Birth weight influences cardiac structure, function, and disease risk: evidence of a causal association.

Birth weight Cardiac MRI Foetal Genetic effects Intrauterine Maternal Mendelian randomization

Journal

European heart journal
ISSN: 1522-9645
Titre abrégé: Eur Heart J
Pays: England
ID NLM: 8006263

Informations de publication

Date de publication:
20 Sep 2023
Historique:
received: 14 06 2023
revised: 09 09 2023
accepted: 10 09 2023
medline: 22 9 2023
pubmed: 22 9 2023
entrez: 22 9 2023
Statut: aheadofprint

Résumé

Low birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization (MR) studies exploring this question do not distinguish the mechanistic contributions of variants that directly influence birth weight through the foetal genome (direct foetal effects), vs. variants influencing birth weight indirectly by causing an adverse intrauterine environment (indirect maternal effects). In this study, MR was used to assess whether birth weight, independent of intrauterine influences, is associated with cardiovascular disease risk and measures of adverse cardiac structure and function. Uncorrelated (r2 < .001), genome-wide significant (P < 5 × 10-8) single nucleotide polymorphisms were extracted from genome-wide association studies summary statistics for birth weight overall, and after isolating direct foetal effects only. Inverse-variance weighted MR was utilized for analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 16 measures of cardiac structure and function. Multiple comparisons were accounted for by Benjamini-Hochberg correction. Lower genetically-predicted birth weight, isolating direct foetal effects only, was associated with an increased risk of coronary artery disease (odds ratio 1.21, 95% confidence interval 1.06-1.37; P = .031), smaller chamber volumes, and lower stroke volume, but higher contractility. The results of this study support a causal role of low birth weight in cardiovascular disease, even after accounting for the influence of the intrauterine environment. This suggests that individuals with a low birth weight may benefit from early targeted cardiovascular disease prevention strategies, independent of whether this was linked to an adverse intrauterine environment during gestation.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Low birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization (MR) studies exploring this question do not distinguish the mechanistic contributions of variants that directly influence birth weight through the foetal genome (direct foetal effects), vs. variants influencing birth weight indirectly by causing an adverse intrauterine environment (indirect maternal effects). In this study, MR was used to assess whether birth weight, independent of intrauterine influences, is associated with cardiovascular disease risk and measures of adverse cardiac structure and function.
METHODS METHODS
Uncorrelated (r2 < .001), genome-wide significant (P < 5 × 10-8) single nucleotide polymorphisms were extracted from genome-wide association studies summary statistics for birth weight overall, and after isolating direct foetal effects only. Inverse-variance weighted MR was utilized for analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 16 measures of cardiac structure and function. Multiple comparisons were accounted for by Benjamini-Hochberg correction.
RESULTS RESULTS
Lower genetically-predicted birth weight, isolating direct foetal effects only, was associated with an increased risk of coronary artery disease (odds ratio 1.21, 95% confidence interval 1.06-1.37; P = .031), smaller chamber volumes, and lower stroke volume, but higher contractility.
CONCLUSIONS CONCLUSIONS
The results of this study support a causal role of low birth weight in cardiovascular disease, even after accounting for the influence of the intrauterine environment. This suggests that individuals with a low birth weight may benefit from early targeted cardiovascular disease prevention strategies, independent of whether this was linked to an adverse intrauterine environment during gestation.

Identifiants

DOI: 10.1093/eurheartj/ehad631 PMID: 37738114
pubmed: 37738114
pii: 7278832
doi: 10.1093/eurheartj/ehad631
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : British Heart Foundation
ID : FS/CRTF/21/24183
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : K08 HL166687
Pays : United States
Organisme : Academy of Medical Sciences
ID : SGL015/1006
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/F/22/110078
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100114
Pays : United Kingdom

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

Auteurs

Maddalena Ardissino (M)

National Heart and Lung Institute, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Department of Medicine, School of Clinical Medicine, University of Cambridge, UK.
ORCID: 0000-0002-2654-8117

Alec P Morley (AP)

Department of Medicine, School of Clinical Medicine, University of Cambridge, UK.

Eric A W Slob (EAW)

Medical Research Council Biostatistics Unit, University of Cambridge, UK.
Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, the Netherlands.
Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus University Rotterdam, the Netherlands.
Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam, the Netherlands.

Art Schuermans (A)

Department of Cardiovascular Sciences, KU Leuven, Flanders, Leuven, Belgium.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Bilal Rayes (B)

National Heart and Lung Institute, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.

Zahra Raisi-Estabragh (Z)

William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, UK.
Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, UK.

Antonio de Marvao (A)

Department of Women and Children's Health, King's College London, UK.
British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King's College London, UK.
Medical Research Council, London Institute of Medical Sciences, Imperial College London, UK.

Stephen Burgess (S)

Medical Research Council Biostatistics Unit, University of Cambridge, UK.
Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, UK.
ORCID: 0000-0001-5365-8760

Tormod Rogne (T)

Department of Chronic Disease Epidemiology, Yale School of Public Health, USA.
ORCID: 0000-0002-9581-7384

Michael C Honigberg (MC)

Department of Cardiovascular Sciences, KU Leuven, Flanders, Leuven, Belgium.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Fu Siong Ng (FS)

National Heart and Lung Institute, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
ORCID: 0000-0002-8681-4368

Classifications MeSH