Prenatal levels of Polybrominated Diphenyl Ethers (PBDEs) in association with Autism Spectrum Disorder

Abstract

Introduction: Increasing evidence suggests prenatal exposure to polybrominated diphenyl ethers (PBDEs) has neurodevelopmental impacts, perhaps via thyroid hormone and immune system dysfunction. This raises the hypothesis that prenatal PBDE exposure may be associated with higher risk of autism spectrum disorder (ASD), but no studies of ASD diagnosis have examined this, to our knowledge. Methods: Using data from a large population-based case-control study in southern California, we examined PBDE levels measured in 2nd trimester maternal serum samples in association with offspring ASD (n=545) or intellectual disability (ID, n=181), relative to controls from the general population (n=418). Six PBDE congeners and their sum were categorized into quartiles (Q) and adjusted odds ratios (AOR) calculated. Results: Prenatal levels of most PBDE congeners were lower for children with ASD or ID than for controls. In adjusted analyses, reduced risks for ASD were observed with higher maternal PBDE levels (Q4 vs. Q1); for BDE153, AOR=0.56 (95% CI 0.38, 0.84) and for the sum, AOR=0.54 (95% CI 0.36, 0.80), with other congeners (BDE-47, 99, 100, and 153) showing consistent patterns. When stratified by child gender, the inverse associations were limited to boys, whereas odds ratios were elevated in girls, with BDE28 and, more so BDE47, approaching statistical significance (AOR=2.6; 95% CI 0.86, 7.8, and AOR=2.6; 95% CI 0.97, 7.2, respectively). For ID risk, similar overall and sex-specific patterns were seen with some congeners, but no associations were significant. Conclusions: Contrary to expectation, our primary analyses did not suggest increased risk of ASD or ID with higher prenatal PBDE levels; however, stratifying by child gender revealed striking differences that appeared stronger for ASD than ID. These findings therefore suggest the potential for sexual dimorphism, as has been demonstrated in animal studies, in neurodevelopmental effects of prenatal exposure to PBDEs.