Dysregulated Maternal and Newborn Fatty Acid, Sugar and Amino Acid Metabolism Associated with High Birth Weight

Objective This study focuses on identifying maternal and neonatal metabolomic profiles linked to adverse birthweight, while also exploring how altered metabolomic signatures influence the underlying pathophysiological mechanisms connecting maternal risk factors and adverse birthweight. 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 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 associated with high birth weight. These alternations may reflect the increased susceptibility to the effects of greater gestational weight gain and multiparity on high birth weight.