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Background <p>The association between benzodiazepine receptor agonist (BZRA) exposure and adverse perinatal outcomes remains inconclusive. This study aimed to assess the risks of adverse pregnancy and neonatal outcomes associated with maternal BZRA exposure across pregnancy trimesters.</p> Methods <p>Data from 170,144 maternal BZRA users and 1,098,172 nonusers were obtained from the Taiwan’s National Health Insurance database. We used cross-sectional study design with inverse probability of treatment weighting (IPTW) to evaluate the association between maternal BZRA exposure during each trimester and adverse pregnancy outcomes. The pregnancy period was classified into 4 intervals: preconception, first trimester, second trimester, and third trimester. Logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs).</p> Results <p>Maternal BZRA exposure was associated with an increased risk of stillbirth (IPTW-OR 1.19, 95% CI 1.14–1.25), preterm birth (IPTW-OR:1.11, 95% CI 1.09–1.13), low birth weight (IPTW-OR:1.05, 95% CI 1.03–1.07), Apgar score &lt; 7 (IPTW-OR:1.17, 95% CI 1.12–1.22), and cesarean delivery (IPTW-OR:1.15, 95% CI 1.14–1.17) compared with nonusers. By timing, preconception exposure was modestly associated with preterm birth and cesarean delivery, and first-trimester exposure showed similar associations. The associations were most pronounced in the second trimester, with significantly elevated risks of stillbirth (2.29, 95% CI 2.11–2.48), preterm birth (1.38, 95% CI 1.33–1.43), Apgar score &lt; 7 (2.05, 95% CI 1.92–2.20), low birth weight (1.35, 95% CI 1.29–1.40), small for gestational age (1.07, 95% CI 1.03–1.11), cesarean Sect.&#xa0;(1.21, 95% CI 1.18–1.24), and overall congenital malformations (1.27, 95% CI 1.13–1.43).</p> Conclusions <p>This study observed a small but statistical association between BZRA exposure and several adverse pregnancy outcomes, which extended from the pre-pregnancy period through all trimesters. Clinicians should carefully weigh the risks and benefits when treating women who are pregnant or planning pregnancy.</p>

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Use of benzodiazepine receptor agonists in different pregnancy trimesters and risk of maternal and neonatal outcomes: a propensity weighted cohort study in Taiwan

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  • 发表日期：

    2025年12月6日

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  • Ruei-Siang Yu,
  • Sheng-Yin To,
  • Yi-Lin Chiang,
  • Yu-Chieh Huang,
  • Ke-Ting Pan,
  • Hui-Wen Yang,
  • Liang-Hsuan Chen,
  • Li-Ting Kao,
  • Ming-Fa Hsieh

摘要

Background

The association between benzodiazepine receptor agonist (BZRA) exposure and adverse perinatal outcomes remains inconclusive. This study aimed to assess the risks of adverse pregnancy and neonatal outcomes associated with maternal BZRA exposure across pregnancy trimesters.

Methods

Data from 170,144 maternal BZRA users and 1,098,172 nonusers were obtained from the Taiwan’s National Health Insurance database. We used cross-sectional study design with inverse probability of treatment weighting (IPTW) to evaluate the association between maternal BZRA exposure during each trimester and adverse pregnancy outcomes. The pregnancy period was classified into 4 intervals: preconception, first trimester, second trimester, and third trimester. Logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Maternal BZRA exposure was associated with an increased risk of stillbirth (IPTW-OR 1.19, 95% CI 1.14–1.25), preterm birth (IPTW-OR:1.11, 95% CI 1.09–1.13), low birth weight (IPTW-OR:1.05, 95% CI 1.03–1.07), Apgar score < 7 (IPTW-OR:1.17, 95% CI 1.12–1.22), and cesarean delivery (IPTW-OR:1.15, 95% CI 1.14–1.17) compared with nonusers. By timing, preconception exposure was modestly associated with preterm birth and cesarean delivery, and first-trimester exposure showed similar associations. The associations were most pronounced in the second trimester, with significantly elevated risks of stillbirth (2.29, 95% CI 2.11–2.48), preterm birth (1.38, 95% CI 1.33–1.43), Apgar score < 7 (2.05, 95% CI 1.92–2.20), low birth weight (1.35, 95% CI 1.29–1.40), small for gestational age (1.07, 95% CI 1.03–1.11), cesarean Sect. (1.21, 95% CI 1.18–1.24), and overall congenital malformations (1.27, 95% CI 1.13–1.43).

Conclusions

This study observed a small but statistical association between BZRA exposure and several adverse pregnancy outcomes, which extended from the pre-pregnancy period through all trimesters. Clinicians should carefully weigh the risks and benefits when treating women who are pregnant or planning pregnancy.