Deborah H Bennett1, Stefanie A Busgang2, Kurunthachalam Kannan3, Patrick J Parsons4, Mari Takazawa5, Christopher D Palmer4, Rebecca J Schmidt6, John T Doucette2, Julie B Schweitzer7, Chris Gennings2, Irva Hertz-Picciotto6. 1. Department of Public Health Sciences, School of Medicine, University of California at Davis (UC Davis), Davis, CA, USA. Electronic address: dhbennett@ucdavis.edu. 2. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 3. Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Albany, NY, USA; Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA; Department of Pediatrics and Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA. 4. Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Albany, NY, USA; Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA. 5. Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Albany, NY, USA. 6. Department of Public Health Sciences, School of Medicine, University of California at Davis (UC Davis), Davis, CA, USA; UC Davis MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, UC Davis, Sacramento, CA, USA. 7. UC Davis MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, UC Davis, Sacramento, CA, USA; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California at Davis (UC Davis), Sacramento, CA, USA.
Abstract
OBJECTIVE: To determine if higher exposures measured in early childhood to environmental phenols, phthalates, pesticides, and/or trace elements, are associated with increased odds of having a diagnosis of Autism Spectrum Disorder (ASD), Developmental Delay (DD), or Other Early Concerns (OEC) compared to typically developing children (TD). METHODS: This study included 627 children between the ages of 2-5 who participated in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Urine samples were collected at the same study visit where diagnostic assessments to confirm diagnosis indicated during the recruitment process were performed. Adjusted multinomial regression models of each chemical with diagnosis as the outcome were conducted. Additionally, two methods were used to analyze mixtures: repeated holdout multinomial weighted quantile sum (WQS) regression for each chemical class; and a total urinary mixture effect was assessed with repeated holdout random subset WQS. RESULTS: Many urinary chemicals were associated with increased odds of ASD, DD or OEC compared to TD; however, most did not remain significant after false discovery rate adjustment. Repeated holdout WQS indices provided evidence for associations of both a phenol/paraben mixture effect and a trace element mixture effect on DD independently. In analyses adjusted for confounders and other exposures, results suggested an association of a pesticide mixture effect with increased risk for ASD. Results also suggested associations of a total urinary mixture with greater odds of both ASD and DD separately. CONCLUSION: Higher concentrations of urinary biomarkers were associated with ASD, DD, and OEC compared to TD, with consistency of the results comparing single chemical analyses and mixture analyses. Given that the biospecimens used for chemical analysis were generally collected many months after diagnoses were made, the direction of any causal association is unknown. Hence findings may reflect higher exposures among children with non-typical development than TD children due to differences in behaviors, metabolism, or toxicokinetics.
OBJECTIVE: To determine if higher exposures measured in early childhood to environmental phenols, phthalates, pesticides, and/or trace elements, are associated with increased odds of having a diagnosis of Autism Spectrum Disorder (ASD), Developmental Delay (DD), or Other Early Concerns (OEC) compared to typically developing children (TD). METHODS: This study included 627 children between the ages of 2-5 who participated in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Urine samples were collected at the same study visit where diagnostic assessments to confirm diagnosis indicated during the recruitment process were performed. Adjusted multinomial regression models of each chemical with diagnosis as the outcome were conducted. Additionally, two methods were used to analyze mixtures: repeated holdout multinomial weighted quantile sum (WQS) regression for each chemical class; and a total urinary mixture effect was assessed with repeated holdout random subset WQS. RESULTS: Many urinary chemicals were associated with increased odds of ASD, DD or OEC compared to TD; however, most did not remain significant after false discovery rate adjustment. Repeated holdout WQS indices provided evidence for associations of both a phenol/paraben mixture effect and a trace element mixture effect on DD independently. In analyses adjusted for confounders and other exposures, results suggested an association of a pesticide mixture effect with increased risk for ASD. Results also suggested associations of a total urinary mixture with greater odds of both ASD and DD separately. CONCLUSION: Higher concentrations of urinary biomarkers were associated with ASD, DD, and OEC compared to TD, with consistency of the results comparing single chemical analyses and mixture analyses. Given that the biospecimens used for chemical analysis were generally collected many months after diagnoses were made, the direction of any causal association is unknown. Hence findings may reflect higher exposures among children with non-typical development than TD children due to differences in behaviors, metabolism, or toxicokinetics.
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