Reducing the risk of CVD in future generations

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New research from BMJ indicates that children of mothers with diabetes have higher rates of early-onset cardiovascular disease (CVD) from childhood to age 40. 

Methods
The population-based cohort study examined all 2,432,000 livebirth children without congenital heart disease born in Denmark between 1977 and 2016. Follow-up with the participants began at birth up to the first diagnosis of CVD, death, emigration, or through the end of the study (December 31, 2016). 

The authors examined associations between types of maternal diabetes and early onset of CVD in offspring and the combined effect of maternal diabetes and maternal history of CVD on the rate of early-onset CVD in offspring. They also looked at whether pregestational complications of diabetes further increased risk of CVD in offspring. They hypothesized that intrauterine exposure to maternal diabetes could lead to an excess risk of early-onset CVD in offspring from childhood to early adulthood (up to 40 years).

The authors considered offspring born to mothers diagnosed with diabetes before childbirth to have been prenatally exposed to maternal diabetes mellitus. Maternal diabetes was categorized as gestational diabetes or pregestational diabetes. Women with pregestational diabetic complications were classified into two groups: those with one complication and those with multiple complications. The outcome of interest was early-onset CVD in offspring, defined as the first occurrence of CVD in the Danish Register of Cause of Death. The authors identified the outcomes using ICD-8 and ICD-10 codes for CVD or surgery codes for coronary artery bypass graft surgery and percutaneous coronary interventions. 

Findings
Of the 2,432,000 births included in the study, 54,864 (2.3%) were exposed to maternal pregestational diabetes and the proportion of offspring born to mothers with diabetes increased over time. Compared with mothers who did not have diabetes, mothers with diabetes were more likely to be older, to have had higher education, to have higher parity, to live alone, and to smoke less during pregnancy. Compared with unexposed offspring, offspring exposed to maternal diabetes were more likely to have a perinatal history of CVD and to have a higher rate of developing diabetes, obesity, hypertension, hypercholesterolemia, and chronic kidney diseases. 

During 40 years of follow-up, 1,153 offspring of mothers with diabetes and 91,311 offspring of mothers who did not have diabetes were diagnosed with CVD. Exposed offspring had a higher rate of CVDs than unexposed offspring (hazard ratio [HR] 1.29, 95% CI 1.21 – 1.37); cumulative incidence among offspring unexposed offspring at 40 years of age (13.07% [12.92% to 13.21%]);  cumulative incidence difference between the exposed and the unexposed offspring (4.72% [2.37% to 7.06%]).  An increased rate of early onset CVD was seen in offspring exposed to pregestational diabetes (HR 1.34, 1.25-1.43) or gestational diabetes (HR 1.19, 95% CI 1.07-1.32). 

The authors found a higher incidence of CVD in offspring born to mothers with both diabetes and comorbid CVD (HR 1.73, 95% CI 1.36-2.20) than in the offspring of mothers with diabetes only (HR 1.29, 95% CI 1.21-1.37). Offspring born to mothers with pregestational diabetes and diabetic complications had a higher incidence of CVD (HR 1.60, 95% CI 1.25-2.05) than the offspring of mothers with pregestational diabetes but without diabetic complications (HR 1.31, 95% CI 1.16-1.48).

Conclusions
The authors believe the results from the study show that children of mothers with diabetes, and particularly those with a history of CVD or diabetic complications, have increased rates of early-onset CVD from childhood to age 40. These findings reinforce the importance of prevention, screening, and treatment of diabetes in women of childbearing age to help reduce the risk of CVD in future generations.