Ondansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital malformations (MCM), cardiac defects and orofacial clefts associated with first trimester exposure to ondansetron using a meta‐analytic approach. MEDLINE, ClinicalTrials.gov and Scopus were searched until November 2019. All comparative cohort and case–control studies on MCM, cardiac or orofacial defects and use of ondansetron during pregnancy were included. A team of paired reviewers independently extracted data using a proprietary collaborative WEB‐based meta‐analysis platform (metaPreg.org). Pooled odd ratios with corresponding 95% CIs were calculated using random effects models. From 214 records initially retrieved, 12 studies were included. Using all available information to date, first trimester exposure to ondansetron was found to be associated with an increased risk of (a) ventricular septal defects (VSD) (OR 1.11, 95% CI 1.00–1.23; p < .05; n = 6 studies; I² = 0%) and (b) oral clefts (OR 1.22, 95% CI 1.00–1.49; p < .05; n = 4 studies; I² = 0%). No significant association was observed for the risk of cleft palate but, when excluding the study that contributed to the study heterogeneity, we found an OR of 1.48 (95% CI 1.19–1.84; p < .01; n = 5 studies; I² = 0%). No statistically significant association was found for MCM, overall cardiac malformations, atrial septal defects and cleft lip with or without cleft palate. Exploratory investigations of other malformations showed an increased risk of diaphragmatic hernia, hypoplastic left heart and “respiratory system anomalies.”

中文翻译：

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妊娠期昂丹司琼后畸形的风险：更新的系统评价和荟萃分析。

昂丹司琼越来越多地被用于治疗怀孕期间的恶心和呕吐。本研究的主要目的是使用荟萃分析方法评估与孕早期暴露于昂丹司琼相关的严重先天性畸形 (MCM)、心脏缺陷和口颌面裂的风险。检索了 MEDLINE、ClinicalTrials.gov 和 Scopus，直至 2019 年 11 月。 纳入了所有关于 MCM、心脏或口面部缺陷以及怀孕期间使用昂丹司琼的比较队列和病例对照研究。一组配对审查员使用专有的基于 WEB 的协作元分析平台 (metaPreg.org) 独立提取数据。使用随机效应模型计算具有相应 95% CI 的合并奇数比。从最初检索的 214 条记录中，包括 12 项研究。p  < .05；n = 6 项研究；I ² = 0%) 和 (b) 口腔裂隙（OR 1.22，95% CI 1.00–1.49；p  < .05；n = 4 项研究；I ² = 0%）。未观察到腭裂风险的显着关联，但排除导致研究异质性的研究后，我们发现 OR 为 1.48（95% CI 1.19–1.84；p  < .01；n = 5 项研究；I ²= 0%）。未发现 MCM、整体心脏畸形、房间隔缺损和唇裂伴或不伴腭裂的显着相关性。对其他畸形的探索性调查显示膈疝、左心发育不良和“呼吸系统异常”的风险增加。