Maternal Diabetes Raises Offspring Cardiovascular Disease Risk by Up to 29%

Maternal diabetes during pregnancy — including both gestational diabetes mellitus (GDM) and pregestational diabetes (type 1 and type 2) — is already known to raise risks of complications at birth, but its long-term cardiovascular consequences for offspring have remained poorly characterized. This large Swedish registry study addresses that gap with unprecedented statistical power, following more than 4.27 million individuals for a median of 27.6 years (IQR 17.2–37.4 years), making it one of the most comprehensive investigations of intergenerational cardiovascular risk ever published.

The cohort included everyone born in Sweden between January 1, 1973, and December 31, 2014, with follow-up through December 31, 2023. Of the total, 61,336 individuals (1.46%) were exposed to maternal diabetes in utero. Cardiovascular disease diagnoses were captured from national inpatient and outpatient registers. Exposures were categorized as any maternal diabetes, gestational diabetes only, and pregestational diabetes (type 1 or type 2). Cox proportional hazards regression models estimated hazard ratios after adjusting for relevant covariates. Crucially, sibling-matched analyses were conducted to control for shared familial genetic and environmental confounders.

The primary finding was that any maternal diabetes was associated with a 16% increased risk of overall CVD in offspring (HR 1.16; 95% CI, 1.12–1.20). The risk gradient was clearly related to diabetes severity: gestational diabetes conferred an HR of 1.11 (95% CI, 1.05–1.17), while pregestational diabetes carried an HR of 1.29 (95% CI, 1.21–1.38). Among specific CVD subtypes, the most striking association was with heart failure (HR 1.65; 95% CI, 1.37–2.00), followed by cerebrovascular diseases (HR 1.31; 95% CI, 1.12–1.52), atrial fibrillation (HR 1.27; 95% CI, 1.05–1.54), and venous thromboembolism (HR 1.20; 95% CI, 1.07–1.34). These findings held in sibling analyses, strengthening the causal interpretation.

Mediation analyses identified three key perinatal and early-life pathways. Congenital heart disease (CHD) was the largest mediator, directly and/or indirectly explaining 31.87% of the association between maternal diabetes and offspring CVD risk. Preterm birth mediated 16.06% of the association, and being large for gestational age (LGA) mediated 14.18%. These results suggest that a substantial proportion of risk operates through identifiable, clinically actionable perinatal events, while meaningful residual risk remains unexplained.

The clinical and public health implications are substantial. With gestational diabetes prevalence rising globally alongside obesity rates, the downstream CVD burden in offspring populations could grow considerably. Identifying offspring of diabetic mothers — especially those also born preterm, with CHD, or LGA — as a high-risk group from birth could enable earlier cardiovascular surveillance, lifestyle intervention, and preventive care. For clinicians, these findings argue for flagging maternal diabetes in pediatric and adult medical records as a cardiovascular risk factor in its own right.