A landmark study led by researchers at the University of Nebraska Medical Center (UNMC) and published in Molecular Psychiatryhas identified a significant association between prenatal prescription of commonly used medications and risk of autism spectrum disorder (ASD) in children.
Analyzing 6.14 million maternal-child health records from the Epic Cosmos database—representing nearly a third of all US births between 2014 and 2023—the team found that prescription drugs known to inhibit the cholesterol synthesis pathway were consistently associated with higher rates of ASD at birth.
While previous studies grouped drugs based on their indications, the UNMC team grouped prescription drugs based on common effects and side effects on sterol biosynthesis.
These sterol biosynthesis inhibitor drugs (SBIMs) include certain antidepressants, antipsychotics, anxiolytics, beta-blockers, and statins. These are the generic names of the 14 drugs studied: aripiprazole, atorvastatin, bupropion, buspirone, fluoxetine, haloperidol, metoprolol, nebivolol, pravastatin, propranolol, rosuvastatin, sertraline, simvastatin and trazodone. Many of these are among the most commonly prescribed drugs in the United States, accounting for more than 400 million annual prescriptions.
Key findings
- Mothers who were prescribed at least one SBIM during pregnancy had a 1.47 times higher risk of having a child diagnosed with ASD. The risk increased in a dose-dependent manner. For each additional SBIM prescribed, there was a 1.33-fold increased risk of ASD, reaching a 2.33-fold risk when four or more SBIMs were prescribed simultaneously.
- Among the 196,447 children diagnosed with ASD in the cohort, 14.2% had prenatal exposure to SBIM.
- The use of SBIMs during pregnancy has increased sharply over time, rising from 4.3% 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 to produce its own sterols around 19-20 weeks of gestation. Genetic disturbances 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 commonly used drugs can inadvertently interfere with this pathway. This study is the first nationwide survey to assess neurodevelopmental outcomes associated with prenatal exposure to this group of drugs.
A public health signal that requires attention
Our findings do not suggest that these drugs are unsafe for adults. But they raise important questions about their use during pregnancy, a time when even small biochemical disturbances can have large effects on fetal brain development.”
Karoly Mirnics, MD, PhD, senior author, dean and director of the UNMC Munroe-Meyer Institute
The authors emphasize that no pregnant patient should stop or change medication without medical supervision, as many SBIMs are essential, often life-saving treatments. Instead, the study calls for re-evaluation of prescribing practices and development of safer alternatives for use during pregnancy.
Possible next steps
The research team suggests several actions to improve the safety of medicines for pregnant patients:
- Create a comprehensive list of drugs with sterol inhibitory effects.
- Evaluate all new pharmaceuticals for inadvertent sterol pathway inhibition.
- Increase provider education about drug-related sterol disruption during pregnancy.
- Discuss safer alternatives when stopping treatment is not possible.
- Avoid prescribing multiple SBIMs for pregnant women whenever possible.
- Identify patients with genetic vulnerabilities in sterol metabolism, as they may be particularly sensitive to the effects of SBIM.
- Invest in further research to understand mechanisms and mitigate risk.
The work was conducted using the Epic Cosmos national data platform and involved collaboration between the UNMC Department of Pediatrics, the Department of Biostatistics, the Munroe-Meyer Institute, other UNMC departments, and the Child Health Research Institute (CHRI). The study received support from UNMC/CHRI internal resources, the Dorothy B. Davis Foundation, and the Nebraska Tobacco Settlement Fund.
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