Exploring the link between grandmaternal air pollution exposure and Grandchild's ASD risk: A multigenerational population-based study in California.

BACKGROUND

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with increasing prevalence. While genetics play a strong causal role, among environmental factors, air pollution (AP) exposure in pregnancy and infancy has been strongly endorsed as a risk factor. However, potential multigenerational impacts through the exposure of the grandmother during her pregnancy remain unexplored.

METHODS

Using a multigenerational, population-based cohort from California spanning three decades (1990-2019), we examined the association between grandmother's gestational AP exposure (PM2.5, NO2, O3) and ASD risk in grandchildren using logistic regression per 1-IQR unit increase, adjusting for maternal exposure in pregnancy or infant's exposure in the first year of life. We used continuous AP exposure as well as a categorical variable representing high and/or low (above or below median) exposure levels for both the grandmaternal and maternal pregnancies. Pregnancy and first year of life AP exposures were assigned using a land-use regression model with advanced machine-learning approaches.

RESULTS

We observed associations between PM2.5 (OR = 1.07, 95 % CI: 1.05, 1.10) and NO2 (OR = 1.09, 95 % CI: 1.05, 1.13) exposure during the grandmaternal pregnancy and increased ASD risk in the grandchild. However, only for PM2.5 did the increased effect estimates persist after adjusting for maternal pregnancy exposure (OR = 1.05; 95 % CI: 1.02, 1.08). High compared to low exposures in both grandmaternal and maternal pregnancies to PM2.5 (OR = 1.16, 95 % CI: 1.11, 1.23) and NO2 (OR = 1.12, 95 % CI: 1.06, 1.17) showed the strongest joint effects for ASD in the grandchild.

CONCLUSIONS

Multigenerational exposure to air pollution, particularly PM2.5 exposure in grandmaternal pregnancy, may influence ASD risk. Our study also suggests that ASD risk due to air pollution may be compounded by multigenerational exposures.