Search

Background: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance., Objectives: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort., Methods: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height-weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine., Results: CARES participants who completed the adolescent postural balance assessment ( n = 123 ) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males., Discussion: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381.

Background: Environmental manganese exposure has been associated with adverse neurodevelopmental outcomes among school-aged children; yet, few studies have evaluated prenatal exposure., Objectives: Our study examines associations between prenatal manganese concentrations and placental transfer of manganese with neurodevelopment in 224 2-y-old children residing near the Tar Creek Superfund Site., Methods: We collected maternal and cord blood at delivery, measured manganese using inductively coupled plasma mass spectrometry, and assessed neurodevelopment using the Bayley Scales of Infant Development-II. Associations between manganese and mental (MDI) and psychomotor (PDI) development indices were estimated in multivariable models. Placental transfer, approximated by cord/maternal manganese ratio, cord/total manganese ratio (total=maternal+cord), and by joint classification according to high or low (above or below median) maternal and cord manganese, was evaluated as a predictor of neurodevelopment., Results: Median levels [interquartile ranges (IQR)] of manganese in maternal and cord blood, respectively, were 24.0 (19.5-29.7) and 43.1 (33.5-52.1) μg/L. Adjusting for lead, arsenic, and other potential confounders, an IQR increase in maternal manganese was associated with -3.0 (95% CI: -5.3, -0.7) points on MDI and -2.3 (95% CI: -4.1, -0.4) points on PDI. Cord manganese concentrations were not associated with neurodevelopment scores. Cord/maternal and cord/total manganese ratios were positively associated with MDI [cord/maternal: β=2.6 (95% Cl: −0.04, 5.3); cord/total: β=22.0 (95% Cl: 3.2, 40.7)] and PDI (cord/maternal: β=1.7 (95% Cl: −0.5, 3.9); cord/total: β=15.6 (95% Cl: 0.3, 20.9)). Compared to mother-child pairs with low maternal and cord manganese, associations with neurodevelopment scores were negative for pairs with either high maternal, high cord, or high maternal and cord manganese., Conclusions: Maternal blood manganese concentrations were negatively associated with early childhood neurodevelopment scores in our study. Findings highlight the importance of understanding maternal exposures during pregnancy and factors influencing placental transfer. https://doi.org/10.1289/EHP925.

Background: Manganese is both an essential element and a known toxicant, and it plays important roles in many mechanisms in relation to type 2 diabetes (T2D). However, epidemiological studies of this relationship are rare., Objective: We investigated the association between plasma manganese and newly diagnosed T2D as well as whether the association could be modified by manganese superoxide dismutase (MnSOD) polymorphisms., Methods: We conducted a case-control study of 3,228 participants in China: 1,614 T2D patients and 1,614 controls. Concentrations of plasma magnesium were measured, and all participants were genotyped for the MnSOD Val16Ala polymorphism (rs4880)., Results: A U-shaped association was observed between plasma manganese and T2D, with increased odds ratios (ORs) in relation to either low or high plasma manganese levels. Compared with the middle tertile, the multivariate-adjusted ORs [95% confidence intervals (CIs)] of T2D associated with the lowest tertile and the highest tertile of plasma manganese were 1.89 (1.53, 2.33) and 1.56 (1.23, 1.97), respectively. In spline analysis, the U-shaped association was consistently indicated, with the lowest odds of T2D at the plasma manganese concentration of 4.95 μg/L. Minor allele frequencies (C allele) of the MnSOD Val16Ala polymorphism (rs4880) in the normal glucose tolerance (NGT) and the T2D groups were 13.57% and 14.50%, respectively. The MnSOD rs4880 polymorphism was not associated with T2D, and no interaction was found between plasma manganese and the MnSOD rs4880 polymorphism in relation to T2D., Conclusions: Our results suggested a U-shaped association between plasma manganese and T2D; both low and high levels of plasma manganese were associated with higher odds of newly diagnosed T2D. The U-shaped association was not modified by the MnSOD rs4880 polymorphism. Citation: Shan Z, Chen S, Sun T, Luo C, Guo Y, Yu X, Yang W, Hu FB, Liu L. 2016. U-shaped association between plasma manganese levels and type 2 diabetes. Environ Health Perspect 124:1876-1881; http://dx.doi.org/10.1289/EHP176., Competing Interests: The authors declare they have no actual or potential competing financial interests.

