Mathilde Lizé1, Christine Monfort2, Florence Rouget3, Gwendolina Limon4, Gaël Durand5, Hélène Tillaut6, Cécile Chevrier7. 1. Université Rennes 1, CHU Rennes, Irset (institut de recherche en santé, environnement et travail), UMR_S 1085, F-35000, Rennes, France. Electronic address: mathilde.lize@chu-rennes.fr. 2. Université Rennes 1, CHU Rennes, Irset (institut de recherche en santé, environnement et travail), UMR_S 1085, F-35000, Rennes, France. Electronic address: christine.monfort@univ-rennes1.fr. 3. CHU Rennes, Université Rennes 1, Inserm, EHESP, Irset (institut de recherche en santé, environnement et travail), UMR_S 1085, F-35000 Rennes, France. Electronic address: florence.rouget@univ-rennes1.fr. 4. LABOCEA (Laboratoire public Conseil, Expertise et Analyse in Brittany), F-29280, Plouzané, France. Electronic address: gwendolina.limon@labocea.fr. 5. LABOCEA (Laboratoire public Conseil, Expertise et Analyse in Brittany), F-29280, Plouzané, France. Electronic address: gael.durand@labocea.fr. 6. Université Rennes 1, Inserm, EHESP, Irset (institut de Recherche en santé, environnement et travail), UMR_S 1085, F-35000, Rennes, France. Electronic address: helene.tillaut@univ-rennes1.fr. 7. Université Rennes 1, Inserm, EHESP, Irset (institut de Recherche en santé, environnement et travail), UMR_S 1085, F-35000, Rennes, France. Electronic address: cecile.chevrier@univ-rennes1.fr.
Abstract
BACKGROUND: Organophosphate (OP) pesticides act by inhibiting acetylcholinesterase activity at synaptic junctions and have already been linked with deleterious effects on neurodevelopment, including autism spectrum disorders (ASD). OBJECTIVES: To investigate the association of prenatal exposure to OP pesticides with traits related to ASD in 11-year-old children. METHODS: The "Childhood Autism Spectrum Test" (CAST) parent questionnaire was used to screen for autistic traits in 792 children from the French PELAGIE cohort. Prenatal maternal urine samples were collected <19 weeks of gestation in which metabolites of organophosphate insecticides were assessed for 185 of them. Negative binomial regression models were performed to explore the association between the CAST score and 8 groups of urine components, adjusted for potential ASD risk factors. RESULTS: In these urine samples, dialkylphosphates (DAP) were detected most often (>80%), terbufos and its metabolites least often (<10%). No association with ASD was found for DAP, terbufos or its metabolites. Incidence rate ratios (IRRs) increased with maternal urinary diazinon concentrations, from 1.11 (95% CI: 0.87-1.42) to 1.17 (95% CI: 0.94-1.46). Higher CAST scores were statistically significantly associated with the maternal urine samples in which chlorpyrifos or two of its metabolites (chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol) were detected. The IRR for exposure to chlorpyrifos or chlorpyrifos-oxon was 1.27 (95%CI: 1.05-1.52) among all children, and 1.39 (95%CI: 1.07-1.82) among boys. CONCLUSION: These findings suggest an increase in autistic traits among 11-year-old children in association with prenatal maternal exposure to chlorpyrifos and possibly diazinon. These associations were previously suspected in the literature, in particular for chlorpyrifos. Further work establishing the causal mechanisms behind these risk association is needed.
BACKGROUND: Organophosphate (OP) pesticides act by inhibiting acetylcholinesterase activity at synaptic junctions and have already been linked with deleterious effects on neurodevelopment, including autism spectrum disorders (ASD). OBJECTIVES: To investigate the association of prenatal exposure to OP pesticides with traits related to ASD in 11-year-old children. METHODS: The "Childhood Autism Spectrum Test" (CAST) parent questionnaire was used to screen for autistic traits in 792 children from the French PELAGIE cohort. Prenatal maternal urine samples were collected <19 weeks of gestation in which metabolites of organophosphate insecticides were assessed for 185 of them. Negative binomial regression models were performed to explore the association between the CAST score and 8 groups of urine components, adjusted for potential ASD risk factors. RESULTS: In these urine samples, dialkylphosphates (DAP) were detected most often (>80%), terbufos and its metabolites least often (<10%). No association with ASD was found for DAP, terbufos or its metabolites. Incidence rate ratios (IRRs) increased with maternal urinary diazinon concentrations, from 1.11 (95% CI: 0.87-1.42) to 1.17 (95% CI: 0.94-1.46). Higher CAST scores were statistically significantly associated with the maternal urine samples in which chlorpyrifos or two of its metabolites (chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol) were detected. The IRR for exposure to chlorpyrifos or chlorpyrifos-oxon was 1.27 (95%CI: 1.05-1.52) among all children, and 1.39 (95%CI: 1.07-1.82) among boys. CONCLUSION: These findings suggest an increase in autistic traits among 11-year-old children in association with prenatal maternal exposure to chlorpyrifos and possibly diazinon. These associations were previously suspected in the literature, in particular for chlorpyrifos. Further work establishing the causal mechanisms behind these risk association is needed.