Systematic review of studies on exposure to arsenic in drinking water and cognitive and neurobehavioral effects

An association between exposure to arsenic (As) and neurologic and behavioral effects has been reported in some studies, but no systematic review is available of the evidence linking As in drinking water and neurobehavioral effects after consideration of study quality and potential confounding, with focus on low-level circumstances of exposure. We conducted a systematic review and reported it in compliance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, through a search of the databases PubMed, Web of Science, Scopus, and Embase. We included in the review the studies reporting results based on exposure from drinking water in humans. Endpoints were heterogeneous across studies, so we classified them into eight broad domains and developed an ad-hoc system to evaluate their methodological quality, based on three tiers. It was not possible to conduct meta-analysis because of the heterogeneity in exposure assessment and in the definition and assessment of outcomes. The search identified 18,518 articles. After elimination of duplicates and irrelevant articles, we retained 106 articles which reported results on As exposure and neurobehavioral effects, of which 22 reported risk estimates from exposure in drinking water (six among adults and 16 among children). None of the studies was conducted blindly. Among the studies in adults, two, which were conducted in highly exposed populations, were classified as high quality. These two studies were broadly consistent in reporting an association between exposure to As and decline in cognitive function; however, they provide no evidence of an association for exposure below 75 μg/L. The four lower-quality studies were based on populations with low exposure; these studies reported associations with inconsistent outcomes, few of which remained statistically significant after adjustment for multiple comparisons. Among the five high-quality studies of children, one reported an association between As in drinking water and intellectual function, whereas none of the other studies reported an association with different neurobehavioral indicators, after adjusting for potential confounders and multiple comparisons. Out of seven intermediate-quality studies, three reported an association with cognitive function or other outcomes; but sources of bias were not adequately controlled. The remaining studies were negative. The four low-quality studies did not contribute to the overall evidence because of methodological limitations. Our assessment of the available literature showed a lack of evidence for a causal association between exposure to As in drinking water and neurobehavioral effects. To clarify whether such an association exists, further studies prospectively evaluating changes in both the concentration of As in drinking water during the life course, and neurobehavioral outcomes, as well as appropriately controlling for potential confounders, are needed.