title: Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes.
abstract: Maternal obesity increases the risk for large-for-gestational-age birth and excess newborn adiposity, which are associated with adverse long-term metabolic outcomes in offspring, probably due to effects mediated through the intrauterine environment. We aimed to characterise the maternal metabolic milieu associated with maternal BMI and its relationship to newborn birthweight and adiposity.
  
  
  
  Fasting and 1 h serum samples were collected from 400 European-ancestry mothers in the Hyperglycaemia and Adverse Pregnancy Outcome Study who underwent an OGTT at ∼28 weeks gestation and whose offspring had anthropometric measurements at birth. Metabolomics assays were performed using biochemical analyses of conventional clinical metabolites, targeted MS-based measurement of amino acids and acylcarnitines and non-targeted GC/MS.
  
  
  
  Per-metabolite analyses demonstrated broad associations with maternal BMI at fasting and 1 h for lipids, amino acids and their metabolites together with carbohydrates and organic acids. Similar metabolite classes were associated with insulin resistance with unique associations including branched-chain amino acids. Pathway analyses indicated overlapping and unique associations with maternal BMI and insulin resistance. Network analyses demonstrated collective associations of maternal metabolite subnetworks with maternal BMI and newborn size and adiposity, including communities of acylcarnitines, lipids and related metabolites, and carbohydrates and organic acids. Random forest analyses demonstrated contribution of lipids and lipid-related metabolites to the association of maternal BMI with newborn outcomes.
  
  
  
  Higher maternal BMI and insulin resistance are associated with broad-based changes in maternal metabolites, with lipids and lipid-related metabolites accounting, in part, for the association of maternal BMI with newborn size at birth.
authors.affiliation: Feinberg School of Medicine, Northwestern University, 420 E. Superior Street, Rubloff 12, Chicago, IL, 60611, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Sandler
authors.affiliation: Feinberg School of Medicine, Northwestern University, 420 E. Superior Street, Rubloff 12, Chicago, IL, 60611, USA.
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, USA.|Duke Molecular Physiology Institute, Durham, NC, USA.|Duke University School of Medicine, Durham, NC, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Bain
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Durham, NC, USA.|Duke University School of Medicine, Durham, NC, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Muehlbauer
authors.affiliation: Feinberg School of Medicine, Northwestern University, 420 E. Superior Street, Rubloff 12, Chicago, IL, 60611, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nodzenski
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Durham, NC, USA.|Duke University School of Medicine, Durham, NC, USA.
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, USA.|Duke Molecular Physiology Institute, Durham, NC, USA.|Duke University School of Medicine, Durham, NC, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Ilkayeva
authors.affiliation: Feinberg School of Medicine, Northwestern University, 420 E. Superior Street, Rubloff 12, Chicago, IL, 60611, USA.
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Lowe
authors.affiliation: Feinberg School of Medicine, Northwestern University, 420 E. Superior Street, Rubloff 12, Chicago, IL, 60611, USA.
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, USA.|Duke Molecular Physiology Institute, Durham, NC, USA.|Duke University School of Medicine, Durham, NC, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.affiliation: Feinberg School of Medicine, Northwestern University, 420 E. Superior Street, Rubloff 12, Chicago, IL, 60611, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Scholtens
authors.affiliation: Feinberg School of Medicine, Northwestern University, 420 E. Superior Street, Rubloff 12, Chicago, IL, 60611, USA. wlowe@northwestern.edu.
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; D005865:Gestational Age; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D055442:Metabolome / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose
keywords: Fetal growth; Maternal BMI; Maternal insulin resistance; Maternal metabolism; Pregnancy