A groundbreaking study led by researchers at the University of Nebraska Medical Center (UNMC) and published in 2016. molecular psychiatryidentified a significant association between prenatal prescription of commonly used medications and the risk of autism spectrum disorder (ASD) in children.
Analyzing 6.14 million maternal and child health records from the Epic Cosmos database (representing nearly one-third of U.S. births from 2014 to 2023), the researchers found that prescription of drugs known to inhibit the cholesterol synthesis pathway was consistently associated with increased rates of ASD in offspring.
While previous studies grouped drugs by indication, the UNMC team grouped prescribed drugs based on common effects and side effects on sterol biosynthesis.
These sterol biosynthesis inhibitors (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, trazodone. Many of these are among the most commonly prescribed drugs in the United States, with over 400 million prescriptions filled annually.
Main 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. Risk increased in a dose-dependent manner. For each additional SBIM co-prescribed, the risk of ASD increased by 1.33-fold, and when four or more SBIMs were prescribed simultaneously, the risk reached 2.33-fold.
- Of the 196,447 children diagnosed with ASD in this cohort, 14.2% had prenatal exposure to SBIM.
- The use of SBIM during pregnancy has increased rapidly over time, from 4.3% of all pregnancies in 2014 to 16.8% in 2023.
Why sterol biosynthesis is important
Cholesterol is essential for fetal development, especially the brain, which is the organ richest in cholesterol. The fetal brain begins producing its own sterols around 19 to 20 weeks of pregnancy. Genetic disruption of this pathway is known to cause severe developmental syndromes such as Smith-Lemli-Opitz syndrome (SLOS), where up to 75% of children meet criteria for ASD. Many widely used drugs can unintentionally interfere with this pathway. This study is the first national survey to assess neurodevelopmental outcomes associated with prenatal exposure to this group of drugs.
Public health signals that require attention
Our findings do not suggest that these drugs are unsafe for adults. However, these studies raise important questions about use during pregnancy, where even small biochemical perturbations can have profound effects on fetal brain development. ”
Karoly Myrnicus, MD, Senior Author, Dean, and Director of the UNMC Munro-Meyer Institute
The authors emphasize that pregnant patients should not stop or change medications without medical supervision, as many SBIMs are essential and often life-saving treatments. Instead, this study calls for a reassessment of prescribing practices and the development of safer alternatives for use during pregnancy.
Possible next steps
The research team suggests several measures to improve drug safety for pregnant patients.
- Create a comprehensive list of drugs with sterol-inhibiting effects.
- Evaluate all new drugs for unintended sterol pathway inhibition.
- Strengthen health care provider education about sterol disorders associated with drug therapy during pregnancy.
- If you cannot stop treatment, discuss safer alternatives.
- If possible, avoid prescribing more than one SBIM to pregnant women.
- 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 reduce risks.
The study was conducted using the Epic Cosmos national data platform and included collaboration with UNMC’s Office of Pediatrics, Office of Biostatistics, Munro-Meyer Institute, other departments at UNMC, and the Child Health Research Institute (CHRI). This research received support from UNMC/CHRI Internal Resources, the Dorothy B. Davis Foundation, and the Nebraska Tobacco Settlement Fund.
sauce:
University of Nebraska Medical Center
Reference magazines:
Peoples, E.S.; others. (2026). Disruption of sterol pathways during pregnancy: relevance to autism.molecular psychiatry. DOI: 10.1038/s41380-026-03610-7. https://www.nature.com/articles/s41380-026-03610-7
