Risk of Congenital Heart Defects in Offspring of Affected Mothers and Fathers

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Background: Smaller studies have reported a higher offspring risk of congenital heart defects (CHDs) for mothers with CHDs than for fathers with CHDs. In a large population-based study, we investigated whether offspring risk of CHD differed for mothers and fathers with CHDs. Methods: All people born in Denmark, 1977 to 2011, with at least 1 registered parent, were included in our cohort (n=2 341 061). Parent-child recurrence of CHDs was evaluated using risk ratios (RRs) comparing risks of CHDs in individuals with and without a parent with a CHD, estimated using log-linear binomial regression. Results: The RRs for any CHD in offspring were 5.39 (95% CI, 4.88-5.96) for mothers and 3.04 (95% CI, 2.59-3.57) for fathers affected with any CHD; the ratio of RRs for mothers versus fathers was 1.82 (P<0.0001). Recurrence RRs for the same cardiac phenotype in parent and offspring were significantly stronger for mothers than for fathers for conotruncal defects (ratio of RRs, 4.98), left ventricular outlet tract obstruction (ratio of RRs, 4.98), and ventricular septal defects (ratio of RRs, 2.51) but not for atrioventricular septal defects (ratio of RRs, 1.06). Birth rates among people with CHDs, relative to the general population, were 18% higher for women than for men, regardless of parental cardiac phenotype. Conclusions: Recurrence risks of CHDs were significantly greater in the offspring of affected women than in the offspring of affected men. The excess maternal recurrence risks could not be explained by the slightly higher birth rates in women with CHDs.

OriginalsprogEngelsk
ArtikelnummerE003533
TidsskriftCirculation: Genomic and Precision Medicine
Vol/bind15
Udgave nummer4
ISSN2574-8300
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Dr Øyen was supported by the Danish Heart Foundation (A94-A4677), the Research Council Norway (190858/V50), the Western Norway Regional Health Authorities (911734), the Meltzer foundation, Norway (2021-1326), and the Faculty of Medicine, University of Bergen, Norway.

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© 2022 Lippincott Williams and Wilkins. All rights reserved.

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