Objective To evaluate the association between maternal obesity and congenital heart defects (CHDs) in the offspring when including live births, stillbirths and terminated pregnancies and to investigate if interpregnancy weight change between the first and second pregnancy influences risk of fetal CHDs.

Methods A nationwide cohort study of all singleton pregnancies in Denmark from 2008 to 2018. All data on maternal and offspring characteristics were retrieved from the Danish Fetal Medicine Database including prenatal diagnoses. CHDs and severe CHDs were defined according to European Surveillance of Congenital Anomalies’ definitions. Children or fetuses with chromosomal aberrations were excluded. Relative risks (RRs) were calculated using log-linear Poisson models.

Results Of the 547 178 pregnancies included in the cohort, 5 498 had CHDs (1.00%). Risk of CHDs became gradually higher with higher maternal body mass index (BMI); for BMI 30-34.9, adjusted relative risk (aRR) = 1.23, 95% confidence interval (CI) 1.12-1.36, for BMI 35-39.9, aRR = 1.26, 95% CI 1.09-1.46 and for BMI ≥ 40, aRR = 1.81, 95% CI 1.50-2.15. Data was adjusted for maternal age, smoking status and birth year. The same pattern was seen for the subgroup of severe CHDs. Among the atrioventricular septal defects (n = 245), a particularly strong association with maternal BMI ≥ 40 was seen, aRR = 4.19, 95% CI 2.13-7.42. Interpregnancy BMI change was positively, albeit not significanty, associated with risk of CHDs in the second pregnancy when adjusting for maternal age and BMI, with an aRR = 1.27, 95% CI 0.96-1.64 among persons with a BMI increase of ≥ 4 kg/m2 was found.

Conclusion When including both pre-and post-natally diagnosed CHDs, this study showed a dose-response association between maternal BMI and risk of CHDs in the offspring. However, only a non-significant trend was seen between interpregnancy BMI changes and risk of CHDs.