Association between heavy metals exposure and risk of attention deficit hyperactivity disorder (ADHD) in children: a systematic review and meta-analysis

Heavy metals can negatively affect children's neurodevelopment, yet the relationship between heavy metals exposure and attention deficit hyperactivity disorder (ADHD) in children remains unclear. We aimed to examine associations between exposure to five common heavy metals (lead, arsenic, mercury, cadmium, and manganese) with neurodevelopmental toxicity and the risk of ADHD in children. Online databases of PubMed, Web of Science, and Embase were searched before February 29, 2024. A total of 31 studies involving 25,258 children were included in the final analysis. Our findings revealed that lead exposure was positively associated with ADHD risk in children (OR = 1.95, 95% CI: 1.57-2.41) overall, while the associations varied among different WHO regions, with the strongest in the Americas. Sensitivity analyses revealed significant associations between arsenic (OR = 1.53, 95% CI: 1.01-2.32) and manganese (OR = 1.79, 95% CI: 1.28-2.49) exposure and ADHD risk after omitting one study. Arsenic exposure was positively associated with ADHD risk in studies conducted in the Americas and adjusted for environmental smoke exposure. Positive associations between manganese exposure and ADHD risk were also found in several subgroup analyses. No significant associations were found for mercury and cadmium exposure. Dose-response meta-analysis suggested that children with higher blood lead levels exhibited a higher probability of ADHD diagnosis. Lead exposure consistently increases the risk of ADHD in children, while arsenic and manganese exposure may be associated with ADHD under different occasions. More research is required to understand heavy metals' impact on ADHD across varying exposure levels, particularly in less contaminated regions.