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Summary: Background: Eating behaviours are associated with childhood obesity, but their associations with cardiometabolic risk are less clear. Objectives: We evaluated cross‐sectional associations between eating behaviours and cardiometabolic risk among 185 adolescents (age 12.4 ± 0.7 years; 53% female; body mass index (BMI)‐z 0.72 ± 1.37) from Cincinnati, Ohio (HOME Study; enrolled 2003–2006). Methods: Caregivers assessed adolescents' eating behaviours with the Child Eating Behaviour Questionnaire. We computed adolescents' cardiometabolic risk scores based on HOMA‐IR, triglycerides to high‐density lipoprotein cholesterol ratio, adiponectin to leptin ratio, systolic blood pressure, and cross‐sectional area of fat inside the abdominal cavity. Using multivariable linear regression models, we estimated associations of eating behaviour subscales with cardiometabolic risk scores or individual risk components. Results: Emotional overeating (ß = 1.34, 95% CI: 0.67, 2.01), food responsiveness (ß = 0.99, 95% CI: 0.41, 1.57), and emotional undereating (ß = 0.64, 95% CI: 0.08, 1.21) were associated with higher cardiometabolic risk scores. Satiety responsiveness (ß = −0.79, 95% CI: −1.59, 0.00) was associated with lower cardiometabolic risk scores. Adjusting for adolescent BMI‐z at age 12 attenuated these associations, suggesting that adiposity may mediate these associations. Conclusion: Hedonistic eating behaviours were associated with higher cardiometabolic risk in these adolescents. [ABSTRACT FROM AUTHOR]

Maternal childhood adversity and trauma may elicit biological changes that impact the next generation through epigenetic responses measured in DNA methylation (DNAm). These epigenetic associations could be modified by the early postnatal environment through protective factors, such as early childhood home visiting (HV) programs that aim to mitigate deleterious intergenerational effects of adversity. In a cohort of 53 mother-child pairs recruited in 2015–2016 for the Pregnancy and Infant Development Study (Cincinnati, Ohio), we examined the association between maternal adverse childhood experiences (ACEs) and neonatal DNAm in the secretogranin V gene (SCG5), which is important in neuroendocrine function. We examined prenatal HV as an effect modifier. Mothers completed a questionnaire on ACEs during pregnancy, and infant buccal samples were collected 1 month postpartum. Multivariable linear regression was used to examine the association between maternal ACEs and neonatal DNAm expressed as M-values averaged across 4 cytosine-phosphate-guanine dinucleotide sites. A higher number of maternal ACEs (>3) was associated with a 5.79–percentage-point lower offspring DNAm (95% confidence interval: −10.44, −1.14), and the association was modified by the number of home visits received during pregnancy. In a population of at-risk mother-child dyads, preliminary evidence suggests that maternal ACEs have a relationship with offspring SCG5 DNAm that differs by the amount of prenatal HV. [ABSTRACT FROM AUTHOR]

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 (푛= 266) and peripheral leukocytes at 12 years of age (푛= 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, 푞< 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. [ABSTRACT FROM AUTHOR]

Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑ DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal exposure to endocrine disruptors has been associated with increased risk of childhood obesity. However, epidemiologic studies on polybrominated diphenyl ethers (PBDEs) are limited despite animal studies indicating PBDEs' potential role as an obesogen. OBJECTIVES: We investigated whether maternal concentrations of BDEs 28, 47, 99, 100, 153, and XPBDEs during pregnancy were associated with anthropometric measures in children aged 1-8 years. METHODS: We examined 318 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort enrolled from 2003 through 2006 (Cincinnati, OH). Serum PBDEs were measured at 16 ± 3 weeks gestation. We measured child height (1-8 years), weight (1-8 years), body mass index (BMI) (2-8 years), waist circumference (4-8 years), and body fat (8 years). To account for repeated measures, we used linear mixed models and generalized estimating equations to estimate associations between maternal PBDEs and child anthropometric measures. RESULTS: We found no statistically significant associations between prenatal PBDEs and height or weight z-score. A 10-fold increase in maternal serum BDE-153 was associated with lower BMI z-score (β = -0.36; 95% CI: -0.60, -0.13) at 2-8 years, smaller waist circumference (P = -1.81 cm; 95% CI: -3.13, -0.50) at 4-8 years, and lower percent body fat (β = -2.37%; 95% CI: -4.21, -0.53) at 8 years. A decrease in waist circumference at 4-8 years was observed with a 10-fold increase in BDE-100 (β = -1.50 cm; 95% CI: -2.93, -0.08) and ΣPBDEs (β = -1.57 cm; 95% CI:-3.11,-0.02). CONCLUSIONS: Reverse causality may have resulted in prenatal PBDEs, particularly BDE-153, and decreased BMI, waist circumference, and body fat. CITATION: Vuong AM, Braun JM, Sjödin A, Webster GM, Yolton K, Lanphear BP, Chen A. 2016. Prenatal polybrominated diphenyl ether exposure and body mass index in children up to 8 years of age. Environ Health Perspect 124:1891-1897; http://dx.doi.org/10.1289/EHP139 [ABSTRACT FROM AUTHOR]

BACKGROUND: Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent. OBJECTIVES: We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143). METHODS: Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes. RESULTS: We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.4 cm; 95% CI: -0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1[sub 192RR] genotype, ΣDAP and ΣDMP were negatively associated with length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.5 cm; 95% CI:-0.9, -0.1). CONCLUSIONS: This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1[sub 192RR] genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations. [ABSTRACT FROM AUTHOR]

Objective: To examine relationships between prenatal perfluoroalkyl substance (PFAS) exposure and adiposity in children born to women who lived downstream from a fluoropolymer manufacturing plant.Methods: Data are from a prospective cohort in Cincinnati, Ohio (HOME Study). Perfluorooctanoic (PFOA), perfluorooctane sulfonic (PFOS), perfluorononanoic (PFNA), and perfluorohexane sulfonic (PFHxS) acids were measured in prenatal serum samples. Differences were measured in body mass index z-scores (BMI), waist circumference, and body fat at 8 years of age (n = 204) and BMI between 2-8 years of age (n = 285) according to PFAS concentrations.Results: Children born to women in the top two PFOA terciles had greater adiposity at 8 years than children in the 1st tercile. For example, waist circumference (cm) was higher among children in the 2nd (4.3; 95% CI: 1.7, 6.9) and 3rd tercile (2.2; 95% CI: -0.5, 4.9) compared to children in the 1st tercile. Children in the top two PFOA terciles also had greater BMI gains from 2 to 8 years compared to children in the 1st tercile (P < 0.05). PFOS, PFNA, and PFHxS were not associated with adiposity.Conclusions: In this cohort, higher prenatal serum PFOA concentrations were associated with greater adiposity at 8 years and a more rapid increase in BMI between 2-8 years. