OR07-1 Cord Blood Metabolomics: Association with Newborn Anthropometrics and C-Peptide across Ancestries

Newborn adiposity is associated with a higher risk of childhood obesity and earlier onset of co-morbid metabolic diseases such as type 2 diabetes mellitus. The cord blood metabolome is one early life marker that provides mechanistic insight into fetal fat deposition, insulin sensitivity, and future obesity and metabolic disease risk and integrates in-utero genetic, nutritional and metabolic cues that contribute to newborn phenotype. We hypothesize that a unique cord blood metabolomic signature associated with newborn adiposity or hyperinsulinemia might emerge as a predictive tool to help identify at-risk children early in life, before disease develops. To evaluate this hypothesis, we performed a cross-sectional, observational study of 1600 newborns who participated in the Hyperglycemia and Adverse Pregnancy Outcome Study. Targeted and nontargeted metabolomics assays were performed on cord blood of newborns across four ancestry groups (Afro-Caribbean, Northern European, Thai, and Mexican American). Newborn birth weight and sum of skinfolds were measured by trained personnel and cord blood was additionally assayed for C-peptide. Associations of cord blood metabolites with newborn phenotype were investigated using 1) per-metabolite analyses within and across ancestries and 2) network analyses to identify interconnected metabolites associated with phenotypes. Several metabolites, including branched-chain amino acids, medium- and long-chain acylcarnitines, nonesterified fatty acids, and triglycerides were significantly negatively associated with cord C-peptide but positively associated with birth weight and/or sum of skinfolds. 1,5-Anhydroglucitol was significantly associated with birth weight and sum of skinfolds in nontargeted metabolite analyses. Network analyses revealed groups of interrelated amino acid, acylcarnitine, and fatty acid metabolites associated with all three newborn outcomes. In conclusion, cord blood metabolites are associated with newborn size and cord C-peptide, even after adjustment for maternal BMI and glucose during pregnancy. The paradoxical inverse association of metabolites with cord blood C-peptide suggests that the metabolite-insulin relationship reverses at a critical point in childhood to the well-described positive association seen in adolescents and adults. The well-known associations of branched chain amino acids and medium- and long-chain acylcarnitines with obesity in adolescents and adults appears to begin at birth and might serve as an early-life marker of obesity risk.