Prenatal exposure to key components of fine particulate air pollution, specifically sulfate and ammonium, has been linked to an increased risk for autism spectrum disorder (ASD) in offspring, results of a large study showed.

In this cohort study of more than 2.1 million births, exposure to these air pollutants during the second and third trimesters of pregnancy was most strongly associated with an increased risk for ASD, suggesting critical windows of vulnerability.

Early postnatal exposure to ozone was also associated with an elevated risk for ASD, suggesting the early postnatal period may be an additional window of susceptibility, the researchers noted.

“These findings support further research on air pollution’s role in ASD etiology,” the investigators, led by Maxime Cloutier, MSc, Health Canada, Ottawa, Ontario, Canada, wrote.

The study was published online on October 23 in JAMA Network Open.

Filling a Data Gap

Prenatal and early postnatal exposure to fine particulate matter (PM_2.5) has been associated with neurodevelopmental outcomes, including ASD, but the role of individual components of PM_2.5 and timing of exposure remains unclear.

The new analysis is among the largest and most detailed, to date, to parse out the effects of individual components of PM_2.5 pollutants and ASD diagnosis and identify potential risk periods.

The study included 2,183,324 singleton live births with complete residential histories and follow-up through age 5 years.

Using satellite data, chemical transport models, and ground-based measurements, the team estimated biweekly concentrations of PM_2.5 and its components — including black carbon, organic matter, dust, sulfate, ammonium, nitrate, and sea salt — at each mother’s residential postal code. ASD diagnoses were identified from medical records using validated codes from hospital and outpatient data.

To pinpoint sensitive exposure windows, the researchers used advanced distributed lag nonlinear models, which allow for analysis of weekly exposure during pregnancy.

Overall, 19,569 children (0.8%) were diagnosed with autism by their fifth birthday, including 15,205 boys and 4364 girls.

After adjusting for confounders, prenatal exposure to PM_2.5 sulfate and ammonium components were significantly associated with an increased risk for autism. Hazard ratios (HRs) per interquartile range increase for sulfate and ammonium were 1.15 and 1.12, respectively.

Total PM_2.5 mass without these two components was not significantly associated with ASD (HR, 1.04).

Ozone exposure during late pregnancy (weeks 26-30) and the first year of life also showed modest associations with ASD (HR, 1.09).

‘Environmental Injustice’

The critical periods of vulnerability identified were weeks 14-32 for overall PM_2.5 exposure, weeks 23-36 for sulfate and weeks 21-34 for ammonium. These correspond roughly to the second and third trimesters, key times for neuronal growth, myelination, and synapse formation in the fetal brain.

Stratified analyses showed PM_2.5 exposure in urban, but not rural, areas was associated with a higher risk for ASD, especially in low-income and middle-income neighborhoods with higher proportions of racial minority populations, suggesting “environmental injustice,” the researchers wrote.

While the study did not establish causation, they suggested several biological pathways that could explain the findings. Fine particles may cross the placenta, triggering oxidative stress, inflammation, and epigenetic changes that alter neurodevelopment.

Limitations of the study included potential misclassification of exposure based on postal code, lack of personal exposure data, and imperfect sensitivity of administrative ASD diagnoses.

“These findings underscore the potential importance of early-life environmental exposures and reinforce the need for public health strategies to reduce air pollution, particularly in urban and socioeconomically disadvantaged communities,” the authors concluded.

This study was supported by a research grant from the Air Research Program of Health Canada. The authors had no relevant disclosures.