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) reduce blood concentrations of thyroid hormones in laboratory animals, but it is unclear whether PBDEs disrupt thyroid hormones in pregnant women or newborn infants. OBJECTIVES: We investigated the relationship between maternal PBDE levels and thyroid hormone concentrations in maternal and cord sera. METHODS: We used data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort of 389 pregnant women in Cincinnati, Ohio, who were enrolled from 2003 through 2006 and delivered singleton infants. Maternal serum PBDE concentrations were measured at enrollment (16 ±3 weeks of gestation). Thyroid hormone concentrations were measured in maternal serum at enrollment (n = 187) and in cord serum samples (n = 256). RESULTS: Median maternal serum concentrations of BDEs 28 and 47 were 1.0 and 19.1 ng/g lipid, respectively. A 10-fold increase in BDEs 28 and 47 concentrations was associated with a 0.85-μg/dL [95% confidence interval (CI): 0.05, 1.64] and 0.82-μg/dL (95% CI: 0.12, 1.51) increase in maternal total thyroxine concentrations (TT4), respectively. Both congeners were also positively associated with maternal free thyroxine (FT4). We also observed positive associations between BDE-47 and maternal total and free triiodothyronine (TT3 and FT3). A 10-fold increase in BDE-28 was associated with elevated FT3 concentrations (β = 0.14 pg/mL; 95% CI: 0.02, 0.26). In contrast, maternal PBDE levels were not associated with thyroid hormone concentrations in cord serum. CONCLUSIONS: These findings suggest that maternal PBDE exposure, particularly BDEs 28 and 47, are associated with maternal concentrations of T4 and T3 during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Exposure to phthalates, a class of endocrine disrupting chemicals, is ubiquitous. We examined the association of urinary phthalate metabolite concentrations during pregnancy with maternal blood pressure and risk of pregnancy-induced hypertensive diseases.Methods: We used data from the Health Outcomes and Measures of the Environment Study, a prospective birth cohort of low-risk pregnant women recruited between March 2003 and January 2006. We analyzed maternal urine samples collected at 16 and 26 weeks gestation for 9 phthalate monoester metabolites reflecting exposure to 6 phthalate diesters. Outcomes included maternal blood pressure at <20 and ≥ 20 weeks gestation and pregnancy induced hypertensive diseases (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome).Results: Data were available for 369 women who gave birth to singleton, live-born infants without congenital anomalies. Of the phthalate metabolites evaluated, only mono-benzyl phthalate (MBzP) concentrations were significantly associated with maternal diastolic blood pressure at <20 weeks gestation. Women in the third MBzP tercile at 16 weeks gestation had diastolic blood pressure 2.2 (95% CI: 0.5-3.9) mm Hg higher at <20 weeks gestation and 2.8 (95% CI: 0.9-4.7) mm Hg higher at ≥ 20 weeks gestation compared to women in the first tercile. Compared to women in the first tercile, women in the top MBzP tercile at 16 weeks had an increased risk of developing pregnancy-induced hypertensive diseases (RR = 2.92, 95 % CI 1.15-7.41, p-value for trend = 0.01). MBzP concentrations at 26 weeks gestation were not as strongly associated with blood pressure at ≥ 20 weeks gestation or risk of pregnancy-induced hypertensive diseases.Conclusion: This study suggests that maternal urinary MBzP concentrations may be associated with increased diastolic blood pressure and risk of pregnancy-induced hypertensive diseases. [ABSTRACT FROM AUTHOR]

Prenatal multivitamin/folic acid supplement use may reduce the risk of autism spectrum disorders. We investigated whether 2nd trimester prenatal vitamin use and maternal whole blood folate (WBF) concentrations were associated with Social Responsiveness Scale (SRS) scores at 4-5 years of age in a prospective cohort of 209 mother-child pairs. After confounder adjustment, children born to women taking prenatal vitamins weekly/daily (n = 179) had lower odds of clinically elevated SRS scores (odds ratio 0.26; 95 % confidence interval 0.08, 0.89) than those who rarely/never took them (n = 30). WBF concentrations were not associated with SRS scores. The lack of association between WBF and autistic-behaviors may be due to the timing of biomarker measures relative to critical periods of brain development, confounding, or other modifying factors. [ABSTRACT FROM AUTHOR]

Background: Endocrine-disrupting chemicals (EDCs) may be involved in the etiology of autism spectrum disorders, but identifying relevant chemicals within mixtures of EDCs is difficult. Objective: Our goal was to identify gestational EDC exposures associated with autistic behaviors. Methods: We measured the concentrations of 8 phthalate metabolites, bisphenol A, 25 polychlorinated biphenyls (PCBs), 6 organochlorine pesticides, 8 brominated flame retardants, and 4 perfluoroalkyl substances in blood or urine samples from 175 pregnant women in the HOME (Health Outcomes and Measures of the Environment) Study (Cincinnati, OH). When children were 4 and 5 years old, mothers completed the Social Responsiveness Scale (SRS), a measure of autistic behaviors. We examined confounder-adjusted associations between 52 EDCs and SRS scores using a twostage hierarchical analysis to account for repeated measures and confounding by correlated EDCs. Results: Most of the EDCs were associated with negligible absolute differences in SRS scores (≤ 1.5). Each 2‑SD increase in serum concentrations of polybrominated diphenyl ether-28 (PBDE‑28) (β = 2.5; 95% CI: –0.6, 5.6) or trans-nonachlor (β = 4.1; 95% CI: 0.8–7.3) was associated with more autistic behaviors. In contrast, fewer autistic behaviors were observed among children born to women with detectable versus nondetectable concentrations of PCB‑178 (β = –3.0; 95% CI: –6.3, 0.2), β-hexachlorocyclohexane (β = –3.3; 95% CI: –6.1, –0.5), or PBDE‑85 (β = –3.2; 95% CI: –5.9, –0.5). Increasing perfluorooctanoate (PFOA) concentrations were also associated with fewer autistic behaviors (β = –2.0; 95% CI: –4.4, 0.4). Conclusions: Some EDCs were associated with autistic behaviors in this cohort, but our modest sample size precludes us from dismissing chemicals with null associations. PFOA, β‑hexachlorocyclohexane, PCB‑178, PBDE‑28, PBDE‑85, and trans-nonachlor deserve additional scrutiny as factors that may be associated with childhood autistic behaviors. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to organophosphate (OP) insecticides, a widely used class of pesticides, may be associated with decreased gestational age and lower birth weight. Single nucleotide polymorphisms in paroxanase (PON1) enzyme genotypes may modify the relationships between OP exposure and perinatal outcomes. Objective: We examined the relationship of prenatal OP insecticide exposure, measured using urinary dialkyl phosphate (DAP) metabolite concentrations, with gestational age and birth weight. Methods: We measured the concentrations of six nonspecific DAP metabolites of OP insecticides in two maternal spot urine samples collected in a prospective birth cohort. We performed multivariable regression to examine associations between the sum of six DAP concentrations (&epsillon;DAP) with gestational age and birth weight. We also examined whether these associations differed according to infant PON1192 and PON1-108 genotypes. Results: Among 306 mother-infant dyads, a 10-fold increase in &epsillon;DAP concentrations was associated with a decrease in covariate-adjusted gestational age [-0.5 weeks; 95% confidence interval (CI): -0.8, -0.1] and birth weight (-151 g; CI: -287, -16); the decrements in birth weight were attenuated after adjusting for gestational age. The relationship between &epsillon;DAP concentrations and gestational age was stronger for white (-0.7 weeks; CI: -1.1, -0.3) than for black (-0.1 weeks; 95% CI: -0.9, 0.6) newborns. In contrast, there was a greater decrease in birth weight with increasing urinary &epsillon;DAP concentrations for black (-188 g; CI: -395, 19) than for white (-118 g; CI: -296, 60) newborns. Decrements in birth weight and gestational age associated with &epsillon;DAP concentrations were greatest among infants with PON1192QR and PON-108CT genotypes. Conclusions: Prenatal urinary &epsillon;DAP concentrations were associated with shortened gestation and reduced birth weight in this cohort, but the effects differed by race/ethnicity and PON1192/108 genotypes. [ABSTRACT FROM AUTHOR]

