Maternal obesity, interpregnancy weight changes and congenital heart defects in the offspring

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by The Danish Children Heart Foundation (18-R109-A5193-26043), The A.P. Moller Foundation (19-L-0096), and Aase and Ejnar Danielsen's Foundation (19-10-0493). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Statens Serum Institut has approval from the Danish Data Protection Agency to conduct register-based studies, and the project has been approved (journal no. 19/03354 and 20/09279). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors