Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control studyBMJ 2019; 364 doi: https://doi.org/10.1136/bmj.l962 (Published 20 March 2019) Cite this as: BMJ 2019;364:l962
- Ondine S von Ehrenstein, associate professor1 2,
- Chenxiao Ling, research assistant2,
- Xin Cui, research assistant2 3 4,
- Myles Cockburn, professor5,
- Andrew S Park, research assistant2,
- Fei Yu, researcher6,
- Jun Wu, associate professor7,
- Beate Ritz, professor2 8 9
- 1Department of Community Health Sciences, Fielding School of Public Health, University of California, PO Box 951772, Los Angeles, CA 90095-1772, USA
- 2Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA
- 3Perinatal Epidemiology and Health Outcomes Research Unit, Division of Neonatology, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children’s Hospital, Palo Alto, CA, USA
- 4California Perinatal Quality Care Collaborative, Palo Alto, CA, USA
- 5Preventive Medicine, University of Southern California, Los Angeles, CA, USA
- 6Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA
- 7Program in Public Health, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, CA, USA
- 8Department of Environmental Health Sciences, Fielding School of Public Health, University of California, Los Angeles, CA, USA
- 9Department of Neurology, Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Correspondence to: O von Ehrenstein
- Accepted 11 February 2019
Objective To examine associations between early developmental exposure to ambient pesticides and autism spectrum disorder.
Design Population based case-control study.
Setting California’s main agricultural region, Central Valley, using 1998-2010 birth data from the Office of Vital Statistics.
Population 2961 individuals with a diagnosis of autism spectrum disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, revised (up to 31 December 2013), including 445 with intellectual disability comorbidity, were identified through records maintained at the California Department of Developmental Services and linked to their birth records. Controls derived from birth records were matched to cases 10:1 by sex and birth year.
Exposure Data from California state mandated Pesticide Use Reporting were integrated into a geographic information system tool to estimate prenatal and infant exposures to pesticides (measured as pounds of pesticides applied per acre/month within 2000 m from the maternal residence). 11 high use pesticides were selected for examination a priori according to previous evidence of neurodevelopmental toxicity in vivo or in vitro (exposure defined as ever v never for each pesticide during specific developmental periods).
Main outcome measure Odds ratios and 95% confidence intervals using multivariable logistic regression were used to assess associations between pesticide exposure and autism spectrum disorder (with or without intellectual disabilities) in offspring, adjusting for confounders.
Results Risk of autism spectrum disorder was associated with prenatal exposure to glyphosate (odds ratio 1.16, 95% confidence interval 1.06 to 1.27), chlorpyrifos (1.13, 1.05 to 1.23), diazinon (1.11, 1.01 to 1.21), malathion (1.11, 1.01 to 1.22), avermectin (1.12, 1.04 to 1.22), and permethrin (1.10, 1.01 to 1.20). For autism spectrum disorder with intellectual disability, estimated odds ratios were higher (by about 30%) for prenatal exposure to glyphosate (1.33, 1.05 to 1.69), chlorpyrifos (1.27, 1.04 to 1.56), diazinon (1.41, 1.15 to 1.73), permethrin (1.46, 1.20 to 1.78), methyl bromide (1.33, 1.07 to 1.64), and myclobutanil (1.32, 1.09 to 1.60); exposure in the first year of life increased the odds for the disorder with comorbid intellectual disability by up to 50% for some pesticide substances.
Conclusion Findings suggest that an offspring’s risk of autism spectrum disorder increases following prenatal exposure to ambient pesticides within 2000 m of their mother’s residence during pregnancy, compared with offspring of women from the same agricultural region without such exposure. Infant exposure could further increase risks for autism spectrum disorder with comorbid intellectual disability.
Contributors: OSvE directed the analysis and drafted the manuscript. OSvE and BR contributed to design of the study and interpretation of the results. CL carried out the main statistical analysis. XC contributed to setting up the database and quality control. MC was responsible for the geographical information system methods. FY contributed to the statistical analyses. CL, MC, and ASP contributed to exposure estimation. JW estimated the air pollution exposure. All authors commented on drafts and read and approved the final manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. OSvE is the guarantor.
Funding: This work was supported by the US National Institute of Environmental Health Sciences (grants R21ES022389; R21ES025558). The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funders.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the National Institute of Environmental Health Sciences for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; BR has been acting as an expert witness/consultant in a lawsuit for the plaintiffs against Monsanto in non-Hodgkins lymphoma litigation concerning glyphosate; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This research was approved by the University of California, Los Angeles Office of the Human Research Protection Program and the California Committee for the Protection of Human Subjects, and was exempt from informed consent requirements as there was no contact with the study population.
Data sharing: No additional data are available.
The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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