ArticleArchives of women's mental health2026
Benzodiazepine exposure during early pregnancy and risk of miscarriage: dose-response, half-life classification, and individual agents.
Article in Archives of women's mental health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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Corrections and comments
- Erratum issued
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17 authors.
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Abstract
purposeTo evaluate the association between benzodiazepine exposure during early pregnancy and the risk of miscarriage, with a focus on dose-response, half-life, and individual agents.
methodsThis nested case-control study was conducted using a large Japanese administrative database. Cases were defined as pregnancies ending in miscarriage between 2005 and 2023. Controls were randomly selected through risk-set sampling with replacement and matched in a 3:1 ratio. Conditional logistic regression, adjusted for confounders, was used to assess the associations.
resultsOverall, 44,118 cases were matched with 132,317 controls, with a mean age of 33.2 years. The prevalence of benzodiazepine exposure was 1.7% and 1.2% among cases and controls, respectively. Etizolam (0.3%) had the highest prevalence, followed by alprazolam (0.3%) and brotizolam (0.2%) in both groups. Adjusted odds ratio (OR) for benzodiazepine exposure during early pregnancy was 1.241 (95% confidence interval: 1.136-1.357). Adjusted ORs for high-dose (1.212 [1.050-1.400]) and medium-dose (1.189 [1.037-1.363]) exposure were numerically higher than that for low-dose exposure (1.111 [0.934-1.322]). Adjusted OR for long-acting benzodiazepines (1.308 [1.124-1.522]) was numerically higher than those for intermediate- (1.132 [0.999-1.284]) and short-acting (1.157 [1.030-1.300]) agents. Adjusted ORs for etizolam, alprazolam, and brotizolam were 0.929 (0.782-1.103), 0.853 (0.707-1.030), and 1.454 (1.180-1.791), respectively.
conclusionsBenzodiazepine exposure during early pregnancy was modestly associated with an increased risk of miscarriage. Although associations tended to be stronger with higher dose levels and longer half-life categories, estimates across subgroups lacked precision and should be interpreted with caution.
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