Abstract
Objective: The aim of this study was to investigate the effects of prenatal heavy metal (arsenic, cadmium, manganese) exposure on infant neurodevelopment through a systematic review and meta-analysis, elucidating the toxicological mechanisms and dose-response relationships for consideration in environmental risk assessment. Methods: Following the PRISMA guidelines, systematic searches were conducted in PubMed, Embase, and other databases, ultimately resulting in 17 observational studies involving 6907 participants. Results: Arsenic (As): A 50% increase in arsenic exposure was associated with a reduction of 0.51 points in the Mental Development Index (MDI; 95% CI: -1.43 to 0.4) and 0.15 points in the Psychomotor Development Index (PDI; 95% CI: -0.96 to 0.65). However, these results did not achieve statistical significance (p > 0.05). Cadmium (Cd): Prenatal cadmium exposure significantly decreased the Full-Scale Intelligence Quotient (FSIQ) in children aged 5-9 years. A 50% increase in cadmium exposure resulted in a 0.44-point drop in the FSIQ (95% CI: -0.67 to -0.21, p < 0.05), with stable effects (I(2) = 0%). Manganese (Mn): Manganese exposure showed a negative association with the MDI (β = -0.11) and PDI (β = -0.18). However, a high degree of heterogeneity was observed (I(2) = 20.89-73.35%), and some studies suggested potential risks even at low exposure levels. Sensitivity analyses indicated that the heterogeneity in the arsenic and manganese results mainly stemmed from individual study differences (e.g., sample characteristics), whereas the cadmium effects were consistent. Conclusions: Prenatal heavy metal exposure (notably cadmium) adversely impacts neurodevelopment, even at low doses. Future research should prioritize critical exposure windows, mixed effects, and sex-specific vulnerabilities. Strengthening environmental monitoring and prenatal guidelines is crucial to mitigate developmental risks.