What are the guidelines for using proton pump inhibitors (PPIs) during pregnancy?

Proton Pump Inhibitors in Pregnancy

Proton pump inhibitors (PPIs) can be safely used during pregnancy when clinically indicated, as they have not been associated with increased risk of major malformations or adverse pregnancy outcomes. 1, 2, 3

Safety Profile of PPIs in Pregnancy

• FDA drug labels for pantoprazole and lansoprazole indicate that available data from observational studies do not demonstrate an association between PPIs and major malformations or adverse pregnancy outcomes 1, 2
• The estimated background risk of major birth defects in the general population is 2-4%, and studies of pregnant women exposed to PPIs show comparable rates of malformations 1, 3
• 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 control groups 3
• Meta-analyses comparing pregnant women exposed to PPIs in the first trimester with unexposed pregnant women showed no significant increases in risk for congenital malformations (OR=1.12,95% CI 0.86-1.45) 1, 2

Guidelines for PPI Use During Pregnancy

• PPIs are allowed throughout pregnancy and breastfeeding according to European Society of Cardiology guidelines 4
• For treatment of gastroesophageal reflux disease (GERD) in pregnancy, a step-up approach is recommended:
  1. Start with lifestyle and dietary modifications 5
  2. Progress to antacids and alginates if needed 5
  3. Consider histamine H2 receptor antagonists 5
  4. Use PPIs when symptoms are not adequately controlled by other measures 5

Specific PPI Recommendations

• Pantoprazole: No evidence of harm to the fetus in animal reproduction studies at doses up to 88 times the recommended human dose 1
• Lansoprazole: No adverse effects on embryo-fetal development in animal studies at doses up to 40 times the recommended human dose 2
• Omeprazole has the most pregnancy safety data and may be considered the preferred PPI when treatment is required during pregnancy 6

Clinical Considerations and Precautions

• While PPIs are generally considered safe, they should be used at the lowest effective dose and duration necessary to control symptoms 5
• PPIs can be used throughout all trimesters of pregnancy when clinically indicated 4
• For women with cancer requiring supportive care during pregnancy, PPIs can be used if necessary as part of their treatment regimen 4
• Avoid prolonged or unnecessary use of PPIs during pregnancy, as long-term use may potentially lead to vitamin and mineral deficiencies 6

Breastfeeding Considerations

• PPIs are considered compatible with breastfeeding 4
• Pantoprazole has been detected in breast milk at very low levels, with a milk-to-plasma ratio of 0.022, and the relative dose to the infant was estimated to be only 0.14% of the weight-adjusted maternal dose 1
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PPI therapy 1, 2

In summary, PPIs can be safely used during pregnancy when clinically indicated, with no evidence of increased teratogenic risk. The choice of specific PPI and treatment duration should be based on the severity of symptoms and response to therapy.