Is it safe to use Proton Pump Inhibitors (PPIs) during pregnancy?

Safety of Proton Pump Inhibitors During Pregnancy

Proton pump inhibitors (PPIs) can be safely used during pregnancy when clinically indicated, as they have not been associated with increased risk of congenital malformations or other adverse pregnancy outcomes.

Evidence for PPI Safety in Pregnancy

The safety of PPIs during pregnancy is supported by multiple lines of evidence:

• FDA drug labels for omeprazole and pantoprazole indicate that animal reproduction studies have not demonstrated clear evidence of fetal harm at clinically relevant doses 1, 2.

• A multicentre prospective controlled study by the European Network of Teratology Information Services found no increased risk of major congenital anomalies with omeprazole, lansoprazole, or pantoprazole exposure during pregnancy compared to controls 3.

• A meta-analysis of 7 studies including data from 134,940 patients found no association between PPI use during pregnancy and increased risk for major congenital birth defects (OR=1.12,95% CI: 0.86-1.45), spontaneous abortions (OR=1.29,95% CI: 0.84-1.97), or preterm delivery (OR=1.13,95% CI: 0.96-1.33) 4.

• A 2012 study that included data from medical pregnancy terminations (which strengthens the analysis by avoiding selection bias) found no association between PPI exposure and increased risk of congenital malformations (adjusted OR 1.06; 95% CI = 0.84-1.33) 5.

Clinical Guidelines on PPI Use in Pregnancy

Clinical guidelines specifically mention the acceptability of PPI use during pregnancy:

• The Annals of Oncology guideline (2019) explicitly states that "metoclopramide, 5HT3 antagonists, ranitidine, proton pump inhibitors, methylprednisolone, prednisolone or hydrocortisone can be used if necessary" during pregnancy 6.

• The European Society of Cardiology guidelines on management of cardiovascular diseases during pregnancy acknowledge that PPIs can be used during pregnancy with appropriate risk assessment 6.

Practical Recommendations for PPI Use in Pregnancy

1. Step-wise approach to GERD treatment in pregnancy:

   • Begin with lifestyle and dietary modifications
   • If needed, progress to antacids and alginates
   • If symptoms persist, consider H2-receptor antagonists
   • For refractory symptoms, PPIs can be safely used 7

2. PPI selection in pregnancy:

   • Omeprazole has the most safety data in pregnancy and should be the preferred PPI when treatment is necessary 7, 3
   • Other PPIs (pantoprazole, lansoprazole) also appear safe based on available data 3

3. Duration considerations:

   • Use the lowest effective dose for the shortest duration needed
   • Long-term use should be avoided unless clearly indicated, as chronic use may potentially lead to vitamin and mineral deficiencies 8

Monitoring and Precautions

• Regular reassessment of the need for continued therapy
• Consider supplementation of vitamins and minerals if long-term therapy is required
• Discontinue PPIs if symptoms resolve with lifestyle modifications

Conclusion

The available evidence strongly supports the safety of PPIs during pregnancy when clinically indicated. Multiple studies have shown no increased risk of congenital malformations or other adverse pregnancy outcomes with PPI use. While all medications in pregnancy should be used judiciously, PPIs represent a reasonable therapeutic option for pregnant women with significant gastroesophageal reflux disease or other acid-related conditions that have not responded to more conservative measures.