Department of Psychiatry, 71545Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada.
Evaluative Clinical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada.
Can J Psychiatry. 2020 Dec;65(12):821-834. doi: 10.1177/0706743720904860. Epub 2020 Mar 9.
Understanding the effects of benzodiazepines (BZDs) on maternal/fetal health remains incomplete despite their frequent use. This article quantifies the effects of antenatal BZD exposure on delivery outcomes.
Medline, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched till June 30, 2018.
English-language cohort studies comparing antenatal BZD exposure to an unexposed group on any delivery outcome were eligible. In all, 23,909 records were screened, 56 studies were assessed, and 14 studies were included.
Two reviewers independently assessed quality and extracted data. Estimates were pooled using random effects meta-analysis. Sub-analyses examined several potential moderators including timing of exposure.
There were 9 outcomes with sufficient data for meta-analysis. Antenatal BZD exposure was significantly associated with increased risk of 6 outcomes initially: spontaneous abortion (pooled odds ratio = 1.86; 95% confidence interval [CI], 1.43 to 2.42), preterm birth (1.96; 95% CI, 1.25 to 3.08), low birth weight (2.24; 95% CI, 1.41 to 3.88), low Apgar score (2.19; 95% CI, 1.94 to 2.47), Neonatal Intensive Care Unit (NICU) admission (2.61; 95% CI, 1.64 to 4.14), and induced abortion (2.04; 95% CI, 1.23 to 3.40). There was significant heterogeneity between studies for most outcomes without consistent moderators. Birth weight (mean difference [MD]: -151.35 g; 95% CI, -329.73 to 27.03), gestational age (-0.49 weeks; 95% CI, -1.18 to 0.19), and small for gestational age (SGA; 1.42; 95% CI, 1.00 to 2.01) did not show significant associations although after adjusting for publication bias, gestational age, and SGA became significant, totaling 8 significant outcomes.
Antenatal BZD exposure appears to be statistically associated with increased risk of several adverse perinatal outcomes. Although confounds cannot be ruled out, NICU admission does appear clinically relevant and consistent with the antidepressant literature.
尽管苯二氮䓬类药物（BZDs）经常被使用，但对于其对母婴健康的影响仍不完全了解。本文旨在量化产前 BZD 暴露对分娩结局的影响。
截至 2018 年 6 月 30 日，对 Medline、PsycINFO、CINAHL、Embase 和 Cochrane 图书馆进行了检索。
符合条件的研究为比较产前 BZD 暴露与未暴露组在任何分娩结局上的差异的队列研究。共筛选出 23909 份记录，评估了 56 项研究，最终纳入了 14 项研究。
两名审查员独立评估了质量并提取了数据。使用随机效应荟萃分析汇总了估计值。亚组分析考察了几个潜在的调节因素，包括暴露时间。
有 9 个结局的数据足以进行荟萃分析。产前 BZD 暴露与 6 个结局的风险增加显著相关：自然流产（汇总优势比=1.86；95%置信区间[CI]，1.43 至 2.42）、早产（1.96；95%CI，1.25 至 3.08）、低出生体重（2.24；95%CI，1.41 至 3.88）、低 Apgar 评分（2.19；95%CI，1.94 至 2.47）、新生儿重症监护病房（NICU）入院（2.61；95%CI，1.64 至 4.14）和人工流产（2.04；95%CI，1.23 至 3.40）。大多数结局的研究之间存在显著的异质性，且没有一致的调节因素。出生体重（平均差[MD]：-151.35g；95%CI，-329.73 至 27.03）、胎龄（-0.49 周；95%CI，-1.18 至 0.19）和小于胎龄儿（SGA；1.42；95%CI，1.00 至 2.01）没有显著关联，尽管调整了发表偏倚、胎龄和 SGA 后，胎龄和 SGA 变得显著，总计 8 个显著结局。
产前 BZD 暴露似乎与多种不良围产期结局的风险增加具有统计学关联。尽管不能排除混杂因素，但 NICU 入院似乎具有临床相关性，与抗抑郁药文献一致。
