In Utero Exposure to Toxic Air Pollutants and Risk of Childhood Autism

Autism is a severe neurodevelopmental condition characterized by problems in social interaction and communication, restricted interests or repetitive stereotyped behaviors.1 Recently, 14.7 in 1,000 children have been diagnosed with autism spectrum disorder by the age of 8 years.2 The etiology of autism is heterogeneous, and underlying biological mechanisms remain insufficiently understood. Little is known about non-genetic 3 causes, even though environmental factors have been suggested as major contributors, 4 possibly accounting for at least part of the increase in autism observed over the last decades.5 A few studies have investigated autism related to air pollution, focusing on road traffic. 6–8 In the only large population-based study (7,603 cases) to date, we previously reported 7%–12% increases in risks for autistic disorder per interquartile range (IQR) increase in measured particulate matter less than 2.5μg per m3 and ozone, as well as nitrogen oxides (NO, NO2), our marker of traffic pollutants derived from land-use regression.7 Air toxics, also known as hazardous air pollutants, are defined by the Environmental Protection Agency (EPA) as pollutants that may cause serious health effects or adverse environmental and ecological effects. To date only three studies have investigated the influence of toxic air pollutants on autism spectrum disorder. 9–11 These studies were limited in sample size, and relied solely on modeled annual average pollutant concentrations at the county or census-tract level, which are created every few years (i.e., 1996, 1999, 2002,).12 Thus, estimated exposures did not directly correspond to the time of the pregnancy period, as births were linked with annual averages up to several years before or after the actual pregnancy time period and thus assumed temporal stability of the modeled exposures. This approach may have resulted in considerable exposure misclassification, as air pollution exposure changes over time. Nevertheless, associations with these modeled hazardous air pollutants have been suggested for chlorinated solvents, 9–11 cadmium,10,11 quinolone,9 styrene, 9,10 diesel 10 and an index of metal exposure. 10 Several air toxics (e.g. lead or organic solvents) not only are common in urban air mixtures, but are suspected or known to have adverse effects on the developing central nervous system.13,14 A number of underlying mechanisms contributing to neurological pathology have been suggested, including the initiation of inflammatory processes, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier.14 Small pathology studies have reported increases in inflammatory and oxidative stress markers in the brains of children who had been exposed to high levels of toxic ambient air pollution prior to accidental death.15 Inflammatory or immunological processes similar to those seen in response to air pollutants have been hypothesized to play a role in the development of autism.16 However, whether toxic air-pollutant-induced response pathways also affect prenatal neurodevelopment and lead to autism is currently unknown. We investigated risks for autism in children related to in utero exposure to toxic air pollutants based on monitored ambient concentrations of common air toxics, including aromatic and chlorinated solvents, metals, and polycyclic aromatic hydrocarbons (PAHs).