The association of prenatal exposure to organophosphate esters (OPEs) and replacement brominated flame retardants (RBFRs) with respiratory outcomes has not been previously investigated in humans, despite reports that these chemicals can cross the placenta and alter lung development as well as immune functions. In a cohort of 342 pregnant women recruited between 2003 and 2006 in the greater Cincinnati, Ohio Metropolitan area, we measured indoor dust OPEs and RBFRs at 20 weeks of gestation and urinary OPEs at 16 and 26 weeks of gestation and at delivery. We performed generalized estimating equations and linear mixed models adjusting for covariates to determine the associations of prenatal OPEs and RBFRs exposures with adverse respiratory outcomes in childhood, reported every six months until age 5 years and with lung function at age 5 years. We used multiple informant modeling to examine time-specific associations between maternal urinary OPEs and the outcomes. Dust concentrations of triphenyl phosphate (TPHP) (RR: 1.40, 95% CI: 1.18–1.66), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (RR: 1.51, 95% CI: 1.23–1.85), and bis(2-ethylhexyl) tetrabromophthalate (RR: 1.57, 95% CI: 1.28–1.94) were associated with higher risk of wheezing during childhood. Dust TPHP concentrations were associated with higher risk of respiratory infections (RR: 1.43, 95% CI: 1.08–1.94), and dust tris-(2-chloroethyl) phosphate concentrations were associated with hay fever/allergies (RR: 1.11, 95% CI: 1.01–1.21). We also found that dust tris-(2-chloroethyl) phosphate loadings were associated with lower lung function. Urinary OPEs mainly at week 16 of gestation tended to be associated with adverse respiratory outcome, while bis(1-chloro-2-propyl) phosphate and diphenyl phosphate at delivery were associated with lower risk of hay fever/allergies. In-utero exposure to OPEs and RBFRs may be a risk factor for adverse respiratory outcomes in childhood, depending on the timing of exposure. • In-utero exposure to replacement brominated flame retardants and organophosphate esters tends to be associated with adverse childhood respiratory outcomes. • Urinary bis(1-chloro-2-propyl) phosphate (BCIPP) detection was associated with higher risk of wheeze at any of the prenatal sampling time points. • Urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) at 16 weeks of gestation was associated with higher risk of wheeze. • Urinary bis-2-chloroethyl phosphate and BDCIPP at 16 weeks of gestation were associated with higher risk of respiratory infections. • BDCIPP and diphenyl phosphate around delivery were associated with lower risk of hay fever or allergies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To clarify whether persistent snoring in 2-to 3-year-olds is associated with behavioral and cognitive development, and to identify predictors of transient and persistent snoring. METHODS: Two hundred forty-nine mother/child pairs participated in a prospective birth cohort study. Based upon parental report of loud snoring ≥2 times weekly at 2 and 3 years of age, children were designated as nonsnorers, transient snorers (snored at 2 or 3 years of age, but not both), or persistent snorers (snored at both ages). We compared groups by using validated measures of behavioral and cognitive functioning. Potential predictors of snoring included child race and gender, socioeconomic status (parent education and income), birth weight, prenatal tobacco exposure (maternal serum cotinine), childhood tobacco exposure (serum cotinine), history and duration of breast milk feeding, and body mass relative to norms. RESULTS: In multivariable analyses, persistent snorers had significantly higher reported overall behavior problems, particularly hyper- activity, depression, and inattention. Nonsnorers had significantly stronger cognitive development than transient and persistent snorers in unadjusted analyses, but not after demographic adjustment. The strongest predictors of the presence and persistence of snoring were lower socioeconomic status and the absence or shorter duration of breast milk feeding. Secondary analyses suggested that race may modify the association of childhood tobacco smoke exposure and snoring. CONCLUSIONS: Persistent, loud snoring was associated with higher rates of problem behaviors. These results support routine screening and tracking of snoring, especially in children from low socioeconomic backgrounds; referral for follow-up care of persistent snoring in young children; and encouragement and facilitation of infant breastfeeding. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The goal was to test the effects of high-efficiency, particulate-arresting (HEPA) air cleaners on unscheduled asthma visits and symptoms among children with asthma exposed to secondhand smoke. METHODS: We enrolled 225 eligible children who were 6 to 12 years of age, had physician-diagnosed asthma, and were exposed to ≥5 cigarettes per day. We conducted a double-blind, randomized trial. Children were assigned randomly to receive 2 active or inactive HEPA air cleaners. RESULTS: Of 225 enrolled children, 110 (49%) were assigned to the intervention group and 115 (51%) to the control group; 215 (95%) completed the trial. During the trial, there were 42 fewer unscheduled asthma visits among children in the intervention group (18.5% [95% confidence interval: 1.25%-82.75%1; P = .043), compared with those in the control group, after adjustment for baseline differences. There was a significant difference in the reductions of levels of particles of >0.3 μm according to group assignment; there was a 25% reduction in particle levels in the intervention group, compared with a 5% reduction in the control group (P = .026). There were no significant differences in parent-reported asthma symptoms, exhaled nitric-oxide levels, air nicotine levels, or cotinine levels according to group assignment. CONCLUSIONS: These results hold promise for using HEPA air cleaners as part of a multifaceted strategy to reduce asthma morbidity, but further research is necessary before they can be recommended routinely for the medical management of asthma. [ABSTRACT FROM AUTHOR]

