Scholarlink

Purpose <p>To 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.</p> Methods <p>This 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.</p> Results <p>Overall, 44,118 cases were matched with 132,317 controls, with a mean age of 33.2&#xa0;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.</p> Conclusions <p>Benzodiazepine 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Benzodiazepine exposure during early pregnancy and risk of miscarriage: dose–response, half-life classification, and individual agents

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月23日

查看全文
  • Tomofumi Ishikawa,
  • Takamasa Sakai,
  • Noriyuki Iwama,
  • Ryo Obara,
  • Kei Morishita,
  • Motohiko Adomi,
  • Tadaharu Kunitoki,
  • Aoi Noda,
  • Mami Ishikuro,
  • Saya Kikuchi,
  • Natsuko Kobayashi,
  • Hiroaki Tomita,
  • Masatoshi Saito,
  • Hidekazu Nishigori,
  • Shinichi Kuriyama,
  • Nariyasu Mano,
  • Taku Obara

摘要

Purpose

To 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.

Methods

This 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.

Results

Overall, 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.

Conclusions

Benzodiazepine 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.