Search

Background: 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., Methods: 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., Results: 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., Conclusions: In-utero exposure to OPEs and RBFRs may be a risk factor for adverse respiratory outcomes in childhood, depending on the timing of exposure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph M. Braun has been compensated as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Children are highly exposed to flame retardants in indoor environments, partly through inhalation. However, the associations of early life exposure to novel organophosphate (OPFRs) and replacement brominated flame retardants (RBFRs) with adverse respiratory outcomes during childhood are unclear., Methods: We used a prospective birth cohort of 234 children recruited from the greater Cincinnati, Ohio metropolitan area between 2003 and 2006. OPFRs and RBFRs were analyzed in dust sampled from the homes' main activity room and the children's bedroom floor at child age 1 year. Caregivers reported subsequent respiratory symptoms every six months until child age 5 years and we measured forced expiratory volume in 1 s as well as peak expiratory flow (PEF) at child age 5 years. We performed generalized estimating equations and linear regression modeling adjusted for covariates to examine the exposure-outcome associations., Results: Geometric means (GMs) (standard error [SE]) for dust concentrations were 10.27 (0.63) μg/g for total OPFRs (ΣOPFRs) and 0.48 (0.04) μg/g for total RBFRs (ΣRBFRs); GMs (SE) for dust loadings were 2.82 (0.26) μg/m 2 for ΣOPFRs and 0.13 (0.01) μg/m 2 for ΣRBFRs. Dust ∑OPFRs concentrations at age 1 year were associated with higher subsequent risks of wheezing (relative risk [RR]: 1.68, 95% confidence interval [CI]: 1.20-2.34), respiratory infections (RR: 4.01, 95% CI: 1.95-8.24), and hay fever/allergies (RR: 1.33, 95% CI: 1.10-1.60), whereas ∑OPFRs dust loadings at age 1 year were associated with higher risks of subsequent respiratory infections (RR: 1.87, 95% CI: 1.05-3.34) and hay fever/allergies (RR: 1.34, 95% CI: 1.19-1.51). PEF (mL/min) was lower with higher ∑OPFRs dust loadings (β: -12.10, 95% CI: -21.10, -3.10) and with the RBFR bis(2-ethylhexyl) tetrabromophthalate (β: -9.05, 95% CI: -17.67, -0.43)., Conclusions: Exposure to OPFRs and RBFRs during infancy may be a risk factor for adverse respiratory outcomes during childhood., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph M. Braun has been compensated as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.)

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: Exposure to particulate matter, particularly with aerodynamic diameter < 2.5 µm (PM 2.5 ), may increase inflammation and oxidative stress in pregnant women and affect fetal growth. We examined trimester specific PM 2.5 exposure levels and small for gestational age (SGA) using the statewide birth registry of Ohio from 2007 to 2010., Methods: Exposure to PM 2.5 in each trimester and for each gestational week was determined using data from 57 Environmental Protection Agency network monitoring stations across the state of Ohio. We restricted the data to 224,921 singleton live births, with a gestational age of 20-42 weeks, no genetic disorders or congenital abnormalities, and who had home addresses within a 10 km radius of any PM 2.5 monitoring station. We estimated odds ratios of SGA using Generalized Linear Models (GLMs) and Distributed Lag Models (DLMs), and adjustment for maternal age, race, education, parity, body mass index, insurance type, tobacco use, prenatal care initiation, birth year, season of birth, and sex of the baby., Results: Mean PM 2.5 levels during the entire pregnancy were 13.03 µg/m 3 with a standard deviation of 1.57 µg/m 3 . Covariates adjusted odds ratios and 95% confidence intervals of a 10 µg/m 3 increase in PM 2.5 levels with a 10 km buffer radius for SGA and trimesters modeled separately were 0.94 (0.88, 1.00) for the first trimester, 0.93 (0.86, 1.00) for the second trimester, 1.07 (1.00, 1.15) for the third trimester, and 0.92 (0.81, 1.06) for the entire pregnancy. When a 5 km buffer radius was used, adjusted odds ratios and 95% confidence intervals for SGA were 0.97 (0.89, 1.05) for the first trimester, 0.96 (0.88, 1.05) for the second trimester, 1.09 (1.02, 1.17) for the third trimester, and 0.99 (0.85, 1.14) for the overall pregnancy, indicating sensitivity to buffer choice. DLMs showed gestational weeks 30-35 to be a particular window of vulnerability., Conclusion: Increasing exposure to PM 2.5 during the third trimester of pregnancy was associated with a small increase in risk of SGA in this population-based study. Selection of a buffer radius significantly impacted our results in the first trimester, but not in the third trimester., (Copyright © 2019 Elsevier Inc. All rights reserved.)