Background: Manganese (Mn) plays a vital role in brain growth and development, yet excessive exposure can result in neurotoxicity. Marietta, Ohio, is home to the nation's longest-operating ferromanganese refinery, and community concern about exposure led to the development of the research study., Objectives: Our overall goal was to address the community's primary research question: "Does Mn affect cognitive development of children?" We evaluated the relationships between Mn exposure as measured by blood and hair Mn, along with other neurotoxicants including blood lead (Pb) and serum cotinine, and child cognition., Methods: Children 7-9 years of age were enrolled (n = 404) in the Communities Actively Researching Exposure Study (CARES) from Marietta and Cambridge, Ohio, and their surrounding communities from October 2008 through March 2013. Blood and hair were analyzed for Mn and Pb, and serum was analyzed for cotinine. We used penalized splines to assess potential nonlinear associations between biological measures and IQ subscale scores, followed by multivariable regression models with categorical variables based on quartiles of the distribution for biological measures with nonlinear associations and continuous variables for biological measures with linear associations., Results: Geometric mean blood (n = 327) and hair Mn (n = 370) concentrations were 9.67 ± 1.27 μg/L and 416.51 ± 2.44 ng/g, respectively. After adjusting for potential confounders, both low and high blood and hair Mn concentrations were associated with lower Full Scale IQ and subscale scores, with significant negative associations between the highest quartile and middle two quartiles of blood Mn (β -3.51; 95% CI: -6.64, -0.38) and hair Mn (β -3.66; 95% CI: -6.9, -0.43%) and Full Scale IQ., Conclusions: Both low and high Mn concentrations in blood and hair were negatively associated with child IQ scores. Serum cotinine was negatively associated with child cognitive function.

Background: Manganese is an essential trace element and common component of water, soil, and air. Prenatal manganese exposure may affect fetal and infantile neurodevelopment, but reports on in utero manganese exposure and infant neurodevelopment are rare., Objective: This study was conducted to investigate a relationship between maternal blood manganese level and neurodevelopment of infants at 6 months of age., Methods: Data were obtained from the Mothers and Children's Environmental Health (MOCEH) birth cohort study. The study population included 232 pairs of pregnant women and their infants at 6 months of age. Maternal blood manganese was measured at term, just before delivery. Mental and psychomotor development in infancy was assessed at 6 months of age using the Bayley Scales of Infant Development. The relationship between maternal blood manganese level and the mental and psychomotor development indexes (MDI and PDI) was estimated for manganese modeled as a linear and as a categorical variable and using penalized splines for nonlinear modeling., Results: Mean ± SD maternal blood manganese concentration was 22.5 ± 6.5 μg/L. After adjustment for potential confounders, blood manganese was used as a continuous variable in a linear and nonlinear model. Associations between maternal blood manganese and MDI and PDI scores followed an inverted U-shape dose-response curve after adjustment for potential confounders, with lower scores associated with both low and high blood concentrations [MDI: likelihood-ratio test (LRT) p = 0.075, PDI: LRT p = 0.038]. Associations of both outcomes with increasing blood manganese shifted from positive to negative at concentrations of 24-28 μg/L in this cohort of term, normal birth weight children., Conclusion: Although no cut-off point has been established to define manganese toxicity, both high and low blood manganese levels may be associated with neurobehavioral function in infants.

Background: Most toxicologic studies focus on a single agent, although this does not reflect real-world scenarios in which humans are exposed to multiple chemicals., Objectives: We prospectively studied manganese-lead interactions in early childhood to examine whether manganese-lead coexposure is associated with neurodevelopmental deficiencies that are more severe than expected based on effects of exposure to each metal alone., Methods: Four hundred fifty-five children were enrolled at birth in an longitudinal cohort study in Mexico City, provided blood samples, and were followed until 36 months of age. We measured lead and manganese at 12 and 24 months and assessed neurodevelopment at 6-month intervals from 12 to 36 months of age using Bayley Scales of Infant Development-II., Results: Mean (± SD) blood concentrations at 12 and 24 months were, respectively, 24.7 ± 5.9 μg/L and 21.5 ± 7.4 μg/L for manganese and 5.1 ± 2.6 μg/dL and 5.0 ± 2.9 μg/dL for lead. Mixed-effects models, including Bayley scores at five time points, showed a significant interaction over time: highest manganese quintile × continuous lead; mental development score, β = -1.27 [95% confidence interval (CI): -2.18, -0.37]; psychomotor development score, β = -0.92 (95% CI: -1.76, -0.09). Slopes for the estimated 12-month lead effect on 18-month mental development and 24- through 36-month psychomotor development scores were steeper for children with high manganese than for children with midrange manganese levels., Conclusions: We observed evidence of synergism between lead and manganese, whereby lead toxicity was increased among children with high manganese coexposure. Findings highlight the importance of understanding health effects of mixed exposures, particularly during potentially sensitive developmental stages such as early childhood.

Background: Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children's intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function., Methods: We investigated the associations of WAs and WMn with motor function in 304 children in Bangladesh, 8-11 years of age. We measured As and Mn concentrations in drinking water, blood, urine, and toenails. We assessed motor function with the Bruininks-Oseretsky test, version 2, in four subscales-fine manual control (FMC), manual coordination (MC), body coordination (BC), and strength and agility-which can be summarized with a total motor composite score (TMC)., Results: Log-transformed blood As was associated with decreases in TMC [β = -3.63; 95% confidence interval (CI): -6.72, -0.54; p < 0.01], FMC (β = -1.68; 95% CI: -3.19, -0.18; p < 0.05), and BC (β = -1.61; 95% CI: -2.72, -0.51; p < 0.01), with adjustment for sex, school attendance, head circumference, mother's intelligence, plasma ferritin, and blood Mn, lead, and selenium. Other measures of As exposure (WAs, urinary As, and toenail As) also were inversely associated with motor function scores, particularly TMC and BC. Square-transformed blood selenium was positively associated with TMC (β = 3.54; 95% CI: 1.10, 6.0; p < 0.01), FMC (β = 1.55; 95% CI: 0.40, 2.70; p < 0.005), and MC (β = 1.57; 95% CI: 0.60, 2.75; p < 0.005) in the unadjusted models. Mn exposure was not significantly associated with motor function., Conclusion: Our research demonstrates an adverse association of As exposure and a protective association of Se on motor function in children.

