Search

Pb in bone may serve as a biomarker for cumulative Pb dose over decades. We hypothesized that adult female bone Pb concentrations (BoPb) would be significantly associated with average childhood blood Pb levels (BlPb) in a birth cohort exposed to relatively high levels of Pb from Pb paint residues. 94 African American women with a mean age of 32.7 years were recruited from the Cincinnati Lead Study (CLS) cohort. Subjects were born to women residing where there had been a high incidence of childhood Pb poisoning. Biomarkers of Pb exposure were serial BlPb concentrations spanning the prenatal period to approximately 6.5 years of age. BoPb was assessed in the tibia using the McMaster 109Cd K-XRF fourth generation system. Covariates included nutritional variables related to bone health. BlPb concentrations began to rise around 6 months of age and declined at later ages. Study participants were obese with a mean Body Mass Index of 34.4 and suboptimal vitamin D status as indicated by a mean 25-OH-D of 18.5 ng/ml. Average tibia Pb was −2.0 ± 8.6 μgPb/g bone mineral. In multiple linear regression, there was no significant association between BoPb at approximately age 30 and childhood cumulative BlPb(CumBlPb). Collectively, BoPb of this group of subjects was not detectable. We suggest that the reason these subjects' BoPb did not reflect their early exposure was that a significantly smaller proportion of Pb body burden resides in bone in young children. As the child grows what Pb there was in bone is diluted and any remaining signal is weak. It has been claimed that BoPb in older children, adolescents, and adults can recapitulate historical exposure to Pb during earlier development; however, in some populations, BoPb at later ages may not be an adequate biomarker to capture childhood exposure to Pb. • Bone lead by K-XRF in young adults was not associated with childhood blood lead concentrations. • Adult Bone lead may not be adequate to recapitulate childhood exposure to lead. • Improvements in K-XRF for bone lead may lead to different results in future studies. [ABSTRACT FROM AUTHOR]

Childhood lead exposure has been correlated to acts of delinquency and criminal behavior; however, little research has been conducted to examine its potential long term influence on behavioral factors such as personality, specifically psychopathic personality. Neuroimaging studies have demonstrated that the effects of childhood lead exposure persist into adulthood, with structural abnormalities found in gray and white matter regions involved in behavioral decision making. The current study examined whether measurements of adult psychopathy were associated with neuroanatomical differences in structural brain volumes for a longitudinal cohort with measured childhood lead exposure. We hypothesized that increased total psychopathy scores and increased blood lead concentration at 78 months of age (PbB78) would be inversely associated with volumetric measures of gray and white matter brain structures responsible for executive and emotional processing. Analyses did not display a direct effect between total psychopathy score and gray matter volume; however, reduced white matter volume in the cerebellum and brain stem in relation to increased total psychopathy scores was observed. An interaction between sex and total psychopathy score was also detected. Females displayed increased gray matter volume in the frontal, temporal, and parietal lobes associated with increased total psychopathy score, but did not display any white matter volume differences. Males primarily displayed reductions in frontal gray and white matter brain volume in relation to increased total psychopathy scores. Additionally, reduced gray and white matter volume was associated with increased blood lead levels in the frontal lobes; reduced white matter volume was also observed in the parietal and temporal lobes. Females demonstrated gray and white matter volume loss associated with increased PbB78 values in the right temporal lobe, as well as reduced gray matter volume in the frontal lobe. Males displayed reduced white matter volumes associated with increased PbB78 values in the frontal, temporal, and parietal lobes. Comparison of the two primary models revealed a volumetric decrease in the white matter of the left prefrontal cortex associated with increased total psychopathy scores and increased blood lead concentration in males. The results of this study suggested that increased psychopathy scores in this cohort may be attributable to the neuroanatomical abnormalities observed and that childhood lead exposure may be influential to these outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Electronic waste (e-waste) has been an emerging environmental health issue in both developed and developing countries, but its current management practice may result in unintended developmental neurotoxicity in vulnerable populations. To provide updated information about the scope of the issue, presence of known and suspected neurotoxicants, toxicologic mechanisms, and current data gaps, we conducted this literature review. DATA SOURCES: We reviewed original articles and review papers in PubMed and Web of Science regarding e-waste toxicants and their potential developmental neurotoxicity. We also searched published reports of intergovernmental and governmental agencies and nongovernmental organizations on e-waste production and management practice. DATA EXTRACTION: We focused on the potential exposure to e-waste toxicants in vulnerable populations- that is, pregnant women and developing children-and neurodevelopmental outcomes. In addition, we summarize experimental evidence of developmental neurotoxicity and mechanisms. DATA SYNTHESIS: In developing countries where most informal and primitive e-waste recycling occurs, environmental exposure to lead, cadmium, chromium, polybrominated diphenyl ethers, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons is prevalent at high concentrations in pregnant women and young children. Developmental neurotoxicity is a serious concern in these regions, but human studies of adverse effects and potential mechanisms are scarce. The unprecedented mixture of exposure to heavy metals and persistent organic pollutants warrants further studies and necessitates effective pollution control measures. CONCLUSIONS: Pregnant women and young children living close to informal e-waste recycling sites are at risk of possible perturbations of fetus and child neurodevelopment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Childhood lead exposure adversely affects neurodevelopment. However, few studies have examined changes in human brain metabolism that may underlie known adverse cognitive and behavioral outcomes. OBJECTIVE: We examined the association between mean childhood blood lead levels and in vivo brain metabolite concentrations as adults, determined by proton magnetic resonance spectroscopy (MRS) in a birth cohort with documented low-to-moderate lead exposure. METHODS: Adult participants from the Cincinnati Lead Study [n = 159; mean age (± SD), 20.8 ± 0.9 years] completed a quantitative, short-echo proton MRS protocol evaluating seven regions to determine brain concentrations of N-acetyl aspartate (NAA), creatine and phosphocreatine (Cr), cholines (Cho), myo-inositol, and a composite of glutamate and glutamine (GLX). Correlation and multiple linear regression analyses were conducted. RESULTS: Mean childhood blood lead levels were associated with regionally specific brain metabolite concentrations adjusted for age at imaging and Full-Scale intelligence quotient. Adjusted analyses estimated for a unit (micrograms per deciliter) increase in mean childhood blood lead concentrations, a decrease of NAA and Cr concentration levels in the basal ganglia, a decrease of NAA and a decrease of Cho concentration levels in the cerebellar hemisphere, a decrease of GLX concentration levels in vermis, a decrease of Cho and a decrease of GLX concentration levels in parietal white matter, and a decrease of Cho concentration levels in frontal white matter. CONCLUSIONS: Gray-matter NAA reductions associated with increasing childhood blood lead levels suggest that sustained childhood lead exposure produces an irreversible pattern of neuronal dysfunction, whereas associated white-matter choline declines indicate a permanent alteration to myelin architecture. [ABSTRACT FROM AUTHOR]

