What Proton Pump Inhibitors (PPIs) and Histamine 2 (H2) blockers are safe for use in pregnant women?

PPIs and H2 Blockers in Pregnancy

Lansoprazole and omeprazole are safe PPIs to use during pregnancy, and H2 blockers, particularly ranitidine and famotidine, are also safe options for pregnant women. 1, 2, 3

Approved and Safe PPIs for Pregnancy

Lansoprazole and omeprazole are the preferred PPIs during pregnancy based on the most extensive safety data. 1, 2

• Lansoprazole (FDA Pregnancy Category B) has animal studies showing no fetal risk, and available human observational studies have not demonstrated an association with adverse pregnancy outcomes. 1

• Omeprazole has been studied in multiple large epidemiological studies without showing increased risk of major malformations. A Swedish registry study of 955 infants exposed to omeprazole showed no difference in malformation rates compared to the general population. 2

• A meta-analysis of 1,530 pregnant women exposed to PPIs showed 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), or preterm delivery (OR=1.13,95% CI: 0.96-1.33). 4

• Avoid omeprazole only if other PPIs are available, as some guidelines suggest using PPIs "except omeprazole" after the first trimester, though the evidence for this distinction is weak. 5

• Pantoprazole and lansoprazole showed similar safety profiles in a European multicenter study with major anomaly rates of 2.1% and 3.9% respectively, compared to 3.8% in controls. 6

H2 Blockers Are Safe in Pregnancy

H2 blockers, particularly ranitidine and famotidine, are safe and effective options during pregnancy. 3, 5

• Famotidine is FDA Pregnancy Category B, with animal studies at doses up to 243 times the human dose showing no adverse developmental effects. 3

• Ranitidine is specifically preferred among H2 blockers for pregnant women according to gastroenterology guidelines. 5

• H2 blockers or PPIs are allowed throughout pregnancy and breastfeeding according to European cardiology guidelines for pericarditis management in pregnancy. 7

Treatment Algorithm for Pregnant Women with Acid-Related Disorders

Step 1: First-line therapy (any trimester)

• Lifestyle modifications and dietary changes 5
• Alginic acid or sucralfate (minimal systemic absorption) 5
• Calcium- or magnesium-based antacids (particularly useful in preeclampsia) 5

Step 2: If inadequate response

• Ranitidine (H2 blocker) as the preferred next step 5
• Famotidine as an alternative H2 blocker 3

Step 3: If H2 blockers fail

• Lansoprazole or omeprazole after the first trimester, considering benefit-harm ratio 1, 2, 5
• Can be used in first trimester if benefits clearly outweigh risks 1, 2

Critical Safety Considerations

• All NSAIDs (except low-dose aspirin ≤100 mg/day) must be withdrawn by gestational week 32 to prevent ductus arteriosus constriction and impaired fetal renal function. 7

• Maintaining adequate treatment is safer than withholding therapy, as uncontrolled symptoms can lead to maternal complications that pose greater fetal risk than the medications themselves. 8

• Breastfeeding is safe with both PPIs and H2 blockers. Lansoprazole and omeprazole metabolites appear in rat milk but human data is limited. 1, 2 Famotidine has limited data showing no effects on breastfed infants. 3

Common Pitfalls to Avoid

• Do not withhold necessary PPI or H2 blocker therapy due to pregnancy concerns alone, as the narrow confidence intervals in large studies (95% CI: 0.86-1.45 for major malformations) provide strong reassurance of safety. 4

• Do not rely solely on antacids for moderate-to-severe symptoms, as inadequate acid suppression can lead to complications like esophagitis or aspiration risk. 5

• Do not confuse the limited human data on newer PPIs (pantoprazole, lansoprazole) with actual evidence of harm—the available studies show similar safety profiles to omeprazole. 6