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Analysis of nonlinear associations between prenatal methylmercury exposure from fish consumption and neurodevelopmental outcomes in the Seychelles Main Cohort at 17 years

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Abstract

The Seychelles Child Development Study has been examining the relationship between prenatal methylmercury (MeHg) exposure from consuming fish during pregnancy and child development. This study re-analyzes seven outcomes in the 17 year Main Cohort data to determine if there are nonlinear or non-homogeneous (subgroup) associations that were not identified in the linear analysis. We adopted two statistical approaches. First, we carried out an additive nonlinear analysis assuming homogeneous prenatal MeHg-outcome relationships to explore overall associations. Second, we applied the regression tree to the Woodcock–Johnson Calculation subtest (it was significantly associated in earlier analyses) and identified 4 clusters based on covariates. Then we used additive models to assess the prenatal MeHg association in each of the four clusters for all seven outcomes. This approach assumes nonlinear associations in each cluster and non-homogeneous associations between clusters. The additive nonlinear analysis yielded prenatal MeHg curves similar to the linear analysis. For the regression tree analysis, the curves relating prenatal MeHg to outcomes between the 4 clusters differed and some crossed at higher prenatal MeHg levels, suggesting non-homogeneity in the upper range of exposure. Additionally, some of the curves suggested a possible non-linear relationship within the range of exposure we studied. This non-linear analysis supports the findings from the linear analysis. It shows little evidence to support an adverse association of prenatal MeHg exposure through maternal consumption of fish contaminated with natural background levels. However, the tree analysis suggests that the prenatal exposure/outcome relationship may not be homogeneous across all individuals and that some subpopulations may have an adverse association in the upper range of the exposures studied. More robust data in the higher levels of exposure in this cohort are needed to confirm this finding.

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Funding

This research was supported by Grants RO1-ES008442 and P30-ES01247 from the US National Institute of Environmental Health Sciences, National Institutes of Health, by NSC 100-2118-M-007-001 and 101-2118-M-007-002-MY2 from Taiwan National Science Council, and by the Government of the Republic of Seychelles.

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Authors and Affiliations

  1. Institute of Statistics, National Tsing Hua University, No. 101 Kuang-Fu Road Section 2, Hsinchu City, 30013, Taiwan

    Li-Shan Huang

  2. Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Li-Shan Huang & Sally W. Thurston

  3. Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Deborah A. Cory-Slechta, Gene E. Watson, Edwin van Wijngaarden, Grazyna Zareba, Gary J. Myers & Philip W. Davidson

  4. Eastman Department of Dentistry, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Gene E. Watson

  5. Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Edwin van Wijngaarden

  6. Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Gary J. Myers

  7. Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Deborah A. Cory-Slechta, Gary J. Myers & Philip W. Davidson

  8. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Christopher Cox

  9. Ministry of Health, Victoria, Republic of Seychelles

    Conrad F. Shamlaye

  10. University of Ulster, Coleraine, Northern Ireland, UK

    J. J. Strain

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  1. Li-Shan Huang
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  2. Deborah A. Cory-Slechta
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  3. Christopher Cox
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  4. Sally W. Thurston
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  5. Conrad F. Shamlaye
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  9. J. J. Strain
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  10. Gary J. Myers
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  11. Philip W. Davidson
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Correspondence to Li-Shan Huang.

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We wish to confirm that there are no known conflicts of interest associated with this paper and there has been no significant financial support for this work that could have influenced its outcome.

Protection of human subjects

This research was reviewed and approved by the Institutional Review Boards of both the University of Rochester and the Republic of Seychelles in accordance with national and institutional guidelines for the protection of human subjects.

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Huang, LS., Cory-Slechta, D.A., Cox, C. et al. Analysis of nonlinear associations between prenatal methylmercury exposure from fish consumption and neurodevelopmental outcomes in the Seychelles Main Cohort at 17 years. Stoch Environ Res Risk Assess 32, 893–904 (2018). https://doi.org/10.1007/s00477-017-1451-7

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