Early life exposure to secondhand tobacco smoke and eating behaviors at age 12 years.

BACKGROUND: Prenatal or early childhood secondhand tobacco smoke (SHS) exposure increases obesity risk. However, the potential mechanisms underlying this association are unclear, but obesogenic eating behaviors are one pathway that components of SHS could perturb. Our aim was to assess associations of prenatal and early childhood SHS exposure with adolescent eating behaviors. METHODS: Data came from a prospective pregnancy and birth cohort (N = 207, Cincinnati, OH). With multiple informant models, we estimated associations of prenatal (mean of 16 and 26 weeks of gestation maternal serum cotinine concentrations) and early childhood cotinine (average concentration across ages 12, 24, 36, and 48 months) with eating behaviors at age 12 years (Child Eating Behaviors Questionnaire). We tested whether associations differed by exposure periods and adolescent's sex. Models adjusted for maternal and child covariates. RESULTS: We found no statistically significant associations between cotinine measures and adolescent's eating behaviors. Yet, in females, prenatal cotinine was associated with greater food responsiveness (ß: 0.23; 95% CI: 0.08, 0.38) and lower satiety responsiveness (ß: -0.14; 95% CI: -0.26, -0.02); in males, prenatal and postnatal cotinine was related to lower food responsiveness (prenatal: ß: -0.25; 95% CI: -0.04, -0.06; postnatal: ß: -0.36; 95% CI: -0.06, -0.11). No significant effect modification by sex or exposure window was found for other eating behaviors. CONCLUSION: Prenatal and early childhood SHS exposures were not related to adolescent's eating behavior in this cohort; however, biological sex may modify these associations.

Per- and polyfluoroalkyl substances and bone mineral content in early adolescence: Modification by diet and physical activity.

BACKGROUND: Per- and polyfluoroalkyl substance (PFAS) exposures may negatively impact bone mineral accrual, but little is known about potential mitigators of this relation. We assessed whether associations of PFAS and their mixture with bone mineral content (BMC) in adolescence were modified by diet and physical activity. METHODS: We included 197 adolescents enrolled in a prospective pregnancy and birth cohort in Cincinnati, Ohio (2003-2006). At age 12 years, we collected serum for PFAS measurements and used dual-energy x-ray absorptiometry to measure BMC. We calculated dietary calcium intake and Health Eating Index (HEI) scores from repeated 24-h dietary recalls, physical activity scores using the Physical Activity Questionnaire for Older Children (PAQ-C), and average moderate to vigorous physical activity (MVPA) based on accelerometry. We estimated covariate-adjusted differences in BMC z-scores per interquartile range (IQR) increase of individual PFAS concentrations using linear regression and per simultaneous IQR increase in all four PFAS using g-computation. We evaluated effect measure modification (EMM) using interaction terms between each modifier and PFAS. RESULTS: Higher serum perfluorooctanoic acid, perfluorooctanesulfonic acid, and perfluorononanoic acid concentrations and the PFAS mixture were associated with lower BMC z-scores. An IQR increase in all PFAS was associated with a 0.27 (-0.54, 0.01) lower distal radius BMC z-score. Associations with lower BMC were generally stronger among adolescents classified as < median for calcium intake, HEI scores, or MVPA compared to those ≥ median. The difference in distal radius BMC z-score per IQR increase in all PFAS was -0.38 (-0.72, -0.04) for those with

Neonatal AVPR1a Methylation and In-Utero Exposure to Maternal Smoking.

(1) Introduction: Epigenetic changes have been proposed as a biologic link between in-utero exposure to maternal smoking and health outcomes. Therefore, we examined if in-utero exposure to maternal smoking was associated with infant DNA methylation (DNAm) of cytosine-phosphate-guanine dinucleotides (CpG sites) in the arginine vasopressin receptor 1A AVPR1a gene. The AVPR1a gene encodes a receptor that interacts with the arginine vasopressin hormone and may influence physiological stress regulation, blood pressure, and child development. (2) Methods: Fifty-two infants were included in this cohort study. Multivariable linear models were used to examine the effect of in-utero exposure to maternal smoking on the mean DNAm of CpG sites located at AVPR1a. (3) Results: After adjusting the model for substance use, infants with in-utero exposure to maternal smoking had a reduction in DNAm at AVPR1a CpG sites by -0.02 (95% CI -0.03, -0.01) at one month of age. In conclusion, in-utero exposure to tobacco smoke can lead to differential patterns of DNAm of AVPR1a among infants. Conclusions: Future studies are needed to identify how gene expression in response to early environmental exposures contributes to health outcomes.

