

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The main outcomes of interest were the ORs of CHDs in offspring, with 9 anatomical subgroups of CHD also assessed. Maternal diabetes status was stratified by no diabetes, T1D, type 2 (T2D) or other diabetes, and GD.

Throughout the study period, the prevalence of GD increased from 10.3% in 2006 to 19.2% in 2016. Maternal overweight and obesity rates increased from 20.3% and 10.7%, respectively, in 2006 to 22.2% and 13.3%, respectively, in 2016. Among mothers of children with CHD, GD was more common in those with overweight and obesity (21.1% and 41.1%, respectively) compared with mothers with body mass index (BMI) falling within what is considered normal range (8.2%).

Maternal T1D was associated with significantly greater odds of CHDs in offspring (OR, 4.03; 95% CI, 3.51-4.61). T2D and GD were also associated with increased odds of isolated CHDs in offspring vs no maternal diabetes to a lesser degree (T2D: OR, 1.87; 95% CI, 1.32-2.64; GD: OR, 1.08; 95% CI, 1.02-1.14). T1D was also associated with increased risk in 6 of 9 CHD subgroups, ranging from an OR of 3.28 (95% CI, 1.55-6.95) for other septal defects to an OR of 7.39 (95% CI, 3.00-18.21) for transposition of great arteries.

Further, there were no associations between maternal overweight or obesity with isolated CHDs in offspring when compared with infants born to mothers with normal BMIs. However, there were associations between maternal overweight or obesity and certain CHDs. Maternal overweight was associated with left ventricular outflow tract obstruction (LVOTO) (OR, 1.28; 95% CI, 1.10-1.49) as well as ventricular septal defects (OR, 0.92; 95% CI, 0.86-0.98). Maternal obesity was associated with complex defects (OR, 2.70; 95% CI, 1.14-6.43) and right ventricular outflow tract obstruction (RVOTO) (OR, 1.31; 95% CI, 1.09-1.58).

Study limitations included a relatively low number of offspring in the CHD subgroups and unreliable data on pregnancy terminations and miscarriages, which the authors noted are important because congenital abnormalities are known to be common in miscarriages. Additional studies including pregnancy terminations and stillbirths before 22 gestational weeks would provide important insight, they noted.

Still, the findings stress the impact of maternal T1D as a risk factor associated with CHDs in offspring, and overweight or obesity as lesser risk factors for some CHDs. Notably, the study was conducted in a high-resource setting with universal antenatal care.

“It has been shown that standard treatment of maternal diabetes is associated with reduced risk of anatomical malformations in offspring. Thus, primary prevention of maternal overweight and obesity and careful treatment of PGD may hold the opportunity to reduce the burden of disease,” the authors concluded. “Finally, a better understanding of the underlying mechanisms of maternal overweight and obesity in increased offspring risk for LVOTO, RVOTO, and complex defects may further improve the prevention of these CHD subtypes.”

Reference

Turunen R, Pulakka A, Metsälä J, et al. Maternal diabetes and overweight and congenital heart defects in offspring. JAMA Netw Open. Published online January 5, 2024. doi:10.1001/jamanetworkopen.2023.50579