Associations between maternal prepregnancy body mass index and maternal and cord blood metabolome

Context: Prepregnancy body mass index (pBMI) is associated with the maternal metabolome during pregnancy. However, evidence remains inconclusive whether pBMI is also associated with alterations in the fetal cord blood metabolome, and whether pBMI modifies the associations between maternal and fetal metabolomes. Objective: This work aimed to examine whether pBMI is associated with the fetal cord blood metabolome and whether maternal and fetal metabolomes are associated and vary according to the degree of maternal pBMI. Methods: We derived pBMI from medical records and tested it in relation to 95 cord blood metabolic measures of 1702 newborns in the PREDO, RADIEL, and ITU studies. We tested the associations between maternal and fetal metabolomes and moderation by pBMI in 556 mother-child dyads of the PREDO and RADIEL studies contributing maternal blood samples at 3 time points during pregnancy. Results: In the meta-analysis of the 3 studies, higher pBMI was associated with 12 of the 95 cord blood metabolic measures, including lower levels of high-density lipoprotein-associated measures and higher levels of branched-chain and aromatic amino acids, as well as ketone bodies. Associations between maternal and fetal metabolomes were significant for 61 of the 95 measures; 26 of the 95 associations were modified by maternal pBMI, being stronger among mothers with obesity than those without. Conclusion: Maternal pBMI is associated with alterations in fetal cord blood metabolome. Maternal and fetal metabolomes are associated, and associations vary according to maternal pBMI.