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Introduction: Exposure to perfluoroalkyl substances (PFAS), synthetic and persistent chemicals used in commercial and industrial processes, are associated with cardiometabolic dysfunction and related risk factors including reduced birth weight, excess adiposity, and dyslipidemia. Identifying the metabolic changes induced by PFAS exposure could enhance our understanding of biological pathways underlying PFAS toxicity. Objective: To identify metabolic alterations associated with serum concentrations of four PFAS in children using a metabolome-wide association study. Methods: We performed untargeted metabolomic profiling by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified serum concentrations of perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorononanoic acid, and perfluorohexanesulfonic acid (PFHxS) for 114 8-year old children from Cincinnati, OH. We evaluated associations between each serum PFAS concentration and 16,097 metabolic features using linear regression adjusted for child age, sex, and race with a false discovery rate < 20%. We annotated PFAS-associated metabolites and conducted pathway enrichment analyses. Results: Serum PFAS concentrations were associated with metabolic features annotated primarily as lipids and dietary factors. Biological pathways associated with all four PFAS included arginine, proline, aspartate, asparagine, and butanoate metabolism. Conclusions: In this cross-sectional study, childhood serum PFAS concentrations were correlated with metabolic pathways related to energy production and catabolism. Future studies should determine whether these pathways mediate associations between PFAS exposure and childhood cardiometabolic health. [ABSTRACT FROM AUTHOR]

Purpose: To identify associations between age of onset of overweight/obesity, a child's sociodemographic characteristics, and characteristics of a child's home census tract. Design: Retrospective electronic health record review of children with overweight/obesity. Setting: Three primary care centers associated with a free-standing, tertiary-care pediatric institution in Cincinnati. Subjects: Patients born between August 1, 2013 and July 31, 2014, who had a body mass index (BMI) ≥85th percentile before 5 years of age (n = 794). Measures: Primary outcome was the patient's age at the first encounter when BMI was ≥85th percentile. Patient-level predictors were sex, age, race/ethnicity, health insurance, and number of moves captured in the health record. Census tract-level predictors were density of bus stops, presence of grocery stores, and a Socioeconomic Deprivation Index. Analysis: Multivariable linear regression models assessed for independent associations between age of onset of overweight/obesity and predictors. Results: Patients were 55.8% female, 73.6% black, and 79.1% publicly insured. Each additional move per year was associated with onset of overweight/obesity occurring 4.05 months earlier (P <.0001). No significant associations between age of onset of overweight/obesity and census tract-level density of bus stops (P =.82), presence of grocery stores (P =.39), and socioeconomic deprivation (P =.53) were demonstrated. Conclusion: Public policy efforts toward improving access to grocery stores or public transportation may not be sufficient to prevent childhood obesity. Population-level interventions related to improving housing may also reduce obesity. [ABSTRACT FROM AUTHOR]

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. Image 1 • We measured OPFRs and RBFRs in 317 women's house dust during the PBDE phase-out. • OPFR concentrations were about 10× higher than RBFR concentrations. • RBFR concentrations increased from 2003 to 2006. • Both sociodemographic and housing characteristics were related to dust levels. [ABSTRACT FROM AUTHOR]

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers for commercial and residential purposes, are suspected of being neurotoxic. We aimed to assess exposure to an OPE mixture in early life and its relationship to parent-reported child behavior. We measured urinary concentrations of three OPE metabolites, bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), and diphenyl phosphate (DPHP), at pregnancy (16 and 26 weeks of gestation and delivery) and postnatal time points (ages 1, 2, 3, and 5 years) in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort in Cincinnati, Ohio, USA (enrolled 2003–2006, n = 219). We used latent variable analysis in structural equations models and quantile g-computation to investigate associations of a mixture of the three OPE metabolites with parent-reported child behaviors at 3 and 8 years, measured using the Behavioral Assessment System for Children, Second Edition. Higher log-transformed urinary OPE latent variable values at 16 weeks were associated with fewer externalizing problem behaviors (ß = −5.74; 95% CI = −11.24, −0.24) and fewer overall behavioral problems at age 3 years (ß = −5.26; 95% CI = −10.33, −0.19), whereas having higher OPEs at delivery was associated with poorer overall behavioral problems at age 3 years (ß = 2.87; 95% CI = 0.13, 5.61). OPE latent variable values at 16 weeks, 26 weeks, and delivery were not associated with child behavior at 8 years. However, higher OPE latent variable values at 3 years were associated with fewer externalizing behaviors at 8 years (ß = −2.62; 95% CI = −5.13, −0.12). The quantile g-computation estimates had directions largely consistent with the latent variable analysis results. Pregnancy and postnatal urinary OPE metabolite mixtures were associated with child internalizing, externalizing, and overall negative behaviors at 3 and 8 years, but we did not identify a consistent pattern in terms of the direction of the effects or a particularly sensitive time point. • We studied pregnancy and postnatal OPEs and child behavior in a longitudinal cohort. • We used latent variable analysis and quantile g-computation to assess OPE mixtures. • Pregnancy OPEs were associated with child behavior at 3 years. • The direction of associations and vulnerable time points were inconsistent. [ABSTRACT FROM AUTHOR]

