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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.)

Background Epidemiological studies have historically focused on single toxicants, or toxic chemicals, and neurodevelopment, even though the interactions of chemicals and nutrients may result in additive, synergistic, antagonistic, or potentiating effects on neurological endpoints. Investigating the impact of environmentally-relevant chemical mixtures, including heavy metals and endocrine disrupting chemicals (EDCs), is more reflective of human exposures and may result in more refined environmental policies to protect the public. Objective In this review, we provide a summary of epidemiological studies that have analyzed chemical mixtures of heavy metals and EDCs and neurobehavior utilizing multi-chemical models, including frequentist and Bayesian methods. Content Studies investigating chemicals and neurobehavior have the opportunity to not only examine the impact of chemical mixtures, but they can also identify chemicals from a mixture that may play a key role in neurotoxicity, investigate interactive effects, estimate non-linear dose response, and identify potential windows of susceptibility. The examination of neurobehavioral domains is particularly challenging given that traits emerge and change over time and subclinical nuances of neurobehavior are often unrecognized. To date, only a handful of epidemiological studies examining neurodevelopment have utilized multi-pollutant models in the investigation of heavy metals and EDCs. However, these studies were successful in identifying contaminants of importance from the exposure mixtures. Summary and Outlook Investigators are encouraged to broaden their focus to include more environmentally relevant mixtures of chemicals using advanced statistical approaches, particularly to aid in identifying potential mechanisms underlying associations.

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.)

Background: Toxicological studies indicate that poly- and perfluoroalkyl substances (PFAS) may be neurotoxic, but human studies have yet to provide compelling evidence for PFAS' impact on cognitive abilities., Objective: To test whether prenatal and childhood PFAS are associated with cognitive abilities at 8 years and whether sex modifies these associations., Methods: We included 221 mother-child pairs from the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort in Cincinnati, OH (USA). We quantified PFAS in maternal serum at 16 ± 3 weeks gestation and in child serum at 3 and 8 years. We used the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) at age 8 years, assessing Full Scale IQ (FSIQ), verbal comprehension, perceptual reasoning, working memory, and processing speed. We used multiple informant models to estimate covariate-adjusted differences in WISC-IV scores by repeated ln-transformed PFAS., Results: Prenatal and childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were not associated with WISC-IV measures. We observed an increase of 4.1-points (95% CI 0.3, 8.0) and 5.7-points (95% CI 1.2, 10.2) in working memory with 1-ln unit increase in prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA), respectively. In addition, PFNA at 3 years was associated with better FSIQ and perceptual reasoning. Child sex modified the relationship between prenatal PFOA and FSIQ; the association was positive in females only. Sex also modified the association between concurrent PFOS and FSIQ, with males having higher scores., Conclusion: We did not observe adverse associations between prenatal and childhood PFAS and cognitive function at age 8 years., (Copyright © 2019 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: Prenatal polybrominated diphenyl ether (PBDE) exposure has been associated with decrements in IQ and increased attention deficit/hyperactivity disorder related behaviors in children; however, data are limited for the role of postnatal exposures., Objectives: We investigated the association between a series of childhood PBDE concentrations and Full-Scale Intelligence Quotient (FSIQ) and externalizing problems at 8 years., Methods: We used data from 208 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort. Child serum PBDEs were measured at 1, 2, 3, 5, and 8 years; missing serum PBDE concentrations were estimated via multiple imputation. The Wechsler Intelligence Scales for Children-IV and the Behavior Assessment System for Children-2 was used to assess intelligence and externalizing behavior, respectively, in children at 8 years. We used multiple informant models to estimate associations between repeated lipid-adjusted PBDEs and child neurobehavior and to test for windows of susceptibility., Results: Postnatal exposure to PBDE congeners (- 28, - 47, - 99, - 100, and - 153) at multiple ages was inversely associated with FSIQ at 8 years. For instance, a 10-fold increase in BDE-153 concentrations at 2, 3, 5, and 8 years were all related to lower FSIQ at age 8 (β for 3 years: - 7.7-points, 95% CI - 12.5, - 2.9; β for 8 years: - 5.6-points, 95% CI - 10.8, - 0.4). Multiple PBDE congeners at 8 years were associated with increased hyperactivity and aggressive behaviors at 8 years., Conclusions: Postnatal PBDE exposure was associated with decrements in FSIQ and increases in hyperactivity and aggressive behaviors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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: 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]

Nitrosatable drugs, such as secondary or tertiary amines and amides, form N-nitroso compounds in the presence of nitrite. Various N-nitroso compounds have been associated with neural tube defects in animal models. Using data from the National Birth Defects Prevention Study, the authors examined nitrosatable drug exposure 1 month before and 1 month after conception in 1,223 case mothers with neural tube defect-affected pregnancies and 6,807 control mothers who delivered babies without major congenital anomalies from 1997 to 2005. Nitrite intakes were estimated from mothers’ responses to a food frequency questionnaire. After adjustment for maternal race/ethnicity, educational level, and folic acid supplementation, case women were more likely than were control women to have taken tertiary amines (odds ratio = 1.60, 95% confidence interval (CI): 1.31, 1.95). This association was strongest with anencephalic births (odds ratio = 1.96, 95% CI: 1.40, 2.73); odds ratios associated with tertiary amines from the lowest tertile of nitrite intake to the highest tertile were 1.16 (95% CI: 0.59, 2.29), 2.19 (95% CI: 1.25, 3.86), and 2.51 (95% CI: 1.45, 4.37), respectively. Odds ratios for anencephaly with nitrosatable drug exposure were reduced among women who also took daily vitamin supplements that contained vitamin C. Prenatal exposure to nitrosatable drugs may increase the risk of neural tube defects, especially in conjunction with a mother’s higher dietary intake of nitrites, but vitamin C might modulate this association. [ABSTRACT FROM PUBLISHER]