Abstract: Childhood lead exposure is associated with decreased cognitive abilities and executive functioning localized within the prefrontal cortex. Several studies have observed stronger associations between blood lead measurements obtained later in life than earlier measures, but there are no imaging studies investigating the developmental trajectory of blood lead levels taken during childhood on adult gray matter volume. In this study, we recruited 157 adults (20.8±1.5 years of age) from the Cincinnati Lead Study to undergo high resolution volumetric magnetic resonance imaging. Adjusted voxel-wise regression analyses were performed for associations between adult gray matter volume loss and yearly mean blood lead levels from 1 to 6 years of age in the entire cohort and by sex. We observed significant inverse associations between gray matter volume loss and annual mean blood lead levels from 3 to 6 years of age. The extent of prefrontal gray matter associated with yearly mean blood lead levels increased with advancing age of the subjects. The inverse associations between gray matter volume loss and yearly mean blood lead measurements were more pronounced in the frontal lobes of men than women. Analysis of women yielded significantly weaker associations between yearly mean blood lead levels and gray matter volume at all ages than either men or the combined cohort of men and women together. These results suggest that blood lead concentrations obtained during later childhood demonstrate greater loss in gray matter volume than childhood mean or maximum values. The relationship between childhood blood lead levels and gray matter volume loss was predominantly observed in the frontal lobes of males. This study demonstrates that maximum blood lead levels do not fully account for gray matter changes associated with childhood lead exposure, particularly in the frontal lobes of young men. [Copyright &y& Elsevier]

Childhood lead exposure interferes with brain maturation, which adversely impacts cognitive and behavioral development. Lower intelligence scores, impairments in decision making, and increased rates of delinquent and criminal behavior are adverse outcomes linked to childhood lead absorption. The present study examined the relationships between childhood blood lead concentrations, structural brain volume, and measures of adult criminality. We hypothesized that increased rates of criminal arrests in adulthood would be inversely correlated with regional gray and white matter volumes, especially prefrontal areas responsible for decision making and self-control. We obtained childhood blood lead histories and anatomical magnetic resonance imaging from a subset of the longitudinally followed birth cohort known as the Cincinnati Lead Study. Criminality data for cohort participants were extracted from public databases. Voxel based morphometry was used to examine spatial differences in regional gray and white matter volumes associated with childhood blood lead concentrations and measures of adult criminality, respectively. Conjunction analyses allowed for the exploratory evaluation of common regions of volume change. Childhood blood lead concentrations were inversely associated with gray and white matter volume in the frontal, parietal and temporal lobes. Gray matter volumes were also inversely associated with criminal arrests with key regions within the cingulate, precuneus, several frontal gyri and the supplementary motor area. Conjunction analyses identified regions in the anterior cingulate, frontal gray matter and supplementary motor area associated with childhood lead absorption and criminality. The results from this study suggest that reduced brain volumes in regions responsible for cognition and emotional regulation are associated with childhood lead exposure and criminal arrests. [ABSTRACT FROM AUTHOR]

Kim Dietrich and colleagues find an association between developmental exposure to lead and adult criminal behavior. [ABSTRACT FROM AUTHOR]

Principles and practices of pediatric neurotoxicology are reviewed here with the purpose of guiding the design and execution of the planned National Children's Study. The developing human central nervous system is the target organ most vulnerable to environmental chemicals. An investigation of the effects of environmental exposures on child development is a complex endeavor that requires consideration of numerous critical factors pertinent to a study's concept, design, and execution. These include the timing of neurodevelopmental assessment, matters of biologic plausibility, site, child and population factors, data quality assurance and control, the selection of appropriate domains and measures of neurobehavior, and data safety and monitoring. Here we summarize instruments for the assessment of the neonate, infant, and child that are being employed in the Centers for Children's Environmental Health and Disease Prevention Research, sponsored by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, discuss neural and neurobiologic measures of development, and consider the promises of gene-environment studies. The vulnerability of the human central nervous system to environmental chemicals has been well established, but the contribution these exposures may make to problems such as attention deficit disorder, conduct problems, pervasive developmental disorder, or autism spectrum disorder remain uncertain. Large-scale studies such as the National Children's Study may provide some important clues. The human neurodevelopmental phenotype will be most clearly represented in models that include environmental chemical exposures, the social milieu, and complex human genetic characteristics that we are just beginning to understand. [ABSTRACT FROM AUTHOR]

Increases in peak blood lead concentrations, which occur at 18-30 months of age in the United States, are thought to result in lower IQ scores at 4-6 years of age, when IQ becomes stable and measurable. Data from a prospective study conducted in Boston suggested that blood lead concentrations at 2 years of age were more predictive of cognitive deficits in older children than were later blood lead concentrations or blood lead concentrations measured concurrently with IQ. Therefore, cross-sectional associations between blood lead and IQ in school-age children have been widely interpreted as the residual effects of higher blood lead concentrations at an earlier age or the tendency of less intelligent children to ingest more leaded dust or paint chips, rather than as a causal relationship in older children. Here we analyze data from a clinical trial in which children were treated for elevated blood lead concentrations (20-44 µg/dL) at about 2 years of age and followed until 7 years of age with serial IQ tests and measurements of blood lead. We found that cross-sectional associations increased in strength as the children became older, whereas the relation between baseline blood lead and IQ attenuated. Peak blood lead level thus does not fully account for the observed association in older children between their lower blood lead concentrations and IQ. The effect of concurrent blood level on IQ may therefore be greater than currently believed. [ABSTRACT FROM AUTHOR]

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 µg/dL (0.96-2.12 µmol/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... [ABSTRACT FROM AUTHOR]

Maintaining upright posture is a complex process involving multiple afferent systems. The aim of this study was to measure the postural stability of children with Autism Spectrum Disorder (ASD) compared with children with typical neurodevelopment and to measure the relative contributions of the visual, somatosensory, and vestibular afferent systems in each group. Eight boys with ASD and eight age-, race-, and gender-matched controls participated in this study using force platform technology with customized software to measure postural sway under conditions designed to eliminate or modify visual and somatosensory input. Children with ASD had significantly larger sway areas under all test conditions in which afferent input was modified. These results are consistent with a deficit in the integration of visual, vestibular, and somatosensory input to maintain postural orientation. [ABSTRACT FROM AUTHOR]

Provides information on a study that evaluated potential exposure to lead-based paint in family housing units at a typical U.S. military installation and determined blood lead levels in children residing in these housing units. Methodologies used; Results and discussion; Conclusion.

