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Study Observes Association Between Prenatal Exposure to Sterol-Inhibiting Medications and Autism Spectrum Disorder Diagnosis

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Large-Scale Study Links Certain Pregnancy Medications to Increased Autism Risk in Children

A large-scale observational study has identified an association between maternal use of medications that inhibit sterol biosynthesis during pregnancy and an increased risk of an autism spectrum disorder (ASD) diagnosis in children. The research, published in the journal Molecular Psychiatry, analyzed over 6 million maternal-child health records. The authors note the study design cannot confirm causality and emphasize that many of the medications examined are essential treatments.

Study Scope and Methodology

The research analyzed de-identified health records from the Epic Cosmos database, a national platform containing data from U.S. hospitals and clinics. The cohort included approximately 6.14 million mother-child pairs with births occurring between 2014 and 2023, representing nearly one-third of U.S. births in that period. Follow-up data was available through January 2026.

Researchers identified 14 prescription medications classified as sterol biosynthesis inhibiting medications (SBIMs). This category includes certain antidepressants, antipsychotics, anxiolytics, beta-blockers, and statins. The use of SBIMs during pregnancy in the studied cohort increased from 4.3% of pregnancies in 2014 to 16.8% in 2023.

Reported Findings

Overall Association: Mothers prescribed at least one SBIM during pregnancy had a 1.47-fold higher observed risk of having a child later diagnosed with ASD compared to children with no prenatal SBIM exposure.

  • Dose-Response Pattern: The magnitude of the association increased with the number of SBIM prescriptions. The risk reached 2.33-fold when four or more different SBIMs were prescribed during pregnancy. The study reported an approximately 1.33-fold increase in observed risk with each additional SBIM.
  • Prevalence: Within the cohort, 3.8% of children received an ASD diagnosis. Among the 196,447 children diagnosed with ASD, 14.2% had prenatal exposure to at least one SBIM.
  • Specific Medications: After statistical adjustment, certain SBIMs, such as cariprazine, were associated with more than double the observed risk of ASD compared to no exposure. Medications not affecting sterol biosynthesis showed minimal increases in ASD risk.

Scientific Context and Proposed Mechanism

Cholesterol and related sterols are essential for fetal brain development. Genetic disruptions in sterol biosynthesis are known to cause developmental syndromes, such as Smith-Lemli-Opitz syndrome (SLOS), where a high proportion of affected individuals also meet criteria for ASD.

The study authors propose that SBIM exposure during pregnancy may disrupt fetal brain development through biochemical mechanisms, potentially leading to an accumulation of reactive intermediary compounds and decreased cholesterol availability in the developing brain.

Study Limitations and Author Statements

The authors explicitly note several limitations:

  • The observational design means a causal relationship between SBIM use and ASD risk cannot be confirmed.
  • Maternal characteristics differed between exposure groups; mothers prescribed SBIMs had higher rates of metabolic and psychiatric conditions, which are themselves associated with ASD risk.
  • Sensitivity analyses that accounted for maternal psychiatric diagnoses modestly reduced several observed associations but did not eliminate the overall signal.

Senior author Karoly Mirnics stated the findings raise questions about medication use during pregnancy but clarified they do not suggest these medications are unsafe for adults. The authors caution against overinterpreting the findings and note that discontinuing necessary treatments can pose significant health risks.

Recommendations and Conclusions

The research team proposed several actions based on the findings:

  • Creating a comprehensive list of medications with sterol-inhibiting effects.
  • Evaluating new pharmaceuticals for unintended sterol pathway inhibition.
  • Increasing provider education about medication-associated sterol disruption.
  • For clinicians, considering safer alternatives when discontinuing treatment is not possible and avoiding prescribing multiple SBIMs for pregnant patients when feasible.
  • Investing in further research to understand the biological mechanisms and identify patients with potential genetic vulnerabilities.

The study was conducted by researchers from the University of Nebraska Medical Center and was supported by UNMC internal resources, the Dorothy B. Davis Foundation, and the Nebraska Tobacco Settlement Fund.