Few studies have considered household interventions for reducing endocrine disrupting chemical (EDC) exposures. We conducted a secondary analysis of a randomized controlled trial, originally designed to reduce lead exposure, to evaluate if the intervention lowered EDC exposures in young children. Study participants were children from the Cincinnati, Ohio area (n = 250, HOME Study). Prenatally, families received a housing intervention that included paint stabilization and dust mitigation, or as a control, injury prevention measures. At 24-months, we measured organophosphate esters (OPEs) and phthalates or their metabolites in dust and urine. We measured perfluoroalkyl substances (PFAS) in dust and serum at 24- and 36-months, respectively. We assessed associations between dust and biomarker EDCs using Spearman correlations, characterized EDC mixtures via principal components analysis, and investigated treatment effects using linear regression. To mitigate selection bias, we fit statistical models using inverse probability of retention weights. Correlations between dust EDCs and analogous biomarkers were weak-to-moderate (ρ's ≤ 0.3). The intervention was associated with 23 % (95 % CI: -38, -3) lower urinary DEHP metabolites and, in a per-protocol analysis, 34 % lower (95 % CI: -55, -2) urinary MBZP. Additionally, among Black or African American children, the intervention was associated with lower serum concentrations of several PFAS (e.g., -42 %; 95 % CI: -63, -8 for PFNA). Household interventions that include paint stabilization and dust mitigation may reduce childhood exposures to some phthalates and PFAS in Blacks/African Americans. These findings highlight the need for larger studies with tailored and sustained housing interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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

Background: Organophosphate esters (OPEs) have replaced flame retardant polybrominated diphenyl ethers as flame retardants in consumer products, but few longitudinal studies have characterized childhood OPE exposure., Objective: We aimed to examine the exposure pattern of urinary OPE metabolites in children., Methods: We quantified three urinary OPE metabolites five times in children (1, 2, 3, 5, 8 years) from 312 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA. We examined the associations of average maternal OPE metabolite concentrations with OPE metabolite concentrations in childhood, characterized childhood OPE trajectories with latent class growth analysis (LCGA), and examined factors related to trajectory membership., Results: Bis(2-chloroethyl) phosphate (BCEP) had the lowest median concentrations over time (0.66-0.97 mg/L) while the median concentrations of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) increased with age (1.44-3.80 mg/L). The median concentrations of diphenyl phosphate (DPHP) fluctuated between 1.96 and 2.69 mg/L. Intraclass correlation coefficients for urinary metabolites measured at five time points indicated high variability within individuals (0.13-0.24). Average maternal urinary BCEP and BDCIPP were associated with concentrations in early childhood. Maternal education, the birth year of the child, and having a carpet in the main activity room were associated with BCEP and BDCIPP trajectory while none of the factors were associated with DPHP trajectory., Significance: The trajectory analysis showed different patterns of urinary OPE metabolite concentrations, suggesting the need to collect multiple samples to adequately reflect OPE exposure., Impact Statement: In this well-established cohort, we evaluated the patterns of urinary OPE metabolites in children ages 1-8 years. The number of repeated measures over childhood has not been achieved in prior studies. Our results suggested the high variability of urinary OPE metabolites within individuals. Maternal metabolite concentrations during pregnancy were related to child concentrations at ages 1-3 years. BCEP, BDCIPP, and DPHP demonstrated different trajectories in children, which suggests that multiple samples may be required to capture OPE exposure patterns in childhood., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The United States Environmental Protection Agency (EPA) recently lowered residential floor and windowsill dust lead hazard standards, but maintained previous post-abatement clearance standards. We examined whether the discrepancy in these regulations places children at higher risk of lead poisoning., Methods: In 250 children from Cincinnati, Ohio (2004-2008) living in homes built before 1978, we measured residential floor and windowsill dust lead loadings and blood lead concentrations at ages 1 and 2 years. Using linear regression with generalized estimating equations, we estimated covariate-adjusted associations of dust lead levels with blood lead concentrations and risk of lead poisoning., Results: An increase in floor dust lead from 10 (revised dust lead hazard standard) to 40 μg/ft 2 (post-abatement clearance standard) was associated with 26% higher (95% confidence interval (CI):15, 38) blood lead concentrations and 2.1 times the risk of blood lead concentrations ≥5 μg/dL (95% CI: 1.44, 3.06). Extrapolating our findings to US children age 1-5 years, we estimated that 6.9% (95% CI: 1.5, 17.2) of cases of blood lead concentrations ≥5 μg/dL are attributable to floor dust lead loadings between 10 and ≤40 μg/ft 2 ., Conclusions: The EPA's residential dust lead regulations place children at increased risk of lead poisoning. We recommend adopting more protective dust lead standards., Impact: We determined whether children are at increased risk of lead poisoning with the 2019 EPA residential post-abatement lead clearance standards being higher than dust lead hazard standards. In this observational study, 2019 EPA dust lead clearance standards were associated with increased risk of lead poisoning compared to the revised dust lead hazard standard. Both EPA standards were associated with increased risk of lead poisoning compared to more stringent standards employed in our study. Extrapolating our findings to US children, the 2019 EPA dust lead clearance standards could place up to 36,700 children at risk of lead poisoning., (© 2020. International Pediatric Research Foundation, Inc.)

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., Competing Interests: Competing interests: JMB received an honoraria from Quest Diagnostic for serving on an expert panel related to endocrine disrupting chemicals. JMB’s institution was financially compensated for his services as an expert witness for plaintiffs in litigation related to per- and polyfluoroalkyl (PFAS)-contaminated drinking water; these funds were not paid to JMB directly., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study aimed to examine associations of changes in leptin and adiponectin concentrations from birth to age 12 years with adolescent adiposity and cardiometabolic risk in the Health Outcomes and Measures of Environment (HOME) Study, a prospective birth cohort (Cincinnati, Ohio; N = 166)., Methods: Adiposity and cardiometabolic risk factors were assessed at age 12 years using anthropometry, dual-energy x-ray absorptiometry, and fasting serum biomarkers. Cardiometabolic risk scores were calculated by summing age- and sex- standardized z scores for individual cardiometabolic risk factors., Results: Most serum adipocytokine concentrations at birth were not associated with adiposity or cardiometabolic risk outcomes. Leptin and adiponectin concentrations at age 12 years were associated with all outcomes in the expected direction. Adolescents with increasing (β: 4.2; 95% CI: 3.2 to 5.2) and stable (β: 2.2; 95% CI: 1.2 to 3.2) leptin concentrations from birth to age 12 years had higher cardiometabolic risk scores than adolescents with decreasing concentrations (reference group). Adolescents with increasing (e.g., fat mass index = β: -1.04; 95% CI: -1.27 to -0.80) and stable (β: 0.66; 95% CI: -0.92 to -0.40) adiponectin/leptin ratios had more favorable adiposity outcomes than adolescents with decreasing ratios., Conclusions: In this cohort, changes in leptin concentrations and adiponectin/leptin ratios over childhood were associated with adiposity and cardiometabolic risk scores, indicating that adipocytokine concentrations are potential biomarkers for predicting excess adiposity and cardiometabolic risk in adolescence., (© 2021 The Obesity Society (TOS).)