Early life environmental exposures may affect bone mass accrual in childhood, but only one study has assessed the role of environmental phenols on child bone health. We used data from 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, OH; 2003–2006). We quantified benzophenone-3, bisphenol A (BPA), 2,5-dichlorophenol, and triclosan in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry at age 12 years and calculated Z-scores for whole body (less head), total hip, femoral neck, and 1/3rd distal radius bone mineral content (BMC) and areal bone mineral density (aBMD) as well as ultra-distal radius aBMD and spine BMC and bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per doubling of maternal urinary environmental phenol concentrations in linear regression models. We also examined effect measure modification by child's sex and estimated associations of the environmental phenol mixture with BMC and aBMD using quantile g-computation. We observed generally null associations for all analytes and bone measures. Yet, in adjusted models, higher urinary 2,5-dichlorophenol concentrations were associated with higher 1/3rd distal radius BMC (β: 0.09; 95% CI: 0.02, 0.17) and aBMD (β: 0.09; 95% CI: 0.02, 0.17) Z-scores in the overall sample. In sex-stratified analyses, the magnitude of the BMC association was positive for females (β: 0.16; 95% CI: 0.06, 0.26) and null for males (β: 0.02; 95% CI: 0.08, 0.13). The environmental phenol mixture was associated with greater 1/3rd distal radius BMC and aBMD Z-scores in both sexes, which was mostly driven by benzophenone-3 in males and 2,5-dichlorophenol in females. In this prospective cohort study, we observed generally null associations for environmental phenols with BMC and aBMD at age 12 years. While there was a positive association of 2,5-dichlorophenol concentrations during fetal development with distal radius BMC and aBMD at age 12 years, future studies utilizing methods capable of differentiating cortical and trabecular bone are needed to elucidate potential mechanisms and implications for bone strength and microarchitecture. • Gestational urinary 2,5-dichlorophenol concentrations were associated with greater distal radius bone mineral density. • Associations for gestational urinary benzophenone-3, bisphenol A, and triclosan were null. • The environmental phenol mixture was associated with greater distal radius bone mineral content and density. [ABSTRACT FROM AUTHOR]

The use of organophosphate esters (OPEs) as flame retardants, which has increased over the past two decades, raises concerns that OPEs may be harmful to humans, especially children. Animal studies and some human studies have reported that OPEs may adversely impact brain development, but few human studies evaluated OPE exposure during early childhood and neurodevelopmental outcomes. We aimed to fill this knowledge gap with the present study on urinary OPE metabolite concentrations at ages 1–5 years and cognitive abilities at 8 years. We used data of 223 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio. The point estimates for bis-2-chloroethyl-phosphate (BCEP) and bis(1,3-dichloro-2-propyl)-phosphate (BDCIPP) in association with IQ tended to be small and positive, while the point estimates for diphenyl-phosphate (DPHP) were small and negative, with 95% CIs including the null. However, we did find that socioeconomic status (SES) variables modified associations between OPEs and child IQ, with adverse OPE-IQ associations being stronger in socioeconomically disadvantaged children than in others. We identified an additional 1- to 2-point decrease in Full Scale IQ for every log-unit increase in BDCIPP, BCEP, and DPHP among those with lower maternal education, non-white race, lower income, or living in more deprived neighborhoods. We observed similar results for the Perceptual Reasoning, Verbal Comprehension, and Working Memory Index Scores. We suspect that there is residual confounding related to socioeconomic disadvantage, which was not captured with the available SES variables typically used in epidemiologic studies. • This cohort study examines OPEs at ages 1–5 years and cognition at age 8 years. • In child urine, BCEP was detected at 90–95%, BDCIPP at 99%, and DPHP at 99–100%. • Point estimates for OPEs and cognition were small, and 95% CIs included the null. • SES variables modified associations; disadvantaged children have worse outcomes. [ABSTRACT FROM AUTHOR]

