Maternal Diabetes Associated With Early-Onset Cardiovascular Disease in Offspring

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Children of women with diabetes diagnosed before or during pregnancy are at increased risk for early-onset cardiovascular disease.

Children of women with diabetes diagnosed before or during pregnancy are at increased risk for early-onset cardiovascular disease (CVD), according to study results published in The BMJ.

Previous studies have reported that maternal diabetes before or during pregnancy is associated with increased risk for metabolic syndrome and congenital heart disease in offspring. The goal of the current study was to explore the association between prenatal exposure to maternal diabetes with early-onset CVD.

The researchers collected data from more than 2.4 million children in Danish national health registries who were born without congenital heart disease between 1977 and 2016. The children were followed from birth to first diagnosis of CVD, death, emigration, or the end of 2016.

The study cohort included 22,055 women with pregestational diabetes (including type 1 diabetes), 6537 women with type 2 diabetes, and 26,272 women with gestational diabetes. Compared with mothers who did not have diabetes, those with diabetes tended to be older, have higher education, and smoke less during pregnancy.

Overall, during up to 40 years of follow-up, CVD developed in 1153 children of mothers with diabetes compared with 91,311 children of mothers without a history of diabetes.

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The overall rate of early-onset CVD was 29% higher in children of mothers with diabetes vs children of mothers without diabetes (hazard ratio [HR], 1.29; 95% CI, 1.21-1.37). Rate of early-onset CVD was higher for children of mothers who had pregestational diabetes (HR, 1.34; 95% CI, 1.25-1.43) or gestational diabetes (HR, 1.19; 95% CI, 1.07-1.32).

In offspring of mothers with both diabetes and comorbid CVD, there was an even higher incidence of CVD (HR, 1.73; 95% CI, 1.36-2.20), which was not attributable to the interaction between diabetes and CVD on the multiplicative scale. Offspring of mothers with pregestational diabetes and complications of diabetes similarly had higher incidence of CVD (HR, 1.60; 95% CI, 1.25-2.05).

The study had several limitations, including possible unmeasured residual confounding, live birth selection bias, and potential misclassification bias for diabetes diagnoses. Furthermore, no assessment of CVD risk in late adulthood was possible, as the longest follow-up period so far is 40 years.

“These findings highlight the importance of effective strategies for screening and preventing diabetes in women of childbearing age,” wrote the researchers. “We need to monitor CVD risks in offspring of mothers with diabetes and investigate possible life course interventions that could reduce the occurrence of CVD.”

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Yu Y, Arah OA, Liew Z, et al. Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up. BMJ. 2019;367:l6398.