Neurodevelopmental Outcomes Associated with Early-Life Exposure to Heavy Metals: A Systematic Review

Globally, approximately 53 million children under the age of five live with some form of developmental disability. Exposure to heavy metals has been identified in the literature as a contributing factor in the etiology of neurodevelopmental disorders, however it usually is understudied. Even at low concentrations, these toxicants pose a risk to neurodevelopment, when affecting children early as in the prenatal period. This study aims to systematically review the literature on the associations between exposure to toxic heavy metals and neurodevelopmental outcomes in children.

The review was registered at the International Prospective Register of Systematic Review-PROSPERO, under number CRD420250653229 and searches were conducted in the PubMed, Scopus, Web of Science, EMBASE, Lilacs and PsycInfo databases.

A total of 68 articles were included, comprising 48 longitudinal studies and 20 cross-sectional studies, published between 2006 and 2025, with a combined sample of 215,195 individuals from 23 countries. Lead was the most consistently investigated metal, appearing in 75% of the studies, followed by mercury, cadmium, and arsenic. Most findings referred to prenatal exposure. Cognitive and motor outcomes were predominantly affected by exposure to Pb and Hg, while behavioral outcomes showed negative associations mainly with Pb and As.

The majority of the studies analyzed indicated adverse effects resulting from exposure to heavy metals during pregnancy, especially in the early months, highlighting the vulnerability of the developing brain.