Biomarkers of environmental manganese exposure and associations with childhood neurodevelopment: a systematic review and meta-analysis

Abstract

Background Although 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. Methods We 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. Results Of 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). Conclusions Higher 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.

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

“…Mn neurotoxicity is also known to affect neurodevelopment [ 19 ]. Specifically, maternal or early-life Mn exposure was shown to be associated with poorer cognitive and behavioral performance in children under six years old [ 20 ]. However, in view of the essentiality of physiological Mn levels and its toxicity upon overexposure [ 21 ], the association between Mn and adverse neurodevelopmental outcome may be U-shaped [ 22 ].…”

Concentrations of Lead, Mercury, Selenium, and Manganese in Blood and Hand Grip Strength among Adults Living in the United States (NHANES 2011–2014)

“…Another limitation is our reliance on blood as a biomarker for manganese and mercury, as other biological matrices might be better biomarkers of exposure. For instance, a review and meta-analysis has concluded that hair was a better biomarker of exposure to manganese than blood [35]. Likewise, to the extent that the largest and most concerning form of mercury exposure is methylmercury, measurements made in hair might be more useful in future studies aimed at detecting neurofunctional effects resulting from overexposure to this metal [36].…”

Particulate Matter and Associated Metals: A Link with Neurotoxicity and Mental Health

“…Given the link emerging between inhaled PM and its metal constituents and neurological health, this section will review recent information in this area to help delineate research pathways (Table 1). Several researchers have studied the association between airborne Mn exposure and neurodevelopmental outcomes among children [33]. A 2018 cross-sectional study found a significant negative association between airborne Mn exposure and Full Scale IQ (β = −1.91, p < 0.05; β and p refer to the regression coefficient and statistical significance, respectively) among 106 children ages seven to nine living in East Liverpool, Ohio, which hosts both a hazardous waste incinerator and a Mn processor [34].…”