Maternal metabolites during pregnancy are associated with newborn outcomes and hyperinsulinaemia across ancestries
We aimed to determine the association of maternal metabolites with newborn adiposity and hyperinsulinaemia in a multi-ethnic cohort of mother–newborn dyads.
Targeted and non-targeted metabolomics assays were performed on fasting and 1 h serum samples from a total of 1600 mothers in four ancestry groups (Northern European, Afro-Caribbean, Mexican American and Thai) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, underwent an OGTT at ~28 weeks gestation and whose newborns had anthropometric measurements at birth.
In this observational study, meta-analyses demonstrated significant associations of maternal fasting and 1 h metabolites with birthweight, cord C-peptide and/or sum of skinfolds across ancestry groups. In particular, maternal fasting triacylglycerols were associated with newborn sum of skinfolds. At 1 h, several amino acids, fatty acids and lipid metabolites were associated with one or more newborn outcomes. Network analyses revealed clusters of fasting acylcarnitines, amino acids, lipids and fatty acid metabolites associated with cord C-peptide and sum of skinfolds, with the addition of branched-chain and aromatic amino acids at 1 h.
The maternal metabolome during pregnancy is associated with newborn outcomes. Maternal levels of amino acids, acylcarnitines, lipids and fatty acids and their metabolites during pregnancy relate to fetal growth, adiposity and cord C-peptide, independent of maternal BMI and blood glucose levels.
KeywordsAdiposity Fetal growth Metabolomics Pregnancy outcomes
Aromatic amino acid
Branched-chain amino acid
False discovery rate
Gestational diabetes mellitus
Hyperglycemia and Adverse Pregnancy Outcome
Sum of skinfolds
RK contributed to data interpretation and manuscript writing. MN, OT and AK contributed to analysis and interpretation of data. MN and DMS led data analysis. JRB, MJM, RDS, ORI, SON, LPL, BEM and CBN contributed to acquisition and interpretation of data. DMS and WLL were involved in all aspects of the study, including study design and data collection, analysis and interpretation. All authors made critical intellectual contributions to drafting and/or revising the manuscript and all approved the final version. DMS and WLL are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
This study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095963) and the National Institute of Child Health and Human Development (R01-HD34242, R01-HD34243).
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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