Academic journal article Environmental Health Perspectives

Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses' Health Study II Participants

Academic journal article Environmental Health Perspectives

Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses' Health Study II Participants

Article excerpt


Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in communication and social skills beginning before 3 years of age. Although ASD etiology is poorly understood, environmental exposures during gestation in particular have been implicated in the etiology of ASD (Gardener et al. 2009; Larsson et al. 2005; Roberts et al. 2007).

Air pollution contains many toxicants known to affect neurological function and to have effects on the fetus in utero [U.S. Environmental Protection Agency (EPA) 2010]. Several recent studies have reported associations between perinatal exposure to air pollution and ASD in children. (Kalkbrenner et al. 2010; Palmer et al. 2009; Volk et al. 2011; Windham et al. 2006). In this study, we tested the hypothesis that perinatal exposure to hazardous air pollutants increases risk of ASD by estimating associations between the U.S. EPA-modeled levels of hazardous air pollutants at the time and place of birth and ASD in the children of participants in a national prospective longitudinal cohort, the Nurses' Health Study II, focusing our analysis on toxicants associated with ASD in prior studies.

In previous studies, metals (antimony, arsenic, cadmium, chromium, lead, mercury, manganese, nickel) (Palmer et al. 2009; Windham et al. 2006), styrene (Kalkbrenner et al. 2010), quinoline (Kalkbrenner et al. 2010), trichloroethylene (Windham et al. 2006), methylene chloride (Kalkbrenner et al. 2010; Windham et al. 2006), vinyl chloride (Windham et al. 2006), and diesel particulate matter (Volk et al. 2011; Windham et al. 2006) have been associated with ASD. U.S. EPA reviews have indicated that all of these pollutants have established or suspected effects on the nervous system and on the developing fetus from human or animal studies, except for nickel, which has no known effects on the nervous system, and quinoline, for which possible developmental effects have not been studied (U.S. EPA 2010). Arsenic, cadmium, chromium, mercury, methylene chloride, nickel, styrene, trichloroethylene, and vinyl chloride are also known or suspected mutagens (Agency for Toxic Substances and Disease Registry 2011), and de novo DNA mutations have been implicated in ASD etiology (Kinney et al. 2010; Sebat et al. 2007; Smith et al. 2009). Therefore, we focused on these pollutants a priori.

We also examined whether there are sex differences in associations between pollutants and ASD. Sex-specific etiological subtypes of ASD (Fombonne 2007) and sex differences in the association of environmental toxicants with executive function (Braun et al. 2011) have been suggested by prior research. The one previous study that reported associations between exposure to pollutants and ASD according to sex did not find statistically significant differences (Kalkbrenner et al. 2010).


Selection of cases and controls. We used data from the Nurses' Health Study II, a cohort of 116,430 female nurses from 14 U.S. states that was established in 1989 and has been followed over time with biennial questionnaires. Initially nurses were recruited from 14 U.S. states, but since that time they have moved throughout the United States. Thus, children in the current analyses were born in all 50 U.S. states. In the 2005 questionnaire, respondents were asked "Have any of your children been diagnosed with the following diseases?" with autism, Asperger's syndrome, or other ASD listed as separate responses. In 2007-2008, we sent a questionnaire to the 756 women who had reported having a child with any of these conditions, querying the affected child's sex, birth date, and whether they were adopted. In addition, they were asked "What ASD diagnosis has the child been given?" with autism, Asperger syndrome, and PDD-NOS (PDD not otherwise specified) as possible answers. Women were also asked about other diagnoses (such as attention deficit hyperactivity disorder and obsessive compulsive disorder) (response rate = 84%, n = 636). …

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