Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth

Denise M. Scholtens, James R. Bain, Anna C. Reisetter, Michael J. Muehlbauer, Michael Nodzenski, Robert D. Stevens, Olga Ilkayeva, Lynn P. Lowe, Boyd E. Metzger, Christopher B. Newgard, William L. Lowe

Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and non-targeted gas-chromatography/mass-spectrometry metabolomics on maternal serum collected at fasting and 1-hour following Trutol consumption during an oral glucose tolerance test for 400 Northern European mothers at ∼28 weeks gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines and products of lipid metabolism decreased and triglycerides increased following glucose ingestion during the OGTT. Analyses of individual metabolites indicated limited maternal glucose associations at fasting, but broader associations including amino acids, fatty acids, carbohydrates and lipids at 1-hour. Network analyses modeling metabolite correlations provided context for individual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates and organic acids. Random forest analyses indicated improved ability to predict newborn size outcomes using maternal metabolomics data beyond traditional risk factors including maternal glucose. Broad scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity.