Gestational exposure to benzodiazepines or z-hypnotics and neurodevelopmental disorders in offspring: Systematic review and meta-analysis

IF 5.3 2区医学 Q1 PSYCHIATRY Acta Psychiatrica Scandinavica Pub Date : 2024-05-15 DOI:10.1111/acps.13696

Chittaranjan Andrade, Natarajan Varadharajan, Sharmi Bascarane, Vikas Menon

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Abstract

Introduction

Benzodiazepine (BDZP) and/or z-hypnotic dispensing during pregnancy has increased globally, as have rates of autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This systematic review and meta-analysis aimed to estimate the association between gestational exposure to BDZP and/or z-hypnotics and diagnosis of ASD or ADHD in offspring.

Methods

We searched MEDLINE, EMBASE, and SCOPUS from inception till December 2023 for relevant English-language articles. Outcomes of interest were risk of ASD and ADHD, two independent primary outcomes, in children exposed anytime during pregnancy to BDZP and/or z-hypnotics versus those unexposed. Secondary outcomes were trimester-wise analyses. Using a random effects model, we pooled the overall and trimester-wise hazard ratios (HRs), with 95% confidence intervals (CIs), separately for risk of ASD and ADHD.

Results

We found six eligible retrospective cohort studies and no case–control studies. There was no increased risk of ASD associated with anytime gestational BDZP and/or z-hypnotic exposure (primary outcome, HR, 1.10; 95% CI, 0.81–1.50; 4 studies; n = 3,783,417; 80,270 exposed, 3,703,147 unexposed) nor after first trimester exposure (HR, 1.15; 95% CI, 0.83–1.58; 3 studies; n = 1,539,335; 70,737 exposed, 1,468,598 unexposed) or later trimester exposures. A very small but significantly increased risk of ADHD was noted with anytime gestational exposure to these drugs (primary outcome, HR, 1.07; 95% CI, 1.03–1.12; 4 studies; n = 2,000,777; 78,912 exposed, 1,921,865 unexposed) and also with (only) second trimester exposure (HR, 1.07; 95% CI, 1.03–1.12; 3 studies; n = 1,539,281; 33,355 exposed, 1,505,926 unexposed). Findings were consistent in sensitivity analyses.

Conclusion

Gestational exposure to benzodiazepines or z-hypnotics was not associated with an increased risk of ASD and with only a marginally increased risk of ADHD in offspring. Given the likelihood of confounding by indication and by unmeasured variables in the original studies, our findings should reassure women who need these medications for severe anxiety or insomnia during pregnancy.

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妊娠期接触苯并二氮杂卓或z-催眠药与后代的神经发育障碍：系统回顾和荟萃分析。

导言：在全球范围内，妊娠期苯二氮卓（BDZP）和/或z-催眠药的配药量有所增加，自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）的发病率也有所上升。本系统综述和荟萃分析旨在估算妊娠期暴露于BDZP和/或z-催眠药与后代ASD或ADHD诊断之间的关联：方法：我们检索了MEDLINE、EMBASE和SCOPUS从开始到2023年12月的相关英文文章。我们关注的结果是，在怀孕期间任何时候接触过 BDZP 和/或 z-hypnotics 的儿童与未接触过的儿童相比，患 ASD 和 ADHD 的风险（这是两个独立的主要结果）。次要结果是按孕期进行的分析。利用随机效应模型，我们分别汇总了总的和三个月的ASD和ADHD风险危险比（HRs）及95%置信区间（CIs）：我们发现了六项符合条件的回顾性队列研究，但没有病例对照研究。任何妊娠期BDZP和/或z-催眠药暴露均不会增加ASD风险（主要结果，HR，1.10；95% CI，0.81-1.50；4项研究；n=3）。50；4 项研究；n = 3,783,417；80,270 人接触过，3,703,147 人未接触过），也不包括妊娠头三个月接触后（HR，1.15；95% CI，0.83-1.58；3 项研究；n = 1,539,335；70,737 人接触过，1,468,598 人未接触过）或妊娠后三个月接触后。妊娠期任何时候接触这些药物都会增加患多动症的风险（主要结果，HR，1.07；95% CI，1.03-1.12；4 项研究；n = 2,000,777；78,912 人接触过，1,921,865 人未接触过），而且（仅）妊娠期后三个月接触这些药物也会增加患多动症的风险（HR，1.07；95% CI，1.03-1.12；3 项研究；n = 1,539,281；33,355 人接触过，1,505,926 人未接触过）。敏感性分析结果一致：结论：妊娠期接触苯二氮卓类药物或z-催眠药与后代罹患ASD的风险增加无关，仅与后代罹患ADHD的风险略有增加有关。考虑到原始研究中的适应症和未测量变量可能会造成混淆，我们的研究结果应该能让那些在怀孕期间因严重焦虑或失眠而需要服用这些药物的妇女放心。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Psychiatrica Scandinavica 医学-精神病学

CiteScore

11.20

自引率

3.00%

发文量

135

审稿时长

6-12 weeks

期刊介绍： Acta Psychiatrica Scandinavica acts as an international forum for the dissemination of information advancing the science and practice of psychiatry. In particular we focus on communicating frontline research to clinical psychiatrists and psychiatric researchers. Acta Psychiatrica Scandinavica has traditionally been and remains a journal focusing predominantly on clinical psychiatry, but translational psychiatry is a topic of growing importance to our readers. Therefore, the journal welcomes submission of manuscripts based on both clinical- and more translational (e.g. preclinical and epidemiological) research. When preparing manuscripts based on translational studies for submission to Acta Psychiatrica Scandinavica, the authors should place emphasis on the clinical significance of the research question and the findings. Manuscripts based solely on preclinical research (e.g. animal models) are normally not considered for publication in the Journal.