Maternal BMI and Glycemia Impact the Fetal Metabolome

Diabetes Care. 2017 Jul;40(7):902-910. doi: 10.2337/dc16-2452.

Abstract

Objective: We used targeted metabolomics to determine associations of maternal BMI and glucose levels with cord blood metabolites and associations of cord blood metabolites with newborn birth weight and adiposity in mother-offspring dyads.

Research design and methods: Targeted metabolomic assays were performed on cord blood serum samples from European ancestry, Afro-Caribbean, Thai, and Mexican American newborns (400 from each ancestry group) whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and who had anthropometric measurements at birth.

Results: Meta-analysis across the four cohorts demonstrated significant correlation of all cord blood metabolites analyzed with maternal fasting levels of the same metabolites at ∼28 weeks' gestation except for triglycerides, asparagine/aspartate, arginine, and the acylcarnitine C14-OH/C12-DC. Meta-analyses also demonstrated that maternal BMI with or without adjustment for maternal glucose was associated with cord blood metabolites including the branched-chain amino acids and their metabolites as well as phenylalanine. One-hour but not fasting glucose was associated with cord blood 3-hydroxybutyrate and its carnitine ester, a medium-chain acylcarnitine, and glycerol. A number of cord blood metabolites were associated with newborn birth weight and sum of skinfolds, including a negative association of triglycerides and positive association of 3-hydroxybutyrate, its carnitine ester, and serine with both newborn outcomes.

Conclusions: Maternal BMI and glycemia are associated with different components of the newborn metabolome, consistent with their independent effects on newborn size at birth. Maternal BMI is associated with a newborn metabolic signature characteristic of insulin resistance and risk of type 2 diabetes in adults.

Publication types

  • Observational Study

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Adiposity
  • Adult
  • Amino Acids, Branched-Chain / blood
  • Birth Weight
  • Blood Glucose / metabolism*
  • Body Mass Index*
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Ethnicity
  • Female
  • Fetal Blood / chemistry
  • Fetus / metabolism*
  • Glucose Tolerance Test
  • Humans
  • Infant, Newborn
  • Insulin Resistance
  • Linear Models
  • Male
  • Meta-Analysis as Topic
  • Metabolome*
  • Metabolomics
  • Obesity / blood
  • Phenylalanine / blood
  • Pregnancy
  • Prenatal Exposure Delayed Effects / blood
  • Triglycerides / blood
  • Young Adult

Substances

  • Amino Acids, Branched-Chain
  • Blood Glucose
  • Triglycerides
  • Phenylalanine
  • 3-Hydroxybutyric Acid