Can Proton Pump Inhibitors (PPIs) cause retrograde necrosis in term babies?

Proton Pump Inhibitors and Risk of Necrotizing Enterocolitis in Term Infants

Proton pump inhibitors (PPIs) should not be used in term infants due to evidence suggesting they may increase the risk of necrotizing enterocolitis (NEC) and other serious infections. 1

Evidence on PPI Use and NEC Risk

The American Academy of Pediatrics (AAP) guidelines specifically caution that acid suppression therapy, including both H2-receptor antagonists (H2RAs) and PPIs, may be a risk factor for necrotizing enterocolitis in preterm infants 1. While the question specifically asks about term infants, this serious concern warrants careful consideration across all infant populations.

The evidence shows that:

• A growing body of evidence suggests that acid suppression with either H2RAs or PPIs may increase the risk of pediatric community-acquired pneumonia, gastroenteritis, candidemia, and necrotizing enterocolitis 1
• PPIs alter the gut microbiome composition, which may contribute to these adverse outcomes 2, 3
• A 2023 nationwide cohort study of over 1.2 million children found that PPI use was associated with significantly increased risk of serious infections (adjusted HR 1.34; 95% CI, 1.32-1.36), particularly digestive tract infections (aHR 1.52; 95% CI, 1.48-1.55) 4

Mechanism of PPI-Associated NEC Risk

The pathophysiological mechanism explaining the potential link between PPIs and NEC includes:

1. Microbiome alteration: PPIs significantly change gut microbial composition, reducing beneficial commensals and increasing potentially harmful bacteria 2, 3
2. Barrier disruption: By reducing gastric acid, PPIs remove a natural barrier that prevents pathogenic bacteria from the upper GI tract from reaching the lower gut 2
3. Immune system effects: PPIs may have direct actions on the immune system that could impair defense against pathogens 4

Management Recommendations for Infant Reflux

For term infants with symptoms of gastroesophageal reflux:

First-line approaches (preferred):

• Conservative management through feeding modifications:
  • For breastfed infants: Continue breastfeeding with possible 2-4 week maternal elimination diet of milk and eggs 1, 5
  • For formula-fed infants: Consider thickened formula or extensively hydrolyzed protein/amino acid-based formula 1, 5
  • Implement smaller, more frequent feedings 5
  • Position infant upright after feedings (while awake and supervised) 1

Second-line approaches (if conservative management fails):

• H2-receptor antagonists may be considered for short-term use (less than 6 weeks) due to tachyphylaxis development, though they also carry risks 1, 5
• Surgical intervention (fundoplication) should only be considered in severe cases with life-threatening complications or high aspiration risk 5

Important Cautions and Monitoring

• Overuse concern: The AAP specifically warns about overuse and misuse of PPIs in infants with reflux, noting that placebo-controlled trials have not demonstrated superiority of PPIs over placebo for reducing irritability in infants 1
• Monitoring: If any acid-suppressing medication is used, close monitoring for signs of infection is essential 1
• Duration: If acid suppression is absolutely necessary, limit to shortest possible duration 5

Conclusion

The evidence strongly suggests avoiding PPIs in term infants due to the potential risk of necrotizing enterocolitis and other serious infections. Conservative management approaches should be exhausted before considering any pharmacological intervention. When medication is deemed necessary, the benefits must be carefully weighed against the well-documented risks, with close monitoring and limited duration of use.