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Metabolomic profiling of intrauterine growth-restricted preterm infants: a matched case–control study

Pediatric Research volume 93, pages 1599–1608 (2023)Cite this article

Abstract

Background

The biochemical variations occurring in intrauterine growth restriction (IUGR), when a fetus is unable to achieve its genetically determined potential, are not fully understood. The aim of this study is to compare the urinary metabolomic profile between IUGR and non-IUGR very preterm infants to investigate the biochemical adaptations of neonates affected by early-onset-restricted intrauterine growth.

Methods

Neonates born <32 weeks of gestation admitted to neonatal intensive care unit (NICU) were enrolled in this prospective matched case–control study. IUGR was diagnosed by an obstetric ultra-sonographer and all relevant clinical data during NICU stay were captured. For each subject, a urine sample was collected within 48 h of life and underwent untargeted metabolomic analysis using mass spectrometry ultra-performance liquid chromatography. Data were analyzed using multivariate and univariate statistical analyses.

Results

Among 83 enrolled infants, 15 IUGR neonates were matched with 19 non-IUGR controls. Untargeted metabolomic revealed evident clustering of IUGR neonates versus controls showing derangements of pathways related to tryptophan and histidine metabolism and aminoacyl-tRNA and steroid hormones biosynthesis.

Conclusions

Neonates with IUGR showed a distinctive urinary metabolic profile at birth. Although results are preliminary, metabolomics is proving to be a promising tool to explore biochemical pathways involved in this disease.

Impact

  • Very preterm infants with intrauterine growth restriction (IUGR) have a distinctive urinary metabolic profile at birth.

  • Metabolism of glucocorticoids, sexual hormones biosynthesis, tryptophan-kynurenine, and methionine-cysteine pathways seem to operate differently in this sub-group of neonates.

  • This is the first metabolomic study investigating adaptations exclusively in extremely and very preterm infants affected by early-onset IUGR.

  • New knowledge on metabolic derangements in IUGR may pave the ways to further, more tailored research from a perspective of personalized medicine.

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Fig. 1: Chromatographic profile of the pool of the analyzed urine samples.
Fig. 2: Over-representation pathway analysis.
Fig. 3: Scheme representing the metabolites involved in the tryptophan metabolism.
Fig. 4: Scheme representing the metabolites involved in the steroid hormone biosynthesis.

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Data availability

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

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Authors and Affiliations

  1. Department of Women’s and Children’s Health, Neonatal Intensive Care Unit, University Hospital of Padua, Padua, Italy

    Elena Priante, Giovanna Verlato, Luca Bonadies, Laura Moschino & Eugenio Baraldi

  2. Institute of Pediatric Research, Città della Speranza, Laboratory of Mass Spectrometry and Metabolomics, Padua, Italy

    Matteo Stocchero, Giuseppe Giordano, Paola Pirillo & Eugenio Baraldi

  3. Department of Women’s and Children’s Health, Unit of Gynecology and Obstetrics, University Hospital of Padua, Padua, Italy

    Silvia Visentin

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Contributions

E.P. contributed to study conception and design, acquisition, and interpretation of data and drafted the article. G.V. and E.B. contributed to study conception and design, interpretation of data, and critically reviewed the manuscript. M.S., G.G., and P.P. contributed to study conception and design, analysis, and interpretation of data, and critically reviewed the manuscript. L.B., S.V., and L.M. critically reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Elena Priante.

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A written informed consent was collected from all parents/guardians before the enrollment of the neonates in the study.

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Priante, E., Verlato, G., Stocchero, M. et al. Metabolomic profiling of intrauterine growth-restricted preterm infants: a matched case–control study. Pediatr Res 93, 1599–1608 (2023). https://doi.org/10.1038/s41390-022-02292-5

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