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Introduction: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. Method: We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. Results: Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. Conclusion: In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes. [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]

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. 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. 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/m2 for ΣOPFRs and 0.13 (0.01) μg/m2 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). Exposure to OPFRs and RBFRs during infancy may be a risk factor for adverse respiratory outcomes during childhood. • We studied the associations of house dust organophosphate (OPFRs) and replacement brominated flame retardants (RBFRs) during infancy with adverse respiratory outcomes. • Dust OPFRs and RBFRs levels were associated with higher risks of subsequent wheeze, respiratory infections, and/or hay fever/allergies. • Peak expiratory flow (PEF) during childhood was lower with higher OPFRs dust loadings in infancy. • PEF during childhood was also lower with bis(2-ethylhexyl) tetrabromophthalate dust loadings in infancy. [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]

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]

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]

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]