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 (푛 = 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. [ABSTRACT FROM AUTHOR]

ABSTRACT. The relationship between asymptomatic lead exposure and subtle deficits in intellectual attainment has been relatively well established by modern studies. However, neuromotor performance has rarely been the focus of these investigations. It was postulated that motor developmental outcomes may be more sensitive indicators of lead's adverse effects on the central nervous system as they are probably less confounded with social factors than cognitive and academic outcomes. A comprehensive neuromotor assessment battery was administered to 245 six-year-old urban inner-city children enrolled in the Cincinnati Lead Study. These children have been followed since birth with quarterly assessments of blood lead concentrations, medical status, and neurobehavioral development. Prior to covariate adjustment, neonatal, but not prenatal blood lead levels were associated with poorer scores on assessments of bilateral coordination, upper-limb speed and dexterity, and a composite index of fine-motor coordination. Averaged postnatal blood lead levels were also associated with lower scores on the aforementioned subtests as well as a measure of visual-motor control. Following statistical adjustment for covariates, neonatal blood lead levels were associated with poorer performance on a measure of upper-limb speed and dexterity and the fine-motor composite. Postnatal blood lead levels remained significantly associated with poorer scores on measures of bilateral coordination, visual-motor control, upper-limb speed and dexterity, and the fine-motor composite. Low to moderate lead exposure is associated with moderate deficits in gross and especially fine-motor developmental status. Results of this study provide support for recent initiatives to reduce the exposure of... [ABSTRACT FROM AUTHOR]

Abstract. This report is a follow-up of an earlier study of the effects of low to moderate prenatal and postnatal lead exposure on children's growth in stature. Two hundred thirty-five subjects were assessed every 3 months for lead exposure (blood lead level) and stature (recumbent length) up to 33 months of age. Fetal lead exposure was indexed by maternal blood lead level during pregnancy. The adverse effects of lead on growth during the first year of life were reported previously. This analysis covers essentially the second and third years of life. The results indicate that mean blood lead level during this period was negatively associated with attained height at 33 months of age (P = .002). This association was, however, evidenced only among those children who had mean blood lead levels greater than the cohort median (is greater than or equal to 10.77 micro g/dL) during the 3- to 15-month interval. The results also suggest that the effect of lead exposure (both in utero as well as during the first year of life) are transient provided that subsequent exposure to lead is not excessive. It appears that maintaining an average blood lead level of 25 micro g/dL or more during the second and third year of life was detrimental to the child's attained stature at 33 months of age. Approximately 15% of this cohort experienced these levels of lead exposure. Continued follow-up of this cohort will reveal whether these lead-related deficits persist and whether they continue to be dependent on the level of exposure in an earlier period. [ABSTRACT FROM AUTHOR]

Abstract. A prospective method was used in this study to assess the effects of fetal lead exposure on neurodevelopmental status in 3- and 6-month old infants. At their first prenatal medical appointments, 305 lower socioeconomic status women residing in predesignated lead-hazardous areas of Cincinnati were recruited. Lead was measured in whole blood in both the mother and fetal-placental unit (prenatal and cord) and the neonate (ten days and 3 months). All blood lead levels were less than 30 micro g/dL. Infant development was assessed with the Bayley scales at 3 and 6 months of age. Multiple regression analyses which treated perinatal health factors such as birth weight and gestation as confounders indicated an independent, inverse relationship between both prenatal and neonatal blood lead levels and performance on the Bayley Mental Developmental Index at both ages. Male infants and infants from the poorest families appeared to be especially sensitive to these psychoteratogenic influences. Further study using a structural equations approach indicated that neurobehavioral deficits were partly mediated by lead-related reductions in birth weight and gestation. [ABSTRACT FROM AUTHOR]

Abstract. The social and developmental correlates of early lead exposure were explored in an interim analysis of data from an ongoing longitudinal investigation in Cincinnati. Regardless of the apparent net availability of lead in the infant's physical environment, parental behavior was still significantly associated with infant blood lead levels. However, this was only the case after infants in the study reached 6 months of age and beyond when prewalking progression and early walking made parental management all the more critical. Future lead screening and abatement programs should include supports for the caretaker-child relationship. Pediatrics 1985;75:1114-1119; lead exposure, child development, caretaker-child interaction. [ABSTRACT FROM AUTHOR]

Abstract. A total of 53 mother-infant dyads, divided into five diagnostic groups (nonaccidental trauma combined with failure-to-thrive, nonaccidental trauma combined with iron-deficiency anemia, nonaccidental trauma only, neglect only, and normal control subjects) were observed during a feeding session. Qualitative differences were found in the relational characteristics of dyads in which multiple forms of maltreatment existed. Developmental examinations revealed that infants subjected to severe abuse and neglect were significantly retarded in their mental and motor development compared with the remaining index and control groups. The results were interpreted to suggest that relational disturbances are at the core of the problem of infant maltreatment and that on the basis of interactional symptomatology, two broadly different clinical conditions have been identified. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) are recognized neurotoxicants, but the extent to which PBDEs influence various domains of behavior in children is not fully understood. As such, we reviewed epidemiologic studies published to date to provide an overview of the current state of knowledge on PBDEs' potential role in behavioral development. We identified 19 epidemiologic studies reporting on associations of prenatal and childhood concentrations of PBDEs with behaviors assessed in children from 1 to 12 years, including executive function, attention, externalizing and internalizing behaviors, adaptive skills, and social behaviors/Autism Spectrum Disorder (ASD). While the mechanisms of PBDE neurotoxicity in humans are still not clearly elucidated, findings from this review indicate that PBDE exposure during fetal development is associated with impairments in executive function and poorer attentional control in children. Results from large prospective cohorts demonstrate that prenatal and postnatal PBDE exposure adversely impacts externalizing behavior ( e.g. , hyperactivity and conduct problems). Additional studies are needed to determine whether PBDEs are associated with internalizing problems, adaptive skills, and social behaviors/ASD in children. Future studies will help better understand the potential neurotoxic effects of PBDE exposures during adolescence, possible sex-dependent effects, and the impact of exposure to BDE-209 and alternative flame retardants. Future studies should also examine chemical mixtures to capture real-world exposures when examining PBDEs and their impact on various behavioral domains in the context of multiple chemical exposures. [ABSTRACT FROM AUTHOR]

Background: Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment. Methods: We enrolled 780 children with blood lead levels of 20 to 44 μg per deciliter (1.0 to 2.1 μmol per liter) in a randomized, placebo-controlled, double-blind trial of up to three 26-day courses of treatment with succimer, a lead chelator that is administered orally. The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up included tests of cognitive, motor, behavioral, and neuropsychological function over a period of 36 months. Results: During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 μg per deciliter (0.2 μmol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 μg per deciliter [0.2 to 0.3 μmol per liter]). At 36 months of follow-up, the mean IQ score of children given succimer was 1 point lower than that of children given placebo, and the behavior of children given succimer was slightly worse as rated by a parent. However, the children given succimer scored slightly better on the Developmental Neuropsychological Assessment, a battery of tests designed to measure neuropsychological deficits thought to interfere with learning. All these differences were small, and none were statistically significant. Conclusions: Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition, behavior, or neuropsychological function in children with blood lead levels below 45 μg per deciliter. Since succimer is as effective as any lead chelator currently available, chelation therapy is not indicated for children with these blood lead levels. (N Engl J Med 2001;344:1421-6.) [ABSTRACT FROM AUTHOR]

Presents several letters to the editors concerning the effects of lead on child development. Correlation between neonatal blood lead concentration and neurobehavioral outcomes; Complexity of Kaufman assessment battery for children; Advantage of the Kaufman test.

