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

Maddalena Ardissino; Alec P Morley; Eric A W Slob; Art Schuermans; Bilal Rayes; Zahra Raisi-Estabragh; Antonio de Marvao; Stephen Burgess; Tormod Rogne; Michael C Honigberg; Fu Siong Ng

doi:10.1093/eurheartj/ehad631

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

Eur Heart J. 2024 Feb 7;45(6):443-454. doi: 10.1093/eurheartj/ehad631.

Authors

Maddalena Ardissino^{1

2}, Alec P Morley², Eric A W Slob^{3

4

5

6}, Art Schuermans^{7

8

9}, Bilal Rayes¹, Zahra Raisi-Estabragh^{10

11}, Antonio de Marvao^{12

13

14}, Stephen Burgess^{3

15}, Tormod Rogne¹⁶, Michael C Honigberg^{7

8

17}, Fu Siong Ng¹

Affiliations

¹ National Heart and Lung Institute, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
² Department of Medicine, School of Clinical Medicine, University of Cambridge, UK.
³ Medical Research Council Biostatistics Unit, University of Cambridge, UK.
⁴ Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, the Netherlands.
⁵ Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus University Rotterdam, the Netherlands.
⁶ Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam, the Netherlands.
⁷ Department of Cardiovascular Sciences, KU Leuven, Flanders, Leuven, Belgium.
⁸ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁹ Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁰ William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, UK.
¹¹ Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, UK.
¹² Department of Women and Children's Health, King's College London, UK.
¹³ British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King's College London, UK.
¹⁴ Medical Research Council, London Institute of Medical Sciences, Imperial College London, UK.
¹⁵ Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, UK.
¹⁶ Department of Chronic Disease Epidemiology, Yale School of Public Health, USA.
¹⁷ Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Abstract

Background and aims: 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: 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: 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: 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.

Keywords: Birth weight; Cardiac MRI; Foetal; Genetic effects; Intrauterine; Maternal; Mendelian randomization.

MeSH terms

Birth Weight / genetics
Brain Ischemia* / genetics
Coronary Artery Disease*
Female
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide / genetics
Pregnancy
Stroke*

Abstract

MeSH terms

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