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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]

Background: Heavy metals, such as lead (Pb), mercury (Hg), and cadmium (Cd), are known toxicants, but their associations with the thyroid axis have not been well quantified at U.S. background levels. Objectives: We investigated the relationships between thyroid hormones (total and free thyroxine [TT4 and FT4], total and free triiodothyronine [TT3 and FT3], thyroid-stimulating hormone [TSH], and thyroglobulin [Tg]) and levels of Pb, Hg, and Cd in blood and Cd in urine. Methods: We separately analyzed a sample of 1,109 adolescents (12–19 years of age) and a sample of 4,409 adults from the U.S. National Health and Nutrition Examination Survey (NHANES) 2007–2008. We estimated associations after adjusting for age, sex, race, urinary iodine, body mass index, and serum cotinine. Results: The geometric mean (GM) levels of blood Pb (BPb), total Hg, and Cd were 0.81 μg/dL, 0.47 μg/L, and 0.21 μg/L in adolescents and 1.43 μg/dL, 0.96 μg/L, and 0.38 μg/L in adults, respectively. The GMs of urinary Cd were 0.07 and 0.25 μg/g creatinine in adolescents and adults, respectively. No consistent pattern of metal and thyroid hormone associations was observed in adolescents. In adults, blood Hg was inversely related to TT4, TT3, and FT3 and urinary Cd was positively associated with TT4, TT3, FT3, and Tg, but there were no associations with Pb. Associations were relatively weak at an individual level, with about 1–4% change in thyroid hormones per interquartile range increase in Hg or Cd. Conclusions: Our analysis suggests an inverse association between Hg exposure and thyroid hormones, and a positive association between Cd exposure and thyroid hormones in adults. [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]

The article presents the author's views regarding the comments made by other researchers on the evaluation of the case study regarding the reregistration of phosphine by the U.S. Environmental Protection Agency. According to the author, the case study passed through a thorough peer review and was handled properly in all aspects, which is contrary to the accusations of the researchers that the author improperly used his status in the publication where the study was published. The author reveals that there are legitimate scientific concerns that require resolution but was neglected in the study.

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]

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: Antisocial behavior is a product of multiple interacting sociohereditary variables, yet there is increasing evidence that metal exposure, particularly, manganese and lead, play a role in its epigenesis. Other metals, such as arsenic, cadmium, chromium, and mercury, and exposure to traffic-related air pollution, such as fine particulate matter (≤2.5μm) have been associated with neurological deficits, yet largely unexplored with respect to their relationship with delinquent behavior. The purpose of this study is to evaluate the ecological relationship between county-wide reported airborne emissions of air metals, particulate matter, and youth adjudicated for criminal activity. Metal exposure data were collected from the Environmental Protection Agency AirData. Population statistics were obtained from the United States Census 2000 and adjudication data was obtained from the Courts of Common Pleases from each Ohio County. Simple correlations were calculated with the percentage of adjudications, all covariates, and estimated metal air emissions. Separate negative binomial regression models for each pollutant were used to provide an estimated risk ratio of pollutant emissions on the risk of adjudication for all Ohio counties adjusting for urban–rural residence, percentage of African Americans, median family income, percentage of family below poverty, percentage of high school graduation in 25 years and older populations, and population density. Metal emissions and PM in 1999 were all correlated with adjudication rate (2003–2005 average). Metal emissions were associated with slightly higher risk of adjudication, with about 3–4% increased risk per natural log unit of metal emission except chromium. The associations achieved statistical significance for manganese and mercury. The particulate matter ≤2.5 and ≤10μm emissions had a higher risk estimate, with 12% and 19% increase per natural log unit emission, respectively, and also achieved statistical significance. In summary, airborne exposure to manganese, mercury, and particulate matter are associated with increased risk of adjudication. Causality cannot be proven in observational studies such as this one, but the association warrants further examination in other research studies. Comprehensive epidemiologic investigations of metal exposure in pediatric populations should include social health outcomes, including measures of delinquent or criminal activity. Furthermore, the influence of metals on the neurotoxic pathway leading to delinquent activity should be further explored. [Copyright &y& Elsevier]