Background: Per- and polyfluoroalkyl substances (PFAS) may adversely influence cardiometabolic risk. However, few studies have examined if the timing of early life PFAS exposure modifies their relation to cardiometabolic risk. We examined the influence of gestational and childhood PFAS exposure on adolescents' cardiometabolic risk., Methods: We quantified concentrations of four PFAS (perfluorooctanoate [PFOA], perfluorooctane sulfonate [PFOS], perfluorononanoate [PFNA], and perfluorohexane sulfonate [PFHxS]) in sera collected during pregnancy, at birth, and at ages 3, 8, and 12 years from 221 mother-child pairs in the HOME Study (enrolled 2003-06, Cincinnati, Ohio). We measured cardiometabolic risk factors using physical examinations, fasting serum biomarkers, and dual-energy X-ray absorptiometry scans at age 12 years. Cardiometabolic risk summary scores were calculated by summing age- and sex-standardized z-scores for individual cardiometabolic risk factors. We used multiple informant models to estimate covariate-adjusted associations of serum PFAS concentrations (log 2 -transformed) at each visit with cardiometabolic risk scores and their individual components, and tested for differences in associations across visits., Results: The associations of serum PFOA concentrations with cardiometabolic risk scores differed across visits (P for heterogeneity = 0.03). Gestational and cord serum PFOA concentrations were positively associated with cardiometabolic risk scores (βs and 95% confidence intervals [95% CIs]: gestational 0.8 [0.0, 1.6]; cord 0.9 [-0.1, 1.9] per interquartile range increase). These positive associations were primarily driven by homeostatic model assessment for insulin resistance index (β = 0.3 [0.1, 0.5]) and adiponectin to leptin ratio (β = -0.5 [-1.0, 0.0]). Other individual cardiometabolic risk factors associated with gestational PFOA included insulin and waist circumference. Gestational and cord PFHxS were also associated with higher cardiometabolic risk scores (βs: gestational 0.9 [0.2, 1.6]; cord 0.9 [0.1, 1.7])., Conclusion: In this cohort of children with higher gestational PFOA exposure, fetal exposure to PFOA and PFHxS was associated with unfavorable cardiometabolic risk in adolescence., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Early-life phthalate exposures may adversely influence neurodevelopment by disrupting thyroid hormone homeostasis, altering brain lipid metabolism, or reducing gonadal hormone concentrations. Previous literature examining gestational phthalate exposure and child behavior were inconclusive and few prospective studies have examined childhood phthalate exposure, particularly phthalate mixtures. We investigated whether gestational and childhood phthalate exposures were associated with child behavior., Methods: We used data from 314 mother-child pairs in the HOME Study, a longitudinal pregnancy and birth cohort that enrolled pregnant women from Cincinnati, Ohio. We quantified urinary concentrations of 11 phthalate metabolites in samples collected twice during gestation from women and six times from their children when they were ages 1, 2, 3, 4, 5, and 8 years. We assessed children's behavior at ages 2, 3, 4, 5, and 8 years using the Behavioral Assessment System for Children-2. Using linear mixed models, we estimated covariate-adjusted associations of measurement-error-corrected gestational and childhood phthalate metabolite concentrations (per interquartile range increase) with repeated child behavior assessments. We used Weighted Quantile Sum (WQS) regression to estimate the association of phthalate mixtures with child behavior., Results: Gestational mono(3-carboxypropyl) phthalate (MCPP) concentrations were associated with more problem behaviors (internalizing: β = 0.9, 95% confidence interval [CI] = -0.1, 1.9; externalizing: β = 1.0, 95%CI = -0.1, 2.0; behavioral symptoms index [BSI]: β = 1.1, 95%CI = 0.1, 2.1). Higher childhood monobenzyl phthalate (MBzP) (β = 1.4; 95%CI = 0.0, 2.7), monocarboxynonyl phthalate (MCNP) (β = 3.2; 95%CI = 1.6, 4.8), monocarboxyoctyl phthalate (MCOP) (β = 0.9; 95%CI = 0.0, 1.7), MCPP (β = 1.8; 95%CI = 0.2, 3.5), and monoethyl phthalate (MEP) (β = 1.6; 95%CI = 0.1, 3.1) concentrations were associated with higher BSI composite scores. Consistent with this, the weighted childhood phthalate index was associated with more problem behaviors (internalizing: β = 1.5, 95%CI = -0.2, 3.1; externalizing: β = 1.7, 95%CI = 0.1, 3.5; BSI: β = 1.7, 95%CI = 0.2, 3.2); MBzP, MCNP, and MEP largely contributed to these associations., Conclusion: Our findings suggest that childhood exposure to phthalate mixtures may be associated with children's problem behaviors., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous. Previous studies have found associations between PFAS and thyroid hormones in maternal and cord sera, but the results are inconsistent. To further address this research question, we used mixture modeling to assess the associations with individual PFAS, interactions among PFAS chemicals, and the overall mixture., Methods: We collected data through the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort study that between 2003 and 2006 enrolled 468 pregnant women and their children in the greater Cincinnati, Ohio region. We assessed the associations of maternal serum PFAS concentrations measured during pregnancy with maternal (n = 185) and cord (n = 256) sera thyroid stimulating hormone (TSH), total thyroxine (TT 4 ), total triiodothyronine (TT 3 ), free thyroxine (FT 4 ), and free triiodothyronine (FT 3 ) using two mixture modeling approaches (Bayesian kernel machine regression (BKMR) and quantile g-computation) and multivariable linear regression. Additional models considered thyroid autoantibodies, other non-PFAS chemicals, and iodine deficiency as potential confounders or effect measure modifiers., Results: PFAS, considered individually or as mixtures, were generally not associated with any thyroid hormones. A doubling of perfluorooctanesulfonic acid (PFOS) had a positive association with cord serum TSH in BKMR models but the 95% Credible Interval included the null (β = 0.09; 95% CrI: -0.08, 0.27). Using BKMR and multivariable models, we found that among children born to mothers with higher thyroid peroxidase antibody (TPOAb), perfluorooctanoic acid (PFOA), PFOS, and perfluorohexanesulfonic acid (PFHxS) were associated with decreased cord FT 4 suggesting modification by maternal TPOAb status., Conclusions: These findings suggest that maternal serum PFAS concentrations measured in the second trimester of pregnancy are not strongly associated with thyroid hormones in maternal and cord sera. Further analyses using robust mixture models in other cohorts are required to corroborate these findings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Environmental chemical exposures may adversely affect an array of adolescent health outcomes. Thus, we used the Health Outcomes and Measures of the Environment (HOME) study, a prospective cohort that recruited pregnant women and conducted longitudinal follow-up on children over the first 12 years of life, to determine if and when chemical exposures affect adolescent health., Participants: We recruited 468 pregnant women (age range: 18-45 years) from the Cincinnati, Ohio region to participate in a cohort study between March 2003 and January 2006. Follow-up included two clinic and one