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Maternal metabolites during pregnancy are associated with newborn outcomes and hyperinsulinaemia across ancestries

  • Rachel Kadakia
  • Michael Nodzenski
  • Octavious Talbot
  • Alan Kuang
  • James R. Bain
  • Michael J. Muehlbauer
  • Robert D. Stevens
  • Olga R. Ilkayeva
  • Sara K. O’Neal
  • Lynn P. Lowe
  • Boyd E. Metzger
  • Christopher B. Newgard
  • Denise M. Scholtens
  • William L. LoweJr
  • for the HAPO Study Cooperative Research Group



We aimed to determine the association of maternal metabolites with newborn adiposity and hyperinsulinaemia in a multi-ethnic cohort of mother–newborn dyads.


Targeted and non-targeted metabolomics assays were performed on fasting and 1 h serum samples from a total of 1600 mothers in four ancestry groups (Northern European, Afro-Caribbean, Mexican American and Thai) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, underwent an OGTT at ~28 weeks gestation and whose newborns had anthropometric measurements at birth.


In this observational study, meta-analyses demonstrated significant associations of maternal fasting and 1 h metabolites with birthweight, cord C-peptide and/or sum of skinfolds across ancestry groups. In particular, maternal fasting triacylglycerols were associated with newborn sum of skinfolds. At 1 h, several amino acids, fatty acids and lipid metabolites were associated with one or more newborn outcomes. Network analyses revealed clusters of fasting acylcarnitines, amino acids, lipids and fatty acid metabolites associated with cord C-peptide and sum of skinfolds, with the addition of branched-chain and aromatic amino acids at 1 h.


The maternal metabolome during pregnancy is associated with newborn outcomes. Maternal levels of amino acids, acylcarnitines, lipids and fatty acids and their metabolites during pregnancy relate to fetal growth, adiposity and cord C-peptide, independent of maternal BMI and blood glucose levels.


Adiposity Fetal growth Metabolomics Pregnancy outcomes 



Aromatic amino acid


Branched-chain amino acid


3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid


False discovery rate


Gestational diabetes mellitus


Hyperglycemia and Adverse Pregnancy Outcome


Quality control




Sum of skinfolds


Contribution statement

RK contributed to data interpretation and manuscript writing. MN, OT and AK contributed to analysis and interpretation of data. MN and DMS led data analysis. JRB, MJM, RDS, ORI, SON, LPL, BEM and CBN contributed to acquisition and interpretation of data. DMS and WLL were involved in all aspects of the study, including study design and data collection, analysis and interpretation. All authors made critical intellectual contributions to drafting and/or revising the manuscript and all approved the final version. DMS and WLL are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.


This study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095963) and the National Institute of Child Health and Human Development (R01-HD34242, R01-HD34243).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2018_4781_MOESM1_ESM.pdf (182 kb)
Tables (PDF 181 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Rachel Kadakia
    • 1
    • 2
  • Michael Nodzenski
    • 1
  • Octavious Talbot
    • 1
  • Alan Kuang
    • 1
  • James R. Bain
    • 3
    • 4
    • 5
  • Michael J. Muehlbauer
    • 3
    • 4
    • 5
  • Robert D. Stevens
    • 3
    • 4
    • 5
  • Olga R. Ilkayeva
    • 3
    • 4
    • 5
  • Sara K. O’Neal
    • 3
    • 4
    • 5
  • Lynn P. Lowe
    • 1
  • Boyd E. Metzger
    • 1
  • Christopher B. Newgard
    • 3
    • 4
    • 5
  • Denise M. Scholtens
    • 1
  • William L. LoweJr
    • 1
  • for the HAPO Study Cooperative Research Group
  1. 1.Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  2. 2.Ann and Robert H. Lurie Children’s Hospital of ChicagoChicagoUSA
  3. 3.Sarah W. Stedman Nutrition and Metabolism CenterDuke University Medical CenterDurhamUSA
  4. 4.Duke Molecular Physiology InstituteDurhamUSA
  5. 5.Duke University School of MedicineDurhamUSA

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