Abstract
Background/Objectives
Low-level, in-utero exposure to toxic metals such as lead (Pb) and mercury (Hg) is widespread in the US and worldwide; and, individually, was found to be obesogenic in children. To address the literature gaps on the health effects of co-exposure to low-level toxic metals and the lack of intervention strategy, we aimed to investigate the association between in-utero co-exposure to Hg, Pb, cadmium (Cd) and childhood overweight or obesity (OWO) and whether adequate maternal micronutrients (selenium (Se) and folate) can be protective.
Subjects/Methods
This study included 1442 mother-child pairs from the Boston Birth Cohort, a predominantly urban, low-income, Black, and Hispanic population, who were enrolled at birth and followed prospectively up to age 15 years. Bayesian kernel machine regression (BKMR) was applied to estimate individual and joint effects of exposures to metals and micronutrients on childhood OWO while adjusting for pertinent covariables. Stratified analyses by maternal OWO and micronutrient status were performed to identify sensitive subgroups.
Results
In this sample of understudied US children, low-level in-utero co-exposure to Hg, Pb, and Cd was widespread. Besides individual positive associations of maternal Hg and Pb exposure with offspring OWO, BKMR clearly indicated a positive dose-response association between in-utero co-exposure to the three toxic metals and childhood OWO. Notably, the metal mixture-OWO association was more pronounced in children born to mothers with OWO; and in such a setting, the association was greatly attenuated if mothers had higher Se and folate levels.
Conclusions
In this prospective cohort of US children at high-risk of toxic metal exposure and OWO, we demonstrated that among children born to mothers with OWO, low-level in-utero co-exposure to Hg, Pb, and Cd increased the risk of childhood OWO; and that adequate maternal Se and folate levels mitigated the risk of childhood OWO.
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Data availability
The data, data dictionary, and analytical programs for this manuscript are not currently available to the public. However, they can be made available upon reasonable request and after the review and approval of the institutional review board.
Code availability
The R code supporting the findings of this study are available upon request from the corresponding author.
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Acknowledgements
The authors would like to thank all study participants in the Boston Birth Cohort. The authors also acknowledge the nursing staff at Labor and Delivery of the Boston Medical Center and the field team for their contributions to the Boston Birth Cohort. The Boston Birth Cohort (the parent study) was supported in part by the National Institutes of Health (NIH) grants (R21ES011666, 2R01HD041702, R21HD066471, R01HD086013, R01HD098232, R01ES031272, and R01ES031521); and the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) (UJ2MC31074). Dr. Guoying Wang is also supported by grant R03ES029594 from the NIH/National Institute of Environmental Health Science. This study was possible in part due to funding for programmatic analytical capacity and capability through Cooperative Agreement #CDC-RFA-EH14-140203 between the New Jersey Department of Health (NJDOH) Public Health and Environmental Laboratories (PHEL) and the Centers for Disease Control and Prevention (CDC) States Biomonitoring Grant Program. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by any funding agencies.
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The authors’ responsibilities were as follows—WH, TI, EB, and XW conceived and designed the study; XW, GW, XH participated in biosample collection, storage, and preparation; EB, AS, JM, DH, ZF conducted metals/trace elements lab analysis; XW, GW have full access to the data and verified the underlying data; WH conducted all the statistical analyses, and TI, RX, XH, XW provided assistance; TI, EB, ZF, and XW offered administrative, technical, and material supports; XW, GW, and ZF obtained funding; all authors contributed to the critical review and revision of the manuscript and approved the final manuscript.
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Huang, W., Igusa, T., Wang, G. et al. In-utero co-exposure to toxic metals and micronutrients on childhood risk of overweight or obesity: new insight on micronutrients counteracting toxic metals. Int J Obes 46, 1435–1445 (2022). https://doi.org/10.1038/s41366-022-01127-x
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DOI: https://doi.org/10.1038/s41366-022-01127-x
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