Associations of prenatal and postnatal exposure to perfluoroalkyl substances with pubertal development and reproductive hormones in females and males: The HOME study.

BACKGROUND: Prenatal and childhood exposure to per- and polyfluoroalkyl substances (PFAS) may be associated with lower reproductive hormones and later puberty, but epidemiological studies evaluating these associations are scarce. OBJECTIVES: We examined associations of PFAS concentrations assessed from pregnancy to adolescence with pubertal development and reproductive hormones at age 12 years. METHODS: We studied 200 mother-child pairs from the HOME Study in Cincinnati, OH (enrolled: 2003-2006). We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in pregnant women and their children at age 3, 8 and 12 years. At age 12 years, children self-assessed pubertal development using Tanner staging of pubic hair growth (males and females) and breast growth (females), and age at menarche. We quantified serum concentrations of dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in both sexes; estradiol in females; testosterone in males. We estimated associations of PFAS with pubertal outcomes and reproductive hormones using a combination of ordinal regression, Cox proportional-hazard regression, and linear regression. Quantile-based g-computation was used for PFAS mixture. RESULTS: In females, adolescent PFAS concentrations and their mixture were associated with later pubic hair growth, breast maturation, and age at menarche, but there was no pattern for prenatal or other postnatal concentrations. For instance, in females, each doubling in adolescent PFAS concentrations was associated with 79 % (PFOA), 63 % (PFOS), 56 % (PFNA), and 47 % (PFHxS) lower odds of attaining a higher stage for breast growth. In addition, adolescent PFAS concentrations were consistently associated with lower estradiol concentrations in females. No pattern was observed for associations of PFAS concentrations with pubic hair growth or reproductive hormones in males. CONCLUSIONS: We observed associations between PFAS concentrations in adolescence and later pubertal development in females, but this could be due to reverse causation induced by excretion of PFAS through menstrual fluid.

Pre- and postnatal exposure to secondhand tobacco smoke and cardiometabolic risk at 12 years: Periods of susceptibility.

BACKGROUND: To identify periods of heightened susceptibility to the association of secondhand tobacco smoke (SHS) exposure with cardiometabolic (CM) risk at age 12 years. METHODS: We used data from 212 adolescents from the HOME Study, a prospective pregnancy and birth cohort in Cincinnati, OH. Using multiple informant models, we estimated associations of maternal serum cotinine (mean of concentrations at 16 and 26 weeks of pregnancy) and children's serum cotinine concentrations (mean of concentrations at ages 1, 2, 3, and 4 years) with a CM risk summary score constructed of five risk components measured at age 12 years. We determined if these associations differed for pre- and postnatal exposure periods, and adolescent's sex. RESULTS: We found some evidence that the cotinine-outcome associations differed by exposure period and sex. Postnatal, but not prenatal, cotinine was associated with higher CM risk scores and individual CM risk component values (interaction p-values = 0.04 to 0.35). Each 10-fold increase in postnatal cotinine was associated with 0.57 (95% CI: 0.32, 1.45), 0.09 (95% CI: 0.13, 0.31), 0.14 (-0.08, 0.35), 0.07 (95% CI: 0.34, 0.48), and 0.11 (95% CI: 0.04, 0.27) higher CM risk, HOMA-IR, TG to HDL-C ratio, leptin to adiponectin ratio, and visceral fat area. Postnatal cotinine was associated with higher visceral fat area among females but not males (sex × period × cotinine interaction p-value = 0.01). CONCLUSIONS: Serum cotinine concentrations during the postnatal period had greater influence on adolescent's CM risk compared to the prenatal period, and these associations may be sex-specific. This study reinforces the need for ongoing public health interventions to minimize children's exposure to SHS.

