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Background: Early life exposure to single organophosphate esters (OPEs) and replacement brominated flame retardants (RBFRs) has been associated with adverse childhood respiratory outcomes, but the effects of OPE and RBFR mixtures are unknown., Methods: 377 pregnant women were recruited to the Health Outcomes and Measures of Environment (HOME) Study from 2003 to 2006 in Cincinnati, Ohio and later delivered singleton infants. We measured house dust OPEs and RBFRs prenatally at 20 weeks of gestation and postnatally at child age of 12 months and urinary OPEs prenatally at 16 and 26 weeks of gestation and at delivery and postnatally at child ages of 12 and 24 months. We performed Quantile G-computation (QG-computation) and Bayesian Kernel Machine Regression (BKMR) to assess the association of the exposure mixtures with wheeze and hay fever by child age of 5 years and evaluate the individual exposure effects and their interactions within the mixtures., Results: In QG-computation, a quartile increase in all urinary OPEs sampled at age 12 months was associated with 16% higher risk of wheeze (RR: 1.16, 95% CI: 1.01, 1.35). In BKMR, mixtures of prenatal OPEs and RBFRs, urinary OPEs at 16 weeks of gestation or 12 months of age and prenatal average urinary OPEs were associated with higher risk of childhood wheeze. Mixtures of prenatal average urinary OPEs were positively associated with childhood hay fever. When other exposures were fixed at their median value, prenatal dust tris(2-chloroethyl) phosphate (TCEP) and urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were associated with higher hay fever risk, while dust prenatal tris(1-chloro-2-propyl) phosphate (TCIPP) was associated with lower risk., Conclusions: These results suggest that early life exposure to OPE and RBFR mixtures may be risk factors for adverse respiratory outcomes in childhood., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interestsJoseph M. Braun has been compensated as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water., (Copyright © 2024. Published by Elsevier Inc.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)