Maternal Diabetes Increases Early CVD Risk in Offspring

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Children born to mothers with gestational or pregestational diabetes are at increased risk of developing cardiovascular disease (CVD) at follow-up through young adulthood, reports a study in the British Medical Journal.

The prevalence of CVD among children and young adults has increased in recent decades. Rates of pregestational and gestational diabetes have been rising as well; a growing body of evidence suggests that offspring of women with diabetes are at increased risk of metabolic syndrome and congenital heart disease. This population-based study sought to determine the extent to which exposure to maternal diabetes increases the lifetime risk of diabetes in offspring.

The BMJ study used Danish national health registry data on liveborn children without congenital heart disease between 1977 and 2016. The researchers identified three groups of children exposed to maternal diabetes during gestation: type 1 diabetes, 22,055 children (0.9%); type 2 diabetes, 6537 children (0.3%); and gestational diabetes, 26,272 children (1.1%).

Mothers with diabetes were more likely to be older, to have higher education, to have higher parity, to live alone, and to smoke less during pregnancy.

Follow-up data for up to 40 years were analyzed to examine associations between maternal diabetes and early-onset CVD, defined by hospital diagnosis. Analyses included adjustment for potential confounders including calendar year, sex, singleton birth, maternal risk factors, and paternal history of CVD before childbirth. Cumulative incidence of early-onset CVD was averaged across individuals and adjusted for competing causes of death.

During follow-up, CVD was diagnosed in 1153 offspring whose mothers had diabetes and 91,311 without such exposure: rates per 1000 person-years were 2.02 versus 2.01, respectively. The offspring exposed to maternal diabetes were more likely to have a parental history of CVD and were also at higher risk of developing diabetes, obesity, hypertension, hypercholesterolemia, and chronic kidney disease.

Exposed offspring had a significantly higher overall risk of CVD: hazard ratio (HR) 1.29. The increase in CVD risk was greater for offspring exposed to pregestational diabetes, with a HR 1.34; but remained significant for those exposed to gestational diabetes, HR 1.19. At age 40, cumulative incidence of CVD was 13.07% in the exposed group versus 4.72% in those not exposed to maternal diabetes. Exposure was associated with increased risk of most types of CVD: HR 1.45 for heart failure, 1.78 for hypertensive disease, 1.82 for deep vein thrombosis, and 1.91 for pulmonary embolism [Yu Y, 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].