Physical activity modifies the relation between gestational perfluorooctanoic acid exposure and adolescent cardiometabolic risk.

OBJECTIVE: Exposure to per- and polyfluoroalkyl substances (PFAS) - endocrine disrupting chemicals - may increase cardiometabolic risk. We evaluated whether adolescent lifestyle factors modified associations between gestational PFAS exposure and cardiometabolic risk using a prospective cohort study. METHODS: In 166 mother-child pairs (HOME Study), we measured concentrations of four PFAS in maternal serum collected during pregnancy. When children were age 12 years, we calculated cardiometabolic risk scores from visceral adiposity area, blood pressure, and fasting serum biomarkers. We assessed adolescent physical activity and Healthy Eating Index scores using the Physical Activity Questionnaire for Older Children (PAQ-C), actigraphy, and 24-h diet recalls. Using multivariable linear regression and weighted quantile sum regression, we examined whether physical activity or diet modified covariate-adjusted associations of PFAS and their mixture with cardiometabolic risk scores. RESULTS: Physical activity modified associations between perfluorooctanoic acid (PFOA) and cardiometabolic risk scores. Each doubling of PFOA was associated with worse cardiometabolic risk scores among children with PAQ-C scores < median (ß:1.4; 95% CI:0.5, 2.2, n = 82), but not among those with PAQ-C scores ≥ median (ß: 0.2; 95% CI: 1.2, 0.7, n = 84) (interaction p-value = 0.01). Associations were most prominent for insulin resistance, leptin-adiponectin ratio, and visceral fat area. We observed results suggesting that physical activity modified the association of PFAS mixture with cardiometabolic risk scores, insulin resistance, and visceral fat area (interaction p-values = 0.17, 0.07, and 0.10, respectively); however, the 95% CIs of the interaction terms included the null value. We observed similar, but attenuated patterns for PFOA and actigraphy-based measures of physical activity. Diet did not modify any associations. Physical activity or diet did not modify associations for other PFAS. CONCLUSIONS: Childhood physical activity modified associations of prenatal serum PFOA concentrations with children's cardiometabolic risk in this cohort, indicating that lifestyle interventions may ameliorate the adverse effects of PFOA exposure.

Pre- and postnatal exposure to secondhand tobacco smoke and body composition at 12 years: periods of susceptibility.

OBJECTIVE: The study aimed to identify periods of heightened susceptibility to the effects of pre- and postnatal secondhand tobacco smoke (SHS) exposure on body composition at age 12 years. METHODS: The study used data from 217 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort in Cincinnati, Ohio. Using multiple informant models, the study estimated associations of maternal serum cotinine (16 and 26 weeks of pregnancy) and child serum cotinine concentrations (at age 12, 24, 36, and 48 months) with measures of body composition obtained with anthropometry and dual-energy x-ray absorptiometry at 12 years. We examined whether there were differences between these associations for pre- and postnatal exposure periods and potential effect measure modification by sex. RESULTS: Postnatal cotinine concentrations were associated with higher weight, BMI, body fat and lean mass, waist circumference, and visceral, android, and gynoid fat. Each 10-fold increase in postnatal cotinine was associated with 76% increased risk of overweight or obesity (95% CI: 1.13-2.75). Associations between prenatal concentrations and measures of body composition at 12 years were generally null. CONCLUSIONS: Postnatal exposure to SHS may increase adolescent adiposity and lean mass. Future studies should determine whether early-life exposures to SHS are associated with other cardiometabolic risk markers.

Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study.

BACKGROUND: DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation. OBJECTIVES: We examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006; Cincinnati, Ohio). METHODS: We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children's age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999-2002; Boston, Massachusetts) to replicate significant associations. RESULTS: After adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q<0.05). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children's age. DISCUSSION: In these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. https://doi.org/10.1289/EHP10118.

Comparing adolescent self staging of pubertal development with hormone biomarkers.

