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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, Introduction Manganese (Mn) is an element that exists ubiquitously in the environment, often in combination with other elements. (1) Mn plays a significant role in both human health and global [...]

EnvironHealthPerspect113(7):894-899 (2005); https://doi.org/10.1289/ehp.7688 The source of the errors in this article, which were limited to the Boston cohort, was twofold. Specifically, performance IQ data were used instead of full-scale IQ [...]

Thyroid hormones (THs) play a critical role in the functions of nervous, reproductive, and cardiovascular systems in both children and adults (Danzi and Klein 2012; Williams 2008; Yazbeck and Sullivan [...]

Background Although environmental lead exposure is associated with significant deficits in cognition, executive functions, social behaviors, and motor abilities, the neuroanatomical basis for these impairments remains poorly understood. In this study, we examined the relationship between childhood lead exposure and adult brain volume using magnetic resonance imaging (MRI). We also explored how volume changes correlate with historic neuropsychological assessments. Methods and Findings Volumetric analyses of whole brain MRI data revealed significant decreases in brain volume associated with childhood blood lead concentrations. Using conservative, minimum contiguous cluster size and statistical criteria (700 voxels, unadjusted p < 0.001), approximately 1.2% of the total gray matter was significantly and inversely associated with mean childhood blood lead concentration. The most affected regions included frontal gray matter, specifically the anterior cingulate cortex (ACC). Areas of lead-associated gray matter volume loss were much larger and more significant in men than women. We found that fine motor factor scores positively correlated with gray matter volume in the cerebellar hemispheres; adding blood lead concentrations as a variable to the model attenuated this correlation. Conclusions Childhood lead exposure is associated with region-specific reductions in adult gray matter volume. Affected regions include the portions of the prefrontal cortex and ACC responsible for executive functions, mood regulation, and decision-making. These neuroanatomical findings were more pronounced for males, suggesting that lead-related atrophic changes have a disparate impact across sexes. This analysis suggests that adverse cognitive and behavioral outcomes may be related to lead's effect on brain development producing persistent alterations in structure. Using a simple model, we found that blood lead concentration mediates brain volume and fine motor function., Introduction Lead is widely recognized as a potent neurotoxicant, yet debate continues as to what levels of exposure result in irreversible brain injury. Evidence of lead 'poisoning' is typically observed [...]

Background Childhood lead exposure is a purported risk factor for antisocial behavior, but prior studies either relied on indirect measures of exposure or did not follow participants into adulthood to examine the relationship between lead exposure and criminal activity in young adults. The objective of this study was to determine if prenatal and childhood blood lead concentrations are associated with arrests for criminal offenses. Methods and Findings Pregnant women were recruited from four prenatal clinics in Cincinnati, Ohio if they resided in areas of the city with a high concentration of older, lead-contaminated housing. We studied 250 individuals, 19 to 24 y of age, out of 376 children who were recruited at birth between 1979 and 1984. Prenatal maternal blood lead concentrations were measured during the first or early second trimester of pregnancy. Childhood blood lead concentrations were measured on a quarterly and biannual basis through 6.5 y. Study participants were examined at an inner-city pediatric clinic and the Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio. Total arrests and arrests for offenses involving violence were collected from official Hamilton County, Ohio criminal justice records. Main outcomes were the covariate-adjusted rate ratios (RR) for total arrests and arrests for violent crimes associated with each 5 µg/dl (0.24 µmol/l) increase in blood lead concentration. Adjusted total arrest rates were greater for each 5 µg/dl (0.24 µmol/l) increase in blood lead concentration: RR = 1.40 (95% confidence interval [CI] 1.07-1.85) for prenatal blood lead, 1.07 (95% CI 0.88-1.29) for average childhood blood lead, and 1.27 (95% CI 1.03-1.57) for 6-year blood lead. Adjusted arrest rates for violent crimes were also greater for each 5 µg/dl increase in blood lead: RR =1.34 (95% CI 0.88-2.03) for prenatal blood lead, 1.30 (95% CI 1.03-1.64) for average childhood blood lead, and 1.48 (95% CI 1.15-1.89) for 6-year blood lead. Conclusions Prenatal and postnatal blood lead concentrations are associated with higher rates of total arrests and/or arrests for offenses involving violence. This is the first prospective study to demonstrate an association between developmental exposure to lead and adult criminal behavior., Introduction Early onset of aggressive or violent behavior is a precursor to a life course marred by limited social and educational achievement, incarceration, underemployment, and premature mortality [1,2]. These maladaptive [...]

