Congenital heart defects: familial recurrence patterns in Sweden

Congenital heart defects (CHD) aggregate in families, but recurrence patterns across kinships and generations remain incompletely understood. In light of improved survival and diagnostic precision, updated population-based estimates are needed. This study aimed to investigate familial recurrence patterns of CHD among relatives using nationwide Swedish register data.

A retrospective, population-based case-control study was conducted, including 51 778 individuals with CHD born between 1987 and 2017 and 522 543 matched controls. Relatives (parents, full siblings, half-siblings, and offspring) were identified through linkage to national health and population registers. Logistic regression with robust standard errors clustered on maternal ID was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Dose-response relationships, kinship-specific associations, and interactions with maternal comorbidities (diabetes, hypertension, and obesity) were explored.

Among individuals with at least one affected relative, the OR for CHD was 2.71 (95% CI 2.60-2.83), increasing with each additional affected relative (OR per relative 2.55; 95% CI 2.46-2.64). Recurrence was strongest for mothers (OR 3.12), full siblings (OR 3.22), and offspring (OR 3.18) and lower for fathers and half-siblings. A dose-response was observed by number of affected siblings and offspring. The association between maternal CHD and CHD in index individuals was not explained by maternal comorbidities.

Congenital heart defect in a relative (parent, full or half-siblings, or offspring) is associated with CHD in the index individual, with recurrence patterns varying by kinship and number of affected relatives. These findings may inform genetic counselling and reproductive planning.