Cord Blood Metabolomics: Association With Newborn Anthropometrics and C-Peptide Across Ancestries

Abstract

Context: Newborn adiposity is associated with childhood obesity. Cord blood metabolomics is one approach that can be used to understand early-life contributors to adiposity and insulin resistance.

Objective: To determine the association of cord blood metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of newborns.

Design: Cross-sectional, observational study.

Setting: Hyperglycemia and Adverse Pregnancy Outcome study.

Participants: One thousand six hundred multiethnic mother-newborn pairs.

Main outcome measure: Cord blood C-peptide, birthweight, and newborn sum of skinfolds.

Results: Meta-analyses across four ancestry groups (Afro-Caribbean, Northern European, Thai, and Mexican American) demonstrated significant associations of cord blood metabolites with cord blood C-peptide, birthweight, and newborn sum of skinfolds. Several metabolites, including branched-chain amino acids (BCAAs), medium- and long-chain acylcarnitines, nonesterified fatty acids, and triglycerides were negatively associated with cord C-peptide but positively associated with birthweight and/or sum of skinfolds. 1,5-Anhydroglucitol, an inverse marker of recent maternal glycemia, was significantly inversely associated with birthweight and sum of skinfolds. Network analyses revealed groups of interrelated amino acid, acylcarnitine, and fatty acid metabolites associated with all three newborn outcomes.

Conclusions: Cord blood metabolites are associated with newborn size and cord blood C-peptide levels after adjustment for maternal body mass index and glucose during pregnancy. Negative associations of metabolites with C-peptide at birth were observed. 1,5-Anhydroglucitol appears to be a marker of adiposity in newborns. BCAAs were individually associated with birthweight and demonstrated possible associations with newborn adiposity in network analyses.

Conflict of interest statement

Disclosure Summary: The authors have nothing to disclose.

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Copyright © 2019 Endocrine Society.

Figures

Figure 1.

Heat map displaying positive (red) and negative (blue) associations of cord blood metabolites with newborn outcomes across ancestries in the meta-analysis, with hierarchical clustering of metabolites according to test statistics reflecting strength of association. Analyses were adjusted for field center, mean arterial pressure, maternal age, newborn sex, sample storage time, mode of delivery, and gestational age at delivery (model 1). Model 2 includes model 1 covariates, maternal BMI, and maternal fasting glucose. Model 3 includes model 2 covariates and cord blood C-peptide.

Figure 2.

Heat map displaying ancestry-specific positive (red) and negative (blue) associations of cord blood metabolites with newborn outcomes in the fully adjusted models, with hierarchical clustering of metabolites according to test statistics reflecting strength of association. Analyses were adjusted for field center, mean arterial pressure, maternal age, newborn sex, sample storage time, mode of delivery, gestational age at delivery, maternal BMI, and maternal fasting glucose (model 2). Model 3 includes model 2 covariates and cord blood C-peptide. AC, Afro-Caribbean; EU, Northern European; MA, Mexican American; TH, Thai.

Figure 3.

Subnetworks including cord blood metabolites associated with newborn sum of skinfolds. The subnetwork including cord blood metabolites associated with newborn sum of skinfolds is shown in model 3. Covariates for the model include field center, mean arterial pressure, maternal age, neonatal sex, sample storage time, mode of delivery, gestational age at delivery, maternal BMI, maternal fasting glucose at OGTT, and cord blood C-peptide. Blue shading denotes spin-glass communities within the estimated networks. Edges represent dependence among metabolite pairs conditional on all other metabolites in the network according to graphical lasso. Solid edges represent dependencies for metabolites in the same spin-glass cluster, and red dashed lines represent dependencies for metabolites in different spin-glass clusters. Large nodes represent metabolites that are individually significant with newborn sum of skinfolds, whereas small nodes are correlated with an individually significant metabolite. Nodes are colored by metabolite class (AC, acylcarnitine; AA, amino acid; CHO, carbohydrate; FA, fatty acid; GC/TCA, glycolysis/tricarboxylic acid cycle; MISC, miscellaneous; OA, organic acid; PUR/PYR, purine or pyrimidine). Abbreviated metabolites are as follows: 3-OHB, 3-hydroxybutyrate; Asn/Asx, asparagine/aspartic acid; Glu/Glx, glutamine/glutamic acid; Leu/Ile, leucine/isoleucine; NM/2AA/NE, N-methylamine/2-aminobutanoic acid/N-ethylglycine; OHPro, hydroxyproline.