BACKGROUND: Prenatal polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) exposures may influence children's neurodevelopment. OBJECTIVE: We examined the association of prenatal PBDE and PCB exposures with children's reading skills at ages 5 and 8 years, Full-Scale Intelligence Quotient (FSIQ), and externalizing behavior problems at age 8 years. METHODS: From 239 mother-child pairs recruited (2003-2006) in Cincinnati, Ohio, we measured maternal serum PBDE and PCB concentrations, assessed child's reading skills using the Woodcock-Johnson Tests of Achievement III (WJ-III) at age 5 years and the Wide Range Achievement Test-4 (WRAT-4) at age 8 years, tested FSIQ using the Wechsler Intelligence Scale for Children-IV (WISC-IV), and externalizing behavior problems using the Behavioral Assessment System for Children-2 (BASC-2) at age 8 years. We used multiple linear regression to examine the association of prenatal PBDE and PCB concentrations and reading, FSIQ, and externalizing behavior problems after adjusting for covariates. RESULTS: An increase of [Sum.sub.4]PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) by 10 times was not significantly associated with reading scores at age 5 years at the p = 0.05 level but was inversely associated with Reading Composite scores ([beta]: -6.2, 95% CI: -11.7, -0.6) and FSIQ ([beta]: -5.3, 95% CI: -10.6, -0.02) at age 8 years; it was positively associated with the score for externalizing behavior problems ([beta]: 3.5, 95% CI: -0.1, 7.2) at age 8 years. Prenatal [Sum.sub.4]PCBs (PCB-118, -153, -138-158, and -180) was not significantly associated with a child's reading skills, FSIQ, and externalizing behavior problems. CONCLUSION: Prenatal PBDE concentration was inversely associated with reading skills and FSIQ and positively associated with externalizing behavior problems at age 8 years. No significant associations were found in prenatal PCB concentration., Introduction PBDEs were widely used as flame retardants in the manufacture of electronics, fUrniture, carpets, and textiles and are detectable in indoor dust, fish, birds, human serum, and adipose tissue. [...]

OBJECTIVES. The purpose of this work was to assess the long-term impact of childhood lead exposure on the neurosubstrate of language function and brain organization. METHODS. Young adults from the Cincinnati Lead Study were recruited to undergo functional magnetic resonance image scanning while performing a verb generation task. These subjects have been followed from birth through early childhood with extensive documentation of lead exposure, neuropsychology, and behavior. Forty-two subjects provided useful imaging data. The locale, strength, and the correlation between brain language activation and childhood blood lead concentration were studied. RESULTS. After adjusting for potential confounders, the activation in left frontal cortex, adjacent to Broca&apos;s area, and left middle temporal gyrus, including Wernicke&apos;s area, were found to be significantly associated with diminished activation in subjects with higher mean childhood blood lead levels, whereas the compensatory activation in the right hemisphere homolog of Wernicke&apos;s area was enhanced in subjects with higher blood lead levels. CONCLUSION. This study indicates that childhood lead exposure has a significant and persistent impact on brain reorganization associated with language function. www.pediatrics.org/cgi/doi/10.1542/ peds.2006-0467 doi:10.1542/peds.2006-0467 Key Words environmental pollutants, lead poisoning, neuroimaging, language development, pediatric research Abbreviations fMRI--functional magnetic resonance imaging CLS--Cincinnati Lead Study EPI--echo planar imaging BOLD--blood oxygen level dependant SES--socioeconomic status IQ--intelligence quotient ROI--region of interest, CHILDHOOD LEAD EXPOSURE is inversely associated with intellectual abilities, academic achievement, and psychomotor development. (1-4) Even low-level lead exposure can negatively impact a wide range of cognitive functions, such as [...]