Background: The most common route for general population exposure to methyl mercury (MeHg) is fish consumption. Recommendations to pregnant women about consuming fish contaminated with MeHg are also applied to children, but there are few studies available about the effects of low-level postnatal MeHg exposure in them. Objectives: To investigate the association between postnatal methyl mercury exposure and neuropsychological development in a study of children also exposed to lead, both measured at 7 years. Methods: We measured MeHg concentrations in blood samples from the Treatment of Lead-Exposed Children (TLC) trial in which 780 children with elevated concentrations of lead in blood were followed with neuropsychological tests from ages 12–33 months through 7 years. Here we examine blood MeHg concentration and neuropsychological test scores, both measured at age 7 years. We used a maximum likelihood method to estimate geometric mean MeHg concentration and generalized linear regression models to analyze MeHg and neuropsychological test scores. Results: Geometric mean MeHg concentration was 0.56 (95% confidence interval: 0.52, 0.59)μg/L. A 1 μg/L increase in MeHg was associated with a 2.1 (95% confidence interval: 0.4, 3.8) point increase in Full-Scale IQ and 0.2 (95% confidence interval: 0.02, 0.4) point increase in Learning SlopeindexT-score on a test of verbal memory. Conclusions: Our results suggest that the relatively low MeHg exposure in US school-aged children from this population has no detectable adverse effect on neuropsychological development. The positive associations observed between MeHg and neurodevelopment may indirectly reflect consumption of beneficial polyunsaturated fatty acids from seafood. [ABSTRACT FROM AUTHOR]

Exposure to metal mixtures may lead to health impacts greater than the effects associated with singular exposures. Two common childhood environmental exposures, manganese (Mn) and lead (Pb), are associated with similar adverse neurodevelopmental effects; however, the effects surrounding concurrent exposure to both metals remain unclear. We study the impact of joint exposure to Mn and Pb on cognitive performance in school-aged children participating in the Communities Actively Researching Exposure Study (CARES) based in East Liverpool, Ohio. Blood Pb levels were measured for each child (geometric mean (GM) = 1.13 μg/dL, range 0.30 μg/dL – 6.64 μg/dL). Mn was measured in participant blood, hair, and toenails with GMs of 10.1 μg/L, 360 ng/g, 0.974 μg/g, respectively. Trained team members administered the Wechsler Intelligence Scale for Children-IV (WISC-IV) to assess intelligence quotient (IQ). The WISC-IV provides scores for Full Scale IQ, Perceptual Reasoning, Processing Speed, Working Memory, and Verbal Comprehension. Interactions between blood Pb and all Mn biomarkers were tested in linear models adjusted for child sex, household income, and serum cotinine. Separate regression models were run for each of the Mn biomarkers. The cohort was comprised of 106 children with a mean age of 8.4 years. Interactions between blood Pb and hair Mn were significant (p < 0.05) for four out of the five IQ domains. The effect of blood Pb on IQ was more pronounced at higher levels of hair and toenail Mn. No significant associations were observed when characterizing the main effect of Mn using blood. Uncovering the health impacts associated with exposure mixtures is critical to understanding the impact of real-life conditions. Our findings suggest that joint exposure to Mn and Pb may produce heightened neurocognitive impacts even at blood Pb levels below the CDC reference concentration of 5 μg/dL. • The effects surrounding concurrent exposure to manganese and lead remain unclear. • Joint Mn and Pb exposure may produce heightened neurocognitive impacts. • This association was observed when Mn was measured in hair and toenail samples. • Even at low blood Pb levels, the interactive effects of Mn and Pb are apparent. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to bisphenol A (BPA) increases offspring aggression and diminishes differences in sexually dimorphic behaviors in rodents. Objective: We examined the association between prenatal BPA exposure and behavior in 2-yearold children. Methods: We used data from 249 mothers and their children in Cincinnati, Ohio (USA). Maternal urine was collected around 16 and 26 weeks of gestation and at birth. BPA concentrations were quantified using high-performance liquid chromatography-isotope-dilution tandem mass spectrometry. Child behavior was assessed at 2 years of age using the second edition of the Behavioral Assessment System for Children (BASC-2). The association between prenatal BPA concentrations and BASC-2 scores was analyzed using linear regression. Results: Median BPA concentrations were 1.8 (16 weeks), 1.7 (26 weeks), and 1.3 (birth) ng/mL. Mean (± SD) BASC-2 externalizing and internalizing scores were 47.6 ± 7.8 and 44.8 ± 7.0, respectively. After adjustment for confounders, log10-transformed mean prenatal BPA concentrations were associated with externalizing scores, but only among females [β = 6.0; 95% confidence interval (CI), 0.1-12.0]. Compared with 26-week and birth concentrations, BPA concentrations collected around 16 weeks were more strongly associated with externalizing scores among all children (β = 2.9; 95% CI, 0.2-5.7), and this association was stronger in females than in males. Among all children, measurements collected at = 16 weeks showed a stronger association (β = 5.1; 95% CI, 1.5-8.6) with externalizing scores than did measurements taken at 17-21 weeks (β = 0.6; 95% CI, -2.9 to 4.1). Conclusions: These results suggest that prenatal BPA exposure may be associated with externalizing behaviors in 2-year-old children, especially among female children. [ABSTRACT FROM AUTHOR]

Background: Susceptibility to lead toxicity is often assumed to be greatest during early childhood (e.g., 2 years of age), but recent studies suggest that blood lead concentrations (BPb) taken at 5-7 years of age are more strongly associated with IQ. Objective: We aimed to determine the age of greatest susceptibility to lead exposure using an innovative statistical approach that avoids the problem of correlated serial BPb measurements. Methods: We analyzed two cohorts of children that were followed from infancy to 6 years of age in Rochester, New York (n = 211), and Cincinnati, Ohio (n = 251). Serial BPb levels were measured and IQ tests were done when children were 6 years of age. After adjustment for relevant covariates, the ratio of 6-year BPb to 2-year BPb was added to the multiple regression model to test whether the pattern of BPb profiles during childhood had additional effect on IQ. Results: The ratio of BPb at 6 years to the BPb at 2 years showed a strong effect on IQ (p < 0.001) when added to the multiple regression model that included the average childhood BPb. IQ decreased by 7.0 points for children whose BPb at 6 years of age was 50% greater than that at 2 years compared with children whose 6-year BPb was 50% less than their 2-year BPb. Similarly, criminal arrest rates were a factor of 3.35 higher for those subjects whose 6-year BPb was 50% higher than their 2-year BPb. Conclusions: We conclude that 6-year BPb is more strongly associated with cognitive and behavioral development than is BPb measured in early childhood. [ABSTRACT FROM AUTHOR]

