Effect of Maternal Prepregnancy/Early-Pregnancy Body Mass Index and Pregnancy Smoking and Alcohol on Congenital Heart Diseases: A Parental Negative Control Study

Background Congenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown. Higher prenatal body mass index (BMI), smoking, and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear. Methods and Results Seven European birth cohorts, including 232 390 offspring (2469 CHD cases [1.1%]), were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking, and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression, adjusting for confounders and the other parent's exposure and combined estimates using a fixed-effects meta-analysis. In adjusted analyses, maternal overweight (odds ratio [OR], 1.15 [95% CI, 1.01-1.31]) and obesity (OR, 1.12 [95% CI, 0.93-1.36]), compared with normal weight, were associated with higher odds of CHD, but there was no clear evidence of a linear increase in odds across the whole BMI distribution. Associations of paternal overweight, obesity, and mean BMI were similar to the maternal associations. Maternal pregnancy smoking was associated with higher odds of CHD (OR, 1.11 [95% CI, 0.97-1.25]) but paternal smoking was not (OR, 0.96 [95% CI, 0.85-1.07]). The positive association with maternal smoking appeared to be driven by nonsevere CHD cases (OR, 1.22 [95% CI, 1.04-1.44]). Associations with maternal moderate/heavy pregnancy alcohol consumption were imprecisely estimated (OR, 1.16 [95% CI, 0.52-2.58]) and similar to those for paternal consumption. Conclusions We found evidence of an intrauterine effect for maternal smoking on offspring CHDs, but no evidence for higher maternal BMI or alcohol consumption. Our findings provide further support for the importance of smoking cessation during pregnancy.