Exposure to Aluminum, Cadmium, and Mercury and Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis.

Autism spectrum disorder (ASD) is a complex neurobehavioral disorder that is believed to be multifactorial in origin. As the incidence of ASD is rising along with industrialization, and because certain metals have been linked to neurological problems, it is important to consider whether such metals may play a role in the development of ASD. Previously, we performed a meta-analysis of existing literature to examine the potential link between inorganic arsenic and lead exposure and ASD. This is a continuation of that study investigating the association of the exposure to aluminum (Al), cadmium (Cd), and mercury (Hg) and ASD. These metals were chosen because they are abundant in our environment, are known to cause neurological problems in humans, and have multiple published studies examining their potential links with ASD. Following the same approach as our previous paper, we conducted a systematic review of the existing literature and performed a meta-analysis to evaluate the current evidence regarding these metals and their potential relationship with autism. We reviewed 18 studies on Al, 18 on Cd, and 23 on Hg, and the individual studies showed inconsistent results. When the measurements were integrated into the meta-analysis, we found significant associations between all the metals and ASD, but the associations were not always in the same direction. Levels of Hg in hair, urine, and blood were all positively associated with ASD. Levels of Al in hair and urine were positively associated with ASD, while levels of Al in blood were negatively associated. In comparison, levels of Cd in hair and urine were negatively associated with ASD. These results imply that, while these metals are all neurotoxic, their impact on the development of ASD and their modes of action could be different. Further research is warranted to examine the longitudinal effects of these toxic metals on the risk of ASD, to assess the critical period when exposure may affect development, and to investigate potential factors that may enhance or ameliorate the effect of metals. Overall, these findings support policies that advocate limiting exposure to neurotoxic metals, particularly for pregnant women and young children, in order to help reduce the rising incidence of ASD.

Exposure to Inorganic Arsenic and Lead and Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis.

Inorganic arsenic (iAs) and lead (Pb) rank first and second on the U.S. Environmental Protection Agency's priority list of hazardous substances. Both are known neurotoxic metals that cause detrimental effects on brain development and lead to deficits in cognitive function and behavioral performance in children. Studies have indicated a potential link between iAs and Pb exposure and a higher risk for autism spectrum disorder (ASD). To provide further insight into whether developmental exposure to iAs or Pb is associated with ASD, we conducted a systematic review and combined data into a meta-analysis to evaluate the available human evidence on the relationships. We systematically reviewed relevant studies published through December 30, 2018 and identified 14 studies on iAs and 37 studies on Pb exposure and their respective associations with ASD. Among them, 8 (53.3%) and 19 (51.3%) studies reported a positive association for iAs and Pb, respectively, and none reported a sole inverse association. In the following meta-analysis, we found statistically significant higher iAs concentrations, in hair and in blood, for children diagnosed with ASD compared with controls across studies. However, the findings on Pb exposure were inconsistent, with a significant association for hair Pb, no association for urinary Pb, and an inverse association for blood Pb. After considering strengths and limitations of the body of research, we concluded that there is consistent evidence supporting a positive association between early life iAs exposure and diagnosis of ASD and inconsistent evidence for Pb exposure and ASD risk. We believe it is in the best interest of policy makers and the public to reduce exposures to iAs and Pb among pregnant women and children. Further, our research supports the need for large perspective human studies with accurate measurement and determination of the long-term body burden of iAs and Pb exposures to assess the impact of iAs and Pb exposures on ASD risk.