Objectives: Heartburn and acid reflux are common medical disorders in pregnancy and can result in serious discomfort and complications. Furthermore, some pregnant women also experience 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.
Methods: All original research 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 meta-analysis combined the results from included studies.
Results: 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 no increased 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.
Conclusions: On the basis of these results, PPIs are not associated with an increased risk for major congenital 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.