Background: Excessive exposure to manganese (Mn), an essential trace element, has been shown to be neurotoxic, especially when inhaled. Few studies have examined potential effects of Mn on cognitive functions of environmentally exposed children., Objective: This study was intended to estimate environmental exposure to Mn resulting from mining and processing and to explore its association with intellectual function of school-age children., Methods: Children between 7 and 11 years of age from the Molango mining district in central Mexico (n = 79) and communities with similar socioeconomic conditions that were outside the mining district (n = 93) participated in the cross-sectional evaluation. The revised version of the Wechsler Intelligence Scale for Children adapted for the Mexican population was applied. Concentrations of Mn in blood (MnB) and hair (MnH) were used as biomarkers of exposure., Results: Exposed children had significantly higher median values for MnH (12.6 μg/g) and MnB (9.5 μg/L) than did nonexposed children (0.6 μg/g and 8.0 μg/L, respectively). MnH was inversely associated with Verbal IQ [β = -0.29; 95% confidence interval (CI), -0.51 to -0.08], Performance IQ (β = -0.08; 95% CI, -0.32 to 0.16), and Total Scale IQ (β = -0.20; 95% CI, -0.42 to 0.02). MnB was inversely but nonsignificantly associated with Total and Verbal IQ score. Age and sex significantly modified associations of MnH, with the strongest inverse associations in young girls and little evidence of associations in boys at any age. Associations with MnB did not appear to be modified by sex but appeared to be limited to younger study participants., Conclusions: The findings from this study suggest that airborne Mn environmental exposure is inversely associated with intellectual function in young school-age children.

Context: Manganese is a trace element, essential for physiologic functioning but neurotoxic at high doses. Common exposure sources include dietary intake as well as drinking water in some regions; toxicity is most often associated with inhalation exposures in occupational settings. In this article we describe the investigation of a pediatric case of manganism using both clinical and environmental assessment methods., Case Presentation: A previously healthy 6-year-old child presented with severe Mn neurotoxicity, iron deficiency, and elevated cobalt levels. Immediate and selected extended family members had elevated plasma Mn but remained asymptomatic. An exposure assessment identified seasonal ingestion exposures to Mn at the family's summer cottage; these were common to the four immediate family members. Well water used for drinking and cooking exceeded recommended guidelines, and foods high in Mn predominated in their diet. No inhalation exposures were identified. Only pica was unique to the patient., Discussion: The combined evidence of the environmental assessment and biomonitoring of blood Mn levels supported a seasonal ingestion exposure source; this alone was insufficient to explain the toxicity because the patient's 7-year-old sibling was asymptomatic with almost identical exposures (except pica). A metabolic disorder involving divalent metals (Mn, Fe, and Co) interacting with environmental exposures is the most likely explanation., Relevance to Clinical or Professional Practice: This case report adds to the emerging body of evidence linking neurologic effects to ingestion Mn exposure.

Exposure to manganese via inhalation has long been known to elicit neurotoxicity in adults, but little is known about possible consequences of exposure via drinking water. In this study, we report results of a cross-sectional investigation of intellectual function in 142 10-year-old children in Araihazar, Bangladesh, who had been consuming tube-well water with an average concentration of 793 microg Mn/L and 3 microg arsenic/L. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children's intellectual function was assessed on tests drawn from the Wechsler Intelligence Scale for Children, version III, by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead, As, Mn, and hemoglobin concentrations. After adjustment for sociodemographic covariates, water Mn was associated with reduced Full-Scale, Performance, and Verbal raw scores, in a dose-response fashion; the low level of As in water had no effect. In the United States, roughly 6% of domestic household wells have Mn concentrations that exceed 300 microg Mn/L, the current U.S. Environmental Protection Agency lifetime health advisory level. We conclude that in both Bangladesh and the United States, some children are at risk for Mn-induced neurotoxicity.

Epidemiological studies on metal levels in blood were carried out. Evidence suggested the existence of a different trend in serum-iron levels in relation to blood lead levels in nonoccupationally exposed males (negative trend) and females (positive trend). There was a positive relation between blood lead levels and blood manganese levels in children and occupationally exposed male workers. Blood metal levels increased with age in young children. There was evidence for an influence of socioeconomic class on blood lead levels in children. A direct and an indirect effect of smoking was found on blood lead levels and on the activity of delta-aminolevulinic acid dehydratase activity in erythrocytes in adult nonoccupationally exposed females.