Pre-existing maternal cardiovascular disease and the risk of offspring cardiovascular disease from infancy to early adulthood

BACKGROUND AND AIMS: A variety of maternal heart conditions are associated with abnormal placentation and reduced foetal growth. However, their impact on offspring's long-term cardiovascular health is poorly studied. This study aims to investigate the association between intrauterine exposure to pre-existing maternal cardiovascular disease (CVD) and offspring CVD occurring from infancy to early adulthood, using paternal CVD as a negative control. METHODS: This nationwide cohort study used register data of live singletons without major malformations or congenital heart disease born between 1992 and 2019 in Sweden. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for essential maternal characteristics. Paternal CVD served as a negative control for assessment of unmeasured genetic and environmental confounding. RESULTS: Of the 2 597 786 offspring analysed (49.1% female), 26 471 (1.0%) were born to mothers with pre-existing CVD. During a median follow-up of 14 years (range 1-29 years), 17 382 offspring were diagnosed with CVD. Offspring of mothers with CVD had 2.09 times higher adjusted HR of CVD (95% CI 1.83, 2.39) compared with offspring of mothers without CVD. Compared with maternal CVD, paternal CVD showed an association of smaller magnitude (HR 1.49, 95% CI 1.32, 1.68). Increased hazards of offspring CVD were also found when stratifying maternal CVD into maternal arrhythmia (HR 2.94, 95% CI 2.41, 3.58), vascular (HR 1.59, 95% CI 1.21, 2.10), and structural heart diseases (HR 1.48, 95% CI 1.08, 2.02). CONCLUSIONS: Maternal CVD was associated with an increased risk of CVD in offspring during childhood and young adulthood. Paternal comparison suggests that genetic or shared familial factors may not fully explain this association.