title: Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth.
abstract: 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 nontargeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) 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 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, were found at 1 h. 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 an improved ability to predict newborn size outcomes by 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.
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL dscholtens@northwestern.edu.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Scholtens
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC Duke University School of Medicine, Durham, NC.
authors.forename: James R
authors.initials: JR
authors.lastname: Bain
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Reisetter
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC Duke University School of Medicine, Durham, NC.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Muehlbauer
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Michael
authors.initials: M
authors.lastname: Nodzenski
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC Duke University School of Medicine, Durham, NC.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC Duke University School of Medicine, Durham, NC.
authors.forename: Olga
authors.initials: O
authors.lastname: Ilkayeva
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Lowe
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Boyd E
authors.initials: BE
authors.lastname: Metzger
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC Duke University School of Medicine, Durham, NC.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: William L
authors.initials: WL
authors.lastname: Lowe
mesh_terms: D000328:Adult; D001724:Birth Weight / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005951:Glucose Tolerance Test; D006801:Humans; D007231:Infant, Newborn; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D014280:Triglycerides