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Environmental causes of birth defects: challenges and opportunities

Pediatric Research (2024)Cite this article

In the late 1950s, severe metal poisoning caused thousands of deaths and severe illness in Minamata Bay, Japan. The cause was methylmercury, a potent neurotoxicant derived from mercury that had been discharged into the bay from a chemical manufacturing plant and bioaccumulated in local seafood. Developing fetuses (and children) were most impacted, raising awareness about placental transfer of toxicants and the sensitivity of the fetus to environmental exposures. This devastating mercury poisoning spurred concerns about the teratogenicity of metals more broadly, and although effects of methylmercury on the brain are now well described, the impacts of other metals and their mixtures on fetal development remain poorly understood.

In this issue of Pediatric Research, Nakamura and colleagues address this knowledge gap in the Japan Environment and Children’s Study (JECS), a large prospective birth cohort in Japan designed to investigate environmental factors and their links with fetal development and early childhood health.1 Prenatal exposure to five metals (cadmium, lead, mercury, selenium, manganese) was estimated by measuring concentrations in second or third trimester maternal blood samples from ~90,000 mother–infant pairs. Metals were examined individually and as a mixture in relation to both major and minor structural malformations or “physical abnormalities,” as documented around the time of birth. Key findings were an increased odds of any physical abnormality among infants with higher (highest quartile) maternal blood manganese levels; no individual associations were observed with other toxic (e.g., cadmium, lead, mercury) or essential (e.g., selenium) metals. When examined as a mixture, higher quartiles of all metals were jointly associated with a modest, but not statistically significant, increase in odds of abnormalities. This study improves upon prior work: its prospective study design measures exposure during pregnancy and captures birth outcomes including early and late deaths and live births; the large sample of ~90,000 mother-infant pairs provides more statistical power; and examining associations of the metal mixture as opposed to only individual metals is more reflective of real-world exposure. Given the dearth of research on the influence of environmental factors on birth defects, this paper represents a promising step forward.

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Authors and Affiliations

  1. Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA

    Birgit Claus Henn

  2. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

    Martha M. Werler

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  1. Birgit Claus Henn
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  2. Martha M. Werler
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Correspondence to Birgit Claus Henn.

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Claus Henn, B., Werler, M.M. Environmental causes of birth defects: challenges and opportunities. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03051-4

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