TOPLINE:

Congenital heart defects (CHD) showed clear familial clustering, with the odds rising steadily as more relatives were affected and reaching up to a 45‑fold increase when four or more relatives had CHD. The association was stronger through the maternal line than the paternal line.

METHODOLOGY:

• Researchers conducted a retrospective, population‑based case‑control study using data from linked Swedish national registers to evaluate patterns of familial recurrence of CHD.
• They included 51,778 individuals with CHD (index individuals) born in Sweden between 1987 and 2017 and matched them with 522,543 control individuals. Both groups had 49.9% male patients.
• Researchers identified parents, full and half-siblings, and offspring; analysed whether having affected relatives — by degree of kinship and number — was associated with CHD in the index individual; and tested interactions with maternal diabetes, obesity, and hypertension.
• The primary outcome was a diagnosis of CHD in the index individual, assessed in relation to whether any relative had CHD. Register data were collected until December 2020.

TAKEAWAY:

• Individuals with at least one affected relative had higher odds of CHD (adjusted odds ratio [aOR], 2.71; 95% CI, 2.60-2.83) than control individuals.
• The adjusted odds of CHD increased from 2.52 (95% CI, 2.41-2.64) with one affected relative to 45.16 (95% CI, 16.27-125.33) with four or more affected relatives. Each additional affected relative was associated with a 2.55-fold increase in the odds of CHD (P < .001).
• The adjusted odds of CHD were higher when the mother (aOR, 3.12), a full sibling (aOR, 3.22), or an offspring (aOR, 3.18) was affected; lower adjusted odds were seen for individuals with an affected father (aOR, 2.25), a maternal half‑sibling (aOR, 1.67), or a paternal half‑sibling (aOR, 1.32).
• The association between maternal CHD and offspring CHD was attenuated when the mother had pregestational diabetes but was similar when mothers had obesity or hypertension; tests showed a reduced relative effect with diabetes but no evidence of additive interaction.

IN PRACTICE:

"These findings highlight the clinical importance of detailed family history in risk assessment and the need to integrate genomic data in future research to better elucidate recurrence mechanisms and improve counselling," the researchers of the study wrote.

SOURCE:

The study was led by Kalliopi Kazamia, Karolinska University Hospital in Stockholm, Sweden. It was published online on January 08, 2026, in the European Heart Journal.

LIMITATIONS:

CHD may have been misclassified because diagnoses were captured from registers. Lack of genetic data limited the ability to distinguish inherited from non‑genetic factors. Differences in ancestry and parental country of birth may have influenced recurrence patterns. 

DISCLOSURES:

The study received funding from multiple sources including Hjärt-lungfonden, the Norwegian Research Council, Stiftelsen Samariten, the Gillbergska Foundation, and the Pediatric Research Foundation at Astrid Lindgren Children's Hospital. One author reported receiving research funding that supported salary during research time, software licences, and statistical consulting services from Red Door Analytics AB; another author reported being employed by Red Door Analytics AB and receiving payment for statistical support and data management for the study. A third author reported receiving research funding related to the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.