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Updated: Aug 12, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study
Jian Zhao1, Isobel D Stewart2, Denis Baird3
1MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Bristol NIHR Biomedical Research Centre, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; The Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Institute of Early Life Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Maternal and Child Health, School of Public Health, Shanghai Jiao Tong University, Shanghai, China.
Background:
Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear.
Methods:
We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 × 10-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations.
Findings:
Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (-59 g, 95% CI: -106, -11) and phenylalanine (-25 g, 95% CI: -47, -4) lower offspring birthweight. These findings are supported by sensitivity analyses.
Interpretation:
Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.
Funding:
A full list of funding bodies that contributed to this study can be found under Acknowledgments.
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