Journal
JOURNAL OF THE AMERICAN HEART ASSOCIATION
Volume 10, Issue 11, Pages -Publisher
WILEY
DOI: 10.1161/JAHA.120.020051
Keywords
congenital heart disease; negative control; risk factors
Categories
Funding
- 452 European Union's Horizon 2020 Research and Innovation Programme 453 [733206 LifeCycle]
- British Heart Foundation [AA/18/7/34219, CS/16/4/32482]
- Bristol National Institute for Health Research (NIHR) Biomedical Research Centre grant
- European Research Council [669545]
- US National Institutes of Health [R01 DK10324]
- British Heart Foundation Doctoral Training Program [FS/17/60/33474]
- University of Bristol
- UK Medical Research Council [MC_UU_00011/6, 217065/Z/19/, MR/N024397/1]
- British Heart Foundation Chair in Cardiovascular Science and Clinical Epidemiology [CH/F/20/90003]
- NIHR Senior Investigator [NF-0616-10102]
- British Heart Foundation Chair in Congenital Heart Disease [CH/1/32804]
- Lundbeck Foundation Fellowship [R264-2017-3099]
- Research Council of Norway through its Centers of Excellence Funding Scheme [262700]
- Netherlands Organization for Health Research and Development [2100.0076]
- Electromagnetic Fields and Health Research Program [85600004, 85800001]
- Wellcome Trust [217065/Z/19, WT101597MA]
- National Children's Research Centre
- UK Economic and Social Science Research Council [MR/N024397/1]
- NIHR Applied Research Collaboration Yorkshire and Humber [NIHR200166]
- Clinical Research Network
- Danish Epidemiology Science Centre
- Lundbeck Foundation [195/04]
- Egmont Foundation
- March of Dimes Birth Defect Foundation
- Augustinus Foundation
- Medical Research Council [SSVF 0646]
- Norwegian Ministry of Health and Care Services
- Ministry of Education and Research
- Compagnia San Paolo Foundation
- MRC [MC_PC_19009] Funding Source: UKRI
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The study found evidence of an intrauterine effect of maternal smoking on offspring congenital heart diseases, but no evidence for higher maternal BMI or alcohol consumption. The findings provide further support for the importance of smoking cessation during pregnancy.
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.
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