A systematic literature review on the association between exposures to toxic elements and an autism spectrum disorder

Background and aim: Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by difficulties in social communication and repetitive behaviors. There have beenmany previous studies of toxic metals in ASD. Therefore, the priority of this study is to review the relationships between exposure to toxic metals and ASD. Materials & methods: This study was based on a comprehensive search of international databases, such as Web of Science, Science Direct, Scopus, PubMed, and Google Scholar, for all works related to the subject under discussion from 1982 to 2022. We further summarize published data linked to this topic and discuss with clarifying evidence that agrees and conflicts with the association between exposure to toxic metals, including mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As), and aluminum (Al) and ASD. Results: 40 out of 63 papers met the requirements for meta-analysis. Blood Pb levels (standardized mean difference (SMD) = 0.81; 95 % confidence interval (CI): 0.36-1.25), blood Hg (SMD = 0.90; CI: 0.30-1.49), hair Pb (SMD = 1.47; CI: 0.03-2.92), urine As (SMD= 0.65; CI: 0.22-1.09), and urine Al levels (SMD= 0.85; CI: 0.40-1.29) in autistic individuals were significantly higher than those of healthy control (HC). Whereas, blood As levels (SMD = 1.33; CI: -1.32-3.97), hair As (SMD= 0.55; CI: -0.14-1.24), hair Cd (SMD= 0.60; CI: -0.31-1.51), hair Hg (SMD= 0.41; CI: -0.30-1.12), hair Al (SMD = 0.87; CI: -0.02-1.77), urine Pb (SMD = -0.68; CI: -2.55-1.20), urine Cd (SMD = -0.26; CI: -0.94-0.41), and urine Hg levels (SMD = 0.47; CI: -0.09-1.04) in autistic individuals were significantly lower than those of HC. Conclusion: Toxic metal content significantly differed between individuals with ASD and HC in the current metaanalysis. The results assist in clarifying the significance of toxic metals as environmental factors in the development of ASD.