Digestive Diseases and Sciences

, Volume 47, Issue 7, pp 1526–1529 | Cite as

Use of Proton Pump Inhibitors During Pregnancy and Rates of Major Malformations: A Meta-Analysis

  • Shekoufeh Nikfar
  • Mohammad Abdollahi
  • Myla E. Moretti
  • Laura A. Magee
  • Gideon Koren


Proton pump inhibitors are used to treat gastroesophageal reflux, a symptom common in pregnancy. The aim of this study was to systematically analyze the available data on the risk for malformations following use of these agents in the first trimester of pregnancy. Medline, EMBASE, published abstracts, and reference lists were searched for articles reporting on proton pump inhibitor use in pregnancy. Summary relative risks and 95% confidence intervals (95% CI) were calculated using the Mantel-Haenszel method. Five cohort studies met the inclusion criteria for this meta-analysis. With almost 600 exposed pregnancies, the overall relative risk was 1.18 with a 95%CI of 0.72–1.94. In conclusion, proton pump inhibitors do not present a major teratogenic risk when used in recommend doses. These data are reassuring for the countless patients who have used these agents in the early part of their pregnancies.

pregnancy drug-induced malformations omeprazole antiulcer agents proton pump inhibitors 


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  1. 1.
    Cappell MS, Garcia A: Gastric and duodenal ulcers during pregnancy. Gastroenterol Clin North Am 27:169–195, 1998Google Scholar
  2. 2.
    Charan M, Katz PO: Gastroesophageal reflux disease in pregnancy. Curr Treat Options Gastroenterol 4:73–81, 2001Google Scholar
  3. 3.
    AstraZeneca: Annual report. AstraZeneca, 2000Google Scholar
  4. 4.
    Ching MS, Morgan DJ, Mihaly GW, Hardy KJ, Smallwood RA: Placental transfer of omeprazole in maternal and fetal sheep. Dev Pharmacol Ther 9:323–331, 1986Google Scholar
  5. 5.
    Moore J, Flynn RJ, Sampaio M, Wilson CM, Gillon KR: Effect of single-dose omeprazole on intragastric acidity and volume during obstetric anaesthesia. Anaesthesia 44:559–562, 1989Google Scholar
  6. 6.
    Merck: Product information: Prilosec Omeprazole. West Point, Pennsylvania, Merck & Company, 2000Google Scholar
  7. 7.
    Shimazu H, Matsuoka T, Ishikawa Y, Imanishi M, Fujii T: Reproductive and developmental toxicity study of omeprazole sodium in rats. Pharmacometrics 49:573–592, 1995Google Scholar
  8. 8.
    Einarson TR: Pharmacoeconomic applications of metaanalysis for single groups using antifungal onychomycosis lacquers as an example. Clin Ther 19:559–569, 1997Google Scholar
  9. 9.
    Ruigó mez A, Garcia Rodriguez LA, Cattaruzzi C, Troncon MG, Agostinis L, Wallander MA, Johansson S: Use of cimetidine, omeprazole, and ranitidine in pregnant women and pregnancy outcomes. Am J Epidemiol 150:476–481, 1999Google Scholar
  10. 10.
    Nielsen GL, Sorensen HT, Thulstrup AM, Tage-Jensen U, Olesen C, Ekbom A: The safety of proton pump inhibitors in pregnancy. Aliment Pharmacol Ther 13:1085–1089, 1999Google Scholar
  11. 11.
    Källén B: Delivery outcome after the use of acid-suppressing drugs in early pregnancy with special reference to omeprazole. Br J Obstet Gynaecol 105:877–881, 1998Google Scholar
  12. 12.
    Lalkin A, Loebstein R, Addis A, Ramezani-Namin F, Mastroiacovo P, Mazzone T, Vial T, Bonati M, Koren G: The safety of omeprazole during pregnancy: a multicenter prospective controlled study. Am J Obstet Gynecol 179:727–730, 1998Google Scholar
  13. 13.
    Källén BA: Use of omeprazole during pregnancy—no hazard demonstrated in 955 infants exposed during pregnancy. Eur J Obstet Gynecol Reprod Biol 96:63–68, 2001Google Scholar
  14. 14.
    Harper MA, McVeigh JE, Thompson W, Ardill JE, Buchanan KD: Successful pregnancy in association with Zollinger-Ellison syndrome. Am J Obstet Gynecol 173:863–864, 1995Google Scholar
  15. 15.
    Tsirigotis M, Yazdani N, Craft I: Potential effects of omeprazole in pregnancy. Hum Reprod 10:2177–2178, 1995Google Scholar
  16. 16.
    Brunner G, Meyer H, Athmann C: Omeprazole for peptic ulcer disease in pregnancy. Digestion 59:651–654, 1998Google Scholar
  17. 17.
    Rocke DA, Rout CC, Gouws E: Intravenous administration of the proton pump inhibitor omeprazole reduces the risk of acid aspiration at emergency cesarean section. Anesth Analg 78:1093–1098, 1994Google Scholar
  18. 18.
    Stuart JC, Kan AF, Rowbottom SJ, Yau G, Gin T: Acid aspiration prophylaxis for emergency Caesarean section. Anaesthesia 51:415–421, 1996Google Scholar

Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Shekoufeh Nikfar
    • 1
  • Mohammad Abdollahi
    • 2
  • Myla E. Moretti
    • 1
  • Laura A. Magee
    • 1
  • Gideon Koren
    • 1
  1. 1.The Motherisk ProgramHospital for Sick ChildrenTorontoCanada
  2. 2.Faculty of PharmacyUniversity of TorontoCanada

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