Using two large U.S. insurance databases, researchers compared more than 4 million pregnancies with and without a first-trimester benzodiazepine fill. The pooled adjusted relative risk for any congenital malformation was 0.99 (95% CI 0.96–1.03), indicating no elevated risk. Absolute risks were similar in both Medicaid and commercially insured populations.
Most organ-specific malformations also showed no significant association. The only notable exception was a slightly elevated risk for gastrointestinal malformations (adjusted RR 1.10, 95% CI 1.01–1.19), and a secondary analysis found an increase in eye malformations among commercially insured women exposed to diazepam. Sensitivity analyses, including dose and number of fills, produced largely consistent results.
The findings, published in Annals of Internal Medicine, provide the most comprehensive U.S. evidence to date on this question. The authors stress that benzodiazepines are not risk-free and that the study was restricted to live births, so severe malformations ending in miscarriage or termination could not be captured. They call for further research on other pregnancy outcomes and on the risks of untreated psychiatric conditions.