Arginine Supplementation in Necrotizing Enterocolitis (NEC)
Arginine supplementation should be considered for prevention of NEC in preterm infants, but should only be introduced when reintroducing feeds after the acute phase of NEC has resolved. 1, 2
Management During Active NEC
- During active NEC, immediate bowel rest is essential with discontinuation of all enteral feeds as recommended by ESPGHAN and other societies 1, 2
- Implement broad-spectrum antibiotics, fluid resuscitation, and nasogastric decompression during the acute phase of NEC 2
- Parenteral nutrition should be provided during bowel rest to ensure adequate protein intake (minimum 1.0 g/kg/day) to avoid negative nitrogen balance 2
- Ensure adequate non-protein caloric intake (minimum 30-40 kcal per 1g amino acids) to guarantee amino acid utilization 1, 2
When to Introduce Arginine
- Arginine supplementation should only be introduced when enteral feeds are being reintroduced after the acute phase of NEC has resolved 1, 2
- Enteral administration is the preferred route when feeds are tolerated 1
- The rationale for arginine supplementation is based on:
- Arginine is the substrate for nitric oxide production, which is important for vascular perfusion in neonates with NEC 1
- Low plasma arginine levels are observed in preterm neonates and may predispose them to NEC 1
- Arginine depletion is related to immune suppression that occurs in newborn models of bacterial challenge 1
Evidence Supporting Efficacy
- The ESPGHAN/ESPEN/ESPR/CSPEN guidelines provide a conditional recommendation (Level of Evidence: 1-, Recommendation Grade B) for arginine supplementation in the prevention of NEC in preterm infants 1
- A randomized, double-blind, placebo-controlled study demonstrated that arginine supplementation at 1.5 mmol/kg/day (261 mg/kg/day) significantly reduced the incidence of all stages of NEC in premature infants with birth weight ≤1250g and gestational age ≤32 weeks 3
- Arginine supplementation has been associated with significant reduction in mortality due to NEC 4
Monitoring and Safety Considerations
- Monitor for signs of feeding intolerance when reintroducing enteral feeds with arginine supplementation 1
- The recommended dosage based on available evidence is 1.5 mmol/kg/day (261 mg/kg/day) of arginine 4, 3
- Be aware that some experimental studies have shown mixed results - one rat model study showed higher mortality with L-arginine alone, suggesting careful monitoring is needed 5
Prevention of Recurrence
- Consider continued arginine supplementation after recovery from NEC to help prevent recurrence 2
- Consider combining with probiotic supplementation for prevention of recurrent NEC, particularly combinations of Lactobacillus spp. and Bifidobacterium spp. 2
By following this approach to arginine supplementation in NEC, you can potentially reduce the incidence and mortality of this serious condition while ensuring patient safety through appropriate timing and monitoring.