Childhood and In utero Exposure to Organophosphate and Replacement Brominated Flame Retardants and Child Respiratory Outcomes

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PROJECT SUMMARY Due to environmental and health concerns, polybrominated diphenyl ethers (PBDEs) previously used as flame retardants were phased out in the U.S. starting 2004 and substituted with organophosphate (OPFRs) and replacement brominated flame retardants (RBFRs). Inhalation of contaminated house dust and vapor as a route of exposure to these chemicals has raised concerns for respiratory health due to their ability to cause irritation, oxidative stress, bronchoconstriction, endocrine disruption, and epigenetic changes. Yet, the association of these exposures with respiratory outcomes is unknown, especially in children who may be at higher risk due to higher exposure to the chemicals. The goal of this project is to test the hypothesis that childhood and in utero exposure to OPFRs and RBFRs is associated with respiratory symptoms and impaired lung function. We will use the Health Outcomes and Measures of the Environment (HOME) Study, a multiethnic pregnancy and birth cohort from the Greater Cincinnati, Ohio, with environmental exposures similar to U.S. national averages. Exposure will include dust OPFRs and RBFRs measured at child age 1 year and prenatally at 20 weeks of gestation as well as urine OPFR esters measured annually for the first 3 years and prenatally at 16 and 26 weeks of gestation and at delivery. Respiratory outcomes will include symptoms assessed biannually until age 5 years and forced expiratory volume in 1 second (FEV1) measured at ages 4 and 5 years. DNA methylation of cord-blood was profiled using the Illumina Infinium MethylationEPIC BeadChip array. The 3 specific aims to test our hypothesis will be to determine 1) the association of childhood and in utero exposure to OPFRs and RBFRs with adverse respiratory outcomes; 2) the association of OPFRs and RBFRs interactions and mixtures with adverse respiratory outcomes for prenatal and postnatal exposures; and 3) the cord blood DNA methylation changes related to prenatal OPFRs and RBFRs associated with children’s respiratory outcomes. This innovative project will be the first prospective study on flame retardants and respiratory health to include RBFRs, prenatal exposure assessments, and objective measures of lung function. Upon completion, we will have identified the replacement flame retardants, alone or in mixtures, associated with adverse respiratory outcome. We will have also determined the exposure cut-offs for increased respiratory risk, the windows of susceptibility, and the DNA methylation changes mediating the associations.