Women's Mood and Anxiety Clinic: Reproductive Transitions, Department of Psychiatry, Sunnybrook Health Sciences Centre, FG 29, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada.
Mood and Anxiety Disorders Clinic: Reproductive Transitions, Department of Psychiatry, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario, Canada.
J Clin Psychiatry. 2019 Jul 9;80(4):18r12412. doi: 10.4088/JCP.18r12412.
To summarize the effects of antenatal benzodiazepine exposure as monotherapy and in combination with antidepressants on the risk of congenital malformations.
MEDLINE, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched from inception to June 30, 2018, using controlled vocabulary and keywords (eg, prenatal, benzodiazepines, malformation).
English-language cohort studies with prospectively collected data on the risk of malformations in benzodiazepine-exposed and -unexposed offspring were evaluated. 23,909 records were screened, 56 studies were assessed for eligibility, and 8 studies were included.
Quality was assessed by 2 independent reviewers and data extracted. Random-effects models were used for outcomes (≥ 3 studies). Subanalyses examined effect of potential moderators including study quality and timing of exposure, among others.
Prenatal benzodiazepine use was not associated with an increased risk of congenital malformations (odds ratio [OR] = 1.13; 95% CI, 0.99 to 1.30, 8 studies, n = 222/5,195 exposed and 64,335/2,082,467 unexposed), including with first trimester exposure specifically (OR = 1.08; 95% CI, 0.93 to 1.25, P = .33; 5 studies, n = 181/4,331 exposed and 64,308/2,081,463 unexposed). There was no significant association with cardiac malformation following exposure (OR = 1.27; 95% CI, 0.98 to 1.65, P = .07; 4 studies, n = 61/4,414 exposed and 19,260/2,033,402 unexposed). However, concurrent use of benzodiazepine and antidepressants during pregnancy was associated with a significantly increased risk of congenital malformations (OR = 1.40; 95% CI, 1.09 to 1.80, P = .008; 3 studies).
Benzodiazepine exposure during pregnancy does not appear to be associated with congenital malformations or with cardiac malformations specifically. There may be an increased risk of congenital malformations when benzodiazepines are used in conjunction with antidepressants, suggesting that caution with this combination is warranted.
总结产前苯二氮䓬类药物单药治疗和联合抗抑郁药治疗对先天性畸形风险的影响。
从建库到 2018 年 6 月 30 日，通过使用受控词汇和关键词（例如产前、苯二氮䓬类药物、畸形），在 MEDLINE、PsycINFO、CINAHL、Embase 和 Cochrane 图书馆中进行了检索。
评估了具有前瞻性收集苯二氮䓬类药物暴露后代畸形风险数据的英语队列研究。筛选了 23909 条记录，评估了 56 项研究的合格性，纳入了 8 项研究。
由 2 名独立评审员评估质量并提取数据。使用随机效应模型进行（≥ 3 项研究的）结局分析。亚分析检查了潜在调节因素的影响，包括研究质量和暴露时间等。
产前苯二氮䓬类药物使用与先天性畸形风险增加无关（比值比[OR] = 1.13；95%置信区间，0.99 至 1.30，8 项研究，n = 222/5195 暴露和 64335/2082467 未暴露），包括特定的孕早期暴露（OR = 1.08；95%置信区间，0.93 至 1.25，P =.33；5 项研究，n = 181/4331 暴露和 64308/2081463 未暴露）。暴露后心脏畸形无显著相关性（OR = 1.27；95%置信区间，0.98 至 1.65，P =.07；4 项研究，n = 61/4414 暴露和 19260/2033402 未暴露）。然而，怀孕期间同时使用苯二氮䓬类药物和抗抑郁药与先天性畸形风险显著增加相关（OR = 1.40；95%置信区间，1.09 至 1.80，P =.008；3 项研究）。
怀孕期间苯二氮䓬类药物暴露似乎与先天性畸形或特定的心脏畸形无关。当苯二氮䓬类药物与抗抑郁药联合使用时，先天性畸形的风险可能会增加，因此谨慎使用这种联合用药是有必要的。
