- Design
- Population-based cohort with propensity score weighting
- Population
- About 4.2 million US pregnancies; about 79,000 benzodiazepine-exposed
- Primary outcome
- Major congenital malformations
- Effect
- Pooled adjusted RR 0.99 (95% CI 0.96 to 1.03)
A US cohort in Annals of Internal Medicine, published on 13 October 2026, analysed more than 4.2 million pregnancies in Medicaid and commercial insurance data, about 79,000 of them with at least one benzodiazepine fill in the first trimester. Propensity-score weighting was used to balance exposed and unexposed pregnancies.
Adjusted absolute risks of any major malformation were 4.0% against 4.1% in Medicaid and 4.9% against 4.8% in commercial data, giving a pooled relative risk of 0.99 (95% CI 0.96 to 1.03). Organ-specific signals were inconsistent across sensitivity analyses, there was no dose-response, and individual benzodiazepines behaved similarly. Some combinations with other psychoactive drugs showed raised risks in some analyses, without a consistent pattern.
This is reassuring for a woman exposed before she knew she was pregnant. It says nothing about later-pregnancy effects such as neonatal withdrawal or sedation, and benzodiazepines still need a clear indication in pregnancy.
- Reassure a woman exposed to a benzodiazepine in early pregnancy that this large study found no rise in major malformations.
- Do not stop a benzodiazepine abruptly on discovering pregnancy; withdrawal carries its own risks.
- Review co-prescribed psychoactive drugs, where the data were less consistent.
- Plan for neonatal sedation or withdrawal if use continues near delivery.
Why it matters
Fear of malformations still drives abrupt stopping and even termination decisions that this evidence does not support.
Don't overread it
Observational claims data covering live births only; it does not address neonatal withdrawal or later neurodevelopment.
The statistics, in plain English
A relative risk of 0.99 with an interval of 0.96 to 1.03 is tightly centred on no effect, and well below the 1.3 the authors set in advance as clinically important.
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