Maternal obesity, interpregnancy weight changes and congenital heart defects in the offspring: a nationwide cohort study
Authors: Hedermann Gitte , Thagaard Ida N , Hedley Paula L , Krebs Lone , Hagen Christian M , Sørensen Thorkild I A , Christiansen Michael , Ekelund Charlotte K 
Published: February 2023

AbstractBackgroundMaternal obesity has been positively associated with increased risk of congenital heart defects in the offspring. However, none of the large studies have included the considerable proportion of congenital heart defects that are identified due to improvements in prenatal diagnostics and terminated in pregnancy. The mechanism behind the association is poorly understood, and a relation to interpregnancy weight changes is to be investigated.ObjectivesTo evaluate the association between maternal obesity and congenital heart defects in the offspring when including all pregnancies and to investigate if interpregnancy weight change between the first and second pregnancy influences risk of fetal congenital heart defects.Study DesignA 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. The database included data on postnatal diagnoses of congenital heart defects in live births and prenatal diagnoses of congenital heart defects from ultrasound examinations during pregnancy resulting in live birth, stillbirth, spontaneous abortion after gestational week 12 or termination of pregnancies after gestational week 12. As this cohort encompassed all pregnancies over a 10-year period, it was possible for women to experience multiple pregnancies. Congenital heart defects and severe congenital heart defects were grouped according to European Surveillance of Congenital Anomalies’ definitions. Children or fetuses with chromosomal aberrations were excluded. Relative risks were calculated using log-linear Poisson models for congenital heart defects overall, severe congenital heart defects and for five of the most prevalent subtypes of congenital heart defects.ResultsOf the 547 178 pregnancies included in the cohort, 5 498 had congenital heart defects (1.0%). Risk of congenital heart defects became gradually higher with higher maternal BMI; for BMI 30-34.9 kg/m2, adjusted relative risk = 1.23 (95% confidence interval 1.12-1.36), for BMI 35-39.9 kg/m2, adjusted relative risk = 1.26 (95% confidence interval 1.09-1.46) and for BMI ≥ 40 kg/m2, adjusted relative risk = 1.81 (95% confidence interval 1.50-2.15). Data was adjusted for maternal age, smoking status and year of estimated due date. The same pattern was seen for the subgroup of severe congenital heart defects. Among the atrioventricular septal defects (n = 245), a particularly strong association with maternal BMI ≥ 40 kg/m2was seen, adjusted relative risk = 4.19 (95% confidence interval 2.13-7.42). 107 627 women were identified with their first and second pregnancies in the cohort. Interpregnancy BMI change was positively, albeit not statistically significant, associated with risk of congenital heart defects in the second pregnancy when adjusting for maternal age and BMI, with an adjusted relative risk = 1.27 (95% confidence interval 0.96-1.64) among persons with a BMI increase of ≥ 4 kg/m2.ConclusionsWhen including both pre- and postnatally diagnosed congenital heart defects, this study showed a positive dose-response association between maternal BMI and risk of congenital heart defects in the offspring. However, only a non-significant trend was seen between interpregnancy BMI changes and risk of congenital heart defects in the second pregnancies.CondensationTweetable statement: The risk of fetal congenital heart defect is associated with high maternal BMI, and it may also be affected by a substantial weight gain between pregnancies.AJOG at a GlanceA. Why was this study conducted?None of the large cohort studies on the association between maternal BMI and congenital heart defects (CHDs) have included the proportion of CHDs that are identified in terminated pregnancies.No previous studies have investigated the association between interpregnancy weight changes and CHDs.B. What are the key findings?Risk of CHDs became gradually higher with higher maternal BMI when including live births, stillbirths, abortions and terminated pregnancies.A trend was found between interpregnancy weight gain and risk of CHDs.C. What does this study add to what is already known?The association between high maternal BMI and risk of CHDs are not caused by a lower detection rate of fetal CHDs in pregnant women with obesity.