What is the treatment for hyperbilirubinemia?

Treatment of Hyperbilirubinemia

Phototherapy is the primary treatment for hyperbilirubinemia, with exchange transfusion reserved for severe cases when total serum bilirubin (TSB) reaches critical levels or signs of acute bilirubin encephalopathy are present. 1

Assessment and Risk Stratification

• Evaluate all jaundiced infants by measuring total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) levels, as visual estimation of jaundice is unreliable, especially in darkly pigmented infants 1
• Risk factors for developing severe hyperbilirubinemia include:
  • Family history of neonatal jaundice
  • Exclusive breastfeeding
  • Bruising or cephalohematoma
  • Asian or Black ethnicity
  • Maternal age >25 years
  • Male sex
  • Glucose-6-phosphate dehydrogenase deficiency
  • Gestational age <38 weeks 1
• Laboratory evaluation for significant hyperbilirubinemia should include:
  • TSB and direct bilirubin levels
  • Blood type (ABO, Rh)
  • Direct antibody test (Coombs')
  • Serum albumin
  • Complete blood count with differential
  • Reticulocyte count
  • G6PD testing if suggested by ethnic origin or poor response to phototherapy 1

Treatment Guidelines

Phototherapy

• Initiate phototherapy based on TSB levels, gestational age, and presence of risk factors 1
• Use intensive phototherapy for severe hyperbilirubinemia, which should:
  • Deliver irradiance in the blue-green spectrum (430-490 nm)
  • Provide at least 30 μW/cm²/nm at the infant's skin
  • Cover as much of the infant's surface area as possible 1
• Continue phototherapy until TSB falls below treatment threshold, typically to 13-14 mg/dL (239 μmol/L) 1
• For infants receiving phototherapy:
  • Monitor TSB levels every 2-3 hours if ≥25 mg/dL
  • Monitor every 3-4 hours if 20-25 mg/dL
  • Monitor every 4-6 hours if <20 mg/dL 1
• If TSB doesn't decrease despite intensive phototherapy, suspect hemolysis 1

Exchange Transfusion

• Exchange transfusion is indicated when:
  • TSB reaches exchange level threshold based on age and risk factors
  • TSB ≥25 mg/dL (428 μmol/L) at any time
  • Signs of intermediate to advanced acute bilirubin encephalopathy are present, even if TSB is falling 1
• Exchange transfusion should be performed only by trained personnel in a neonatal intensive care unit with full monitoring and resuscitation capabilities 1
• Consider TSB/albumin ratio when determining need for exchange transfusion 1
• Significant complications occur in approximately 5% of exchange transfusions, including apnea, bradycardia, cyanosis, vasospasm, thrombosis, and necrotizing enterocolitis 1

Additional Interventions

• For isoimmune hemolytic disease (e.g., Rh, ABO incompatibility):
  • Administer intravenous immunoglobulin (0.5-1 g/kg over 2 hours) if:
    • TSB is rising despite intensive phototherapy
    • TSB is within 2-3 mg/dL of exchange level 1
  • IVIG has been shown to reduce the need for exchange transfusions in Rh and ABO hemolytic disease 1

Special Considerations

Breastfeeding

• Continue breastfeeding in infants requiring phototherapy when possible 1
• If breastfeeding is temporarily interrupted, supplement with expressed breast milk or formula 1
• Encourage adequate caloric intake, as inadequate breastfeeding increases hyperbilirubinemia risk 2
• Interrupting breastfeeding solely for jaundice treatment may increase risk of early breastfeeding discontinuation 2

Follow-up

• All infants should have follow-up after discharge to assess for jaundice, with timing based on:
  • Age at discharge
  • Presence of risk factors
  • Risk of other neonatal problems 1
• Recommended follow-up schedule:
  • Discharge before 24h: see by 72h of age
  • Discharge between 24-47.9h: see by 96h of age
  • Discharge between 48-72h: see by 120h of age 1
• Consider delaying discharge if appropriate follow-up cannot be ensured for infants at high risk of severe hyperbilirubinemia 1

Special Cases

Crigler-Najjar Syndrome Type I

• Characterized by complete deficiency of uridine diphosphate glucuronosyl transferase (UGT)
• Initial management includes exchange transfusions and long-term phototherapy
• Liver transplantation is the only definitive treatment and should be considered before brain damage develops 1

Direct Hyperbilirubinemia

• In situations where direct bilirubin is ≥50% of total bilirubin, consultation with an expert is recommended 1
• Direct hyperbilirubinemia may indicate underlying liver disease, requiring specific evaluation and management 3

Pitfalls and Caveats

• Do not subtract direct bilirubin from total bilirubin when using treatment guidelines 1
• Severe hyperbilirubinemia (TSB ≥25 mg/dL) is a medical emergency requiring immediate hospital admission for intensive phototherapy; do not refer these infants to the emergency department as it delays treatment 1
• Not all infants with chronic bilirubin encephalopathy have a history of hyperbilirubinemia, and there is no screening test that reliably identifies all at-risk infants 1
• Potential harms of phototherapy include weight loss, gastrointestinal problems, disruption of maternal-infant bonding, and possible growth of melanocytic nevi 1
• Blood group incompatibility cases, especially ABO+Rh and pure Rh incompatibility, may require longer phototherapy duration 4