Comparative metabolomics of paired maternal-cord samples identifies pathway-level divergence.

INTRODUCTION: During pregnancy, the maternal and fetal metabolomes are linked and can influence one another through factors such as maternal diet. However, there is a lack of understanding of baseline maternal and neonate metabolomic similarities and differences. OBJECTIVES: To investigate whether, for typical dyads, maternal metabolomic profiles can serve as a proxy for fetal metabolomic profiles, we conducted a cross-sectional study among a cohort of 65 pregnant persons and their neonates. METHODS: We collected maternal and cord blood at the time of the delivery and utilized high-resolution mass spectrometry to perform untargeted metabolomics on maternal (n = 65) and neonate (n = 65) samples. We performed principal component analysis of the detected features to assess differences between mothers and neonates. We then performed a metabolome-wide association study to identify significant features and subsequently performed pathway enrichment analysis to identify associated metabolic pathways. RESULTS: We observed distinct separation between features detected in mothers and neonates from both negative and positive ionization data. Our pathway analysis indicated that maternal and neonate metabolomes differ with respect to five major classes of metabolism, with 16 pathways implicated in metabolic differences between mothers and neonates. We observed pathway-specific metabolomic differences in mothers only, for fatty acid and lipid metabolism, with neonate metabolomic differences driven by non-pathway specific alterations in the global fetal metabolic profile. CONCLUSION: Our study provides evidence to support that maternal metabolomes are not proxies for fetal metabolomes and provides important insight on neonate metabolic changes in the window immediately before and after birth.