Abstract
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 (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.
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.
| Original language | English |
|---|---|
| Article number | e020051 |
| Journal | Journal of the American Heart Association |
| Volume | 10 |
| Issue number | 11 |
| Early online date | 27 May 2021 |
| DOIs | |
| Publication status | Published - Jun 2021 |
Bibliographical note
Funding Information:The LifeCycle project received funding from the 452 European Union?s Horizon 2020 Research and Innovation Programme 453 (Grant Agreement No. 733206 LifeCycle). This study is also supported by the British Heart Foundation (AA/18/7/34219), Bristol National Institute for Health Research (NIHR) Biomedical Research Centre grant, European Research Council (Advanced Grant; 669545), and US National Institutes of Health (R01 DK10324). K. Taylor is supported by a British Heart Foundation Doctoral Training Program (FS/17/60/33474). K. Taylor, Dr Elhakeem, and Prof Lawlor work in a unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_00011/6). Prof Lawlor is supported by a British Heart Foundation Chair in Cardiovascular Science and Clinical Epidemiology (CH/F/20/90003) and a NIHR Senior Investigator (NF-0616-10102). Prof Caputo is supported by the British Heart Foundation Chair in Congenital Heart Disease (CH/1/32804). Dr Pinot de Moira is funded by a Lundbeck Foundation Fellowship (R264-2017-3099). Work by Dr Harris is partly supported by the Research Council of Norway through its Centers of Excellence Funding Scheme, project No. 262700. Details of funding for each individual LifeCycle cohort that has contributed to this study are provided below. ABCD (The Amsterdam Born Children and Their Development Study) was supported by the Netherlands Organization for Health Research and Development (grant 2100.0076) and the Electromagnetic Fields and Health Research Program (grants 85600004 and 85800001). Core funding for ALSPAC (Avon Longitudinal Study of Parents and Children) is provided by the UK Medical Research Council and Wellcome (217065/Z/19/) and the University of Bristol. Many grants have supported different data collections, including for some of the data used in this publication, and a comprehensive list of grant funding is available on the ALSPAC website (http://www.brist?ol.ac.uk/alspa?c/exter?nal/docum?ents/grant?-ackno?wledg? ements.pdf). The BASELINE (Cork Scope Baseline Study) Birth Cohort Study was funded by the National Children?s Research Centre (Project grant: Jan 2009). BiB (Born in Bradford) study has received core support from Wellcome Trust (WT101597MA), a joint grant from the UK Medical Research Council and UK Economic and Social Science Research Council (MR/N024397/1), the British Heart Foundation (CS/16/4/32482), and the NIHR Applied Research Collaboration Yorkshire and Humber (NIHR200166) and Clinical Research Network. The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. The DNBC (Danish National Birth Cohort) study was supported by the Danish Epidemiology Science Centre, the Lundbeck Foundation (grant 195/04), the Egmont Foundation, the March of Dimes Birth Defect Foundation, the Augustinus Foundation, and the Medical Research Council (grant SSVF 0646). The MoBa (Norwegian Mother, Father and Child Cohort Study) is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The NINFEA (Nascita e Infanzia: gli Effetti dell?Ambiente [Birth and Childhood: Effects of the Environment]) study was partially funded by the Compagnia San Paolo Foundation.
