Which proton pump inhibitors (PPIs) are safe for use during pregnancy?

Safety of Proton Pump Inhibitors During Pregnancy

Proton pump inhibitors (PPIs) are generally safe to use during pregnancy, with omeprazole having the most safety data available. 1, 2

Safety Profile of Specific PPIs

• Omeprazole has the most extensive safety data in pregnancy, with multiple studies showing no increased risk of major congenital malformations compared to the general population 1, 2
• Lansoprazole has been studied in pregnancy with no evidence of increased risk for major birth defects, spontaneous abortions, or preterm delivery 3, 2
• Pantoprazole also appears safe based on available data, with no significant difference in congenital anomaly rates compared to controls 2

Evidence Supporting PPI Safety in Pregnancy

• FDA labeling for omeprazole states that "available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use" 1
• A multicentre prospective controlled study by the European Network of Teratology Information Services found no difference in the rate of major congenital anomalies between women exposed to PPIs (omeprazole, lansoprazole, pantoprazole) and controls 2
• A meta-analysis of 1,530 pregnancies exposed to PPIs showed no increased risk for major congenital birth defects (OR=1.12,95% CI: 0.86-1.45), spontaneous abortions, or preterm delivery 4
• A study that included data from medical pregnancy terminations also found no association between PPI exposure and increased risk of congenital malformations (adjusted OR 1.06; 95% CI = 0.84-1.33) 5

Guidelines for PPI Use in Pregnancy

• According to clinical guidelines, PPIs can be safely used if necessary during pregnancy for treatment of GERD and other acid-related disorders 6
• PPIs are listed among medications that "can be used if necessary" in pregnancy according to maternal-fetal medicine guidelines 6
• When treating GERD in pregnancy, a step-up approach is recommended, starting with lifestyle modifications and antacids, then progressing to H2-receptor antagonists, and finally PPIs if symptoms persist 7

Considerations and Precautions

• While PPIs are considered safe, they should be used at the lowest effective dose for the shortest duration needed to control symptoms 7, 8
• Long-term use of PPIs during pregnancy should be avoided unless clearly indicated, as some studies suggest potential risks with prolonged use 8
• For women with severe GERD symptoms requiring PPI therapy during pregnancy, omeprazole is often considered the preferred choice due to having the most safety data 1, 2, 7

Clinical Decision Algorithm

1. Start with lifestyle modifications and dietary changes for mild GERD symptoms in pregnancy
2. If symptoms persist, consider antacids or alginates as first pharmacological intervention
3. For moderate symptoms not responding to antacids, consider H2-receptor antagonists (e.g., ranitidine)
4. For severe symptoms or those not responding to H2-blockers, use PPIs with preference for omeprazole due to most extensive safety data 1, 2
5. Use the lowest effective dose for the shortest duration needed to control symptoms 7

In conclusion, omeprazole has the most safety data in pregnancy, but lansoprazole and pantoprazole also appear safe based on available evidence. The benefit of treating severe GERD symptoms during pregnancy generally outweighs the minimal potential risks of PPI therapy.