Maternal Metabolites during Pregnancy Are Associated with Newborn Outcomes

Abstract

The maternal metabolome serves as a proxy for the fetus’s metabolic environment, but its impact on newborn outcomes is largely unknown. To address this, we determined the association of maternal metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of mother-newborn dyads. Targeted and nontargeted metabolomics assays were performed on fasting and 1 hour serum samples from 1600 mothers in four ancestry groups (Northern European, Afro-Caribbean, Mexican-American, and Thai) who participated in the Hyperglycemia and Adverse Pregnancy Outcome Study, underwent an OGTT at ∼28 weeks gestation, and whose newborns had anthropometric measurements at birth. Maternal metabolite-newborn phenotype associations were investigated using 1) per-metabolite analyses within and across ancestries and 2) network analyses to identify interconnected metabolites associated with phenotypes. Meta-analyses demonstrated more associations of maternal 1 hour vs. fasting metabolites with newborn outcomes. At fasting, maternal triglycerides, valine, pyruvate, and acylcarnitine (AC) C20 were associated with newborn birthweight, cord C-peptide, and/or sum of skinfolds (SSF). At 1 hour, several amino acids (AAs), ACs, fatty acids (FA), and lipid metabolites were associated with one or more of these same outcomes in models adjusted for maternal BMI or glucose. For example, the branched-chain amino acid valine and its carnitine ester AC C4/Ci4 were associated with cord C-peptide at 1 hour independent of maternal BMI or glucose. Network analyses revealed clusters of fasting ACs, AAs, FA and lipid metabolites associated with cord C-peptide and SSF, with the addition of branched-chain and aromatic amino acids at 1 hour. Maternal metabolites during pregnancy, particularly 1 hour post glucose, are associated with fetal adiposity and hyperinsulinemia, independent of maternal BMI and glycemia, and provide insight into the interrelationship between maternal metabolism and newborn size. Disclosure R. Kadakia: None. M. Nodzenski: None. O. Talbot: None. A. Kuang: None. J.R. Bain: None. M. Muehlbauer: None. O. Ilkayeva: None. S.K. O'Neal: None. L.P. Lowe: None. B.E. Metzger: None. D. Scholtens: None. W. Lowe: None.