Association between historical lead exposure, population density, and autism prevalence: a county-level ecological...

Autism spectrum disorder (ASD) prevalence has increased markedly across high-income countries, including Norway, yet environmental drivers remain poorly understood. We hypothesized that historical lead exposure may inversely associate with ASD risk and potentially suppress the effects of vehicle emissions associated with urbanicity.

We conducted a county-level ecological study using ASD prevalence data from the Norwegian Patient Register for children aged 6-12 years (born 1999-2005). Mean dental lead concentrations, measured in deciduous teeth collected between 1990 and 1994 (n = 2,746), served as a proxy for early-life lead exposure. Population density in 2002 was used as a proxy for vehicle emissions associated with urbanicity. ADHD and cerebral palsy (CP) were included as negative controls. Associations with log-transformed ASD prevalence were assessed using multivariable linear regression. Sensitivity analyses examined a later birth cohort and excluded an outlier county.

Dental lead levels were inversely associated with ASD prevalence (p < 0.01), while population density was not significantly associated until adjusted for lead exposure (p = 0.08 and p < 0.05 with outlier excluded), consistent with a suppressor effect or negative confounding. No associations were observed for ADHD or CP. In sensitivity analyses, lead remained inversely associated with ASD only in multivariable models, while population density became a significant predictor.

Higher historical lead exposure was associated with lower ASD prevalence in Norway. Declining lead exposure may have unmasked the neurodevelopmental effects of vehicle emissions. These findings support further investigation into metal interactions and highlight the complexity of environmental influences on ASD risk.