Does albumin (human albumin) administration cause necrotizing enterocolitis (NEC) in neonates?

Albumin Administration and Necrotizing Enterocolitis in Neonates

Albumin administration in neonates is associated with an increased risk of necrotizing enterocolitis (NEC) and should be avoided unless absolutely necessary for other critical indications. 1

Evidence on Albumin and NEC Risk

The relationship between albumin administration and NEC in neonates is supported by several key findings:

• Exchange transfusions, which involve albumin administration, have been associated with significant morbidity including necrotizing enterocolitis in up to 5% of procedures 1

• Recent international guidelines strongly recommend against albumin use in preterm neonates (≤32 weeks or ≤1,500g) with or without hypoperfusion for volume replacement, citing very low certainty of evidence but potential harm 1

• In pediatric patients, both albumin and saline boluses have been associated with excess mortality compared to no bolus strategies, with higher rates of respiratory and neurologic dysfunction 1

Pathophysiological Mechanisms

The mechanism by which albumin may contribute to NEC development likely involves:

1. Altered intestinal perfusion: Rapid volume expansion with albumin may cause fluctuations in mesenteric blood flow, potentially leading to ischemia-reperfusion injury in the immature gut

2. Inflammatory response: Albumin administration may trigger inflammatory cascades that can damage the intestinal mucosa

3. Disruption of normal intestinal barrier function: Studies have shown that hypoalbuminemia itself may be a risk factor for NEC 2, but paradoxically, rapid correction with exogenous albumin may cause harm through osmotic shifts and altered perfusion

Clinical Implications and Recommendations

For Volume Replacement in Neonates:

• First-line fluid choice: Crystalloids should be preferred over albumin for routine volume replacement in neonates 1
• Bolus administration caution: Both albumin and saline boluses have been associated with adverse outcomes in pediatric patients 1

For Preterm Infants:

• Alternative preventive strategies for NEC should be prioritized:
  • Human breast milk feeding 3
  • Standardized feeding protocols with slow advancement 3
  • Probiotics (particularly combinations of Lactobacillus and Bifidobacterium species) 1, 3
  • Arginine supplementation may be considered for NEC prevention 1

For Hypoalbuminemia:

• While hypoalbuminemia has been associated with increased NEC risk 2, rapid correction with albumin administration may paradoxically increase risk
• Address underlying causes of hypoalbuminemia rather than simply correcting the albumin level

Caveats and Special Considerations

• Timing matters: The risk appears greatest with bolus administration rather than slow infusion
• Context-specific use: In certain critical situations (severe shock unresponsive to crystalloids, severe hypoalbuminemia with edema affecting vital organ function), the benefits of albumin may outweigh the risks
• Monitoring: If albumin must be used, close monitoring for signs of NEC is essential (abdominal distension, feeding intolerance, bloody stools)

Alternative Approaches for NEC Prevention

Focus on evidence-based preventive strategies for NEC:

• Breast milk feeding whenever possible 3
• Standardized feeding protocols 3
• Probiotics administration 1, 3
• Restrictive antibiotic use to preserve normal microbiome development 3, 4
• Antenatal corticosteroids for fetal lung maturation 3

In conclusion, the evidence suggests that albumin administration carries risks for neonates, including potential contribution to NEC development. Alternative fluid management strategies and preventive approaches for NEC should be prioritized in neonatal care.