Heavy metals and neurodevelopment of children in low and middle-income countries: A systematic review

BACKGROUND: The presence of harmful environmental exposures, which disproportionately affects low-and-middle income countries (LMICs), contributes to >25% of deaths and diseases worldwide and detrimentally affects child neurodevelopment. Few resources succinctly summarize the existing literature on this topic. Our objective is to systematically review and characterize the evidence regarding the relationship between heavy metals and neurodevelopment of children in LMICs. METHODS: We conducted a medical librarian-curated search on multiple online databases to identify articles that included individuals <18 years living in a LMIC, quantitatively measured exposure to a heavy metal (either prenatal or postnatal), and used a standardized measurement of neurodevelopment (i.e. cognitive, language, motor, and behavior). Reviews, editorials, or case studies were excluded. Results were analyzed qualitatively, and quality was assessed. RESULTS: Of the 18,043 screened articles, 298 full-text articles were reviewed, and 100 articles met inclusion criteria. The included studies represented data from 19 LMICs, only one of which was classified as a low-income country. Ninety-four percent of postnatal lead and all postnatal manganese studies showed a negative association with metal exposure and neurodevelopment, which were the strongest relationships among the metals studied. Postnatal exposure of mercury was associated with poor neurodevelopment in only half of studies. Limited data on postnatal arsenic and cadmium suggests an association with worse neurodevelopment. Findings were mixed for prenatal arsenic and lead, although some evidence supports that the neurotoxicity of lead was amplified in the presence of manganese. CONCLUSIONS AND POTENTIAL IMPACT: We found that lead and manganese appear to consistently have a detrimental effect on the neurodevelopment of children, and more evidence is needed for mercury, arsenic, and cadmium. Better characterization of these effects can motivate and inform prioritization of much needed international policies and programs to reduce heavy metal exposures for young children within LMICs.