home visits during pregnancy, a delivery hospital visit, and four home and six clinic visits when children were aged 4 weeks and 1, 2, 3, 4, 5 and 8 years. Of 441 children available for follow-up, 396 (90%) completed at least one follow-up and 256 (58%) completed the most recent follow-up at 12 years of age (range: 11-14)., Findings to Date: Our new measures include maternal/child report of internalising symptoms, neuroimaging, dual-energy X-ray absorptiometry-derived estimates of lean/adipose tissue and bone mineral density, and cardiometabolic risk biomarkers. We assessed adolescent exposure to perfluoroalkyl substances, phenols, phthalates and flame retardants. Participants completing follow-up at 12 years of age were similar to the original cohort in terms of baseline factors. Most children had typical and expected values for this age on measures of internalising symptoms, body composition, bone density and cardiometabolic risk markers. Notably, 36% and 11% of children had scores indicative of potential anxiety and depressive disorders, respectively. Approximately 35% of children were overweight or obese, with higher prevalence among girls. Thirty-three per cent of children had borderline or high triglyceride concentrations (>90 mg/dL)., Future Plans: We will examine associations of early life environmental chemical exposures with adolescent health measures while considering potential periods of heightened susceptibility and mixture effects., Trial Registration Number: NCT00129324., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Polybrominated diphenyl ethers, a class of flame retardants and endocrine disruptors, have been substituted in new products by organophosphate (OPFR) and replacement brominated flame retardants (RBFR). OPFRs and RBFRs readily migrate from consumer products into dust where humans are exposed via incidental ingestion and inhalation. We quantified concentrations and loadings of OPFRs and RBFRs in house dust samples (n = 317) collected from the homes of Cincinnati women between 2003 and 2006 and examined their associations with demographic and house characteristics. Tris-(1-chloro-2-propyl)-phosphate (TCIPP, geometric mean [GM]: 2140 ng g -1 , range: 70.1-166,000 ng g -1 ), tris-(1,3-dichloro-2-propyl)-phosphate (TDCIPP, GM: 1840 ng g -1 , range: 55.2-228,000 ng g -1 ), triphenyl phosphate (TPHP, GM: 1070 ng g -1 , range: 34.1-62,100 ng g -1 ), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB, GM: 59.5 ng g -1 , range: 2.82-7800 ng g -1 ), and bis-(2-ethylhexyl)-tetrabromophthalate (BEH-TEBP, GM: 121 ng g -1 , range 2.17-13,600 ng g -1 ) were all detected in >90% of dust samples; tris-(2-chloroethyl)-phosphate (TCEP, GM: 669 ng g -1 , range: 56.8-160,000 ng g -1 ) was detected in 80.1% of samples. Concentrations of EH-TBB and BEH-TEBP increased in house dust from 2003 to 2006. The number of people living in the home, race, education, floor type, and year of sample collection were associated with some OPFR and RBFR concentrations and loadings. This study suggests that OPFRs and RBFRs were ubiquitous in house dust during the PBDE phase-out and justifies more research on the consequences of exposure to these environmental chemicals., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Triclosan exposure may decrease circulating thyroxine levels or cause neuron apoptosis, which in turn may adversely affect neurodevelopment. However, few studies have examined the association of early life triclosan exposure with child behavior., Objective: To quantify the association between early-life triclosan exposure and child behavior at age 8-years in 202 mother-child pairs from the HOME study (Cincinnati, OH; enrolled: 2003-2006)., Methods: We quantified urinary triclosan concentrations up to 3 times in mothers (16-weeks, 26-weeks, and delivery) and up to 6 times in children (1, 2, 3, 4, 5, and 8 years). Parents rated children's problem behaviors at age 8-years using the Behavioral Assessment System for Children-2 (BASC-2). Adjusting for covariates and accounting for exposure measurement error, we estimated changes in behavior problem scores per 10-fold increase in mean gestational and childhood triclosan concentrations. In addition, we estimated sex-specific associations., Results: Child sex modified the association of gestational and childhood triclosan with several BASC-2 scales (sex × triclosan p-values < 0.2). In boys, increasing gestational triclosan was associated with higher behavioral symptom index (β: 4.5; 95% CI: 1.0, 8.1), externalizing problems (β: 5.0; 95% CI: 1.2, 9.0), attention problem (β: 6.6; 95% CI: 2.4, 11), hyperactivity (β: 6.4; 95% CI: 2.1, 11), and somatization (β: 3.8; 95% CI: 0.3, 7.3) scores. In contrast, triclosan-BASC-2 associations in girls were generally null and not statistically significant. We observed similar patterns of associations between childhood triclosan and these same behavioral scores; however, their magnitude decreased substantially after adjusting for gestational triclosan and associations were not statistically significant., Conclusion: In this cohort, increasing gestational and childhood urinary triclosan concentrations were associated with higher behavior problem scores in 8-year old boys, but not girls., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Early-life phthalate exposures may adversely affect children's neurodevelopment by disrupting thyroid function, reducing gonadal hormone levels, or altering fatty acid concentrations in the brain. This study aimed to identify periods of heightened susceptibility during gestation, infancy, and childhood to the impact of phthalates on children's cognitive abilities., Methods: We used data from 253 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio), a longitudinal pregnancy and birth cohort. We quantified urinary concentrations of 11 phthalate metabolites in samples collected twice during gestation and 6 times during study visits when children were aged 1-8 years using a modified method of on-line solid phase extraction coupled with isotope dilution-high performance liquid chromatography-tandem mass spectrometry. We assessed children's intelligence (IQ) at ages 5 and 8 years using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV, respectively. We estimated covariate-adjusted associations between a 1-standard deviation increase in log 10 -transformed urinary phthalate metabolite concentrations at each visit and children's IQ, adjusting for demographic, perinatal, and child factors; we tested for differences in these associations across visits using multiple informant models., Results: Associations between some phthalate metabolites and IQ varied by visit (phthalate x visit interaction p-values<0.20). The sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), mono(3-carboxypropyl) phthalate, and monoethyl phthalate at age 3 years, and monobenzyl phthalate at 16 weeks gestation and child ages 3, 5, and 8 years were inversely associated with children's full-scale IQ. For example, each 1-standard deviation increase in ΣDEHP at age 3 was associated with a 1.9-point decrease in full-scale IQ (95% confidence interval: -3.7, -0.2). Mono-n-butyl phthalate and mono-isobutyl phthalate at age 4 years were positively associated with children's full-scale IQ., Conclusion: Urinary concentrations of several phthalate metabolites at age 3 years, compared to other time periods, were more strongly