First-trimester maternal exposures and offspring congenital heart defects: a Hungarian population-based case–control study, 1980–2009

Background Congenital heart defects (CHDs) are a major cause of infant morbidity and mortality. Identifying modifiable maternal exposures during early pregnancy is important for CHD prevention and maternal and child health. Objectives To examine associations between first-trimester maternal active smoking and alcohol consumption and offspring CHDs, and to explore associations of selected maternal diseases and related treatments with CHD outcomes. Methods This population-based case–control study used data from the Hungarian Case–Control Surveillance of Congenital Abnormalities (1980–2009), including 7,362 CHD cases and 56,894 controls. Overall CHDs were the primary outcome, with ventricular septal defect (VSD) and atrial septal defect (ASD) examined as secondary outcomes. Complete-case multivariable logistic regression estimated odds ratios (ORs) for smoking and alcohol consumption, with mutual adjustment and additional adjustment for maternal age, socioeconomic status, and offspring sex. Multiple imputation was performed as a sensitivity analysis. Maternal disease and treatment analyses were crude and exploratory. Results First-trimester maternal smoking was associated with higher odds of overall CHDs (adjusted OR 1.50, 95% confidence interval [CI] 1.30–1.71), VSD (1.36, 1.11–1.66) and ASD (1.62, 1.35–1.93). Multiple-imputation estimates were similar to the complete-case estimates. No statistically significant associations were observed between maternal alcohol consumption and CHD outcomes in either the adjusted complete-case analysis or the multiple-imputation analysis. Maternal epilepsy, migraine, anxiety disorder and anemia showed positive crude associations with one or more CHD outcomes. Conclusion Maternal smoking reported during the first trimester was associated with higher odds of overall CHDs, VSD, and ASD, supporting smoking cessation before conception and during pregnancy as a prevention priority. Exploratory associations involving maternal diseases and treatments require further investigation and should not be used to infer treatment effects or guide treatment decisions.