Importance: Childhood lead exposure is associated with neurobehavioral deficits. The effect of a residential lead hazard intervention on blood lead concentrations and neurobehavioral development remains unknown., Objective: To determine whether a comprehensive residential lead-exposure reduction intervention completed during pregnancy could decrease residential dust lead loadings, prevent elevated blood lead concentrations, and improve childhood neurobehavioral outcomes., Design, Setting, and Participants: This longitudinal, community-based randomized clinical trial of pregnant women and their children, the Health Outcomes and Measures of the Environment (HOME) Study, was conducted between March 1, 2003, and January 31, 2006. Pregnant women attending 1 of 9 prenatal care clinics affiliated with 3 hospitals in the Cincinnati, Ohio, metropolitan area were recruited. Of the 1263 eligible women, 468 (37.0%) agreed to participate and 355 women (75.8%) were randomized in this intention-to-treat analysis. Participants were randomly assigned to receive 1 of 2 interventions designed to reduce residential lead or injury hazards. Follow-up on children took place at 1, 2, 3, 4, 5, and 8 years of age. Data analysis was performed from September 2, 2017, to May 6, 2018., Main Outcomes and Measures: Residential dust lead loadings were measured at baseline and when children were 1 and 2 years of age. At 1, 2, 3, 4, 5, and 8 years of age, the children's blood lead concentrations as well as behavior, cognition, and executive functions were assessed., Results: Of the 355 women randomized, 174 (49.0%) were assigned to the intervention group (mean [SD] age at delivery, 30.1 (5.5) years; 119 [68.3%] self-identified as non-Hispanic white) and 181 (50.9%) to the control group (mean [SD] age at delivery, 29.2 [5.7] years; 123 [67.9%] self-identified as non-Hispanic white). The intervention reduced the dust lead loadings for the floor (24%; 95% CI, -43% to 1%), windowsill (40%; 95% CI, -60% to -11%), and window trough (47%; 95% CI, -68% to -10%) surfaces. The intervention did not statistically significantly reduce childhood blood lead concentrations (-6%; 95% CI, -17% to 6%; P = .29). Neurobehavioral test scores were not statistically different between children in the intervention group than those in the control group except for a reduction in anxiety scores in the intervention group (β = -1.6; 95% CI, -3.2 to -0.1; P = .04)., Conclusions and Relevance: Residential lead exposures, as well as blood lead concentrations in non-Hispanic black children, were reduced through a comprehensive lead-hazard intervention without elevating the lead body burden. However, this decrease did not result in substantive neurobehavioral improvements in children., Trial Registration: ClinicalTrials.gov identifier: NCT00129324.

Background: Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that have been widely used as flame retardants in furniture, carpet padding, car seats, and other consumer products during the past three decades., Objective: We examined whether in utero exposure to PBDEs is associated with child cognitive function and behavior in a U.S. study sample., Methods: In a prospective birth cohort, we measured maternal serum concentrations of BDE-47 and other PBDE congeners in 309 women at 16 weeks of gestation during 2003-2006 and followed their children in Cincinnati, Ohio. We measured cognitive and motor abilities using the Bayley Scales of Infant Development-II at ages 1, 2, and 3 years; intelligence using the Wechsler Preschool and Primary Scale of Intelligence-III at age 5 years; and children's behaviors using the Behavioral Assessment System for Children-2 annually at ages 2-5 years. We used linear mixed models or generalized estimating equations with adjustment for potential confounders to estimate associations between these outcomes and log10-transformed PBDE concentrations., Results: The geometric mean of BDE-47 in maternal serum (20.1 ng/g lipid) was comparable with U.S. adult national reference values. Prenatal BDE-47 was not significantly associated with Bayley Mental or Psychomotor Development Indices at 1-3 years, but a 10-fold increase in prenatal BDE-47 was associated with a 4.5-point decrease (95% CI: -8.8, -0.1) in Full-Scale IQ and a 3.3-point increase (95% CI: 0.3, 6.3) in the hyperactivity score at age 5 years., Conclusions: Prenatal exposure to PBDEs was associated with lower IQ and higher hyperactivity scores in children.

