Metabolomic signatures of low- and high-adiposity neonates differ based on maternal BMI.

Maternal obesity [body mass index (BMI) > 30 kg/m] is associated with greater neonatal adiposity, cord blood (CB) insulin levels, and a proinflammatory phenotype at birth, contributing to risk of future cardiometabolic disease in the offspring. Variation in neonatal adiposity within maternal BMI groups is underappreciated, and it remains unclear whether the metabolic impairments at birth are an outcome of maternal obesity or excess fetal fat accrual. We examined the hypothesis that CB metabolites associated with fetal fat accrual differ between offspring of normal-weight and obese women. Umbilical venous blood was collected at the time of scheduled cesarean delivery from 50 normal-weight women (LE; pregravid BMI = 22.3 ± 1.7 kg/m) and 50 obese women (OB; BMI = 34.5 ± 3.0 kg/m). Neonatal adiposity was estimated from flank skinfold thickness. The first (low adiposity, LA) and third (high adiposity, HA) tertiles of neonatal %body fat were used to create four groups: OBLA, OBHA, LELA, and LEHA. CB metabolites were measured via untargeted metabolomics. Broadly, the LA offspring of OB women (OBLA) metabolite signature differed from other groups. Lauric acid (C12:0) was 82-118% higher in OBLA vs. all other groups [false discovery rate (FDR) < 0.01]. Several other fatty acids, including palmitate, stearate, and linoleate, were higher in OBLA vs. OBHA groups. CB metabolites, such as lauric acid, a medium-chain fatty acid that may improve insulin sensitivity, were associated with neonatal adiposity differently between offspring of women with and without obesity. Changes in metabolically active lipids at birth may have long-term consequences for offspring metabolism. Using untargeted metabolomics in 100 newborns, we found that cord blood metabolite signatures associated with neonatal adiposity differed between offspring of women with and without obesity.