Abstract

Background: The role of circulating metabolites on child development is understudied. We investigated associations between children's serum metabolome and early childhood development (ECD).

Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children's milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥ 1. The interaction between significant metabolites and the child's age was tested.

Results: Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child's nutritional status, diet quality, and infant age. Cresol sulfate (β = -0.07; adjusted-p < 0.001), hippuric acid (β = -0.06; adjusted-p < 0.001), phenylacetylglutamine (β = -0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = -0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged -1 SD: β = -0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (-1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).

Conclusion: Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.

Funding: Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.

Data availability

Data described in the manuscript, code book, and analytic code is available at: https://dataverse.nutricao.ufrj.br/dataverse/padilha-metab-dev

The following data sets were generated

Article and author information

Author details

  1. Marina Padilha

    Department of Social and Applied Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  2. Victor Nahuel Keller

    Department of Social and Applied Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  3. Paula Normando

    Department of Social and Applied Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  4. Raquel M Schincaglia

    Department of Social and Applied Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  5. Nathalia C Freitas-Costa

    Department of Social and Applied Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  6. Samary SR Freire

    Department of Social and Applied Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7326-1058
  7. Felipe M Delpino

    Department of Social and Applied Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  8. Inês RR de Castro

    Department of Social Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  9. Elisa MA Lacerda

    Department of Nutrition and Dietetics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  10. Dayana R Farias

    Department of Social and Applied Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  11. Zachary Kroezen

    Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9415-7604
  12. Meera Shanmuganathan

    Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  13. Philip Britz-Mckibbin

    Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  14. Gilberto Kac

    Department of Social and Applied Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    For correspondence
    gilberto.kac@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8603-9077

Funding

Brazilian National Research Conuncil

  • Meera Shanmuganathan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The ENANI-2019 was approved by the Research Ethics Committee of the Clementino Fraga Filho University Hospital of the Federal University of Rio de Janeiro (UFRJ) under the number CAAE 89798718.7.0000.5257. Data were collected after a parent/caregiver of the child authorized participation in the study through an informed consent form and following the principles of the Declaration of Helsinki.

Copyright

© 2025, Padilha et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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  1. Marina Padilha
  2. Victor Nahuel Keller
  3. Paula Normando
  4. Raquel M Schincaglia
  5. Nathalia C Freitas-Costa
  6. Samary SR Freire
  7. Felipe M Delpino
  8. Inês RR de Castro
  9. Elisa MA Lacerda
  10. Dayana R Farias
  11. Zachary Kroezen
  12. Meera Shanmuganathan
  13. Philip Britz-Mckibbin
  14. Gilberto Kac
(2025)
Serum metabolome indicators of early childhood development in the Brazilian National Survey on Child Nutrition (ENANI-2019)
eLife 14:e97982.
https://doi.org/10.7554/eLife.97982

Share this article

https://doi.org/10.7554/eLife.97982

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