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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.)

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., Competing Interests: Declaration of competing interest Dr. Braun was financially compensated for serving as an expert witness in litigation related to perfluorooctanonic acid contamination in drinking water., (Copyright © 2023. Published by Elsevier GmbH.)

Background: Few studies have examined whether gestational exposure to organophosphate esters (OPEs), widely used chemicals with potential endocrine-disrupting potency and developmental toxicity, is associated with impaired infant growth., Methods: We analyzed data from 329 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006, Cincinnati, Ohio, USA). We quantified concentrations of four OPE metabolites in maternal urine collected at 16 and 26 weeks of gestation, and at delivery. We calculated z-scores using 2006 World Health Organization (WHO) child growth standards for the 4-week anthropometric measures (weight, length, and head circumference), the ponderal index, and weekly growth rates. We used multiple informant models to examine window-specific associations between individual OPE metabolites and anthropometric outcomes. We further modeled OPEs as a mixture for window-specific associations with 4-week anthropometric outcomes using mean field variational Bayesian inference procedure for lagged kernel machine regression (MFVB-LKMR). We stratified the models by infant sex., Results: Diphenyl phosphate (DPHP) in mothers at 16 weeks, and bis(2-chloroethyl) phosphate (BCEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) at delivery were positively associated with z-scores of weight, length, and head circumference in all infants at 4 weeks of age. After stratifying by infant sex, positive associations were only observed in males for DPHP at 16 weeks and BCEP at delivery and in females for BDCIPP at delivery. Negative associations not present in all infants were observed in males for di-n-butyl phosphate (DNBP) at 26 weeks of gestation with weight z-score and DPHP at delivery with head circumference z-score. Results were generally similar using MFVB-LKMR models with more conservative 95 % credible intervals. We did not identify consistent associations of gestational OPE metabolite concentrations with the ponderal index and weekly growth rates., Conclusion: In this cohort, exposure to OPEs during gestation was associated with altered infant anthropometry at 4 weeks after birth., 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 © 2022 Elsevier B.V. All rights reserved.)

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., 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 © 2022 Elsevier Inc. All rights reserved.)

Background: Few studies have examined the association between maternal exposure to organophosphate esters (OPEs) and systolic/diastolic blood pressure (SBP/DBP) during pregnancy., Methods: 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., Results: 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., Conclusion: Maternal urinary BCEP and DPHP concentrations were associated with increased BP during pregnancy. Maternal urinary DNBP concentrations were associated with HDP, with borderline significance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: 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., Objective: 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)., Methods: 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)., Results: 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)., Discussion: We found gestational PBDE exposure in males was associated with poorer behavioral outcomes, extending previous findings among this cohort into early adolescence., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Organophosphate esters (OPEs) are a group of chemicals used as flame retardants and plasticizers that replaced polybrominated diphenyl ethers in consumer products such as furniture and electronics. To characterize exposure to OPEs during fetal development, we measured urinary OPE metabolite concentrations in women twice during pregnancy (16 and 26 weeks' gestation) and at delivery (n = 357). We also previously quantified house dust OPE parent compound concentrations at 20 weeks' gestation (n = 317). Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.5-2.3 μg/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.75-0.99 μg/g creatinine), and bis(2-chloroethyl) phosphate (BCEP; 0.72-0.97 μg/g creatinine), while dibutyl phosphate (DNBP) had the lowest concentrations (0.25-0.28 μg/g creatinine). Urinary OPE metabolites were moderately correlated with each other at 26 weeks (r s : 0.23-0.38, p < 0.001) while the correlations at 16 weeks and delivery were slightly weaker. Intra-class correlations for urinary metabolites measured at three time points were poor (0.16-0.34), indicating high variability within individuals. Dust concentrations of OPE parent compounds were associated with BCEP, BDCIPP, and DPHP concentrations in urine at some but not all time points. In linear mixed models of urinary OPE metabolite concentrations, household size was inversely associated with BCEP concentrations, and being non-white was associated with lower BDCIPP and DPHP concentrations. Urine samples collected in the summer had the highest OPE metabolite concentrations. This study highlights the need to collect multiple urine samples during pregnancy to define exposure patterns and investigate potential periods of susceptibility., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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: Animal studies suggest polybrominated diphenyl ethers (PBDEs) may be obesogens. However, epidemiologic studies investigating childhood exposure to PBDEs and adiposity are limited, with several reporting an inverse association., Objectives: To investigate associations between repeated childhood PBDE concentrations and adiposity measures at age 8 years., Methods: We examined 206 children from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (2003-2006). Serum PBDEs were measured at ages 1, 2, 3, 5, and 8 years. We used multiple imputation to estimate missing PBDE concentrations. At 8 years, we measured weight, height, waist circumference, and body fat percentage. We used multiple informant models to estimate age-specific associations between PBDEs and adiposity measures., Results: We observed significant inverse associations between BDE-153 with all adiposity measures that became increasingly stronger with later childhood measurements. A 10-fold increase in BDE-153 at ages 1 and 8 years was associated with 2% (95% CI -3.9, -0.1) and 7% (95% CI -9.1, -4.7) lower body fat, respectively. No statistically significant associations were found with BDE-28, -47, -99, or -100. Child sex modified some associations; inverse associations between BDE-153 and body fat were stronger among boys, while positive and null associations were noted among girls., Conclusions: Childhood BDE-153 concentrations were inversely associated with adiposity measures and these associations became stronger as BDE-153 measurements were more proximal to adiposity measures. Inverse associations could be attributed to reverse causality arising from greater storage of PBDEs in adipose tissue of children with higher adiposity., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Exposure to polybrominated diphenyl ethers (PBDEs) during fetal development may be associated with deficits in attention and impulse control. However, studies examining postnatal PBDE exposures and inattention and impulsivity have been inconsistent. Using data from 214 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort with enrollment from 2003 to 2006 in the Greater Cincinnati Area, we investigated the relationship of both prenatal and postnatal PBDE exposures with attention and impulse control. Serum PBDEs were measured at 16±3weeks of gestation and during childhood at 1, 2, 3, 5, and 8years. We assessed children's attention and impulse control using the Conners' Continuous Performance Test-Second Edition (CPT-II) at 8years. We used multiple informant models to estimate associations of repeated PBDE measures with inattention and impulsivity. There was a pattern of associations between PBDEs and poorer performance on CPT-II measures of attention. For BDE-153, adverse associations extended to exposures at preschool and kindergarten ages; ten-fold increases in exposure were associated with higher omission errors (BDE-153 at 3years: β=4.0 [95% CI: -2.4, 10.5]; at 5years: β=4.6 [95% CI: -2.8, 12.0]; at 8years: β=4.1 [95% CI: -3.4, 11.5]). Longer hit reaction times, indicated by the exponential part of the hit reaction curve, were also observed with 10-fold increases in BDE-153 during the prenatal period and throughout childhood (Prenatal: β=15.0 milliseconds (ms) [95% CI: -15.8, 45.8]; 5years: β=20.6ms [95% CI: -20.8, 61.9]; 8years: β=28.6ms [95% CI: -12.1, 69.4]). Significant impairment in discriminability, as indicated by detectability (d'), between targets and non-targets was also noted with 5 and 8-year PBDE concentrations. Associations between PBDEs and inattention significantly differed by child sex, with males performing more poorly than females with regard to omission errors and measures of reaction times. Collectively, these results do not strongly support that PBDEs are associated with poorer impulse and attention control among 8year old children. However, there may be a possible relationship between prenatal and concurrent PBDEs and inattention, which requires additional research., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003–2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose–response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di- n -butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed. [ABSTRACT FROM AUTHOR]