Objectives: To estimate the impact of gestational and childhood bisphenol A (BPA) exposures on behavior and executive function at 3 years of age and to determine whether child gender modified those associations., Methods: We used a prospective birth cohort of 244 mothers and their 3-year-old children from the greater Cincinnati, Ohio, area. We characterized gestational and childhood BPA exposures by using the mean BPA concentrations in maternal (16 and 26 weeks of gestation and birth) and child (1, 2, and 3 years of age) urine samples, respectively. Behavior and executive function were measured by using the Behavior Assessment System for Children 2 (BASC-2) and the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P)., Results: BPA was detected in >97% of the gestational (median: 2.0 μg/L) and childhood (median: 4.1 μg/L) urine samples. With adjustment for confounders, each 10-fold increase in gestational BPA concentrations was associated with more anxious and depressed behavior on the BASC-2 and poorer emotional control and inhibition on the BRIEF-P. The magnitude of the gestational BPA associations differed according to child gender; BASC-2 and BRIEF-P scores increased 9 to 12 points among girls, but changes were null or negative among boys. Associations between childhood BPA exposure and neurobehavior were largely null and not modified by child gender., Conclusions: In this study, gestational BPA exposure affected behavioral and emotional regulation domains at 3 years of age, especially among girls. Clinicians may advise concerned patients to reduce their exposure to certain consumer products, but the benefits of such reductions are unclear.

Background: Marietta, Ohio, is an Appalachian-American community whose residents have long struggled with understanding their exposure to airborne manganese (Mn). Although community engagement in research is strongly endorsed by the National Institutes of Health and the National Institute of Environmental Health Sciences in particular, little has been documented demonstrating how an academic-community partnership that implements the community-based participatory research (CBPR) principles can be created and mobilized for research., Objectives: We created a bidirectional, academic-community partnership with an Appalachian-American community to a) identify the community's thoughts and perceptions about local air quality, its effect on health, and the perception of risk communication sources and b) jointly develop and conduct environmental health research., Methods: We formed a community advisory board (CAB), jointly conducted pilot research studies, and used the results to develop a community-driven research agenda., Results: Persons in the community were "very concerned" to "concerned" about local air quality (91%) and perceived the air quality to have a direct impact on their health and on their children's health (93% and 94%, respectively). The CAB identified the primary research question: "Does Mn affect the cognition and behavior of children?" Although the community members perceived research scientists as the most trusted and knowledgeable regarding risks from industrial emissions, they received very little risk information from research scientists., Conclusions: Engaging a community in environmental health research from its onset enhanced the quality and relevance of the research investigation. The CBPR principles were a useful framework in building a strong academic-community partnership. Because of the current disconnect between communities and research scientists, academic researchers should consider working collaboratively with community-based risk communication sources.