Background: Prior studies have examined independent effects of a dopamine receptor D4 polymorphism (DRD4-7) and lead exposure on executive functions but not their interaction or the role of sex as a modifier of their effects. Methods: Multivariable analyses were used to examine effects of DRD4-7 genotype, 60-month blood lead level, and sex on spatial working memory, rule learning and reversal, spatial span, and planning for 174 children. Results: DRD4-7 was associated with poorer spatial working memory, and increasing blood lead levels were associated with impaired rule learning and reversal, spatial span, and planning. Adverse effects of lead on planning and rule learning and reversal were seen primarily for boys. In addition, the effect of lead on rule learning and reversal was evident predominately for those lacking DRD4-7. Conclusions: We observed independent effects of DRD4-7 and lead on various executive functions and modifications of lead effects by DRD4 genotype and sex. [Copyright &y& Elsevier]

Abstract: This prospective study investigated the impact of early exposure to lead on the maturation of children''s postural balance. The effect of lead exposure on age-associated maturation of postural balance was investigated on 91 children from the Cincinnati Lead Study (CLS) with a 5-year geometric mean lead concentration in blood of 11.66μg/dL (range 3.89–28.33μg/dL) by re-assessing their postural balance approximately every 20months starting at mean age of 6.6years through mean age of 12.1years. The results presented in this paper provide evidence that low to moderate lead exposure in early childhood has a measurable and statistically significant impact on the maturation of postural balance. In comparison to less exposed children, of those in the higher lead group showed an impaired postural balance response. The results from this study suggest that children with early childhood lead exposure may need additional time to approach (or “catch up” with) their maturational postural balance status. As these subjects are now adults in their early to mid-twenties, poor postural balance may impact their daily living tasks and pose a higher risk of potential injuries at home and work. [Copyright &y& Elsevier]

Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003–2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose–response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di- n -butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed. [ABSTRACT FROM AUTHOR]

ABSTRACT In an effort to characterize how a child goes about learning and recalling information, the developers of the California Verbal Learning Test for Children (CVLT-C) provided normative data related to both learning outcome and learning process. The present study examined the assertion that CVLT-C process indices relate to executive functioning in a sample of community-dwelling adolescents. Contrary to predictions, measures of executive functioning typically correlated poorly with measures of learning process, despite displaying significant correlations with measures of learning outcome. Although further research is recommended, these findings do not support the clinical interpretation of CVLT-C process indices as reflections of executive functioning. [ABSTRACT FROM AUTHOR]

Using a variety of research designs and measures of lead absorption, numerous studies link childhood lead exposure to a range of cognitive and behavioral deficits, including low IQ, impulsivity, juvenile delinquency, and criminal behavior in adolescence and early adulthood. In this study, we tested the association between multiple measures of blood lead concentration assessed in childhood with criminal behavior in adulthood and across the life-course. Prospective data from the Cincinnati Lead Study (CLS) included blood lead measures quarterly across the first 78 months of life and the number of times a person was arrested across the life-course (from age 18 to 33 years) and in later adulthood (age 27 to 33 years). Childhood blood lead concentration prospectively predicted variation in adult arrests and arrests over the life-course, indicating lead absorption is implicated in the etiology of crime—especially in geographic areas where environmental sources of lead are more prevalent and concentrated. Efforts to decrease lead exposure in both developed and developing countries should be part of a comprehensive strategy to reduce social dislocation and crime. • The Cincinnati Lead Study is the longest running prospective study on the effects of early life lead exposure. • Multiple blood lead concentrations assessed prenatally and through the first 78 months of life, predicted variation in adult arrests when subjects were between 27 and 33 years of age, including a measure of lifetime arrests and arrests for drug crimes. • Total adult arrests when subjects were between 27 and 33 years of age were predicted by prenatal blood lead concentrations (RR = 1.15, 95% CI = 1.03–1.27), by average late childhood blood lead concentrations (RR = 1.07, 95% CI = 1.01–1.14), and by 6-year blood lead concentrations (RR = 1.07, 95% CI = 1.00–1.14). Violent arrests and arrests for property crimes were not significantly predicted by the blood lead concentrations, however, prenatal, late childhood, and 6-year blood lead concentration predicted drug arrests. • Prenatal blood lead (RR = 1.17, 95% CI = 1.06–1.28), average late childhood blood lead (RR = 1.07, 95% CI = 1.01–1.14), and 6-year blood lead levels (RR = 1.08, 95% CI = 1.01–1.16) predicted variation in lifetime (18–33 years) arrests. • Childhood body lead burden are prospectively related to arrests in adulthood, arrests over the lifetime, and especially arrests for drug law violations. [ABSTRACT FROM AUTHOR]

Background: Traffic related air pollution (TRAP) and its component polycyclic aromatic hydrocarbons (PAHs) may be neurotoxic in children. There is limited research on postnatal exposure to TRAP and PAHs and child neurodevelopment.Methods: We linked data from the U.S. NHANES 2001-2004 with the National Highway Planning Network 2005 to examine the proximity to major roads (highway or urban/rural principal arterials), urinary PAH metabolites, and diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder (CD) based on Diagnostic Interview Schedule for Children (C-DISC) in 1253 children aged 8-15 years. We calculated odds ratios (ORs) and 95% Confidence Intervals (CIs) for ADHD and CD by traffic proximity and PAH exposures using logistic regression adjusted for confounders.Results: Higher ADHD prevalence was observed among children living <500 m (9.86%) compared to those ≥500 m (3.84%) from a major road. Prevalence of children with CD was comparable (<500 m: 2.51% and ≥500 m: 2.43%). We found little difference in urinary PAH metabolite levels between children living near major roads and those who did not. Children living <500 m from a major road had a non-significant OR of 2.06 (95% CI 0.85-5.03) for ADHD diagnosis. Children living on ≥2 major roads within 500 m of a highway had a non-significant OR of 2.27 (95% CI 0.71-7.26) for ADHD diagnosis. There was no association between proximity to major roads and CD diagnosis.Conclusion: We found living close to a major road was not associated with increased PAH levels. We did not find statistically significant relation between proximity to a major road or urinary PAH metabolite levels and ADHD or CD diagnosis in this cross-sectional analysis. Prospective studies are needed for the investigation of postnatal TRAP exposure and ADHD and CD diagnosis. [ABSTRACT FROM AUTHOR]

Abstract. The growth of a cohort of 260 infants was prospectively followed up from birth. Blood lead and stature measurements were obtained every 3 months until 15 months of age. Fetal lead exposure was indexed by measuring lead in maternal blood during pregnancy. A longitudinal analysis revealed that covariate adjusted growth rates in stature were negatively related to the infants' postnatal blood lead concentration, as indexed by increase in average blood lead values from 3 to 15 months. However, this relationship between growth rate and change in blood lead concentration was evidenced only among those infants whose mothers had prenatal blood lead levels greater than the maternal cohort median of 7.7 micro g/dL (P = .01). The expected stature of a child born to a mother with a prenatal blood lead concentration more than 7.7 micro g/dL is about 2 cm shorter at 15 months of age if, postnatally, the infant incurred a 10-micro g/dL blood lead increase during the 3- to 15-month interval of life, compared with an infant who has no increase. [ABSTRACT FROM AUTHOR]

