Pediatric Heavy-Metal Exposome and Chronic Disease Trajectories: From Neurodevelopment to Metabolic and Endocrine Outcomes

Early-life exposure to toxic metals remains a major global public health concern, particularly for children, whose developing neuroendocrine and metabolic systems are highly vulnerable. Within the exposome and Developmental Origins of Health and Disease (DOHaD) frameworks, this narrative review synthesizes human evidence on pediatric exposure to lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) and its associations with neurodevelopmental, metabolic, and endocrine outcomes. We primarily examined epidemiological studies, systematic reviews, and meta-analyses published between 2010 and 2025 that relied on biomonitoring-based exposure assessment and appropriate adjustment for socioeconomic status and passive smoking, while seminal earlier studies were considered to contextualize biological mechanisms and conceptual frameworks. The evidence for neurodevelopmental toxicity is the most consistent, with prenatal and early childhood exposure to Pb and Hg robustly associated with adverse cognitive, behavioral, and motor outcomes and no identified safe exposure threshold for lead. In contrast, associations with obesity and pubertal timing are more heterogeneous and metal-specific, reflecting nonlinear dose–response relationships, sex-specific susceptibility, and critical exposure windows. Emerging data indicate that metals may act as metabolism- and endocrine-disrupting chemicals, with effects amplified by mixture exposures and adverse social conditions, and partially modified by nutritional status. Overall, the findings support life-course–oriented, biomonitoring-based research and prevention strategies that address cumulative exposures and developmental vulnerability to reduce long-term disease risk.