Some prenatal medications linked to increased risk of autism

A landmark study led by researchers at the University of Nebraska Medical Center (UNMC) has been published molecular psychiatryhave identified 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-infant health records from the Epic Cosmos database – representing nearly a third of all US births between 2014 and 2023 – the team found that prescriptions for drugs that inhibit the cholesterol synthesis pathway were consistently associated with higher rates of ASD in offspring.

While previous studies had grouped drugs based on their indications, the UNMC team grouped together prescribed drugs based on common effects and side effects on sterol biosynthesis.

These sterol biosynthesis-inhibiting drugs (SBIM) include some 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, with more than 400 million doses administered annually.

key findings

• Mothers who were prescribed at least one SBIM during pregnancy had a 1.47 times higher risk of a child suffering from ASD. The risk increased in a dose-dependent manner. For each additional SBIM co-prescribed, the risk of ASD was increased by 1.33-fold, with the risk reaching 2.33-fold when four or more SBIMs were prescribed simultaneously.

• Of the 196,447 children with ASD in the group, 14.2% had prenatal SBIM exposure.

• SBIM use during pregnancy increased rapidly over time, from 4.3% of pregnancies in 2014 to 16.8% in 2023.

Why does sterol biosynthesis matter?

Cholesterol is essential for fetal development, especially for the brain, which is the organ with the most cholesterol. The fetal brain begins to produce its own sterols at approximately 19–20 weeks of gestation. Genetic disruptions in this pathway are thought 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 inadvertently interfere with this pathway. This study is the first nationwide investigation to evaluate 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 medicines are unsafe for adults. But they raise important questions about their use during pregnancy, a period when even small biochemical disruptions can have profound effects on fetal brain development.”

Carolee Mirniks, MD, PhD, senior author, dean and director of the UNMC Monroe-Meyer Institute

The authors emphasize that no pregnant patient should stop or change medications without medical supervision, as many SBIMs are essential, often life-saving treatments. Instead, the study calls for re-evaluation of prescribing practices and developing safer alternatives for use during pregnancy.

possible next steps

The research team proposes several actions to improve drug safety for pregnant patients:

• Make a comprehensive list of medications with sterol-inhibiting effects.
• Evaluate all new pharmaceuticals for unintended sterol pathway inhibition.
• Increase provider education regarding medication-associated sterol interference 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 SBIM effects.
• Invest in further research to understand the mechanisms and reduce the risks.

The work was conducted using the EPIC Cosmos national data platform and involved a collaboration between UNMC’s Department of Pediatrics, Department of Biostatistics, Monroe-Meyer Institute, other UNMC departments, and the Child Health Research Institute (CHRI). The study was supported by UNMC/CHRI Internal Resources, Dorothy B. Support was received from the Davis Foundation and the Nebraska Tobacco Settlement Fund.