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Associations between prenatal metal exposure, gene variants, and birth size in Taiwan Birth Panel Study

Pediatric Research (2026)Cite this article

Abstract

Background

Prenatal metal exposure and genetics may affect birth size, and genetic factors could modify metal toxicity. However, few studies examined gene–metal interactions on birth size.

Methods

We used data from 324 mother-infant pairs in the Taiwan Birth Panel Study. Cord blood levels of 16 metals were measured with inductively coupled plasma mass spectrometry, and we selected 13 SNPs related to birth size, folate and metal metabolism. Birth weight, birth length and head circumference were abstracted from medical records. Multivariable generalized linear regression was applied to assess single metal–birth size associations and interactions, and quantile g-computation and Bayesian kernel machine regression were applied for metal mixture analyses.

Results

Prenatal barium exposure was negatively associated with birth size, whereas prenatal zinc exposure was positively associated with birth size. We observed several metal–SNP interactions on birth size, particularly between cobalt and multiple genetic variants. Genetic variants also modified the effects of metal mixtures on birth size.

Conclusions

Genetic factors may influence the impact of prenatal metal exposure on birth size. Identifying these gene–environment interactions may help guide precision strategies to reduce metal-related risks in early life.

Impact

  • Elevated prenatal Ba and Zn levels were associated with birth size in opposite directions.

  • Genetic variants in folate and metal metabolism modified prenatal metal effects, with the strongest interactions seen for cobalt and folate-pathway variants.

  • Metal mixture–birth size associations were most pronounced for the rs10830963 genotype and several other variants.

  • Gene–metal interactions can inform precision prenatal risk reduction strategies for metal exposure.

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Fig. 1
Fig. 2: Correlation between metal concentrations in the study population.
Fig. 3: Association between metal exposure and birth outcomes in the study population.
Fig. 4: Association between metal mixture exposure and birth size among the population with different genotypes.

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Data availability

Data will be made available on reasonable request.

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Acknowledgements

We would like to acknowledge our study team of the Taiwan Birth Panel Study, and the laboratory staff at National Taiwan University. The authors would like to thank all the participating children, parents, practitioners, and researchers who took part in this study during the past two decades.

Funding

This work was supported by the National Council of Science and Technology (112-2621-M-002-024-MY3, 111-2621-M-002-022, 110-2621-M-002-022, 109-2621-M-002-020) and National Health Research Institutes (EM-114-GP-03, EM-114-PP-01, EM-113-GP-03, EM-113-PP-01, PH-112-SP-17, EM-112-PP-01, EM-111-PP-01, EM-110-PP-01) in Taiwan.

Author information

Authors and Affiliations

  1. Department of Environmental and Occupational Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan

    Chih-Fu Wei

  2. Department of Environmental and Occupational Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan

    Chih-Fu Wei & Pau-Chung Chen

  3. Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan

    Mei-Huei Chen

  4. Department of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan

    Mei-Huei Chen & Wu-Shiun Hsieh

  5. Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health, Taipei, Taiwan

    Ching-Chun Lin & Pau-Chung Chen

  6. Institute of Health Data Analytics and Statistics, Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan

    Tzu-Pin Lu

  7. Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA

    Ya-Wen Chen

  8. Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan

    Wu-Shiun Hsieh

  9. School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Wu-Shiun Hsieh

  10. National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan

    Pau-Chung Chen

  11. Department of Public Health, National Taiwan University College of Public Health, Taipei, Taiwan

    Pau-Chung Chen

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  1. Chih-Fu Wei
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  2. Mei-Huei Chen
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  3. Ching-Chun Lin
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  4. Tzu-Pin Lu
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  5. Ya-Wen Chen
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  6. Wu-Shiun Hsieh
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Contributions

Chih-Fu Wei: data curation; formal analysis; investigation; methodology; software; validation; visualization; writing—original draft, review & editing. Mei-Huei Chen: data curation; formal analysis; investigation; methodology; resources; supervision; validation; writing—review & editing. Ching-Chun Lin: data curation; formal analysis; investigation; methodology; resources; supervision; validation; writing—review & editing. Tzu-Pin Lu: data curation; formal analysis; methodology; resources; software; validation; writing—review & editing. Ya-Wen Chen: investigation; methodology; writing—review & editing. Wu-Shiun Hsieh: data curation; formal analysis; investigation; methodology; resources; supervision; validation; writing—review & editing. Pau-Chung Chen: conceptualization; data curation; formal analysis; funding acquisition; investigation; methodology; resources; software; supervision; validation; visualization; writing—review & editing.

Corresponding author

Correspondence to Pau-Chung Chen.

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The authors declare no competing interests.

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Parents provided informed consent for their own participation and that of their children when enrolled in the study, which was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of National Taiwan University Hospital (Project Identification Code: 201112137RIC).

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Wei, CF., Chen, MH., Lin, CC. et al. Associations between prenatal metal exposure, gene variants, and birth size in Taiwan Birth Panel Study. Pediatr Res (2026). https://doi.org/10.1038/s41390-025-04685-8

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