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

Eric M. Roberts; Paul B. English; Judith K. Grether; Gayle C. Windham; Lucia Somberg; Craig Wolff

Disclosures

Environ Health Perspect. 2007;115(10):1482-1489. 

In This Article

Abstract and Introduction

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.

"Autism" refers to a set of neurodevelopmental disorders that are characterized by impaired social interaction, restricted communication, and repetitive, stereotypic behaviors. The number of children reported as having autism spectrum disorders (ASD) has risen dramatically since the early 1990s. In the United States, some of this increase is attributable to changes in diagnosis and reporting, although this pattern is not uniform across all states (Shattuck 2005). Symptoms of classic autism do not typically become evident until early childhood, but current evidence is consistent with a pathogenic process originating during fetal development (Arndt et al. 2005; Hertz-Picciotto et al. 2006; Kemper and Bauman 1998; Nelson et al. 2001).

Many of the hypotheses regarding ASD pathogenesis involve a functional deficit caused by alterations to specific brain structures occurring in utero during defined temporal windows of vulnerability (Polleux and Lauder 2004). The lesions in question might result from genetic factors, environmental insults, or a combination of the two. A variety of lesions could give rise to a "final common pathway" to autism; ASD as currently defined may well include multiple disorders that have not yet been successfully differentiated.

A large number of widely used agricultural pesticides have known neurologic effects (Weiss et al. 2004), raising the possibility that gestational exposure to these compounds could play an etiologic role in ASD and related neurodevelopmental disorders. Most compounds are prone to "drift," and detectable levels in air samples are often measurable at locations beyond the site of application for extended periods afterwards (Kegley et al. 2003; Lee et al. 2002). Elevated levels of agricultural pesticides in household dust and their metabolites in urine have been associated with residential proximity to treated fields (Loewenherz et al. 1997; Lu et al. 2000; Simcox et al. 1995).

Studies of pediatric diseases and their associations with residential proximity or parental occupational exposure to pesticides have been accumulating, most notably for cancer (Birnbaum and Fenton 2002; Daniels et al. 1997; Feychting et al. 2001; Flower et al. 2004; Linet et al. 2003; Meinert et al. 2000; Olshan et al. 2000; Reynolds et al. 2002; Robison et al. 1995; Shannon 1998; Zahm and Devesa 1995) and, more recently, neurodevelopmental delay (Grandjean et al. 2005). Many environmental toxicants are conveyed transplacentally, and the blood–brain barrier remains relatively permeable to many of these compounds until well into the first year of life (Andersen et al. 2000). In general, experimental and epidemiologic evidence regarding pesticides and pediatric neurodevelopment is strikingly lacking, despite considerable knowledge about pesticide toxicity (particularly neurotoxicity) (Kamel and Hoppin 2004; Weiss et al. 2004).

We evaluated a series of hypotheses regarding an association between in utero residential "exposure" to specific agricultural pesticides (that is, maternal residence in close proximity to sites of application) and the development of ASD by linking existing databases using a retrospective case–control design. This study was conducted as part of a demonstration project of the utility of environmental public health tracking, an initiative funded by the Centers for Disease Control and Prevention (McGeehin et al. 2004) to generate clues for further etiologic study.

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