associated with decreased cognitive abilities in these children., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To assess the relationship between greenspace exposure and childhood internalizing and externalizing behaviors., Study Design: We analyzed data from the Cincinnati Childhood Allergy and Air Pollution Study, an ongoing prospective birth cohort. Greenspace exposure was estimated based on children's addresses using normalized difference vegetation index (NDVI) images. Neurobehavioral outcomes were assessed using the Behavioral Assessment System for Children, Second Edition. Regression models adjusted for neighborhood deprivation, maternal education, race, and sex assessed the risk for problematic internalizing and externalizing behaviors at residential greenspace buffers of 200, 400, and 800 m., Results: There were 562 and 313 children in our age 7- and 12-year analyses, respectively. At age 7 years, a 0.1-unit increase in NDVI was associated with decreased conduct scores (β = -1.10, 95% CI [-2.14, -0.06], 200 m). At age 12 years, a 0.1-unit increase in NDVI was associated with a decrease in anxiety scores (β = -1.83, 95% CI [-3.44, -0.22], 800 m), decreased depression scores (β = -1.36, 95% CI [-2.61, -0.12], 200 m), and decreased somatization scores (β = -1.83, 95% CI [-3.22, -0.44], 200 m)., Conclusions: This study provides evidence that increased exposure to residential greenspace is associated with reduced youth's problematic internal and external behaviors, measured by Behavioral Assessment System for Children, Second Edition, at ages 7 and 12 years. Improved understanding of this mechanism could allow for implementation of neighborhood-level approaches for reducing the risk for childhood behavioral problems., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Triclosan is an antimicrobial agent that may affect the gut microbiome and endocrine system to influence adiposity. However, little data from prospective studies examining prenatal and childhood exposures exist. We investigated the relationship between multiple, prospective early life measure of triclosan exposure and child adiposity.  METHODS: In a prospective cohort of 220 mother-child pairs from Cincinnati, OH (enrolled 2003-2006), we quantified triclosan in urine samples collected twice during pregnancy, annually from 1 to 5 years of age, and once at 8 years. We assessed child adiposity at age 8 years using body mass index (BMI), waist circumference, and bioelectric impedance. We estimated covariate-adjusted associations of child adiposity with a 10-fold increase in average prenatal, average early childhood (average of 1-5 years), and 8-year triclosan concentrations., Results: Among all children, there was no association between triclosan and child adiposity. While urinary triclosan concentrations at all three time periods were weakly, imprecisely, and inversely associated with all three measures of adiposity among girls, these associations did not differ significantly from those in boys (sex x triclosan p-values> 0.35). Among girls, the strongest associations were generally observed for prenatal triclosan when we adjusted for all three triclosan concentrations and covariates in the same model; BMI z-score (β: -0.13; 95% CI: -0.42, 0.15), waist circumference (β: - 1.7 cm; 95% CI: -4.2, 0.7), and percent body fat (β :-0.6; 95% CI: -2.7, 1.3). In contrast, the associations between triclosan concentrations and adiposity measures were inconsistent among boys., Conclusion: We did not observe evidence of an association of repeated urinary triclosan concentrations during pregnancy and childhood with measures of child adiposity at age 8 years in this cohort.

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 5.2s (95% Confidence Interval [CI] -9.3, -1.1), 4.5s (95% CI -8.1, -0.9), and 4.7s (95% CI -9.0, -0.3), respectively. However, children with higher BDE-153 at 3 years had longer completion times (β=5.4s, 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., Competing Interests: The authors declare they have no competing financial interests., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Residential injury is a leading cause of morbidity and mortality in US children. Rates and types of injury vary by child age but little is known about injury risk based on child cognitive and motor abilities. The objective of this study was to determine whether cognitive or motor development in young children is associated with residential injury., Methods: We employed data from Health Outcomes and Measures of the Environment (HOME) Study. Parent report of medically attended injury was obtained at regular intervals from 0 to 42 months. Child development was assessed at 12, 24 and 36 months using Bayley Scales of Infant and Toddler Development, 2nd edition, which generates both mental developmental index (MDI) and a psychomotor developmental index (PDI). Injury risk was modelled using multivariable logistic regression as function of child's MDI or PDI. Effects of MDI and PDI on injury risk were examined separately and jointly, adjusting for important covariates., Results: Children with cognitive delay (MDI <77) were at significantly higher risk of injury than children without cognitive delay (OR=3.7, 95% CI 1.4 to 10.5, p=0.012). There was no significant association of PDI with injury. There was, however, significant interaction of MDI and PDI (p=0.02); children with cognitive delay but normal motor development were at significantly higher risk of injury than children with normal cognitive and motor development (OR=9.6, 95% CI 2.6 to 35.8, p=0.001)., Conclusions: Children with cognitive delays, especially those with normal motor development, are at elevated risk for residential injuries. Injury prevention efforts should target children with developmental delays., Clinical Trials Number: NCT00129324; post-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Prenatal exposure to organophosphate pesticides, which is ubiquitous, may be detrimental to neurological development. We examined 327 mother/infant pairs in Cincinnati, Ohio, between 2003 and 2006 to determine associations between prenatal exposure to organophosphate pesticides and neurodevelopment. Twice during pregnancy urinary concentrations of 6 common dialkylphosphates, nonspecific metabolites of organophosphate pesticides, were measured. Aggregate concentrations of diethylphosphates, dimethylphosphates, and total dialkylphosphates were calculated. Bayley Scales of Infant Development, Second Edition-Mental and Psychomotor Developmental indices were administered at ages 1, 2, and 3 years, the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, at age 4, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at age 5. Mothers with higher urinary total dialkylphosphate concentrations reported higher levels of socioeconomic status and increased fresh fruit and vegetable intake. We found no associations between prenatal exposure to organophosphate pesticides and cognition at 1-5 years of age. In our cohort, exposure to organophosphate pesticides during pregnancy was not associated with cognition during early childhood. It is possible that a higher socioeconomic status and healthier diet may protect the fetus from potential adverse associations with gestational organophosphate pesticide exposure, or that dietary exposure to the metabolites is innocuous and not an ideal measure of exposure to the