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BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7–9 y old, and reenrolled at 13–18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height–weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (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]

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]

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]

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]

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. [ABSTRACT FROM AUTHOR]

Background: There is increasing concern about the potential effects of traffic-related air pollution (TRAP) on the developing brain. The impact of TRAP exposure on childhood behavior is not fully understood because of limited epidemiologic studies. Objective: We explored the association between early-life exposure to TRAP using a surrogate, elemental carbon attributed to traffic (ECAT), and attention deficit/hyperactivity disorder (ADHD) symptoms at 7 years of age. Methods: From the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort we collected data on exposure to ECAT during infancy and behavioral scores at 7 years of age. Children enrolled in CCAAPS had at least one atopic parent and a birth residence either < 400 m or > 1,500 m from a major highway. Children were followed from infancy through 7 years of age. ECAT exposure during the first year of life was estimated based on measurements from 27 air sampling sites and land use regression modeling. Parents completed the Behavioral Assessment System for Children, 2nd Edition, when the child was 7 years of age. ADHD-related symptoms were assessed using the Hyperactivity, Attention Problems, Aggression, Conduct Problems, and Atypicality subscales. Results: Exposure to the highest tertile of ECAT during the child's first year of life was significantly associated with Hyperactivity T-scores in the "at risk" range at 7 years of age, after adjustment [adjusted odds ratio (aOR) = 1.7; 95% CI: 1.0, 2.7]. Stratification by maternal education revealed a stronger association in children whose mothers had higher education (aOR = 2.3; 95% CI: 1.3, 4.1). Conclusions: ECAT exposure during infancy was associated with higher Hyperactivity scores in chil­dren; this association was limited to children whose mothers had more than a high school education. [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]