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

Chem Res Toxicol. 2020 Nov 16;33(11):2699-2718. doi: 10.1021/acs.chemrestox.0c00167. Epub 2020 Oct 12.


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aluminum / administration & dosage
  • Aluminum / adverse effects*
  • Autism Spectrum Disorder / chemically induced*
  • Cadmium / administration & dosage
  • Cadmium / adverse effects*
  • Child
  • Humans
  • Mercury / administration & dosage
  • Mercury / adverse effects*


  • Cadmium
  • Aluminum
  • Mercury