Claire Philippat1, Jacqueline Barkoski2, Daniel J Tancredi3, Bill Elms2, Dana Boyd Barr4, Sally Ozonoff5, Deborah H Bennett2, Irva Hertz-Picciotto6. 1. Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, University Grenoble Alpes, 38000 Grenoble, France. Electronic address: claire.philippat@inserm.fr. 2. Department of Public Health Sciences, University of California, Davis, CA, USA. 3. Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA 95817, USA; Center for Healthcare Policy and Research, University of California Davis Medical Center, Sacramento, CA 95817, USA. 4. Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. 5. MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis, Sacramento, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, CA 95817, USA. 6. Department of Public Health Sciences, University of California, Davis, CA, USA; MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California, Davis, Sacramento, CA, USA.
Abstract
INTRODUCTION: Organophosphates are widely used pesticides that have been shown to affect child neurodevelopment. Previous studies that explored their potential effects on Autism Spectrum Disorder (ASD) relied either on proxies of external exposure or on questionnaires completed by the parents to identify autism-like behaviors but did not provide a clinical diagnosis of ASD. AIMS: We studied the associations between prenatal biologic markers for exposure to organophosphate pesticides and the risk of having a child with ASD or other developmental concerns (ODC). METHOD: We analyzed 203 mother-child pairs of the ongoing MARBLES (Markers of Autism Risk in Babies - Learning Early Signs) mother-child cohort, which enrolls mothers who are either pregnant or planning a pregnancy and whose expected child has an elevated risk to develop ASD. Seven metabolites of organophosphate pesticides were assessed in repeated urine samples collected during pregnancy. At 36 months, children were assessed with intruments measuring cognitive function and adaptive behaviors, and with two gold-standard diagnostic instruments for ASD: the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. Children were classified in one of the following groups: ASD (n = 46), ODC (n = 55) and typically developing (TD, n = 102). RESULTS: After adjustment for potential confounders, organophosphate metabolite concentrations were not associated with an increased risk of ASD or ODC when boys and girls were studied together. After stratification by sex, dimethylthiophosphate (DMTP) pregnancy concentration tended to be associated with an increased ASD risk among girls (OR for a doubling in the DMTP concentration: 1.64 (95%CI, 0.95; 2.82)) but not among boys (OR: 0.84, 95%CI: 0.63; 1.11). DISCUSSION: This is the first study of clinically confirmed diagnoses of ASD that utilized repeated measurements of organophosphate metabolites during pregnancy to explore the associations between these pesticides and ASD risk in children. The association we observed among girls, as well as the lack of association in boys, need to be replicated in further studies with similar design and larger sample size. In light of the higher baseline risk for ASD in this cohort, generalizability to children lacking a first degree relative affected by ASD is unknown.
INTRODUCTION: Organophosphates are widely used pesticides that have been shown to affect child neurodevelopment. Previous studies that explored their potential effects on Autism Spectrum Disorder (ASD) relied either on proxies of external exposure or on questionnaires completed by the parents to identify autism-like behaviors but did not provide a clinical diagnosis of ASD. AIMS: We studied the associations between prenatal biologic markers for exposure to organophosphate pesticides and the risk of having a child with ASD or other developmental concerns (ODC). METHOD: We analyzed 203 mother-child pairs of the ongoing MARBLES (Markers of Autism Risk in Babies - Learning Early Signs) mother-child cohort, which enrolls mothers who are either pregnant or planning a pregnancy and whose expected child has an elevated risk to develop ASD. Seven metabolites of organophosphate pesticides were assessed in repeated urine samples collected during pregnancy. At 36 months, children were assessed with intruments measuring cognitive function and adaptive behaviors, and with two gold-standard diagnostic instruments for ASD: the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. Children were classified in one of the following groups: ASD (n = 46), ODC (n = 55) and typically developing (TD, n = 102). RESULTS: After adjustment for potential confounders, organophosphate metabolite concentrations were not associated with an increased risk of ASD or ODC when boys and girls were studied together. After stratification by sex, dimethylthiophosphate (DMTP) pregnancy concentration tended to be associated with an increased ASD risk among girls (OR for a doubling in the DMTP concentration: 1.64 (95%CI, 0.95; 2.82)) but not among boys (OR: 0.84, 95%CI: 0.63; 1.11). DISCUSSION: This is the first study of clinically confirmed diagnoses of ASD that utilized repeated measurements of organophosphate metabolites during pregnancy to explore the associations between these pesticides and ASD risk in children. The association we observed among girls, as well as the lack of association in boys, need to be replicated in further studies with similar design and larger sample size. In light of the higher baseline risk for ASD in this cohort, generalizability to children lacking a first degree relative affected by ASD is unknown.
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