Dysregulated maternal and newborn fatty acid, sugar and amino acid metabolism associated with high birth weight

Objective: This study aims to find maternal and neonatal metabolomic signatures that contribute to the adverse birthweight outcomes including abnormally high and low birth weight. We also investigated the role of metabolomic signatures in the associations of maternal risk factors such as parity and gestational weight gain with adverse birthweight outcomes. Methods: Ninety-six pregnant women and their newborns from the MADRES prospective cohort were studied. Maternal serum at third trimester and newborn cord blood were assayed for untargeted metabolomics using mass-spectrometry. Metabolome-wide association analysis was conducted to assess maternal and newborn metabolomic features association with birth weight Z-score, followed by network analysis of maternal and newborn metabolomics. Lastly, the contribution of maternal and newborn metabolomics to associations between maternal risk factors and newborn birthweight was assessed. Results: Maternal gestational weight gain and parity were positively associated with newborn birthweight. Maternal glucose and branched-chain amino acid metabolism pathways and newborn’s fatty acid, glucose metabolism and C21-steroid hormone biosynthesis were significantly enriched with high birth weight Z-score. Dysregulation in these pathways linked maternal factors such as gestational weight gain and parity with high birth weight Z-score. Conclusion: Our findings indicate that altered maternal sugar and energy metabolism, newborn sugar and amino acid metabolism, and newborn C21-steroid hormone biosynthesis were associated with high birth weight. Dysregulated metabolism in pregnant women and newborn may contribute to the pathophysiological mechanisms linking maternal excessive gestational weight gain and multiparity with high birth weight. (Figure presented.)