parent compound., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Exposure to phthalates, a class of endocrine disrupting chemicals, is ubiquitous. We examined the association of urinary phthalate metabolite concentrations during pregnancy with maternal blood pressure and risk of pregnancy-induced hypertensive diseases., Methods: We used data from the Health Outcomes and Measures of the Environment Study, a prospective birth cohort of low-risk pregnant women recruited between March 2003 and January 2006. We analyzed maternal urine samples collected at 16 and 26 weeks gestation for 9 phthalate monoester metabolites reflecting exposure to 6 phthalate diesters. Outcomes included maternal blood pressure at <20 and ≥ 20 weeks gestation and pregnancy induced hypertensive diseases (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome)., Results: Data were available for 369 women who gave birth to singleton, live-born infants without congenital anomalies. Of the phthalate metabolites evaluated, only mono-benzyl phthalate (MBzP) concentrations were significantly associated with maternal diastolic blood pressure at <20 weeks gestation. Women in the third MBzP tercile at 16 weeks gestation had diastolic blood pressure 2.2 (95% CI: 0.5-3.9) mm Hg higher at <20 weeks gestation and 2.8 (95% CI: 0.9-4.7) mm Hg higher at ≥ 20 weeks gestation compared to women in the first tercile. Compared to women in the first tercile, women in the top MBzP tercile at 16 weeks had an increased risk of developing pregnancy-induced hypertensive diseases (RR = 2.92, 95 % CI 1.15-7.41, p-value for trend = 0.01). MBzP concentrations at 26 weeks gestation were not as strongly associated with blood pressure at ≥ 20 weeks gestation or risk of pregnancy-induced hypertensive diseases., Conclusion: This study suggests that maternal urinary MBzP concentrations may be associated with increased diastolic blood pressure and risk of pregnancy-induced hypertensive diseases.

Bisphenol A (BPA), an endocrine disruptor used in consumer products, may perturb thyroid function. Prenatal BPA exposure may have sex-specific effects on thyroid hormones (THs). Our objectives were to investigate whether maternal urinary BPA concentrations during pregnancy were associated with THs in maternal or cord serum, and whether these associations differed by newborn sex or maternal iodine status. We measured urinary BPA concentrations at 16 and 26 weeks gestation among pregnant women in the HOME Study (2003-2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine (T4) and triiodothyronine (T3) were measured in maternal serum at 16 weeks (n=181) and cord serum at delivery (n=249). Associations between BPA concentrations and maternal or cord serum TH levels were estimated by multivariable linear regression. Mean maternal urinary BPA was not associated with cord THs in all newborns, but a 10-fold increase in mean BPA was associated with lower cord TSH in girls (percent change=-36.0%; 95% confidence interval (CI): -58.4, -1.7%), but not boys (7.8%; 95% CI: -28.5, 62.7%; p-for-effect modification=0.09). We observed no significant associations between 16-week BPA and THs in maternal or cord serum, but 26-week maternal BPA was inversely associated with TSH in girls (-42.9%; 95% CI: -59.9, -18.5%), but not boys (7.6%; 95% CI: -17.3, 40.2%; p-for-effect modification=0.005) at birth. The inverse BPA-TSH relation among girls was stronger, but less precise, among iodine deficient versus sufficient mothers. Prenatal BPA exposure may reduce TSH among newborn girls, particularly when exposure occurs later in gestation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Prenatal tobacco smoke exposure may be associated with low maternal folate levels that increase the risk of adverse infant and child health outcomes by reducing folate availability during fetal development., Methods: Using data from the Health Outcomes and Measures of the Environment Study, we examined the relationship between secondhand or active tobacco smoke exposure and whole blood folate concentrations in pregnant women from Cincinnati, Ohio (n = 362) at approximately 16-week gestation. We used multivariable linear regression to examine the association between continuous or categorical serum cotinine levels and whole blood folate levels, adjusting for sociodemographic, dietary, and perinatal variables., Results: After adjustment for potential confounders, an interquartile range increases in serum cotinine concentration (0.012-0.224 ng/mL) was suggestively associated with decreased whole blood folate levels (β, -23 nmol/L; 95% confidence interval (CI), -49, 3; P value = .08). Compared with unexposed women, reductions in mean whole blood folate were observed among active smokers (β, -94, 95% CI, 195, 6 nmol/L; P value = .40); smaller reductions were observed among women with secondhand exposure (β, 26; CI, 84, 32 nmol/L; P value = .07)., Conclusions: Consistent with prior studies, active smoking was associated with reduced whole blood folate levels among these pregnant women. Secondhand tobacco smoke exposures were associated with small and imprecise reductions in whole blood folate levels., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: National data suggest widespread gestational exposure to organophosphate pesticides (OPs) based on the detection of OP metabolites in the urine of pregnant women. Associations with early infant neurobehavior are largely understudied, with only two studies reporting abnormal reflexes in newborns in association with gestational exposure to OPs. Our objective was to utilize biological markers of OP metabolites in pregnant women and a comprehensive assessment of infant neurobehavior to determine the association of gestational exposure to OPs with neurobehavioral outcomes during early infancy., Methods: Among a cohort of 350 mother/infant pairs, we measured six common dialkylphosphate metabolites of OP pesticides in maternal urine, at two times during pregnancy (16 w & 26 w gestation), then calculated aggregate concentrations of diethylphosphate, dimethylphosphate, and total dialkyphosphate metabolites. We measured infant neurobehavior at about five weeks of age using the NICU Network Neurobehavioral Scale (NNNS), a comprehensive assessment of neurobehavior in young infants. Analyses of associations between gestational exposure to OPs and neurobehavior at five weeks included multiple linear and logistic regression., Results: After adjustment for covariates, higher creatinine-corrected urinary concentrations of diethylphosphate metabolites were associated with improved attention and reduced lethargy and hypotonia in young infants. Higher creatinine-corrected urinary concentrations of total dialkylphosphate metabolites were associated with fewer signs of autonomic stress. Women who were white, married, had advanced education, and reported more frequent consumption of fresh fruits and vegetables had higher concentrations of OP metabolites during pregnancy., Conclusions: In this sample of pregnant women whose urinary concentrations of dialkylphosphate metabolites are representative of national exposure levels, we found no detrimental effects of gestational exposure to OPs on neurobehavioral outcomes among young infants. These results are important as they suggest there may be minimal to no detectable adverse impact of low level prenatal OP exposure on the neurobehavior of young infants.