What are the treatment approaches for hyperbilirubinemia?

Treatment of Hyperbilirubinemia

Phototherapy is the primary treatment for neonatal hyperbilirubinemia and should be initiated based on gestational age-specific and risk factor-based thresholds, with intensive phototherapy reserved for rapidly rising or severe hyperbilirubinemia to prevent kernicterus. 1

Phototherapy Implementation

Light Specifications and Equipment

• Use blue-green light in the 460-490 nm wavelength range with an optimal peak at 478 nm 1
• Deliver irradiance of 25-35 mW/cm²/nm to at least one body surface (ventral or dorsal) 1
• LED light sources are preferred as they deliver specific wavelengths in narrow bandwidths with minimal heat generation 1
• Ensure light rays are perpendicular to the incubator surface to minimize reflectance and loss of efficacy 2

Maximizing Treatment Efficacy

• Expose 35-80% of total body surface area by changing the infant's position every 2-3 hours 2, 1
• Combine multiple devices (fluorescent tubes with fiber-optic pads or LED mattresses) to increase exposed surface area 2
• Minimize distance between the phototherapy device and the infant 2
• Avoid physical obstructions including radiant warmers, large diapers, head covers, electrode patches, and insulating plastic covers 2, 1

Expected Response and Monitoring

• Clinical impact should be evident within 4-6 hours with an anticipated decrease of more than 2 mg/dL (34 μmol/L) in serum bilirubin 2, 1
• Monitor bilirubin levels with the following schedule: 1
  • If TSB ≥ 25 mg/dL: repeat within 2-3 hours
  • If TSB 20-25 mg/dL: repeat within 3-4 hours
  • If TSB < 20 mg/dL: repeat in 4-6 hours
• Discontinue phototherapy when serum bilirubin falls below 13-14 mg/dL 1, 3

Supportive Care During Phototherapy

• Continue feeding every 2-3 hours to maintain adequate hydration 1, 3
• Monitor for adequate hydration, nutrition, and temperature control 2
• Assess for signs of early bilirubin encephalopathy including changes in sleeping pattern, deteriorating feeding pattern, or inability to be consoled while crying 2

Intensive "Crash-Cart" Phototherapy

For excessive hyperbilirubinemia approaching exchange transfusion levels, implement aggressive phototherapy using multiple devices simultaneously to maximize exposed body surface area 2. This approach has been reported to reduce the need for exchange transfusion and possibly reduce the severity of bilirubin neurotoxicity 2.

Pharmacological Interventions

Intravenous Immunoglobulin (IVIG)

• Administer IVIG 0.5-1 g/kg over 2 hours for infants with isoimmune hemolytic disease and rapidly rising TSB levels despite intensive phototherapy 1
• This intervention can reduce the need for exchange transfusion in hemolytic disease 1

Emerging Pharmacological Therapies

• Tin-mesoporphyrin (a heme oxygenase inhibitor) shows promise for preventing or treating hyperbilirubinemia but is not FDA-approved 2, 4
• Other agents under investigation include clofibrate, bile salts, laxatives, and bilirubin oxidase, but none are ready for routine clinical use 4

Exchange Transfusion

Exchange transfusion is indicated when TSB levels approach or exceed exchange level thresholds despite intensive phototherapy 1. This procedure has a complication rate of approximately 5% and a mortality rate of 3-4 per 1,000 infants 5.

• Perform immediate exchange transfusion for any infant showing signs of intermediate to advanced stages of acute bilirubin encephalopathy, even if TSB is falling 1
• Use modified whole blood (red cells and plasma) crossmatched against the mother and compatible with the infant 2
• Send blood for immediate type and crossmatch if TSB is at or approaching the exchange level 2

Special Populations and Considerations

Hemolytic Disease

• Phototherapy may be less effective in infants with hemolysis, requiring more intensive treatment 1, 3
• Measure TSB 24 hours after discharge to check for rebound hyperbilirubinemia, especially in infants with hemolytic disease 1, 3

Breastfed Infants

• Continue breastfeeding during phototherapy if possible 1, 3
• Temporary interruption with formula supplementation is an option to enhance phototherapy efficacy 1
• Milk-based formula can help lower serum bilirubin by inhibiting enterohepatic circulation 3
• Encouragement from healthcare professionals is critical to prevent early discontinuation of breastfeeding 5

Sunlight Therapy (Low-Resource Settings)

• Filtered-sunlight phototherapy may be an effective adjunct to conventional phototherapy in low- and middle-income countries 6
• Filtration is essential to block harmful ultraviolet light 6
• Sunlight therapy carries a probable increased risk of hyperthermia (NNTH 3), requiring frequent temperature monitoring 6
• Sunlight alone has not been demonstrated to be effective for treatment of established hyperbilirubinemia given its sporadic availability 6

Critical Pitfalls to Avoid

• Do not rely on visual assessment of jaundice alone; always obtain TSB or transcutaneous bilirubin measurement 3
• Do not subtract direct bilirubin from total bilirubin when making clinical decisions 3
• Avoid unnecessary prolongation of phototherapy as it separates mother and infant and may interfere with breastfeeding 3
• Do not use sunlight exposure as a reliable therapeutic tool in high-resource settings due to risks of sunburn and temperature instability 3
• Staff must be educated that phototherapy does not use ultraviolet light and that exposure is mostly harmless 2

Post-Treatment Follow-Up

• For infants who received phototherapy for hemolytic disease or before 3-4 days of age, obtain follow-up bilirubin measurement within 24 hours after discharge 1, 3
• Educate parents about signs of worsening jaundice and acute bilirubin encephalopathy, including altered feeding patterns, lethargy, high-pitched crying, hypotonia, hypertonia, opisthotonus, and retrocollis 3
• Instruct parents to seek immediate medical attention if these warning signs develop 3