OBJECTIVES: Physical examinations to characterize pubertal maturation may be unacceptable for children enrolled in research studies. Studies confirm the utility of pubertal self staging for research, but there has been limited comparison of self examination with hormone biomarkers. Our objective was to assess concordance of pubertal self staging with hormone biomarkers of puberty. METHODS: Participants were enrolled in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort study. At age 12 years, 139 females and 112 males completed pubertal self staging including breast and pubic hair development in females and pubic hair development in males. No clinical physical examination was performed. Hormone concentrations were measured in 102 females and 96 males including serum dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in all; estradiol in females; and testosterone in males. RESULTS: Estradiol was significantly associated with female breast stage, even when adjusted for BMI, with geometric least squares means (95%CI) of 13.2 (8.7, 20.2), 38.3 (29.9, 49.1), 59.4 (39.8, 88.6), and 81.2 (45.6, 144) pg/mL for breast stage 1-2, 3, 4, and 5, respectively. Testosterone was significantly associated with male pubic hair stage, with adjusted geometric least squares means (95%CI) of 37.6 (19.9, 71.1), 43.4 (27.7, 68.3), 126 (78.4, 203), 275 (146, 521), and 559 (237, 1319) ng/dL for pubic hair stage 1, 2, 3, 4, and 5, respectively. CONCLUSIONS: Self assessed pubertal development was positively associated with hormonal biomarkers of puberty.

Secondhand tobacco smoke exposure among children under 5 years old: questionnaires versus cotinine biomarkers: a cohort study.

OBJECTIVES: Cotinine is the gold standard to estimate prevalence of secondhand tobacco smoke (SHS) exposure, and assay limit of detection (LOD) cut-points are typically used regardless of age. Our aim was to compare the concordance between mother-reported SHS exposure and serum cotinine categorising children as exposed with the assay LOD or age-specific cut-points. DESIGN: Data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort. SETTING: Hospital or participants' homes. PARTICIPANTS: 389 pregnant women aged 18 years and older, between 13 and 19 weeks of gestation, living in a five-county region of the Cincinnati, Ohio metropolitan area, and with follow-up on their children at birth and ages 12, 24, 36 and 48 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Children's serum cotinine, mother-reported active smoking and SHS exposure were available at birth and during follow-up visits. We used Cohen's kappa index to assess concordance between maternal self-report and child's serum cotinine concentrations. We estimated optimal age-specific cut-points, their sensitivity-specificity and positive-negative predictive values with receiver operating characteristic curves. RESULTS: Self-reported exposure and cotinine data were available for 280 women who gave birth to singleton child. When applying the assay LOD (0.015 ng/mL), concordance between maternal report and serum cotinine, without accounting for age, was below 0.23 at all times. When using age-specific cut-points (12 months: 0.11 ng/mL; 24 months: 0.08 ng/mL; 36 months: 0.05 ng/mL and 48 months: 0.04 ng/mL), concordance improved, being low at 12 months (0.39), moderate at 24 and 36 months (0.47 and 0.43) and high at 48 months (0.62). CONCLUSIONS: Concordance between mother-reported SHS exposure among children under 5 years and serum cotinine improved considerably after applying the cohort-specific and age-specific cut-points. Future studies are necessary to verify these results.

Chemical mixture exposures during pregnancy and cognitive abilities in school-aged children.

INTRODUCTION: Gestational exposure to chemical mixtures, which is prevalent among pregnant women, may be associated with adverse childhood neurodevelopment. However, few studies have examined relations between gestational chemical mixture exposure and children's cognitive abilities. METHODS: In a cohort of 253 pregnant women and their children from Cincinnati, OH (enrolled 2003-2006), we quantified biomarker concentrations of 43 metals, phthalates, phenols, polybrominated diphenyl ethers, organophosphate and organochlorine pesticides, polychlorinated biphenyls, perfluoroalkyl substances, and environmental tobacco smoke in blood or urine. Using k-means clustering and principal component (PC) analysis, we characterized chemical mixtures among pregnant women. We assessed children's cognitive abilities using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV at ages 5 and 8 years, respectively. We estimated covariate-adjusted differences in children's cognitive ability scores ]=cross clusters, and with increasing PC scores and individual biomarker concentrations. RESULTS: Geometric mean biomarker concentrations were generally highest, intermediate, and lowest among women in clusters 1, 2, and 3, respectively. Children born to women in clusters 1 and 2 had 5.1 (95% CI: 9.4,-0.8) and 2.0 (95% CI: 5.5, 1,4) lower performance IQ scores compared to children in cluster 3, respectively. PC scores and individual chemical biomarker concentrations were not associated with cognitive abilities. CONCLUSIONS: In this cohort, combined prenatal exposure to phenols, certain phthalates, pesticides, and perfluoroalkyl substances was inversely associated with children's cognition, but some individual chemical biomarker concentrations were not. Additional studies should determine if the aggregate impact of these chemicals on cognition is different from their individual effects.