Objective: To examine whether succimer, a mercaptan compound known to reduce blood lead concentration in children, reduces blood mercury concentration., Study Design: We used samples from a randomized clinical trial of succimer chelation for lead-exposed children. We measured mercury levels in pre-treatment samples from 767 children. We also measured mercury levels in blood samples drawn 1 week after treatment began (n = 768) and in a 20% random sample of the children who received the maximum 3 courses of treatment (n = 67). A bootstrap-based isotonic regression method was used to compare the trend with time in the difference between the adjusted mean mercury concentrations in the succimer group and that in the placebo group., Results: The adjusted mean organic mercury concentration in the succimer group relative to the placebo group fell from 99% at baseline to 82% after 3 courses of treatment (P for trend = .048), but this resulted from the prevention of the age-related increase in the succimer group., Conclusion: Succimer chelation for low level organic mercury exposure in children has limited efficacy., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: The purpose of this study was to examine the association of tobacco smoke and environmental lead exposure with conduct disorder (CD)., Methods: The National Health and Nutrition Examination Survey (NHANES) 2001-2004 is a nationally representative cross-sectional sample of the noninstitutionalized U.S. population. We examined the association of prenatal tobacco, postnatal tobacco, and environmental lead exposure with CD in children 8-15 years of age (n = 3,081). We measured prenatal tobacco exposure by parent report of cigarette use during pregnancy, and postnatal tobacco using serum cotinine levels. We assessed lead exposure using current blood lead concentration. Parents completed the Diagnostic Interview Schedule for Children to determine whether their children met criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV ) for CD., Results: Overall, 2.06% of children met DSM-IV criteria for CD in the past year, equivalent to 560,000 U.S. children 8-15 years of age. After adjustment, prenatal tobacco exposure was associated with increased odds for CD [odds ratio (OR) = 3.00; 95% confidence interval (CI), 1.36-6.63]. Increased blood lead levels (fourth vs. first quartile) and serum cotinine levels (fifth vs. first quintile) were associated with an 8.64-fold (95% CI, 1.87-40.04) and 9.15-fold (95% CI, 1.47-6.90) increased odds of meeting DSM-IV CD criteria. Increasing serum cotinine levels and blood lead levels were also associated with increased prevalence of CD symptoms (symptom count ratio, lead: 1.73; 95% CI, 1.23-2.43; symptom count ratio, cotinine: 1.97; 95% CI, 1.15-3.40)., Conclusions: These results suggest that prenatal tobacco exposure and environmental lead exposure contribute substantially to CD in U.S. children.

Background: Lead exposure in childhood lowers IQ scores, but its effect on children's behavior is less clear. Because IQ, per se, affects behavior, measuring the direct effect of lead requires measuring and then adjusting for IQ. In addition, either peak blood lead concentration, usually at 2 years old, or the lower blood lead level measured at school age may be the most relevant. Few studies have all of this information., Objectives: The purpose of this work was to differentiate the direct effect of lead on behavior and the indirect effect through IQ and to examine the strength of the association for peak and concurrent blood lead concentration., Methods: Data come from a clinical trial of the chelating drug succimer to prevent cognitive impairment in 780 urban 12- to 33-month-olds with blood lead concentrations of 20 to 44 microg/dL. The children were followed from ages 2 to 7 years. The trial data were analyzed as a prospective observational study., Results: Blood lead concentration at 2 years old was not associated with Conners' Parent Rating Scale-Revised scores at 5 years of age or Behavioral Assessment Systems for Children scores at 7 years of age. Blood lead level at 7 years of age had direct effects on the Behavioral Assessment Systems for Children behavioral symptoms index, externalizing, and school problems at age 7., Conclusions: Concurrent blood lead concentration was associated with externalizing and school problems scales at 7 years of age, and the effect was not entirely mediated through the effect of lead on IQ.

During the past 2 decades, the proportion of US children who have blood lead concentrations of 10 microg/dL or higher declined by over 80% after the elimination of leaded gasoline and lead solder from canned foods, and a ban on leaded paint used in housing and other consumer products. Fatalities and symptomatic lead poisoning are now rare. Residential lead hazards, which are exceedingly difficult to control, are currently the major source of lead intake for children. Undue lead exposure has retreated into 2 major risk groups; impoverished children who live in older, poorly maintained rental housing and more affluent children who live in older housing undergoing renovation. Despite the dramatic decline in children's blood lead levels, lead toxicity remains epidemic among impoverished children who live in older rental housing, especially those who live in the northeastern and midwestern regions of the United States. There are increasing data linking lead exposure with other systemic effects including delinquency, dental caries, and learning problems. Moreover, there is evidence indicating that there is no discernible threshold for lead-associated cognitive deficits. Thus, it is increasingly important to shift our efforts toward the primary prevention of childhood lead exposure from residential hazards. This article reviews the epidemiology and control of childhood lead exposure, focusing especially on steps necessary to shift toward primary prevention.