Perinatal Air Pollants and Autism Spectrum Disorder
Objective: Air pollution contains many toxicants known to affect neurological function and to have effects on the fetus in utero. Recent studies have reported associations between perinatal exposure to air pollutants and autism spectrum disorder (ASD) in children. We tested the hypothesis that perinatal exposure to air pollutants is associated with ASD, focusing on pollutants associated with ASD in prior studies.
Methods: We estimated associations between U.S. Environmental Protection Agency–modeled levels of hazardous air pollutants at the time and place of birth and ASD in the children of participants in the Nurses' Health Study II (325 cases, 22,101 controls). Our analyses focused on pollutants associated with ASD in prior research. We accounted for possible confounding and ascertainment bias by adjusting for family-level socioeconomic status (maternal grandparents' education) and census tract–level socioeconomic measures (e.g., tract median income and percent college educated), as well as maternal age at birth and year of birth. We also examined possible differences in the relationship between ASD and pollutant exposures by child's sex.
Results: Perinatal exposures to the highest versus lowest quintile of diesel, lead, manganese, mercury, methylene chloride, and an overall measure of metals were significantly associated with ASD, with odds ratios ranging from 1.5 (for overall metals measure) to 2.0 (for diesel and mercury). In addition, linear trends were positive and statistically significant for these exposures (p < .05 for each). For most pollutants, associations were stronger for boys (279 cases) than for girls (46 cases) and significantly different according to sex.
Conclusions: Perinatal exposure to air pollutants may increase risk for ASD. Additionally, future studies should consider sex-specific biological pathways connecting perinatal exposure to pollutants with ASD.
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).
Abstract and Introduction
Abstract
Objective: Air pollution contains many toxicants known to affect neurological function and to have effects on the fetus in utero. Recent studies have reported associations between perinatal exposure to air pollutants and autism spectrum disorder (ASD) in children. We tested the hypothesis that perinatal exposure to air pollutants is associated with ASD, focusing on pollutants associated with ASD in prior studies.
Methods: We estimated associations between U.S. Environmental Protection Agency–modeled levels of hazardous air pollutants at the time and place of birth and ASD in the children of participants in the Nurses' Health Study II (325 cases, 22,101 controls). Our analyses focused on pollutants associated with ASD in prior research. We accounted for possible confounding and ascertainment bias by adjusting for family-level socioeconomic status (maternal grandparents' education) and census tract–level socioeconomic measures (e.g., tract median income and percent college educated), as well as maternal age at birth and year of birth. We also examined possible differences in the relationship between ASD and pollutant exposures by child's sex.
Results: Perinatal exposures to the highest versus lowest quintile of diesel, lead, manganese, mercury, methylene chloride, and an overall measure of metals were significantly associated with ASD, with odds ratios ranging from 1.5 (for overall metals measure) to 2.0 (for diesel and mercury). In addition, linear trends were positive and statistically significant for these exposures (p < .05 for each). For most pollutants, associations were stronger for boys (279 cases) than for girls (46 cases) and significantly different according to sex.
Conclusions: Perinatal exposure to air pollutants may increase risk for ASD. Additionally, future studies should consider sex-specific biological pathways connecting perinatal exposure to pollutants with ASD.
Introduction
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).