Ibp in pregnancy

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CLINICAL REVIEWS

1541

The Safety of Proton Pump Inhibitors (PPIs) in Pregnancy: A Meta-Analysis
Simerpal K. Gill1,2, Lisa O’Brien1,3, omas R. Einarson4 and Gideon Koren, MD, FRCPC1,2,3

OBJECTIVES:

Heartburn and acid reflux are common medical disorders in pregnancy and can result in serious discomfort and complications. Furthermore, some pregnant women alsoexperience more severe gastrointestinal conditions, such as Helicobacter pylori infections, peptic ulcers, and Zollinger– Ellison syndrome. To allow the use of proton pump inhibitors (PPIs) in pregnancy, the fetal safety of this drug class must be established. The aim of this study is to determine the fetal safety of PPIs during early pregnancy through systematic literature review. All originalresearch assessing the safety of PPIs in pregnancy was sought from inception to July 2008. Two independent reviewers identified articles, compared results, and settled differences through consensus. The Downs–Black scale was used to assess quality. Data assessed included congenital malformations, spontaneous abortions, and preterm delivery. A random effects metaanalysis combined the results fromincluded studies. Of the 60 articles identified, 7 met our inclusion criteria. Using data from 134,940 patients, including 1,530 exposed and 133,410 not exposed to PPIs, the overall odds ratio (OR) for major malformations was 1.12 (95% confidence interval, CI: 0.86 –1.45). Further analysis revealed no increased risk for spontaneous abortions (OR = 1.29, 95% CI: 0.84 –1.97); similarly, there was noincreased risk for preterm delivery (OR = 1.13, 95% CI: 0.96 –1.33). In the secondary analysis of 1,341 exposed and 120,137 not exposed to omeprazole alone, the OR and 95% CI for major malformations were 1.17 and 0.90 –1.53, respectively. birth defects, spontaneous abortions, or preterm delivery. The narrow range of 95% CIs is further reassuring, suggesting that PPIs can be safely used in pregnancy.METHODS:

RESULTS:

CONCLUSIONS: On the basis of these results, PPIs are not associated with an increased risk for major congenital

Am J Gastroenterol 2009; 104:1541–1545; doi:10.1038/ajg.2009.122; published online 28 April 2009

INTRODUCTION Gastrointestinal (GI) complications in pregnancy are common: the incidence of gastroesophageal re ux disorders (GERD) in pregnancy ranges between 40and 85% (1–5). Serious GI conditions that are fairly common in pregnancy and that require pharmacological treatment include Helicobacter pylori-infections, peptic and duodenal ulcers, and the Zollinger–Ellison syndrome (6). e onset of these medical conditions can occur at any time during pregnancy, and may be related to gastric arrhythmias and to reduced GI motility (7–9). Furthermore,
1these aforementioned medical conditions are associated with increased nausea and vomiting during pregnancy, which, in turn, results in decreased quality of life (10). Although initial treatment in pregnancy usually involves lifestyle and diet modi cations for less severe GERD symptoms, pharmacotherapy is required when symptoms are not controlled, speci cally in the case of H. pylori infections andulcers (3,4). Proton pump inhibitors (PPIs) were introduced in the market in 1989, and are considered a key advancement in the treatment of acid-peptic diseases (11). eir mechanism of action

The Motherisk Program, The Hospital for Sick Children, Toronto, Canada; 2Department of Pharmacology, University of Toronto, Toronto, Canada; 3Institute of Medical Science, University of Toronto, Toronto,Canada; 4Department of Pharmacy, University of Toronto, Toronto, Canada. Correspondence: Gideon Koren, MD, FRCPC, The Motherisk Program, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada. E-mail: gkoren@sickkids.ca Received 22 October 2008; accepted 12 January 2009
© 2009 by the American College of Gastroenterology

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