Funding Information:
The LifeCycle project received funding from the 452 European Union’s Horizon 2020 Research and Innovation Programme 453 (Grant Agreement No. 733206 LifeCycle). This study is also supported by the British Heart Foundation (AA/18/7/34219), Bristol National Institute for Health Research (NIHR) Biomedical Research Centre grant, European Research Council (Advanced Grant; 669545), and US National Institutes of Health (R01 DK10324). K. Taylor is supported by a British Heart Foundation Doctoral Training Program (FS/17/60/33474). K. Taylor, Dr Elhakeem, and Prof Lawlor work in a unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_00011/6). Prof Lawlor is supported by a British Heart Foundation Chair in Cardiovascular Science and Clinical Epidemiology (CH/F/20/90003) and a NIHR Senior Investigator (NF-0616-10102). Prof Caputo is supported by the British Heart Foundation Chair in Congenital Heart Disease (CH/1/32804). Dr Pinot de Moira is funded by a Lundbeck Foundation Fellowship (R264-2017-3099). Work by Dr Harris is partly supported by the Research Council of Norway through its Centers of Excellence Funding Scheme, project No. 262700. Details of funding for each individual LifeCycle cohort that has contributed to this study are provided below. ABCD (The Amsterdam Born Children and Their Development Study) was supported by the Netherlands Organization for Health Research and Development (grant 2100.0076) and the Electromagnetic Fields and Health Research Program (grants 85600004 and 85800001). Core funding for ALSPAC (Avon Longitudinal Study of Parents and Children) is provided by the UK Medical Research Council and Wellcome (217065/Z/19/) and the University of Bristol. Many grants have supported different data collections, including for some of the data used in this publication, and a comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledg ements.pdf). The BASELINE (Cork Scope Baseline Study) Birth Cohort Study was funded by the National Children’s Research Centre (Project grant: Jan 2009). BiB (Born in Bradford) study has received core support from Wellcome Trust (WT101597MA), a joint grant from the UK Medical Research Council and UK Economic and Social Science Research Council (MR/N024397/1), the British Heart Foundation (CS/16/4/32482), and the NIHR Applied Research Collaboration Yorkshire and Humber (NIHR200166) and Clinical Research Network. The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. The DNBC (Danish National Birth Cohort) study was supported by the Danish Epidemiology Science Centre, the Lundbeck Foundation (grant 195/04), the Egmont Foundation, the March of Dimes Birth Defect Foundation, the Augustinus Foundation, and the Medical Research Council (grant SSVF 0646). The MoBa (Norwegian Mother, Father and Child Cohort Study) is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The NINFEA (Nascita e Infanzia: gli Effetti dell’Ambiente [Birth and Childhood: Effects of the Environment]) study was partially funded by the Compagnia San Paolo Foundation.
Funding Information:
We are grateful to all participating hospitals, obstetric clinics, and general practitioners for their assistance in implementing ABCD (The Amsterdam Born Children and Their Development Study) and thank all of the women who participated for their cooperation. We are grateful to all the families who took part in the ALSPAC (Avon Longitudinal Study of Parents and Children), the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The authors thank the families for their continued support and the BASELINE (Cork Scope Baseline Study) Birth Cohort Study research team. BiB (Born in Bradford) study is only possible because of the enthusiasm and commitment of the children and parents. We are grateful to all the participants, practitioners, and researchers who have made BiB study happen. The DNBC (Danish National Birth Cohort) study was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation, and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation. We are grateful to all the participating families in Norway who take part in the ongoing MoBa (Norwegian Mother, Father and Child Cohort Study). The authors thank all families participating in the NINFEA (Nascita e Infanzia: gli Effetti dell’Ambiente [Birth and Childhood: Effects of the Environment]) study cohort. Data access: The Horizon2020 LifeCycle Project is a cross-cohort collaboration that brings together data from multiple birth cohorts from across Europe and Australia. A major product of this collaboration has been the establishment of a findable, accessible, interoperable, and reusable data resource known as the European Union Child Cohort Network (https:// lifecycle-project.eu/for-scientists/variable-catalogue/). The ABCD study welcomes collaboration and the interest of colleagues. A set of guidelines for researchers interested in using data for research purposes is available at http://www.abcd-study.nl. The ALSPAC data management plan (http:// www.bristol.ac.uk/alspac/researchers/data-access/documents/alspac-data-management-plan.pdf) describes in detail the policy on data sharing, which is through a system of managed open access. Researchers interested in using BASELINE data can contact the study ([email protected]), and further information can be found (http://www.baselinestudy.net/ or http://www. birthcohorts.net/). Scientists are encouraged to make use of the BiB study data, which are available through a system of managed open access. Before you contact BiB study, please make sure you have read the Guidance for Collaborators. The DNBC study operates an open access policy. More information can be found on the study website (https://www.dnbc.dk/acces s-to-dnbc-data). MoBa data are used by researchers and research groups at both the Norwegian Institute of Public Health and other research institutions nationally and internationally. The research must adhere to the aims of MoBa and the participants’ given consent. All use of data and biological material from MoBa is subject to Norwegian legislation. More information can be found on the study website (https://www.fhi.no/en/studies/moba/ for-forskere-artikler/research-and-data-access/). Researchers interested in using NINFEA study data can contact [email protected], and more information can be found at the study website (https://www.progettoninfea.it/).
Publisher Copyright:
© 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Keywords
- Adult
- Alcohol Drinking/adverse effects
- Body Mass Index
- Europe/epidemiology
- Fathers/statistics & numerical data
- Female
- Heart Defects, Congenital/epidemiology
- Humans
- Incidence
- Male
- Mothers/statistics & numerical data
- Pregnancy
- Prenatal Exposure Delayed Effects/epidemiology
- Risk Factors
- Smoking/adverse effects
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