What is the efficacy of Proton Pump Inhibitor (PPI) with famotidine (Pepcid) in premature infants at 4 months of age?

From the Guidelines

For a 4-month-old premature infant, a PPI trial with famotidine is not recommended as first-line therapy for suspected gastroesophageal reflux disease (GERD). Instead, I recommend starting with non-pharmacological approaches such as smaller, more frequent feedings, proper positioning after feeds (left side or prone when monitored), and thickened feeds if appropriate. If medication is necessary due to significant symptoms affecting growth or causing complications, famotidine (a H2 blocker) would be preferred over a PPI, starting at 0.5-1 mg/kg/dose given twice daily, as suggested by the American Academy of Pediatrics 1. The duration of therapy should be limited to 2-4 weeks with reassessment of symptoms. PPIs like omeprazole or lansoprazole should be reserved for cases that fail H2 blocker therapy due to concerns about increased risks of infections, necrotizing enterocolitis, and altered gut microbiome in premature infants, as highlighted in the guidelines for the management of gastroesophageal reflux in children 1.

Some key points to consider when managing GERD in premature infants include:

• The potential risks of acid-suppressing medications, including increased susceptibility to infections, micronutrient malabsorption, and altered gut flora 1
• The importance of weighing the benefits and risks of medication therapy, particularly in premature infants who may be at increased risk of complications 1
• The need for careful follow-up and reassessment of symptoms to ensure that treatment is effective and to minimize the risk of adverse effects 1
• The preference for non-pharmacological approaches as first-line therapy, with medication reserved for cases with significant symptoms or complications 1

Overall, a cautious approach to the use of PPIs and H2 blockers in premature infants is warranted, with careful consideration of the potential benefits and risks of therapy. The use of PPIs should be reserved for cases that fail H2 blocker therapy, and the duration of therapy should be limited to the minimum necessary to achieve symptom control.

From the Research

PPI with Famotidine Trial in Preemie at 4 Mo

• The use of proton pump inhibitors (PPIs) in preterm infants with gastroesophageal reflux disease (GERD) has been studied in several trials 2, 3, 4.
• A study published in 2025 found that the evidence is very uncertain about the effect of PPIs on cardiorespiratory events in preterm infants with GERD 2.
• Another study published in 2007 found that omeprazole significantly reduced gastric acidity and esophageal acid exposure in preterm infants with pathological acid reflux 3.
• However, a review of clinical trials published in 2010 found that PPI therapy is not an effective treatment for common infant GERD-associated symptoms, and evidence supporting safety of PPI use in infants is conflicting 5.
• A more recent review published in 2024 highlighted the unmet needs in the management of GERD in preterm infants, including the need for an effective and safe prokinetic and non-drug treatments such as feeding adaptations and positional changes 4.

Safety and Efficacy of PPIs in Preterm Infants

• The safety and efficacy of PPIs in preterm infants with GERD are still uncertain due to the limited number of studies and the small sample sizes 2, 3, 4.
• The FDA has completed its review of four clinical trials evaluating the use of PPIs in infants, and an Advisory Committee meeting was held to discuss the potential reasons why PPI use in these trials failed to show a benefit in infants with GERD 6.
• The use of PPIs in preterm infants should be approached with caution, and further studies are needed to address the safety and efficacy of PPIs for the treatment of diagnosed or suspected GERD in preterm neonates 2, 4.

Treatment Options for GERD in Preterm Infants

• Non-drug treatments such as feeding adaptations (volume, duration, and composition) and positional changes are insufficiently applied in preterm infants with GERD 4.
• Thickened formula is not indicated in preterm babies, and low-quality evidence for alginates is available, but needs further evaluation 4.
• A 2-4 week trial of a proton pump inhibitor may be acceptable in preterm infants with GERD if documentation of acid GER is not possible and other treatment options have failed 4.