Sterol pathway disruption in pregnancy: a link to autism.

Cholesterol is a vital molecule, especially during embryonic development. Disruption of the cholesterol biosynthetic pathway can arise from pathogenic genetic variants or exposure to prescription medications. We investigated the relationship between fifteen sterol biosynthesis inhibiting medications (SBIM) prescribed during pregnancy and the incidence of autism spectrum disorders (ASD) in the resulting offspring. Our study of the Epic Cosmos database queried linked child and maternal health records for births between 2014 and 2023 with follow-up to December 2025. The study included 6,135,213 children with linked maternal health records. We evaluated the incidence of ASD associated with maternal prescription of aripiprazole, atorvastatin, bupropion, buspirone, fluoxetine, haloperidol, metoprolol, nebivolol, pravastatin, propranolol, rosuvastatin, sertraline, simvastatin, and/or trazodone during pregnancy using Cox proportional hazard modeling. We found that exposure to at least one SBIM during pregnancy was associated with a 1.47-fold (95% CI 1.45-1.49) increased risk of an ASD after adjusting for potential confounders. For each additional SBIM co-prescribed, there was a 1.33 (95% CI 1.32-1.34) times increased risk of ASD, reaching 2.33-fold risk when 4 or more SBIMs were prescribed simultaneously. In the ten years of our cohort, we identified 234,971 (3.8%) children with an ASD diagnosis. Of the children with an ASD diagnosis, 35,152 (15.0%) of the mothers were prescribed at least one SBIM during pregnancy. Notably, in our dataset, utilization of SBIM medications by pregnant women increased from 4.6% in 2014 to16.8% in 2023. In conclusion, SBIMs may be potentially harmful to the developing fetus. Given that these drugs account for over 400 million prescriptions annually in the U.S. we recommend these findings be considered before prescribing SBIM medications during pregnancy.