Exploring the link between grandmaternal air pollution exposure and Grandchild's ASD risk: A multigenerational...

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.

Using a multigenerational, population-based cohort from California spanning three decades (1990-2019), we examined the association between grandmother's gestational AP exposure (PM_2.5, 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.

We observed associations between PM_2.5 (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 PM_2.5 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 PM_2.5 (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.

Multigenerational exposure to air pollution, particularly PM_2.5 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.