TY - JOUR

T1 - Risk of Congenital Heart Defects in Offspring of Affected Mothers and Fathers

AU - Øyen, Nina

AU - Boyd, Heather A.

AU - Carstensen, Lisbeth

AU - Søndergaard, Lars

AU - Wohlfahrt, Jan

AU - Melbye, Mads

N1 - Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - birth rate

KW - cohort studies

KW - epidemiology

KW - genetics

KW - heart defects, congenital

KW - population

KW - risk

U2 - 10.1161/CIRCGEN.121.003533

DO - 10.1161/CIRCGEN.121.003533

M3 - Journal article

C2 - 35608601

AN - SCOPUS:85136272786

VL - 15

JO - Circulation. Genomic and precision medicine

JF - Circulation. Genomic and precision medicine

SN - 2574-8300

IS - 4

M1 - E003533

ER -