Prenatal exposure to organophosphate pesticides and risk of autism spectrum disorders and other non-typical development at 3 years in a high-risk cohort

• Type of Material: Article
• Authors: Claire Philippat, University Grenoble Alpes; Jacqueline Barkoski, University of California Davis; Daniel J. Tancredi, University of California Davis; Bill Elms, University of California Davis; Dana Boyd Barr, Emory University; Sally Ozonoff, University of California Davis; Deborah H. Bennett, University of California Davis; Irva Hertz-Picciotto, University of California Davis
• Language: English
• Date: 2018-04-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier GmbH
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ijheh.2018.02.004
• Title of Journal or Parent Work: International Journal of Hygiene and Environmental Health
• ISSN: 1438-4639
• Volume: 221
• Issue: 3
• Start Page: 548
• End Page: 555
• Grant/Funding Information: This research was supported by the following grants: R01ES020392, R01ES014901, P42ES04699 and P01 ES011269 and by the U.S. Environmental Protection Agency (Grant 8354320), the UC Davis MIND Institute, and an unrestricted gift grant from the JB Johnson Foundation.; Claire Philippat is funded by a grant from Fondation de France (grant 2015-00059545).
• Keywords: Science & Technology; Infectious Diseases; CHAMACOS; Life Sciences & Biomedicine; Biomarkers; IN-UTERO; AGRICULTURAL PESTICIDE; Autism spectrum disorder; Prospective cohort; COMMUNICATION; Public, Environmental & Occupational Health; HUMAN URINE; Developmental concerns; MEXICAN-AMERICAN CHILDREN; PREGNANCY; Organophosphate pesticides; NEURODEVELOPMENT; Prenatal exposure; CHLORPYRIFOS; METABOLITES
• Research Categories: Health Sciences, Public Health; Psychology, Physiological

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.