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      Maternal Residence Near Agricultural Pesticide Applications and Autism Spectrum Disorders among Children in the California Central Valley

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          Abstract

          Background

          Ambient levels of pesticides (“pesticide drift”) are detectable at residences near agricultural field sites.

          Objective

          Our goal was to evaluate the hypothesis that maternal residence near agricultural pesticide applications during key periods of gestation could be associated with the development of autism spectrum disorders (ASD) in children.

          Methods

          We identified 465 children with ASD born during 1996–1998 using the California Department of Developmental Services electronic files, and matched them by maternal date of last menstrual period to 6,975 live-born, normal-birth-weight, term infants as controls. We determined proximity to pesticide applications using California Department of Pesticide Regulation records refined using Department of Water Resources land use polygons. A staged analytic design applying a priori criteria to the results of conditional logistic regressions was employed to exclude associations likely due to multiple testing error.

          Results

          Of 249 unique hypotheses, four that described organochlorine pesticide applications—specifically those of dicofol and endosulfan—occurring during the period immediately before and concurrent with central nervous system embryogenesis (clinical weeks 1 through 8) met a priori criteria and were unlikely to be a result of multiple testing. Multivariate a posteriori models comparing children of mothers living within 500 m of field sites with the highest nonzero quartile of organochlorine poundage to those with mothers not living near field sites suggested an odds ratio for ASD of 6.1 (95% confidence interval, 2.4–15.3). ASD risk increased with the poundage of organochlorine applied and decreased with distance from field sites.

          Conclusions

          The association between residential proximity to organochlorine pesticide applications during gestation and ASD among children should be further studied.

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          Most cited references67

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          Sex differences in the brain: implications for explaining autism.

          Empathizing is the capacity to predict and to respond to the behavior of agents (usually people) by inferring their mental states and responding to these with an appropriate emotion. Systemizing is the capacity to predict and to respond to the behavior of nonagentive deterministic systems by analyzing input-operation-output relations and inferring the rules that govern such systems. At a population level, females are stronger empathizers and males are stronger systemizers. The "extreme male brain" theory posits that autism represents an extreme of the male pattern (impaired empathizing and enhanced systemizing). Here we suggest that specific aspects of autistic neuroanatomy may also be extremes of typical male neuroanatomy.
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            Controlling the familywise error rate in functional neuroimaging: a comparative review.

            Functional neuroimaging data embodies a massive multiple testing problem, where 100,000 correlated test statistics must be assessed. The familywise error rate, the chance of any false positives is the standard measure of Type I errors in multiple testing. In this paper we review and evaluate three approaches to thresholding images of test statistics: Bonferroni, random field and the permutation test. Owing to recent developments, improved Bonferroni procedures, such as Hochberg's methods, are now applicable to dependent data. Continuous random field methods use the smoothness of the image to adapt to the severity of the multiple testing problem. Also, increased computing power has made both permutation and bootstrap methods applicable to functional neuroimaging. We evaluate these approaches on t images using simulations and a collection of real datasets. We find that Bonferroni-related tests offer little improvement over Bonferroni, while the permutation method offers substantial improvement over the random field method for low smoothness and low degrees of freedom. We also show the limitations of trying to find an equivalent number of independent tests for an image of correlated test statistics.
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              Pervasive developmental disorders in preschool children.

              Prevalence rates of autism-spectrum disorders are uncertain, and speculation that their incidence is increasing continues to cause concern. To estimate the prevalence of pervasive developmental disorders (PDDs) in a geographically defined population of preschool children. Survey conducted July 1998 to June 1999 in Staffordshire, England. The area's 15 500 children aged 2.5 to 6.5 years were screened for developmental problems. Children with symptoms suggestive of a PDD were intensively assessed by a multidisciplinary team, which conducted standardized diagnostic interviews and administered psychometric tests. Prevalence estimates for subtypes of PDDs. A total of 97 children (79.4% male) were confirmed to have a PDD. The prevalence of PDDs was estimated to be 62.6 (95% confidence interval, 50.8-76.3) per 10 000 children. Prevalences were 16.8 per 10 000 for autistic disorder and 45.8 per 10 000 for other PDDs. The mean age at diagnosis was 41 months, and 81% were originally referred by health visitors (nurse specialists). Of the 97 children with a PDD, 25.8% had some degree of mental retardation and 9.3% had an associated medical condition. Our results suggest that rates of PDD are higher than previously reported. Methodological limitations in existing epidemiological investigations preclude interpretation of recent high rates as indicative of increased incidence of these disorders although this hypothesis requires further rigorous testing. Attention is nevertheless drawn to the important needs of a substantial minority of preschool children.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                October 2007
                30 July 2007
                : 115
                : 10
                : 1482-1489
                Affiliations
                [1 ] Public Health Institute, Oakland, California, USA
                [2 ] California Department of Health Services, Richmond, California, USA
                [3 ] School of Public Health, University of California, Berkeley, California, USA
                Author notes
                Address correspondence to E.M. Roberts, Public Health Institute, California Department of Health Services, 850 Marina Bay Parkway, Building P, 3rd Floor, Richmond, CA 94804 USA. Telephone (510) 620–3699. Fax (510) 620–3720. E-mail: erobert1@ 123456dhs.ca.gov

                The authors acknowledge M. Wong, of the Public Health Institute, and the Central Valley/South Coast Children’s Environmental Health Tracking Advisory Group.

                The authors declare they have no competing financial interests.

                Article
                ehp0115-001482
                10.1289/ehp.10168
                2022638
                17938740
                76b6ad33-e535-428a-a5c8-e65699a5c01a
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 13 February 2007
                : 16 July 2007
                Categories
                Research
                Children's Health

                Public health
                methods,organochlorines,autism spectrum disorders,health surveillance,pesticides
                Public health
                methods, organochlorines, autism spectrum disorders, health surveillance, pesticides

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