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  • Clinical Research Article
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Alterations in newborn metabolite patterns with preterm birth and diabetes in pregnancy

Pediatric Research volume 98, pages 1023–1032 (2025) Cite this article

Abstract

Background

This study examines the influence of prematurity and diabetes (DM) in pregnancy on metabolite patterns at birth, and associations with adiposity development in a prospective cohort.

Methods

Term and preterm (30-36 weeks gestational age [GA]) infants were enrolled and body composition assessments completed through discharge. Targeted metabolomics was used to assess metabolites in cord or infant blood in the first 2 days.

Results

Among 91 infants, 62 were preterm and 27 were exposed to DM. In factor analysis, variation in acylcarnitines’ and non-essential amino acids differed by GA and DM exposure and were associated with adiposity at term age. DM-group had 1.95-fold increase in t4-OH-pro (p = 0.003) and 2.14-fold increase in taurine (p = 0.004) compared with non-DM group. Preterm infants had 1.77-fold increase in glycerophospholipid PC aa C32:2 versus term group (p < 0.001). Pathway analysis revealed differences across DM and GA groups in pathways associated with citrulline metabolism, amino acid transport/ synthesis, and fatty acid quantity/transport.

Conclusion

In this cohort of infants, there are unique metabolite signatures associated with DM exposure, prematurity, and adiposity development after birth. These markers may reflect early metabolism changes in the developing infant which relate to known risks of adverse growth and cardiometabolic outcomes in this group.

Impact

  • In this study of term and preterm infants, diabetes in pregnancy was associated with unique metabolic signatures at birth, including increased expression of metabolites related to protein synthesis and lipid metabolism.

  • Metabolites related to lipid and protein metabolism were associated with adiposity development at term age, including estimated body fat percent, skin fold thickness measures, and arm circumference measures.

  • Unique signatures of metabolites associated with prematurity and exposure to diabetes in pregnancy may reflect early metabolism changes in the developing infant which relate to known risks of adverse growth and cardiometabolic outcomes in this group.

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Fig. 1: Association of body composition outcomes with metabolites from factor 2.
The alternative text for this image may have been generated using AI.
Fig. 2: Association of body composition outcomes with metabolites from factor 3.
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Fig. 3: Volcano plot of the log-fold change in metabolite concentrations, diabetes group versus non-diabetes group.
The alternative text for this image may have been generated using AI.
Fig. 4: Volcano plot of the log-fold change in metabolite concentrations, preterm group versus term group.
The alternative text for this image may have been generated using AI.
Fig. 5
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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the Yale Neonatal NOuRISH Research Team at Yale School of Medicine for their assistance in enrolling subjects into this study and for their involvement in the conduction of body composition assessments for subjects enrolled in this study.

Funding

This publication was made possible by CTSA Grant Number UL1TR001863 from NCATS, a component of the NIH; the COVID-19 Fund to Retain Clinical Scientists at Yale, sponsored by the Doris Duke Charitable Foundation award #2021266, and the Yale Center for Clinical Investigation; the Robert E. Leet and Clara Guthrie Patterson Trust Mentored Research Award, Bank of America, Private Bank, Trustee; and the Society for Pediatric Research Bridging to Success Award. The 4000 QTRAP mass spectrometer at the Keck MS & Proteomics was funded by NIH/CTSA UL1 RR024139.

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Authors and Affiliations

  1. Department of Pediatrics, Yale School of Medicine, Yale University, New Haven, CT, USA

    Catherine O. Buck, Sarah McCollum, Sarah N. Taylor & Veronika Shabanova

  2. Keck MS & Proteomics Resource, Yale School of Medicine, New Haven, CT, USA

    Weiwei Wang & TuKiet T. Lam

  3. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA

    TuKiet T. Lam

Authors
  1. Catherine O. Buck
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  2. Sarah McCollum
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  3. Weiwei Wang
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  4. TuKiet T. Lam
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  5. Sarah N. Taylor
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  6. Veronika Shabanova
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Contributions

Study conceptualization, C.B., S.T.; Methodology, C.B., V.S., S.T.; Formal Analysis S.M., V.S.; Investigation, C.B.; Biological sample analysis, W.W., T.L.; Resources, T.L.; Writing—Original Draft Preparation, C.B.; Writing—Review & Editing, C.B., S.M., V.S., W.W., T.L., S.T., Supervision, S.T., T.L.; Funding Acquisition, C.B.

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Correspondence to Catherine O. Buck.

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The authors declare no competing interests.

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This study was performed in accordance with the declaration of Helsinki and was approved by the Institutional Review Board at Yale University.

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Buck, C.O., McCollum, S., Wang, W. et al. Alterations in newborn metabolite patterns with preterm birth and diabetes in pregnancy. Pediatr Res 98, 1023–1032 (2025). https://doi.org/10.1038/s41390-025-03844-1

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