Prenatal and postnatal exposure to organophosphate esters and replacement flame retardant mixtures and childhood respiratory outcomes

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.