Some medications in pregnancy may disrupt fetal brain development

Clinical takeaway: Sterol biosynthesis inhibition may be an underrecognized factor when evaluating medication safety during pregnancy. Review medication regimens for cumulative exposure to medications with sterol biosynthesis–inhibiting effects, avoid unnecessary polypharmacy when possible, and continue individualized risk-benefit discussions before changing therapy.

A new review argues that sterol biosynthesis–inhibiting effects of some medications may represent an underrecognized mechanism of neurodevelopmental risk that clinicians should consider when evaluating medication use during pregnancy.

Drawing on genetic, laboratory, animal, and epidemiologic evidence, the authors describe cholesterol synthesis as essential for fetal brain development. In addition to statins, they note that several antidepressants, antipsychotics, anxiolytics, beta blockers, and other cardiovascular medications can inhibit sterol biosynthesis through off-target effects, potentially reducing cholesterol availability while increasing toxic cholesterol precursors during critical stages of brain development.

The review also highlights the authors' recent analysis of more than 6.1 million US maternal-child pairs, which found that prenatal exposure to at least one sterol biosynthesis-inhibiting medication was associated with a 47% higher adjusted risk of autism spectrum disorder. The risk increased further when multiple such medications were prescribed during pregnancy, although the review emphasizes that these observational findings do not establish causation.

Prescription of medications with sterol biosynthesis-inhibiting effects during pregnancy increased from 4.6% of pregnancies in 2014 to 16.8% in 2023, according to prior work from the same research group. Particular concern is raised about cumulative exposure when more than one such medication is used.

Current pregnancy drug labeling may inadequately communicate these potential risks, according to the authors. They argue that the FDA's 2015 replacement of the A, B, C, D, and X pregnancy categories with narrative labeling provides more nuanced information but may make clinically important fetal safety information less apparent to prescribers and patients.

Rather than recommending discontinuation of needed medications during pregnancy, they call for greater awareness of this potential mechanism, additional research to identify which patients are most vulnerable, and more routine assessment of sterol pathway effects during drug development and prenatal safety evaluations.

"More research is clearly needed, but these grave concerns should not be ignored," said study author Karoly Mirnics, MD, PhD.

Source: Peeples ES, et al. (2026 Jul 15) J Clin Invest. Sterol biosynthesis, brain development, and disease