Association of Prenatal Exposure to Air Pollution With Autism Spectrum Disorder

Abstract

IMPORTANCEThe etiology of autism spectrum disorder (ASD) is poorly understood, but prior studies suggest associations with airborne pollutants.OBJECTIVE To evaluate the association between prenatal exposures to airborne pollutants and ASD in a large population-based cohort. DESIGN, SETTING, AND PARTICIPANTSThis population-based cohort encompassed nearly all births in Metro Vancouver, British Columbia, Canada, from 2004 through 2009, with follow-up through 2014. Children were diagnosed with ASD using a standardized assessment with the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Monthly mean exposures to particulate matter with a diameter less than 2.5 μm (PM 2.5 ), nitric oxide (NO), and nitrogen dioxide (NO 2 ) at the maternal residence during pregnancy were estimated with temporally adjusted, high-resolution land use regression models. The association between prenatal air pollution exposures and the odds of developing ASD was evaluated using logistic regression adjusted for child sex, birth month, birth year, maternal age, maternal birthplace, and neighborhood-level urbanicity and income band. Data analysis occurred from June 2016 to May 2018.EXPOSURES Mean monthly concentrations of ambient PM 2.5 , NO, and NO 2 at the maternal residence during pregnancy, calculated retrospectively using temporally adjusted, high-resolution land use regression models. MAIN OUTCOMES AND MEASURESAutism spectrum disorder diagnoses based on standardized assessment of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. The hypothesis being tested was formulated during data collection. RESULTSIn a cohort of 132 256 births, 1307 children (1.0%) were diagnosed with ASD by the age of 5 years. The final sample size for the PM 2.5 -adjusted model was 129 439 children, and for NO and NO 2 , it was 129 436 children; of these, 1276 (1.0%) were diagnosed with ASD. Adjusted odds ratios for ASD per interquartile range (IQR) were not significant for exposure to PM 2.5 during pregnancy (1.04 [95% CI, 0.98-1.10] per 1.5 μg/m 3 increase [IQR] in PM 2.5 ) or NO 2 (1.06 [95% CI, 0.99-1.12] per 4.8 ppb [IQR] increase in NO 2 ) but the odds ratio was significant for NO (1.07 [95% CI, 1.01-1.13] per 10.7 ppb [IQR] increase in NO). Odds ratios for male children were 1.04 (95% CI, 0.98-1.10) for PM 2.5 ; 1.09 (95% CI, 1.02-1.15) for NO; and 1.07 (95% CI, 1.00-1.13) for NO 2 . For female children, they were for 1.03 (95% CI, 0.90-1.18) for PM 2.5 ; 0.98 (95% CI, 0.83-1.13) for NO; and 1.00 (95% CI, 0.86-1.16) for NO 2 .CONCLUSIONS AND RELEVANCE In a population-based birth cohort, we detected an association between exposure to NO and ASD but no significant association with PM 2.5 and NO 2 .

Ambient Air Pollution Increases the Risk of Cerebrovascular and Neuropsychiatric Disorders through Induction of Inflammation and Oxidative Stress

“…In the most recent one, a total of 25 studies were investigated to analyze the role of maternal exposure to air pollution and risk of autism spectrum disorders in children, resulting in ORs of 1.06 (95% CI 1.01–1.11) for PM2.5 and 1.02 (95% CI 1.01–1.04) for NO 2 [ 96 ]. In a large Canadian cohort of 132,256 births, maternal exposure to NO was associated with increased risk of development of autism spectrum disorders in children (OR 1.07, 95% CI 1.01–1.13 per IQR increase), whereas associations were less pronounced (or only showed a trend) for PM2.5 (OR 1.04, 95% CI 0.98–1.10) and NO 2 (OR 1.06, 95% CI 0.99–1.12) [ 97 ]. Interestingly, a recent study in the US has shown that gestational diabetes mellitus and maternal exposure to O 3 were associated with additive effects on autism risk, likely due to shared pathways that include inflammation and oxidative stress [ 98 ].…”

Risk and Protective Environmental Factors Associated with Autism Spectrum Disorder: Evidence-Based Principles and Recommendations

“…Recently, in a Canadian population-based birth cohort, a significant association between exposure to nitric oxide and ASD was found. No association was found between ASD and particulate matter with a diameter of <2.5 μm or nitrogen dioxide [74]. These contradictory results might be due to the fact that studies of air pollution have been often limited by indirect and cross-sectional methods of exposure measurement, by different metrics of exposure, by different evaluations of outcomes, and by focusing on different pollutants.…”

Antigenic Targets of Patient and Maternal Autoantibodies in Autism Spectrum Disorder

“…Metallothioneins (MT) are intracellular proteins involved in the homeostasis of essential metals and the detoxification of heavy metals (100). The consequences of environmental exposure to noxious agents and their exact role in the pathology of ASD are still under investigation, but it is known that exposure to pollution and heavy metals is causally implicated in changes of fetal neurodevelopment that are related with autism (8, 101, 102). The presence of anti-MT antibodies has been described in metal-induced diseases such as occupational heavy metal exposure and metal allergy (103, 104).…”