Autism spectrum disorder (ASD) is a behavioral condition characterized by deficits in communication and social interaction, and an increase in restricted and repetitive patterns in behaviors, interests, and activities (Diagnostic and Statistical Manual of Mental Disorders, 2013). ASD is associated with lifelong consequences including functional deficits, difficulty maintaining relationships, and challenges with living and working independently (Lord et al., 2018). ASD is among the most common neurodevelopmental disorders of childhood, and its prevalence is increasing worldwide (Zeidan et al., 2022) and within the United States (Christensen et al., 2019). The prevalence of ASD is 4 times higher among boys than girls, and about 1 in 44 (2.3%) children were identified with ASD (Werling and Geschwind, 2013) in 2018. According to estimates from the Autism and Developmental Disabilities Monitoring Network, 2.3% represents a 23 percent increase from 2016 (1 in 54), and more than double that of 2000 (1 in 150) (National Center on Birth Defects, 2022). The rise in ASD cases is likely partially attributed to increased monitoring and a broadening of diagnostic criteria (Rice et al., 2012); however, these factors do not fully explain the rising prevalence of ASD (Hertz-Picciotto and Delwiche, 2009).

While genetics and family history play a role in ASD, a growing body of evidence suggests that in utero exposure to air pollution, a complex mixture of particles, gases, trace metals and adsorbed organic contaminants, may also be neurotoxic and could contribute to the development of ASD (Ortega et al., 2014; Peters et al., 2006; Muhlfeld et al., 2008; Bekkar et al., 2020; Shang et al., 2021; Costa et al., 2017, 2020). Exposure to air pollution has been linked to adverse physical and developmental effects on the fetus including low birth weight, preterm birth, and high infant mortality (Currie et al., 2009; Stillerman et al., 2008). In children, air pollutants including NO2 and fine particulate matter (PM2.5) have been associated with numerous neurobehavioral outcomes: impaired cognitive abilities (Harris et al., 2015; Suglia et al., 2008), deficits in attention-related behaviors (Chiu et al., 2013; Newman et al., 2013; Siddique et al., 2011), symptoms of anxiety/depression (Ali and Khoja, 2019; Bakolis et al., 2021; Yolton et al., 2019), as well as ASD (Raz et al., 2018; Volk et al., 2013; Roberts et al., 2013; Windham et al., 2013). Toxicological studies have explored plausible biological pathways linked to autism, noting that airborne pollutant particles cause systemic inflammation, alter the neonatal immune system, contribute to neuronal injury, induce oxidative stress, and affect the development of the central nervous system (Peters et al., 2006; Muhlfeld et al., 2008; Li et al., 2003; Pangrazzi et al., 2020). The brain is already vulnerable to oxidative stress due to its high metabolic activity and low levels of antioxidants, and children with ASD may be at greater risk for oxidative stress (Pangrazzi et al., 2020; MohanKumar et al., 2008). Investigating postnatal air pollution exposure is also indicated because brain development continues, doubling in size through a child's first year of life, and environmental toxicant insults can perturb neurodevelopment (Rice and Barone, 2000). Exposure to fine particulate matter in early infancy has been found to influence patterns of structural brain development in childhood, specifically hemispheric differences in gray matter across cortical regions (Cserbik et al., 2020).

Previous studies have found children born to mothers who live close to freeways have twice the risk of ASD (Volk et al., 2011). Furthermore, epidemiological studies have reported associations of ASD diagnosis and prenatal exposure to various air pollutants, including nitrogen dioxide (NO2) (Volk et al., 2013; Ritz et al., 2018) and fine particulate matter (PM2.5) (Volk et al., 2013; Raz et al., 2015; Becerra et al., 2013). The role of postnatal air pollution exposure is uncertain as studies in California (Volk et al., 2013), Pennsylvania (Talbott et al., 2015), Israel (Raz et al., 2018), and Denmark (Ritz et al., 2018) have found that exposure during early childhood is associated with increased odds of ASD, while other studies found the association to be very weak or not significant (Raz et al., 2018; Gong et al., 2014, 2017; Guxens et al., 2016; Pagalan et al., 2019; Kaufman et al., 2019). The objective of this study was to examine the association between NO2 and PM2.5 during early brain development and ASD-related traits and behaviors in two well-characterized longitudinal cohorts with detailed residential histories.