Fetal
overnutrition predisposes offspring to increased metabolic risk. The current study used metabolomics to assess sustained differences in serum metabolites across childhood and adolescence among youth exposed to three typologies of fetal
overnutrition:
maternal obesity only,
gestational diabetes mellitus (GDM) only, and
obesity + GDM. We included youth exposed in utero to
obesity only (BMI ≥ 30; n = 66), GDM only (n = 56),
obesity + GDM (n = 25), or unexposed (n = 297), with untargeted metabolomics measured at ages 10 and 16 years. We used linear mixed models to identify metabolites across both time-points associated with exposure to any
overnutrition, using a false-discovery-rate correction (FDR) <0.20. These metabolites were included in a principal component analysis (PCA) to generate profiles and assess metabolite profile differences with respect to
overnutrition typology (adjusted for prenatal smoking, offspring age, sex, and race/ethnicity). Fetal
overnutrition was associated with 52 metabolites. PCA yielded four factors accounting for 17−27% of the variance, depending on age of measurement. We observed differences in three factor patterns with respect to
overnutrition typology:
sphingomyelin-
mannose (8−13% variance), skeletal muscle metabolism (6−10% variance), and
3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF; 3−4% variance). The
sphingomyelin-
mannose factor score was higher among offspring exposed to
obesity vs. GDM. Exposure to
obesity + GDM (vs. GDM or
obesity only) was associated with higher skeletal muscle metabolism and CMPF scores. Fetal
overnutrition is associated with metabolic changes in the offspring, but differences between typologies of
overnutrition account for a small amount of variation in the metabolome, suggesting there is likely greater pathophysiological overlap than difference.