Prevalence of Mental Health and Neurodevelopmental Conditions in U.S. Children with Tobacco Smoke Exposure.

INTRODUCTION: This study investigated the prevalence and correlates of current mental health and neurodevelopmental conditions among U.S. school-age children with tobacco smoke exposure (TSE). METHOD: Data from the 2016-17 National Survey of Children's Health were analyzed. Multivariable logistic regression analyses among 6-11-year-olds (n = 21,539) and among subsamples aged 6-8 years (n = 10,100) and 9-11 years (n = 11,439) were conducted. RESULTS: Among 6-11-year-olds who lived with a smoker with no home TSE, the top mental health/neurodevelopmental conditions were other mental health conditions (22.1%), behavioral/conduct problems (21.7%), attention deficit disorder or attention deficit hyperactivity disorder (20.5%), depression (21.7%), and learning disability (19.3%). Children who lived with a smoker, with or without home TSE, were at increased odds of having anxiety problems, depression, attention deficit disorder or attention deficit hyperactivity disorder, behavioral/conduct problems, other mental health conditions, or learning disabilities. Many associations were more notable in younger children with home TSE. DISCUSSION: TSE is associated with mental health and neurodevelopmental conditions. Interventions to decrease TSE are needed to protect children.

Maternal cadmium exposure and neurobehavior in children: The HOME study.

BACKGROUND: It is unclear whether cadmium (Cd) exposure during fetal brain development is associated with child neurobehavior. OBJECTIVE: To examine the potential associations between Cd exposure during pregnancy and neurobehavior among children. METHODS: We used data from 276 children in the Health Outcomes and Measures of the Environment (HOME) Study, a well-established prospective pregnancy and birth cohort. We measured maternal urinary Cd concentrations at 26 weeks of gestation. For cognitive function, we assessed Mental Development Index (MDI) and Full-Scale Intelligence Quotient (FSIQ) using the Bayley Scales of Infant Development-II, the Wechsler Preschool and Primary Scales of Intelligence-III, or the Wechsler Intelligence Scales for Children-IV at ages 1, 2, 3, 5, and 8 years. We assessed child behaviors using the Behavior Assessment System for Children-2 at ages 2, 3, 4, 5, and 8 years, yielding four composite measures: Externalizing Problems, Internalizing Problems, Behavioral Symptoms Index, and Adaptive Skills. We used linear mixed models with covariate adjustment to estimate the associations between maternal urinary Cd concentrations and child neurobehavior. RESULTS: We categorized study participants into three groups based on maternal urinary Cd concentrations (Group 1: < limit of detection (LOD), Group 2: 0.06-0.22 µg/g creatinine, Group 3: ＞0.22 µg/g creatinine). In linear mixed models adjusting for maternal and child characteristics, maternal urinary Cd levels were not significantly associated with cognitive function at ages 1, 2, 3, 5, and 8 years or with behavioral composite measures at 2, 3, 4, 5, and 8 years. CONCLUSIONS: No significant associations were observed between maternal urinary Cd and cognitive or behavioral measures in children at 1-8 years of age in this study.

Polybrominated diphenyl ether (PBDE) and poly- and perfluoroalkyl substance (PFAS) exposures during pregnancy and maternal depression.