Toxicological studies indicate that poly- and perfluoroalkyl substances (PFAS) may be neurotoxic, but human studies have yet to provide compelling evidence for PFAS' impact on cognitive abilities. To test whether prenatal and childhood PFAS are associated with cognitive abilities at 8 years and whether sex modifies these associations. We included 221 mother-child pairs from the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort in Cincinnati, OH (USA). We quantified PFAS in maternal serum at 16 ± 3 weeks gestation and in child serum at 3 and 8 years. We used the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) at age 8 years, assessing Full Scale IQ (FSIQ), verbal comprehension, perceptual reasoning, working memory, and processing speed. We used multiple informant models to estimate covariate-adjusted differences in WISC-IV scores by repeated ln-transformed PFAS. Prenatal and childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were not associated with WISC-IV measures. We observed an increase of 4.1-points (95% CI 0.3, 8.0) and 5.7-points (95% CI 1.2, 10.2) in working memory with 1-ln unit increase in prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA), respectively. In addition, PFNA at 3 years was associated with better FSIQ and perceptual reasoning. Child sex modified the relationship between prenatal PFOA and FSIQ; the association was positive in females only. Sex also modified the association between concurrent PFOS and FSIQ, with males having higher scores. We did not observe adverse associations between prenatal and childhood PFAS and cognitive function at age 8 years. • PFOS and PFHxS were not associated with Full Scale IQ (FSIQ) at 8 years. • Prenatal PFOA and PFNA were positively associated with working memory at 8 years. • Child sex modified prenatal PFOA associations, with higher FSIQ scores in females. • We observed higher scores on several WISC scales in males, but not in females. • Findings do not support that PFAS are adversely associated with cognitive function. [ABSTRACT FROM AUTHOR]

Background: Mercury is toxic to the developing brain, but the lowest concentration associated with the development of behavior problems is unclear. The purpose of this study was to examine the association between very low-level mercury exposure during fetal development and behavior problems in children.Methods: We used data from 389 mothers and children in a prospective pregnancy and birth cohort study. We defined mean prenatal mercury concentration as the mean of total whole blood mercury concentrations in maternal samples collected at 16- and 26-weeks of gestation, delivery, and neonatal cord blood samples. We assessed parent-reported child behavior up to five times from two to 8 years of age using the Behavioral Assessment System for Children (BASC-2). At 8 years of age, we assessed self-reported child anxiety using the Spence Children's Anxiety Scale (SCAS). We used multiple linear mixed models and linear regression models to estimate the association between mean prenatal mercury concentrations and child behavior and anxiety, respectively.Results: The median prenatal total blood mercury concentrations was 0.67 μg/L. Overall, we did not find statistically significant associations between mean prenatal mercury concentrations and behavior problems scores, but a 2-fold increase in mercury concentrations at 16-weeks gestation was associated with 0.83 point (95% CI: 0.05, 1.62) higher BASC-2 anxiety scores. Maternal and cord blood mercury concentrations at delivery were associated with parent-reported anxiety at 8 years.Conclusion: We found limited evidence of an association between very-low level prenatal mercury exposure and behaviors in children, with an exception of anxiety. [ABSTRACT FROM AUTHOR]

Abstract Background Toxicological studies highlight the potential neurotoxicity of perfluoroalkyl substances (PFAS) during fetal development. However, few epidemiological studies have examined the impact of childhood PFAS on neurodevelopment. Methods We employed data from 208 children in the Health Outcomes and Measures of the Environment Study, a birth cohort (Cincinnati, OH), to examine associations of six serum PFAS concentrations measured at 3 and 8 years with executive function assessed at 8 years using the validated parent-completed Behavior Rating Inventory of Executive Function survey. We used multiple informant models to identify susceptible windows of neurotoxicity to PFAS and executive function. We investigated trajectories of PFAS concentrations and whether sex modified these associations. Results Each ln-increase in perfluorononanoate (PFNA) at 8 years was associated with a 3.4-point increase (95% CI 0.4, 6.3) in metacognition score, indicating poorer function. Children with PFNA above the median at 8 years had poorer global executive functioning compared to children with concentrations consistently below median levels (β = 6.5, 95% CI 0.2, 12.9). Higher concurrent PFNA was associated with poorer behavior regulation among males, while associations among females were null (p PFNA × sex = 0.018). Children with higher concurrent perfluorooctanoate (PFOA) had increased odds of being at risk of having clinical impairments in metacognition (OR = 3.18, 95% CI 1.17, 8.60). There were no associations between perfluorooctane sulfonate and perfluorohexane sulfonate and executive function. Conclusions PFNA and PFOA at 8 years, but not 3 years, may be related to poorer executive function at 8 years. Results need to be confirmed in cohort studies with larger sample sizes. Highlights • PFAS concentrations at age 3 years were not associated with executive function at age 8 years. • Concurrent PFNA was associated with impairments in metacognition and global executive function at 8 years. • A sexually dimorphic relationship may be present, with males more sensitive to PFNA neurotoxicity. • Childhood PFNA and PFOA, to a lesser extent, may be neurotoxic with regard to executive function. [ABSTRACT FROM AUTHOR]

Abstract Background Despite evidence from toxicological studies describing the potential neurotoxicity of perfluoroalkyl substances (PFAS), their role in neurodevelopment remains uncertain amid inconsistent findings from epidemiological studies. Methods Using data from 218 mother-child dyads from the Health Outcomes and Measures of the Environment Study, we examined prenatal and childhood (3 and 8 years) serum concentrations of four PFAS and inattention, impulsivity, and visual spatial abilities. At 8 years, we used the Conners' Continuous Performance Test-II to assess attention and impulse control and the Virtual Morris Water Maze (VMWM) to measure visual spatial abilities. Results In multiple informant models, there was no evidence to indicate that prenatal or childhood PFAS are associated with attention. However, there was an inverse association between prenatal ln-perfluorooctanoate (PFOA) and errors of commission (β = −2.0, 95% Confidence Interval [CI] −3.8, −0.3). Ln-perfluorononanoate (PFNA) at 3 years was associated with longer (poorer) VMWM completion times of 3.6 seconds (CI 1.6, 5.6). However, higher concurrent concentrations of ln-perfluorohexane sulfonate (PFHxS) (β = −2.4 s, 95% CI −4.4, −0.3) were associated with shorter (better) times. Higher prenatal PFHxS was positively associated with percentage of traveling distance in the correct quadrant (β = 4.2%, 95% CI 0.8, 7.7), indicating better performance. Conclusion Findings were mixed for prenatal and childhood PFAS concentrations and visual spatial abilities. There is not enough evidence to support that PFAS are associated with visual spatial abilities as assessed by the VMWM or CPT-II measures of inattention or impulsivity in children at age 8 years. Highlights • Prenatal and childhood PFAS are not associated with CPT-II measures of inattention at 8 years. • Inconsistent associations were noted between PFNA and PFHxS with VMWM performance at 8 years. • Findings do not support associations between PFAS and VMWM measures of visual spatial abilities. [ABSTRACT FROM AUTHOR]

