Prenatal exposure to mixtures of replacement flame retardant chemicals and children’s neuro-behavioral outcomes in a sample of children from socioeconomically disadvantaged communities

Abstract

BACKGROUND. Organophosphate ester flame retardants (OPFRs) are persistent organic chemicals that are commercially applied to a wide variety of consumer products including electronics, building materials, foam-based furniture and children’s clothing that have individually been shown to adversely impact neurodevelopmental outcomes including hyperactivity symptoms, working memory, IQ and depressive symptoms. METHODS. We quantified nine prenatal OPFR urinary metabolites [DPHP, DNBP+DIBP, BDCIPP, BCEP, BBOEP, BCIPP, BMPP, BEHP and DPRP] by HPLC-MS/MS in samples from participants in the MADRES cohort--an ongoing pregnancy cohort in urban Los Angeles. Detection frequencies ranged from 99.8% for DPHP to 24.2% for DPRP. Specific-gravity adjusted OPFR metabolites detected in 60% or greater samples [DPHP, DNBP+DIBP, BDCIPP, BCEP, and BBOEP] were modeled continuously and log transformed, and values ≤ LOD were imputed as LOD/√2. The remaining four metabolites were modeled as detect/non-detect [BCIPP, BMPP, BEHP, and DPRP]. We assessed prenatal OPFR exposure associations with neurodevelopmental outcomes from the Child Behavior Checklist 1.5/5 in 151 predominantly Hispanic/Latino (~78%) children at age 3 years. RESULTS. We found significant associations between several OPFR metabolite concentrations and neurobehavioral outcomes in single metabolite adjusted models [e.g., a 10% increase in DNBP+DIBP concentration was associated with a 3.3% (95% CI 0.02%-6.49%) increase in internalizing symptoms score and a 4.8% (0.82%-8.95%) increase in DSM pervasive symptoms score]. However, exposure to a particular compound does not occur in isolation; thus it is critical that multiple exposures be considered jointly in human studies. We will discuss various analytical approaches to quantify the effects of environmental mixtures and apply them to understand multiple OPFR chemical exposure effects on early childhood neurobehavioral outcomes in a highly exposed, socioeconomically disadvantaged population. CONCLUSIONS. The application of mixtures methods will yield important insight into the conditional associations of co-exposures and enhance health risk assessment for child neurodevelopmental outcomes. KEYWORDS. Neurodevelopment, children, chemical mixtures