BACKGROUND: Experimental studies in rodents suggest that polybrominated diphenyl ethers (PBDEs) and poly- and perfluoroalkyl substances (PFAS) may contribute to depressive symptoms. Few studies have examined the impact of these chemicals on depression in adults. OBJECTIVE: To examine the associations between serum PBDE and PFAS concentrations during pregnancy and repeated measures of depressive symptoms in women assessed from pregnancy to 8 years postpartum. METHODS: This study was based on 377 women from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (USA). PBDEs (BDE-28, -47, -99, -100, -153, and ∑PBDEs) and PFAS (perfluorooctanoate [PFOA], perfluorooctane sulfonate [PFOS], perfluorohexane sulfonate [PFHxS], perfluorononanoate [PFNA]) were quantified in maternal serum at 16 ± 3 weeks gestation. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI-II) at ~20 weeks gestation and up to seven times during postpartum visits (4 weeks, 1, 2, 3, 4, 5, and 8 years). We used linear mixed models to estimate covariate-adjusted associations between chemical concentrations and repeated measures of BDI-II. Multinomial logistic regression models were used to estimate the relative risk ratios of having a medium or high depression trajectory. RESULTS: We found that a 10-fold increase in BDE-28 at 16 ± 3 weeks gestation was associated with significantly increased BDI-II scores (ß = 2.5 points, 95% confidence interval [CI] 0.8, 4.2) from pregnancy to 8 years postpartum. Significant positive associations were also observed with BDE-47, -100, -153, and ∑PBDEs. A 10-fold increase in ∑PBDEs was associated with a 4.6-fold increased risk (95% CI 1.8, 11.8) of a high trajectory for BDI-II compared to a low trajectory. We observed no significant associations between PFAS and BDI-II scores. CONCLUSION: PBDEs during pregnancy were associated with more depressive symptoms among women in this cohort.

Associations Between Early Low-Level Tobacco Smoke Exposure and Executive Function at Age 8 Years.

OBJECTIVE: To investigate whether exposure to tobacco smoke during early brain development is linked with later problems in behavior and executive function. STUDY DESIGN: We studied 239 children in a prospective birth cohort. We measured tobacco exposures by caregiver report and serum cotinine 3 times during pregnancy and 4 times during childhood. We used linear regression to examine the association between prenatal and childhood serum cotinine concentrations and behavior (the Behavior Assessment System for Children-2) and executive function (the Behavior Rating Inventory of Executive Function) at age 8 years while adjusting for important covariates. RESULTS: Neither prenatal nor child serum cotinine were associated with behavior problems measured by the Behavior Assessment System for Children-2. On the Behavior Rating Inventory of Executive Function, prenatal and childhood exposure was associated with poorer task initiation scores (B = 0.44; 95% CI, 0.03-0.85 and B = 0.69, 95% CI, 0.06-1.32 respectively). Additionally, in a subset of 208 children with nonsmoking mothers, prenatal exposure was associated with task initiation scores (B = 1.17; 95% CI, 0.47-1.87) and additional components of the metacognition index (eg, working memory, B = 1.20; 95% CI, 0.34-2.06), but not components of the behavioral regulation index. CONCLUSIONS: Tobacco exposures during pregnancy (including low-level second-hand smoke) and childhood were associated with deficits in some domains of children's executive function, especially task initiation and metacognition. These results highlight that decreasing early exposure to tobacco smoke, even second-hand exposure, may support ideal brain functioning.

Exposures to chemical mixtures during pregnancy and neonatal outcomes: The HOME study.

