Higher prenatal exposure to wildfire-related fine particulate matter was associated with a 30% higher relative hazard of autism spectrum disorder (ASD) in children for each 0.75 microgram-per-cubic-meter increase in cumulative exposure. No meaningful association was observed for attention-deficit/hyperactivity disorder (ADHD).
Researchers conducted a population-based retrospective cohort study of 893,212 mother-child pairs enrolled in US Medicaid, using birth data from 2007 to 2014 and following them through December 2018. Eligible mothers had continuous Medicaid enrollment from 3 months before pregnancy through 1 month after delivery and had the same residential ZIP code at the beginning and end of pregnancy. Wildfire-related fine particulate matter with an aerodynamic diameter of 2.5 micrometers or smaller (PM2.5) was estimated using a high-resolution exposure model and assigned to residential ZIP codes.
The study evaluated incident ASD and ADHD using validated claims-based diagnostic algorithms. Researchers applied Cox proportional-hazards models incorporating distributed lag nonlinear models to assess cumulative prenatal wildfire PM2.5 exposure and potential gestational windows of susceptibility. Models accounted for maternal age, race and ethnicity, parity, prenatal folate dispensing, smoking, substance and alcohol use, indicators of poor nutrition, socioeconomic and geographic characteristics, background PM2.5 exposure, and temperature.
Among the 893,212 children, 8,357 received an ASD diagnosis, and 22,302 received an ADHD diagnosis. Cumulative incidence by age 8 years was 1.9% for ASD and 10.4% for ADHD.
The 30% higher relative hazard of ASD was accompanied by stronger associations during midpregnancy through late gestation, particularly following approximately 15 weeks of pregnancy. Background PM2.5 unrelated to wildfires was associated with a smaller increase in ASD relative hazard of 10%. No meaningful association with ADHD was observed for either exposure type.
Sex-stratified analyses did not identify meaningful differences in cumulative ASD associations between male and female children, with point estimates corresponding to 31% higher relative hazards in both groups, although the estimate among female children was less precise. Gestational patterns differed. Associations among male children were elevated across much of pregnancy, whereas those among female children were more apparent during midpregnancy through late gestation. ADHD estimates remained close to no association in both groups.
Analyses stratified by race and ethnicity did not identify meaningful differences in associations. ASD estimates were elevated across racial and ethnic groups, whereas ADHD estimates generally remained near no association. Regional analyses suggested larger point estimates in the South, although the estimates were too imprecise to establish meaningful regional differences.
Sensitivity analyses using alternative gestational exposure windows, diagnostic age restrictions, and exposure-response specifications yielded findings generally consistent with the primary analysis. Additional analyses accounting for loss to follow-up and correlations among pregnancies contributed by the same mother also produced similar estimates.
The researchers acknowledged several limitations. Wildfire PM2.5 exposure was assigned at the ZIP code level without accounting for individual activity patterns, indoor air quality, or personal smoke mitigation measures, potentially introducing exposure misclassification. Weekly exposure estimates may also have missed short-term pollution peaks. ASD and ADHD diagnoses were identified through administrative claims, and geographic differences in access to specialists may have influenced diagnostic ascertainment. Residual confounding remained possible despite extensive adjustment. Additionally, the Medicaid population may not represent families with different socioeconomic or health care characteristics, and historical exposure patterns may not reflect contemporary wildfire conditions. The primary gestational analysis assessed exposure only through week 33.
The observational design does not establish causation. Previous studies in California reported inconsistent findings on prenatal wildfire smoke exposure and autism risk. The researchers called for further research to confirm the findings and investigate potential biological mechanisms and the combined effects of wildfire smoke with other environmental and social stressors.
"Efforts to reduce exposure during pregnancy, including improved air quality forecasting and strategies to limit indoor smoke infiltration, may be important for protecting maternal and child health," wrote lead study author Stefania Papatheodorou, PhD, of Rutgers School of Public Health, Piscataway, New Jersey, and colleagues.
Sonia Hernandez-Diaz reported consulting fees and institutional grants from pharmaceutical companies for unrelated work; Christopher J. McDougle reported publishing royalties; and Brent A. Coull and Marc G. Weisskopf reported National Institutes of Health grants during the study. No other disclosures were reported.
Source: JAMA Pediatrics