Objective. Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems. It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity. The objective of this study was to determine whether chelation therapy with succimer (dimercaptosuccinic acid) in children with referral blood lead levels between 20 and 44 [micro]g/dL (0.96-2.12 [micro]mol/L) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years. Methods. The Treatment of Lead-Exposed Children (TLC) study is a randomized, double-blind, placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia, PA; Newark, NJ; Cincinnati, OH; and Baltimore, MD. Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility, 780 were randomized to the active drug and placebo groups stratified by clinical center, body surface area, blood lead level, and language spoken at home. At 7 years of age, 647 subjects remained in the study. Participants were randomly assigned to receive oral succimer or placebo. Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug. Eighty-nine percent had finished treatment by 6 months, with all children finishing by 13 months after randomization. All participants received residential lead hazard control measures before treatment. TLC subjects also received a daily multivitamin supplement before and after treatment(s) with succimer or placebo. Scores on standardized neuropsychological measures that tap cognition, behavior, learning and memory, attention, and neuromotor skills were measured. Results. Chelation therapy with succimer lowered average blood lead levels for ~6 months but resulted in no benefit in cognitive, behavioral, and neuromotor endpoints. Conclusion. These new follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 [micro]g/dL (0.96-2.17 [micro]mol/L). These results emphasize the importance of taking environmental measures to prevent exposure to lead. Chelation therapy with succimer cannot be recommended for children with blood lead levels between 20 and 44 [micro]g/dL (0.96-2.12 [micro]mol/L). Pediatrics 2004;114:19-26; child, lead, environmental exposure, chelation therapy, succimer, cognition, clinical trials. ABBREVIATIONS. CDC, Centers for Disease Control and Prevention; TLC, Treatment of Lead-Exposed Children; NEPSY, Developmental Neuropsychological Assessment; CI, confidence interval., Before the availability of chelating drugs, as many as 45% of lead-poisoned children who presented with signs or symptoms of encephalopathy died, and more than one quarter of surviving patients [...]

Objective. Exposure to lead at levels encountered by urban children impairs cognitive development. An observational study suggested improvement in IQ when blood lead level fell, but the only randomized trial of chelation showed no benefit in IQ. Methods. We did a new analysis of the data from the clinical trial using change in blood lead level as the independent variable. The 741 children began with blood lead levels between 20 and 44 [micro]g/dL, and were 13 to 33 months old at randomization to chelation or placebo. Blood lead levels were measured repeatedly, and cognitive tests were given at baseline, 6 months, and 36 months follow-up. Results. By 6 months after randomization, blood lead levels had fallen by similar amounts in both chelated and placebo children, despite the immediate drops in the chelated group; there was no association between change in blood lead level and change in cognitive test score. Blood lead levels continued to fall. At 36 months follow-up, in the placebo group only, cognitive test scores had increased 4.0 points per 10 [micro]g/dL fall in blood lead level from baseline to 36 months follow-up and 5.1 points from 6 to 36 months. Conclusions. The improvement in scores in the placebo group only implies that factors other than declining blood lead levels per se are responsible for cognitive improvement; it is possible but less likely that succimer, the active drug, impairs cognition. Pediatrics 2002;110: 787-791; child, preschool; environmental exposure; lead poisoning/blood/etiology; cognition/physiology; chelation therapy., ABBREVIATIONS. TLC, Treatment of Lead-Exposed Children; MDI, Mental Development Index; SD, standard deviation. Prospective data from multiple studies in several countries show that lead exposure insufficient to produce symptoms still [...]