INTRODUCTION: Exposure to mixtures of environmental chemicals are prevalent among pregnant women and may be associated with altered fetal growth and gestational age. To date, most research regarding environmental chemicals and neonatal outcomes has focused on the effect of individual agents. METHODS: In a prospective cohort of 380 pregnant women from Cincinnati, OH (enrolled 2003-2006), we used biomarkers to estimate exposure to 43 phenols, phthalates, metals, organophosphate/pyrethroid/organochlorine pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, perfluoroalkyl substances (PFAS), and environmental tobacco smoke. Using three approaches, we estimated covariate-adjusted associations of chemical mixtures or individual chemicals with gestational-age-specific birth weight z-scores, birth length, head circumference, and gestational age: k-means clustering, principal components (PC), and one-chemical-at-a-time regression. RESULTS: We identified three chemical mixture profiles using k-means clustering. Women in cluster 1 had higher concentrations of most phenols, three phthalate metabolites, several metals, organophosphate/organochlorine pesticides, polychlorinated biphenyls, and several PFAS than women in clusters 2 and 3. On average, infants born to women in clusters 1 (-1.2 cm; 95% CI: -1.9, -0.5) and 2 (-0.5 cm; 95% CI: -1.1, 0.1) had lower birth length than infants in cluster 3. Six PCs explained 50% of the variance in biomarker concentrations and biomarkers with similar chemical structures or from shared commercial/industrial settings loaded onto commons PCs. Each standard deviation increase in PC 1 (organochlorine pesticides, some phenols) and PC 6 (cadmium, bisphenol A) was associated with 0.2 cm (95% CI: -0.4, 0.0) and 0.1 cm (95% CI: -0.4, 0.1) lower birth length, respectively. Organochlorine compounds, parabens, and cadmium were inversely associated with birth length in the one-chemical-at-a-time analysis. Cluster membership, PC scores, and individual chemicals were not associated with other birth outcomes. CONCLUSION: All three methods of characterizing multiple chemical exposures in this cohort identified inverse associations of select organochlorine compounds, phenols, and cadmium with birth length, but not other neonatal outcomes.

Serum Cotinine versus Parent Reported Measures of Secondhand Smoke Exposure in Rural Appalachian Children.

BACKGROUND: Secondhand smoke (SHS) exposure in Appalachian children and associated adverse effects is understudied and not well documented. This study assessed the prevalence of SHS exposure in Appalachian children by parental self-report and internal biological measure. METHODS: SHS exposure was determined in children residing in rural Appalachian communities during their participation in the Communities Actively Researching Exposure Study between 2009 and 2013. Parents reported the number of smokers in the household and number of cigarettes smoked/day. Children ages 7-9 provided a serum sample for cotinine analysis. Parent reported measures and child serum cotinine measures of SHS exposure were compared with national and Appalachian-state estimates. Data analysis for the study was done in 2013. RESULTS: Approximately 37% parents reported at least one smoker in the home, yet 50% of children had a detectible level of cotinine in serum. The mean serum cotinine level in children was 0.7 + 1.6 ng/mL. In homes of at least one reported smoker, an average of 20 cigarettes were smoked//day. Compared to 7.6% children, aged 3-19 years, exposed to SHS nationally, 36.6% children in our study were exposed to SHS living in Appalachian counties. IMPLICATIONS: Children living in rural Appalachian counties are significantly exposed to SHS exposure. Parental self-reports of smoking underestimates child exposure to SHS as measured by serum cotinine levels. Developing risk communication messages and implementing culturally appropriate interventions aimed at reducing tobacco dependence in rural Appalachian regions should be explored.

