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

Safety of Proton Pump Inhibitors (PPIs) During Pregnancy

Proton pump inhibitors are generally safe to use during pregnancy, with no evidence of increased risk for major congenital malformations, spontaneous abortions, or preterm delivery. 1

Evidence on PPI Safety in Pregnancy

• FDA drug labels for PPIs such as lansoprazole and omeprazole indicate that available epidemiological data do not demonstrate an association with adverse pregnancy outcomes or increased risk of birth defects 2, 3

• A meta-analysis of studies including 1,530 pregnant women exposed to PPIs in the first trimester compared to 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations (OR=1.12,95% CI: 0.86-1.45) or spontaneous abortions (OR=1.29,95% CI: 0.84-1.97) 1

• A prospective controlled study by the European Network of Teratology Information Services followed 295 pregnancies exposed to omeprazole, 62 to lansoprazole, and 53 to pantoprazole, finding no difference in major congenital anomalies compared to controls 4

• A study that included data from medical pregnancy terminations (which strengthens the analysis by avoiding selection bias) confirmed that PPI exposure was not associated with increased risk of congenital malformations (adjusted OR 1.06; 95% CI = 0.84-1.33) 5

Clinical Considerations for PPI Use in Pregnancy

• PPIs are considered appropriate for pregnant women when symptoms of gastroesophageal reflux disease (GERD) do not respond to lifestyle modifications and less intensive therapies 6

• A step-up approach is recommended for treating GERD in pregnancy:

  1. Start with lifestyle and dietary modifications
  2. Progress to antacids and alginates if needed
  3. Consider histamine H2 receptor antagonists
  4. Use PPIs when symptoms remain uncontrolled with previous measures 6

• The European Society of Cardiology guidelines note that PPIs are allowed throughout pregnancy and breastfeeding 7

Specific PPI Medications in Pregnancy

• Omeprazole has the most data supporting its safety in pregnancy, with population-based studies showing no increased risk of adverse outcomes 3, 4

• Lansoprazole safety data shows no difference in the rate of major malformations between exposed and unexposed pregnancies 2, 4

• Pantoprazole also appears to have a favorable safety profile in pregnancy based on available data 4

Important Considerations and Precautions

• When prescribing any medication during pregnancy, use the lowest effective dose for the shortest duration necessary 6

• The benefits of treating significant GERD symptoms during pregnancy generally outweigh the potential risks of PPI therapy 6

• For women who are breastfeeding, PPIs are considered compatible with lactation 7

• If a pregnant woman requires medication for GERD, the potential adverse effects of untreated symptoms (poor nutrition, weight loss, insomnia) should be weighed against the minimal risks associated with PPI therapy 1, 6