A study led by researchers at the University of Nebraska Medical Center (UNMC) and published in Molecular Psychiatry has identified a significant association between prenatal prescription of commonly utilized medications and the risk of autism spectrum disorder (ASD) in children.
Analyzing 6.14 million maternal-child health records from the Epic Cosmos database — representing nearly one-third of all U.S. births between 2014 and 2023 — the team found that prescription of medications known to inhibit the cholesterol synthesis pathway were consistently associated with higher rates of ASD in offspring.
While previous studies grouped medications by their indications, the UNMC team grouped prescribed medications together based on common effects and side effects on sterol biosynthesis.
These sterol biosynthesis–inhibiting medications (SBIMs) include certain antidepressants, antipsychotics, anxiolytics, beta-blockers and statins. These are the generic names of the 15 medications studied: aripiprazole, atorvastatin, bupropion, buspirone, fluoxetine, haloperidol, metoprolol, nebivolol, pravastatin, propranolol, rosuvastatin, sertraline, simvastatin, cariprazine and trazodone. Many of these are among the most commonly prescribed medications in the United States, accounting for more than 400 million annual prescriptions.
Key findings
- Mothers prescribed at least one SBIM during pregnancy had a 1.47-fold higher risk of having a child diagnosed with ASD. Risk increased in a dose-dependent manner. For each additional SBIM co-prescribed, there was a 1.33 times increased risk of ASD, reaching 2.33-fold risk when four or more SBIMs were prescribed simultaneously.
- Among the 234,971 children diagnosed with ASD in the cohort, 15% had prenatal SBIM exposure.
- Use of SBIMs during pregnancy increased sharply over time, rising from 4.6% of pregnancies in 2014 to 16.8% in 2023.
Why sterol biosynthesis matters
Cholesterol is essential for fetal development, especially for the brain, the most cholesterol-rich organ. The fetal brain begins producing its own sterols around 19–20 weeks of gestation. Genetic disruptions in this pathway are known to cause severe developmental syndromes such as Smith-Lemli-Opitz syndrome (SLOS), in which up to 75% of children meet criteria for ASD.
Many widely used medications can unintentionally interfere with this pathway. This study is the first nationwide investigation to evaluate the neurodevelopmental outcomes associated with prenatal exposure to this group of medications.
A public health signal requiring attention
“Our findings do not suggest that these medications are unsafe for adults,” said corresponding author Karoly Mirnics, MD, PhD, dean and director of the UNMC Munroe-Meyer Institute. “But they raise important questions about their use during pregnancy, a period when even small biochemical disruptions may have outsized effects on fetal brain development.”
The authors stress that no pregnant patient should discontinue or alter medication without medical supervision, as many SBIMs are essential, often life-saving treatments. Instead, the study calls for a re-evaluation of prescribing practices and for developing safer alternatives for use during pregnancy.
Potential next steps
The research team proposes several actions to improve drug safety for pregnant patients:
- Create a comprehensive list of medications with sterol-inhibiting effects.
- Evaluate all new pharmaceuticals for unintended sterol pathway inhibition.
- Increase provider education about medication-associated sterol disruption during pregnancy.
- Discuss safer alternatives when discontinuing treatment is not possible.
- Avoid prescribing multiple SBIMs for pregnant women whenever feasible.
- Identify patients with genetic vulnerabilities in sterol metabolism, as they might be particularly sensitive to SBIM effects.
- Invest in further research to understand mechanisms and mitigate risk.
