Methods and Results: Seven European birth cohorts including 232,390 offspring (2,469 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% Confidence Interval (CI) 1.01, 1.31) and obesity (OR: 1.12 (0.93, 1.36), compared to 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 (0.97, 1.25)) but paternal smoking was not (OR: 0.96 (0.85, 1.07)). The positive association with maternal smoking appeared to be driven by non-severe CHD cases (OR: 1.22 (1.04, 1.44)). Associations with maternal moderate/heavy pregnancy alcohol consumption were imprecisely estimated (OR: 1.16 (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.
|Journal||Journal of the American Heart Association|
|Publication status||Accepted/In press - 29 Mar 2021|
- congenital heart disease
- risk factors
- negative control