Maternal BMI and Glycemia Impact the Fetal Metabolome

OBJECTIVE: We used targeted metabolomics to determine associations of maternal BMI and glucose levels with cord blood metabolites and associations of cord blood metabolites with newborn birth weight and adiposity in mother-offspring dyads. RESEARCH DESIGN AND METHODS: Targeted metabolomic assays were performed on cord blood plasma samples from European ancestry, Afro-Caribbean, Thai, and Mexican American newborns (400 from each ancestry group) whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and who had anthropometric measurements at birth. RESULTS: Meta-analysis across the four cohorts demonstrated significant correlation of all cord blood metabolites analyzed with maternal fasting levels of the same metabolites at ∼28 weeks’ gestation except for triglycerides, asparagine/aspartate, arginine, and the acylcarnitine C14-OH/C12-DC. Meta-analyses also demonstrated that maternal BMI with or without adjustment for maternal glucose was associated with cord blood metabolites including the branched-chain amino acids and their metabolites as well as phenylalanine. One-hour but not fasting glucose was associated with cord blood 3-hydroxybutyrate and its carnitine ester, a medium-chain acylcarnitine, and glycerol. A number of cord blood metabolites were associated with newborn birth weight and sum of skinfolds, including a negative association of triglycerides and positive association of 3-hydroxybutyrate, its carnitine ester, and serine with both newborn outcomes. CONCLUSIONS: Maternal BMI and glycemia are associated with different components of the newborn metabolome, consistent with their independent effects on newborn size at birth. Maternal BMI is associated with a newborn metabolic signature characteristic of insulin resistance and risk of type 2 diabetes in adults.