Is omeprazole (proton pump inhibitor) safe to use during pregnancy?

Safety of Omeprazole During Pregnancy

Omeprazole is considered safe for use during pregnancy, with no evidence of increased risk of major congenital malformations or other adverse pregnancy outcomes. 1

Evidence on Omeprazole Safety in Pregnancy

FDA Labeling and Epidemiological Data

• The FDA drug label indicates there are no adequate and well-controlled studies showing increased risk of major congenital malformations or adverse pregnancy outcomes with first-trimester omeprazole use 1
• Multiple epidemiological studies have demonstrated safety:
  • A population-based retrospective cohort study from the Swedish Medical Birth Registry covering 955 infants exposed to omeprazole during pregnancy showed no increase in malformations 1
  • A Danish population-based study of 1,800 live births with first-trimester omeprazole exposure found birth defect rates of 2.9% compared to 2.6% in unexposed pregnancies 1

Meta-Analysis and Controlled Studies

• A meta-analysis of 134,940 patients (including 1,530 exposed to PPIs) found no increased risk for:
  • Major malformations (OR 1.12,95% CI: 0.86-1.45)
  • Spontaneous abortions (OR 1.29,95% CI: 0.84-1.97)
  • Preterm delivery (OR 1.13,95% CI: 0.96-1.33) 2
• A multicenter prospective controlled study by the European Network of Teratology Information Services followed 295 pregnancies exposed to omeprazole (233 in first trimester) and found no difference in major congenital anomalies compared to controls (3.6% vs 3.8%) 3

Clinical Applications and Recommendations

Use in Pregnancy

• Omeprazole can be used when clinically indicated for treatment of gastroesophageal reflux disease (GERD) or peptic ulcer disease during pregnancy
• The 2019 Annals of Oncology guidelines specifically list proton pump inhibitors among medications that can be used if necessary during pregnancy 4
• For GERD in pregnancy, a step-up approach is recommended:
  1. Start with lifestyle modifications and dietary changes
  2. Progress to antacids and alginates if needed
  3. Consider H2-receptor antagonists
  4. Use PPIs like omeprazole for refractory symptoms 5

Dosing Considerations

• Standard dosing of omeprazole 20mg daily is appropriate during pregnancy 4
• Equivalent doses of other PPIs may also be considered if preferred:
  • Lansoprazole 30mg once daily
  • Esomeprazole 20mg once daily
  • Pantoprazole 40mg once daily
  • Rabeprazole 20mg once daily 4

Important Caveats and Considerations

• While omeprazole is considered safe, it should be used at the lowest effective dose for the shortest duration necessary to control symptoms
• PPIs may decrease the absorption of medications requiring acidic gastric pH for optimal absorption
• For women with severe reflux symptoms during pregnancy, the benefits of symptom relief and prevention of complications generally outweigh the minimal risks of medication exposure
• Small studies have shown minimal secretion of omeprazole into breast milk, with concentrations less than 7% of serum levels, suggesting it is likely safe during lactation 6

By following these evidence-based recommendations, clinicians can confidently prescribe omeprazole when indicated during pregnancy while minimizing any theoretical risks to the developing fetus.