BACKGROUND There have been safety concerns considering long-term proton pump inhibitor (PPI) use, also during pregnancy. AIMS To assess the risk of adverse neonatal outcomes associated with maternal intake of PPIs by means of systematic review and meta-analysis. METHODS The systematic search included PubMed, Web of Science, Cochrane Database and Embase (inception until June 2019). All studies reporting ≥1 adverse pregnancy outcome comparing PPI users to non-users. Histamine-2 receptor antagonists (H2RA) were also compared to both non-users and PPI users. Outcomes included congenital malformations, abortion, stillbirth, neonatal death, preterm birth, small for gestational age and low birth weight. Pooled odds ratios (OR) and 95% confidence intervals (CI) were obtained by random-effects modelling. PROSPERO study-protocol: CRD42018103320. RESULTS In total, 26 observational studies (20 cohort, 6 case-control studies) were identified, of which 19 assessed PPIs and 12 H2RA. PPI use was associated with an increased risk of congenital malformations (OR 1.28, 95% CI 1.09-1.52), especially in case-control studies (OR 2.04, 1.46-2.86). No associations were found between H2RA and congenital malformations. No significant associations were found between PPI use and abortions, stillbirth, neonatal death, preterm birth and low-birth weight, although H2RA use may be associated with an increased risk of preterm birth (OR 1.25, 95% CI 1.02-1.56). Although statistical heterogeneity and the risk of bias were overall low, clinical heterogeneity, information and selection bias may be present in the individual studies. CONCLUSIONS This meta-analysis suggests an association between maternal PPI use and congenital malformations in humans, yet power was insufficient to assess specific malformations and drugs.

中文翻译：

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荟萃分析的系统评价：孕期质子泵抑制剂的风险。

背景技术在怀孕期间，考虑长期使用质子泵抑制剂（PPI）也存在安全隐患。目的通过系统评价和荟萃分析评估与孕妇摄入PPI相关的新生儿不良结局的风险。方法系统搜索包括PubMed，Web of Science，Cochrane数据库和Embase（成立至2019年6月）。所有比较PPI使用者和非使用者的不良妊娠结局均≥1的研究。组胺2受体拮抗剂（H2RA）也与非使用者和PPI使用者进行了比较。结果包括先天性畸形，流产，死产，新生儿死亡，早产，胎龄小和低出生体重。通过随机效应模型获得合并的优势比（OR）和95％置信区间（CI）。PROSPERO研究协议：CRD42018103320。结果总共确定了26项观察性研究（20项队列研究，6项病例对照研究），其中19项评估了PPI和12项H2RA。PPI的使用与先天性畸形风险增加有关（OR 1.28，95％CI 1.09-1.52），尤其是在病例对照研究中（OR 2.04，1.46-2.86）。在H2RA与先天性畸形之间未发现关联。尽管使用H2RA可能与早产风险增加相关，但使用PPI与流产，死产，新生儿死亡，早产和低出生体重之间无显着关联（OR 1.25，95％CI 1.02-1.56）。尽管统计异质性和偏倚风险总体较低，但个别研究中可能存在临床异质性，信息和选择偏倚。