Few studies have examined the association between maternal exposure to organophosphate esters (OPEs) and systolic/diastolic blood pressure (SBP/DBP) during pregnancy. We analyzed data from 346 women with a singleton live birth in the HOME Study, a prospective birth cohort in Cincinnati, Ohio, USA. We quantified four OPE metabolites in maternal spot urine samples collected at 16 and 26 weeks pregnancy, standardized by specific gravity. We calculated intraclass correlation coefficients (ICCs). We extracted the first two recorded BP measurements (<20 weeks), the two highest recorded BP measurements (≥20 weeks), and diagnoses of hypertensive disorders of pregnancy (HDP) via chart review. Women with two BP measurements ≥140/90 mmHg or HDP noted in the chart at ≥20 weeks pregnancy were defined as HDP cases. We used linear mixed models and modified Poisson regression with covariate adjustment to estimate associations between OPE concentrations as continuous variables or in tertiles with maternal BP and HDP. ICCs of OPEs were 0.17–0.45. Diphenyl phosphate (DPHP) had the highest geometric mean concentration among OPE metabolites. Increasing the average bis(2-chloroethyl) phosphate (BCEP) concentrations were positively associated with two highest recorded DBP ≥20 weeks pregnancy. Compared with women in the 1st DPHP tertile, women in the 3rd tertile at 16 weeks pregnancy had 1.72 mmHg (95% CI: -0.01, 3.46) higher DBP <20 weeks pregnancy, and women in the 3rd tertile of the average DPHP concentrations had 2.25 mmHg (95% CI: 0.25, 4.25) higher DBP ≥20 weeks pregnancy. 33 women (9.5%) were identified with HDP. Di-n-butyl phosphate (DNBP) concentrations at 16 weeks were positively associated with HDP, with borderline significance (RR = 2.98, 95% CI 0.97–9.15). Other OPE metabolites were not significantly associated with HDP. Maternal urinary BCEP and DPHP concentrations were associated with increased BP during pregnancy. Maternal urinary DNBP concentrations were associated with HDP, with borderline significance. [ABSTRACT FROM AUTHOR]

[Display omitted] • We examined associations between gestational PBDE exposure and outcomes at age 12. • Outcomes included self- and caregiver-reported social skills and problem behaviors. • Gestational PBDE exposure was associated with poorer outcomes in adolescent males. • No associations were noted among female participants. Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants used as flame retardants. Gestational PBDE exposure has been associated with a variety of behavior problems in children, but little is known about its impact into adolescence, particularly on social skills, which are important for achieving social competence, establishing identity, and forming lasting relationships. We investigated associations between gestational exposure to PBDEs and social skills and problem behaviors in early adolescence in a longitudinal pregnancy and birth cohort in Cincinnati, Ohio (recruited 2003–2006). We measured maternal serum concentrations of five PBDE congeners during gestation. At age 12, we measured social skills and problem behaviors scores for 243 adolescents using self- and caregiver-report on the Social Skills Improvement System (SSiS). We used multivariable linear regression models to estimate associations between maternal PBDE concentrations and SSiS scores, controlling for potential covariates. We report associations for the five congeners and a summary exposure variable (∑ 5 BDE: the sum of BDE- 28, 47, 99, 100, and 153, n = 197). We found sex-specific associations of ∑ 5 BDE concentrations with adolescent-reported Problem Behaviors (∑ 5 BDE × sex p int = 0.02) and caregiver-reported Social Skills (∑ 5 BDE × sex p int = 0.02). In sex-stratified models, log 10 transformed data revealed increased maternal ∑ 5 BDE concentration among males was associated with decreased caregiver-reported Social Skills composite score (β = -10.2, 95% CI: −19.5, −1.0), increased adolescent-reported Problem Behaviors composite score (β = 12.1, 95% CI: 5.4, 18.8), and increased caregiver-reported Problem Behaviors composite score (β = 6.2, 95% CI: 0.7, 11.7). Further analysis on SSiS subscales revealed similar patterns in significant associations among males. There were no statistically significant associations in stratified models among females despite higher ∑ 5 BDE exposure (Female GM=40.15 ng/g lipid, GSE=1.10; Male GM=35.30 ng/g lipid, GSE=1.09). We found gestational PBDE exposure in males was associated with poorer behavioral outcomes, extending previous findings among this cohort into early adolescence. [ABSTRACT FROM AUTHOR]

• PBDEs and PFAS during pregnancy may play a role in the pathogenesis of depression. • BDI-II was used to assess pregnancy and postpartum depressive symptoms. • PBDEs during pregnancy were associated with higher depressive symptoms in mothers. • ∑PBDEs were associated with higher risk of mothers having a high BDI-II trajectory. • Findings between PFAS during pregnancy and BDI-II scores were not significant. 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 (β = 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. [ABSTRACT FROM AUTHOR]