Childhood polybrominated diphenyl ether (PBDE) serum concentration and reading ability at ages 5 and 8 years: The HOME Study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment and human beings. PBDE concentrations are higher in children than adults. A previous study found that prenatal PBDE exposure was associated with decreased reading skills in children; however, evidence is limited on the potential impact of childhood exposure to PBDEs. The study examined the association between childhood PBDE exposures and reading ability in children at ages 5 and 8 years. METHODS: The study included 230 children from an ongoing prospective pregnancy and birth cohort study, the Health Outcomes and Measures of Environment (HOME) Study, conducted in Cincinnati, Ohio. Children's serum concentrations of eleven PBDE congeners were measured at 1, 2, 3, 5, and 8 years. The Woodcock-Johnson Tests of Achievement - III and the Wide Range Achievement Test - 4 were administered to assess children's reading skills at ages 5 and 8 years, respectively. We used multiple informant models to examine the associations between repeated measures of PBDEs and reading scores at ages 5 and 8 years. We also estimated the ßs and 95% CIs of the association of PBDE measure at each age by including interaction terms between PBDE concentrations and child age in the models. RESULTS: All childhood BDE-153 concentrations were inversely associated with reading scores at 5 and 8 years, but associations were not statistically significant after covariate adjustment. For example, a 10-fold increase in BDE-153 concentrations at ages 3 and 5 years was associated with a -5.0 (95% confidence interval (CI): -11.0, 1.0) and -5.5 (95% CI: -12.5, 1.4) point change in Basic Reading score at age 5 years, respectively. Similarly, the estimates for Brief Reading score at age 5 years were -4.5 (95% CI: -10.5, 1.5) and -5.2 (95% CI: -12.2, 1.7) point changes, respectively. Serum concentration of BDE-47, -99, -100, and Sum4PBDEs (sum of BDE-47, 99, 100, and 153) at every age were inversely associated with reading scores at ages 5 and 8 years in unadjusted analyses. While the adjusted estimates were much attenuated and became non-significant, the direction of most of the associations was not altered. CONCLUSION: Our study has shown a suggestive but non-significant trend of inverse associations between childhood PBDE serum concentrations, particularly BDE-153, and children's reading skills. Future studies with a larger sample size are needed to examine these associations.

Profiles and Predictors of Environmental Chemical Mixture Exposure among Pregnant Women: The Health Outcomes and Measures of the Environment Study.

Pregnant women are exposed to numerous environmental chemicals, but there is limited understanding of chemical mixture exposure profiles and predictors. In a prospective cohort of 389 pregnant women from Cincinnati, OH, we used biomarkers to estimate exposure to 41 phenols, phthalates, metals, organophosphate/pyrethroid/organochlorine pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, perfluoroalkyl substances, and environmental tobacco smoke. Using pairwise correlations, k-means clustering, and principal component analysis (PCA), we identified several profiles of chemical exposure. Chemicals within structurally, commercially, or industrially related chemical classes (e.g., phthalates) were moderate to strongly correlated compared to unrelated chemicals (e.g., pyrethroid pesticides and environmental tobacco smoke). Using k-means clustering and PCA, we identified 3 clusters of women ( N = 106, 158, and 125) and 6 PC scores, respectively, that characterized profiles of cumulative chemical exposure. The first two PC scores significantly varied by cluster, indicating that some of these profiles could be identified using both methods. Cluster membership and PCA scores were associated with race, marital status, consumption of fresh fruits and vegetables, and parity. Future work could use clusters and PCA scores to characterize environmental chemical mixture exposures in other cohorts of pregnant women and predict potential health effects of environmental chemical mixture exposure.

Polybrominated diphenyl ether (PBDE) exposures and thyroid hormones in children at age 3 years.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) reduce serum thyroid hormone concentrations in animal studies, but few studies have examined the impact of early-life PBDE exposures on thyroid hormone disruption in childhood. METHODS: We used data from 162 mother-child pairs from the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, OH). We measured PBDEs in maternal serum at 16 ±â€¯3 weeks gestation and in child serum at 1-3 years. Thyroid hormones were measured in serum at 3 years. We used multiple informant models to investigate associations between prenatal and early-life PBDE exposures and thyroid hormone levels at age 3 years. RESULTS: Prenatal PBDEs were associated with decreased thyroid stimulating hormone (TSH) levels at age 3 years. A 10-fold increase in prenatal ∑PBDEs (BDE-28, -47, -99, -100, and -153) was associated with a 27.6% decrease (95% CI -40.8%, -11.3%) in TSH. A ten-fold increase in prenatal ∑PBDEs was associated with a 0.25 pg/mL (0.07, 0.43) increase in free triiodothyronine (FT3). Child sex modified associations between prenatal PBDEs and thyroid hormones, with significant decrements in TSH among females and decreased free T4 (FT4) in males. Prenatal ∑PBDEs were not associated with TT4, FT4, or total T3. CONCLUSIONS: These findings suggest an inverse relationship between prenatal ∑PBDEs and TSH at 3 years. Associations may be sexually dimorphic, with an inverse relationship between prenatal BDE-47 and -99 and TSH in females and null associations among males.