Abstract
BackgroundAlthough prior studies showed a correlation between environmental manganese (Mn) exposure and neurodevelopmental disorders in children, the results have been inconclusive. There has yet been no consistent biomarker of environmental Mn exposure. Here, we summarized studies that investigated associations between manganese in biomarkers and childhood neurodevelopment and suggest a reliable biomarker.MethodsWe searched PubMed and Web of Science for potentially relevant articles published until December 31th 2019 in English. We also conducted a meta-analysis to quantify the effects of manganese exposure on Intelligence Quotient (IQ) and the correlations of manganese in different indicators.ResultsOf 1754 citations identified, 55 studies with 13,388 subjects were included. Evidence from cohort studies found that higher manganese exposure had a negative effect on neurodevelopment, mostly influencing cognitive and motor skills in children under 6 years of age, as indicated by various metrics. Results from cross-sectional studies revealed that elevated Mn in hair (H-Mn) and drinking water (W-Mn), but not blood (B-Mn) or teeth (T-Mn), were associated with poorer cognitive and behavioral performance in children aged 6–18 years old. Of these cross-sectional studies, most papers reported that the mean of H-Mn was more than 0.55 μg/g. The meta-analysis concerning H-Mn suggested that a 10-fold increase in hair manganese was associated with a decrease of 2.51 points (95% confidence interval (CI), − 4.58, − 0.45) in Full Scale IQ, while the meta-analysis of B-Mn and W-Mn generated no such significant effects. The pooled correlation analysis revealed that H-Mn showed a more consistent correlation with W-Mn than B-Mn. Results regarding sex differences of manganese associations were inconsistent, although the preliminary meta-analysis found that higher W-Mn was associated with better Performance IQ only in boys, at a relatively low water manganese concentrations (most below 50 μg/L).ConclusionsHigher manganese exposure is adversely associated with childhood neurodevelopment. Hair is the most reliable indicator of manganese exposure for children at 6–18 years of age. Analysis of the publications demonstrated sex differences in neurodevelopment upon manganese exposure, although a clear pattern has not yet been elucidated for this facet of our study.
Highlights
Prior studies showed a correlation between environmental manganese (Mn) exposure and neurodevelopmental disorders in children, the results have been inconclusive
Higher manganese exposure is adversely associated with childhood neurodevelopment
Studies included in this systematic review had to meet the following criteria of being: (1) An original peer reviewed article; (2) A study of populations up to 18 years of age; (3) Manganese exposure was assessed through medicinal biomarkers or environmental samples; (4) A study of neurodevelopment derived from manganese exposure, including: cognitive, behavioral and/or motor changes; (5) Potential confounders were adjusted in the mathematical model for the estimated association between Mn indicator and a specific neurological outcome in children
Summary
Prior studies showed a correlation between environmental manganese (Mn) exposure and neurodevelopmental disorders in children, the results have been inconclusive. Environmental metal exposure normally occurs in coexposure to multiple metals, such as lead, cadmium, arsenic, mercury, chromium and manganese. Among these metals, manganese (Mn) is an essential trace element [1], but it is toxic, especially for brain functions, when abnormally deposition occurs in the body [2]. Meta-analysis about autism spectrum disorder (ASD) indicated that the mean difference in blood and hair manganese concentrations between ASD and control individuals was not significant [5]. No comprehensive meta-analysis has been performed to examine Mn associations between different indicators and neurodevelopment. The potential for sex difference in the consequences of manganese exposure has drawn attention, as there may be some differences between males and females in patterns of exposure, gastrointestinal absorption of chemicals, metabolism and detoxification [13]
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