What are the guidelines for using human albumin (HA) 20% in neonates?

Human Albumin 20% in Neonates: Evidence-Based Guidelines

Human albumin 20% should NOT be used routinely in neonates for volume expansion, hypoalbuminemia, or critical illness, as there is insufficient evidence of benefit and potential for harm. 1

Key Recommendations Against Routine Use

Critical Care and Volume Expansion

• The International Collaboration for Transfusion Medicine Guidelines (2024) explicitly recommends against routine albumin use in neonatal critical care. 1
• A Cochrane systematic review of preterm neonates (≤36 weeks' gestation) with hypoalbuminemia found only two small RCTs (64 neonates total) showing no mortality difference and no improvement in clinically important outcomes. 1
• For early volume expansion in preterm neonates (≤32 weeks or ≤1,500g) in the first 3 days of life, eight studies comparing albumin to alternatives showed no benefit. 1

Pediatric Critical Care Context

• While the evidence is primarily from older children, a large trial (FEAST trial, 3,141 children) demonstrated excess mortality with albumin bolus strategy (RR 1.45; 95% CI 1.10-1.92) compared to no bolus in children with febrile illness and hypoperfusion. 1
• This finding raises significant safety concerns about aggressive fluid bolus strategies in critically ill children, though applicability to neonates requires caution in interpretation. 1

Limited Evidence for Specific Neonatal Indications

Hyperbilirubinemia

• One small RCT (50 term neonates) showed that 1 g/kg of 20% albumin given one hour before exchange transfusion significantly reduced post-exchange bilirubin levels and phototherapy duration without adverse effects. 2
• This represents the only neonatal indication with positive trial data, but evidence is limited to a single study in term infants requiring exchange transfusion. 2

Hypoalbuminemia Without Specific Indication

• A Cochrane review found insufficient evidence to support albumin infusion for low serum albumin alone in preterm neonates. 3
• One small study (10 premature infants) showed transient increases in blood volume (15.5%) and colloid osmotic pressure, but blood volume returned to baseline by 3 hours in most cases with unpredictable individual responses. 4
• Another small study showed improved urine output and weight reduction 6 hours post-infusion in infants with respiratory distress syndrome and albumin <30 g/L, but no long-term outcomes were assessed. 5

Important Clinical Caveats

Physiologic Considerations

• Neonatal albumin concentrations vary greatly with gestational and postnatal age, making "hypoalbuminemia" difficult to define. 6
• Albumin infusion initiates complex processes that vary by individual and disease pathophysiology, with potential for harm when misused. 6
• The cardiovascular response to albumin in individual neonates is highly unpredictable, with wide variations both between and within subjects. 4

Safety Concerns

• Potential adverse effects include fluid overload, hemodilution, anaphylaxis, and theoretical infection risk as a blood product. 7, 3
• The transient nature of volume expansion (lasting only 3 hours in most cases) questions the clinical utility of albumin for hemodynamic support. 4

Cost Considerations

• Albumin 20% costs approximately $130 per 25g, making it significantly more expensive than crystalloid alternatives without proven superiority in neonates. 7

Practical Algorithm for Decision-Making

When considering albumin 20% in a neonate:

1. First-line approach: Use crystalloid solutions for volume expansion and resuscitation. 1

2. Consider albumin ONLY in these specific scenarios:

   • Term neonate requiring exchange transfusion for severe hyperbilirubinemia (1 g/kg one hour before procedure). 2
   • No other neonatal indications have sufficient evidence to support use. 1, 3

3. Do NOT use albumin for:

   • Routine volume expansion in preterm or term neonates. 1
   • Treatment of low serum albumin without other specific indications. 7, 3
   • Delivery room resuscitation. 6
   • Sepsis or postoperative fluid management (insufficient neonatal evidence). 6

4. If albumin is used despite limited evidence:

   • Monitor closely for fluid overload and unpredictable hemodynamic responses. 7, 4
   • Recognize that effects may be transient (3 hours or less). 4
   • Document clear rationale given lack of evidence-based support. 3