Background Exposure to perfluoroalkyl substances (PFASs) may impact children's neurodevelopment. Objective To examine the association of prenatal and early childhood serum PFAS concentrations with children's reading skills at ages 5 and 8 years. Methods We used data from 167 mother-child pairs recruited during pregnancy (2003–2006) in Cincinnati, OH, quantified prenatal serum PFAS concentrations at 16 ± 3 weeks of gestation and childhood sera at ages 3 and 8 years. We assessed children's reading skills using Woodcock-Johnson Tests of Achievement III at age 5 years and Wide Range Achievement Test-4 at age 8 years. We used general linear regression to quantify the covariate-adjusted associations between natural log-transformed PFAS concentrations and reading skills, and used multiple informant model to identify the potential windows of susceptibility. Results Median serum PFASs concentrations were PFOS > PFOA > PFHxS > PFNA in prenatal, 3-year, and 8-year children. The covariate-adjusted general linear regression identified positive associations between serum PFOA, PFOS and PFNA concentrations and children's reading scores at ages 5 and 8 years, but no association between any PFHxS concentration and reading skills. The multiple informant model showed: a) Prenatal PFOA was positively associated with higher children's scores in Reading Composite (β: 4.0, 95% CI: 0.6, 7.4 per a natural log unit increase in exposure) and Sentence Comprehension (β: 4.2, 95% CI: 0.5, 8.0) at age 8 years; b) 3-year PFOA was positively associated with higher children's scores in Brief Reading (β: 7.3, 95% CI: 0.9, 13.8), Letter Word Identification (β: 6.6, 95% CI: 1.1, 12.0), and Passage Comprehension (β: 5.9, 95% CI: 1.5, 10.2) at age 5 years; c) 8-year PFOA was positively associated with higher children's Word Reading scores (β: 5.8, 95% CI: 0.8, 10.7) at age 8 years. Prenatal PFOS and PFNA were positively associated with children's reading abilities at age 5 years, but not at age 8 years; 3-year PFOS and PFNA were positively associated with reading scores at age 5 years. But PFHxS concentrations, at any exposure windows, were not associated with reading skills. Conclusion Prenatal and childhood serum PFOA, PFOS and PFNA concentrations were positively associated with better children's reading skills at ages 5 and 8 years, but no association was found between serum PFHxS and reading skills. [ABSTRACT FROM AUTHOR]

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β=4.6, 95% CI 0.5, 8.7) and BDE-153 (β=4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function. [ABSTRACT FROM AUTHOR]

This study was to investigate whether exposure to cadmium (Cd) during pregnancy is associated with an increased risk of adverse birth outcomes in a sex-dependent manner. Cd concentrations in maternal urine (U-Cd) samples were measured in 237 subjects from Guiyu (e-waste area) and 212 subjects from Haojiang. A significance level of p < 0.05 was used for all analyses. The maternal U-Cd levels in Guiyu residents were significantly higher than Haojiang. We found significant inverse associations between U-Cd concentrations and birth anthropometry (birth weight, birth length, Head Circumference and Apgar scores with 1 min and 5 mins) in female neonates, but no significant associations were observed in male neonates except Apgar (1 min) score after adjustment. The association was more pronounced among female neonates than male neonates, suggesting an association between Cd and adverse birth outcomes may be sex-specific. [ABSTRACT FROM AUTHOR]

Background East Liverpool, Ohio, the site of a hazardous waste incinerator and a manganese (Mn) processor, has had air Mn concentrations exceeding United States Environmental Protection Agency reference levels for over a decade. Save Our County, Inc., a community organization, was formed to address community environmental health concerns related to local industry. Researchers from the University of Cincinnati partnered with Save Our County to determine if air Mn had an impact on the neurocognitive function of children in the community. Methods Children 7–9 years of age from East Liverpool and its surrounding communities, were enrolled (N = 106) in the Communities Actively Researching Exposure Study from between March 2013–June 2014. Blood and hair were analyzed for Mn and lead, and serum was analyzed for cotinine. We used linear regression to assess associations between biological measures and IQ subscale scores. Results Geometric mean blood lead (n = 67), blood Mn (n = 66), hair Mn (n = 98), and serum cotinine (n = 69) concentrations were 1.13 ± 1.96 μg/dL, 10.06 ± 1.30 μg/L, and 360.22 ± 2.17 ng/g, 0.76 ± 6.12 μg/L respectively. After adjusting for potential confounders, hair Mn was negatively associated with Full Scale IQ. Conclusions Hair Mn was negatively associated with child IQ scores. Community partners were instrumental in the conception and implementation of this study. [ABSTRACT FROM AUTHOR]

Exposure to polybrominated diphenyl ethers (PBDEs) during fetal development may be associated with deficits in attention and impulse control. However, studies examining postnatal PBDE exposures and inattention and impulsivity have been inconsistent. Using data from 214 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort with enrollment from 2003 to 2006 in the Greater Cincinnati Area, we investigated the relationship of both prenatal and postnatal PBDE exposures with attention and impulse control. Serum PBDEs were measured at 16 ± 3 weeks of gestation and during childhood at 1, 2, 3, 5, and 8 years. We assessed children's attention and impulse control using the Conners' Continuous Performance Test-Second Edition (CPT-II) at 8 years. We used multiple informant models to estimate associations of repeated PBDE measures with inattention and impulsivity. There was a pattern of associations between PBDEs and poorer performance on CPT-II measures of attention. For BDE-153, adverse associations extended to exposures at preschool and kindergarten ages; ten-fold increases in exposure were associated with higher omission errors (BDE-153 at 3 years: β = 4.0 [95% CI: − 2.4, 10.5]; at 5 years: β = 4.6 [95% CI: − 2.8, 12.0]; at 8 years: β = 4.1 [95% CI: − 3.4, 11.5]). Longer hit reaction times, indicated by the exponential part of the hit reaction curve, were also observed with 10-fold increases in BDE-153 during the prenatal period and throughout childhood (Prenatal: β = 15.0 milliseconds (ms) [95% CI: − 15.8, 45.8]; 5 years: β = 20.6 ms [95% CI: − 20.8, 61.9]; 8 years: β = 28.6 ms [95% CI: − 12.1, 69.4]). Significant impairment in discriminability, as indicated by detectability (d′), between targets and non-targets was also noted with 5 and 8-year PBDE concentrations. Associations between PBDEs and inattention significantly differed by child sex, with males performing more poorly than females with regard to omission errors and measures of reaction times. Collectively, these results do not strongly support that PBDEs are associated with poorer impulse and attention control among 8 year old children. However, there may be a possible relationship between prenatal and concurrent PBDEs and inattention, which requires additional research. [ABSTRACT FROM AUTHOR]

Background Prenatal polybrominated diphenyl ether (PBDE) exposure has been associated with decrements in IQ and increased attention deficit/hyperactivity disorder related behaviors in children; however, data are limited for the role of postnatal exposures. Objectives We investigated the association between a series of childhood PBDE concentrations and Full-Scale Intelligence Quotient (FSIQ) and externalizing problems at 8 years. Methods We used data from 208 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort. Child serum PBDEs were measured at 1, 2, 3, 5, and 8 years; missing serum PBDE concentrations were estimated via multiple imputation. The Wechsler Intelligence Scales for Children-IV and the Behavior Assessment System for Children-2 was used to assess intelligence and externalizing behavior, respectively, in children at 8 years. We used multiple informant models to estimate associations between repeated lipid-adjusted PBDEs and child neurobehavior and to test for windows of susceptibility. Results Postnatal exposure to PBDE congeners (− 28, − 47, − 99, − 100, and − 153) at multiple ages was inversely associated with FSIQ at 8 years. For instance, a 10-fold increase in BDE-153 concentrations at 2, 3, 5, and 8 years were all related to lower FSIQ at age 8 (β for 3 years: − 7.7-points, 95% CI − 12.5, − 2.9; β for 8 years: − 5.6-points, 95% CI − 10.8, − 0.4). Multiple PBDE congeners at 8 years were associated with increased hyperactivity and aggressive behaviors at 8 years. Conclusions Postnatal PBDE exposure was associated with decrements in FSIQ and increases in hyperactivity and aggressive behaviors. [ABSTRACT FROM AUTHOR]

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 Sum4PBDEs (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 (β: -6.2, 95% CI: -11.7, -0.6) and FSIQ (β: -5.3, 95% CI: -10.6, -0.02) at age 8 years; it was positively associated with the score for externalizing behavior problems (β: 3.5, 95% CI: -0.1, 7.2) at age 8 years. Prenatal Sum4PCBs (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. CITATION: Zhang H, Yolton K, Webster GM, Sjödin A, Calafat AM, Dietrich KN, Xu Y, Xie C, Braun JM, Lanphear BP, Chen A. 2017. Prenatal PBDE and PCB exposures and reading, cognition, and externalizing behavior in children. Environ Health Perspect 125:746-752; http://dx.doi.org/10.1289/EHP478 [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) are associated with impaired visual spatial abilities in toxicological studies, but no epidemiologic study has investigated PBDEs and visual spatial abilities in children. The Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003–2006, Cincinnati, OH), was used to examine prenatal and childhood PBDEs and visual spatial abilities in 199 children. PBDEs were measured at 16±3 weeks gestation and at 1, 2, 3, 5, and 8 years using gas chromatography/isotope dilution high-resolution mass spectrometry. We used the Virtual Morris Water Maze to measure visual spatial abilities at 8 years. In covariate-adjusted models, 10-fold increases in BDE-47, −99, and −100 at 5 years were associated with shorter completion times by 5.2 s (95% Confidence Interval [CI] −9.3, −1.1), 4.5 s (95% CI −8.1, −0.9), and 4.7 s (95% CI −9.0, −0.3), respectively. However, children with higher BDE-153 at 3 years had longer completion times (β=5.4 s, 95% CI −0.3, 11.1). Prenatal PBDEs were associated with improved visual spatial memory retention, with children spending a higher percentage of their search path in the correct quadrant. Child sex modified some associations between PBDEs and visual spatial learning. Longer path lengths were observed among males with increased BDE-47 at 2 and 3 years, while females had shorter paths. In conclusion, prenatal and postnatal BDE-28, −47, −99, and −100 at 5 and 8 years were associated with improved visual spatial abilities, whereas a pattern of impairments in visual spatial learning was noted with early childhood BDE-153 concentrations. [ABSTRACT FROM AUTHOR]

Executive function is a critical behavioral trait rarely studied in relation to potential neurotoxicants. Prenatal exposure to polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFASs) has been associated with adverse neurodevelopment, but there is limited research on executive function. Data from 256 mother–child pairs in the Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003–2006, Cincinnati, OH), was used to examine maternal serum PBDEs and PFASs and executive function in children ages 5 and 8 years. Maternal serum PBDEs and PFASs were measured at 16±3 weeks gestation. Executive function was assessed with the parent-rated Behavior Rating Inventory of Executive Function (BRIEF), which yields composite measures: behavioral regulation index, metacognition index, and global executive composite. Higher BRIEF scores indicate executive function impairments. Linear mixed models and generalized estimating equations were used to estimate covariate-adjusted associations between PBDEs and PFASs and executive function. A 10-fold increase in BDE-153 was associated with poorer behavior regulation ( β =3.23, 95% CI 0.60, 5.86). Higher odds of having a score ≥60 in behavior regulation (OR=3.92, 95% CI 1.76, 8.73) or global executive functioning (OR=2.34, 95% CI 1.05, 5.23) was observed with increased BDE-153. Each ln-unit increase in perfluorooctane sulfonate (PFOS) was associated with poorer behavior regulation ( β =3.14, 95% CI 0.68, 5.61), metacognition ( β =3.10, 95% CI 0.62, 5.58), and global executive functioning ( β =3.38, 95% CI 0.86, 5.90). However, no association was observed between perfluorooctanoate (PFOA) and executive function. Prenatal exposures to BDE-153 and PFOS may be associated with executive function deficits in school-age children. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. OBJECTIVES: The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. METHODS: Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. RESULTS: Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = -0.0014; 95% CI: -0.0023, -0.0005, p = 0.002), stronger in males (β = -0.0024; 95% CI: -0.0038, -0.0009, p = 0.003) than in females (β = -0.0009; 95% CI: -0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = -0.0013; 95% CI: -0.0023, -0.0003, p = 0.01) DMR methylation, but primarily in females, (β = -0.0017; 95% CI: -0.0029, -0.0006, p = 0.005) rather than in males, (β = -0.0004; 95% CI: -0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. CONCLUSIONS: Our findings provide evidence that early childhood lead exposure results in sex-dependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood. [ABSTRACT FROM AUTHOR]

Federal funding agencies increasingly support stakeholder participation in environmental health studies, and yet there is very little published research on engagement of community members in the development of data disclosure (DD) strategies. The Ohio Environmental Protection Agency reported airborne manganese (Mn) concentrations in East Liverpool, Ohio, 30 times higher than the reference concentration, which led to an academic--community research partnership to address community concern about Mn exposure, particularly among children. Children and their families were recruited to participate in a pilot study. Samples of blood and hair were collected from the children and analyzed for metals. DD mechanisms were developed using an iterative approach between community and academic partners. Individual DD letters were mailed to each participating family, and a community meeting was held. A post-meeting survey was administered to gauge community perception of the DD strategies. The purpose of this article is to demonstrate the effectiveness of engaging community partners in the conduct of environmental health research and in the development of DD strategies for individuals and the community at large. Scientists should include community partners in the development of DD strategies to enhance translation of the research findings and support the right of study participants to know their individual results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]