Treatment of Hyperbilirubinemia
Neonatal Hyperbilirubinemia (≥35 Weeks Gestation)
Phototherapy is the primary treatment for neonatal hyperbilirubinemia, with specific hour-based bilirubin thresholds determining when to initiate therapy, and exchange transfusion reserved for cases approaching critical levels or showing signs of acute bilirubin encephalopathy. 1
Risk Assessment and Monitoring
- Universal systematic assessment for risk of severe hyperbilirubinemia is essential for all newborns ≥35 weeks gestation to prevent kernicterus 1
- Measure total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) in all infants, using hour-specific nomograms to determine risk level 1
- Do not subtract direct (conjugated) bilirubin from total bilirubin when using treatment guidelines, unless direct bilirubin is ≥50% of total (which requires expert consultation) 1
Phototherapy Initiation
Intensive phototherapy should be initiated based on hour-specific TSB thresholds that account for gestational age, postnatal age, and presence of neurotoxicity risk factors 1:
- Intensive phototherapy requires irradiance of ≥30 μW/cm²/nm in the blue-green spectrum (460-490 nm, optimal 478 nm) delivered to maximal body surface area 1
- Use LED light sources when available, as they deliver specific wavelengths with minimal heat generation 1
- Line bassinet sides with aluminum foil or white material when TSB approaches exchange transfusion levels to increase exposed surface area 1
Treatment thresholds for phototherapy (lower thresholds apply to higher-risk infants with isoimmune hemolytic disease, G6PD deficiency, asphyxia, lethargy, temperature instability, sepsis, acidosis, or albumin <3.0 g/dL) 1:
- Infants 25-48 hours old: TSB ≥15 mg/dL (257 μmol/L) 2
- Infants 49-72 hours old: TSB ≥18 mg/dL (308 μmol/L) 2
- Infants >72 hours old: TSB ≥20 mg/dL (342 μmol/L) 2
Phototherapy Management
- Continue breastfeeding during phototherapy when possible; supplementation with expressed breast milk or formula is appropriate if intake appears inadequate, weight loss is excessive, or infant appears dehydrated 1
- Feed every 2-3 hours during treatment 1
- Monitor TSB response: Repeat TSB within 2-3 hours if ≥25 mg/dL; within 3-4 hours if 20-25 mg/dL; within 4-6 hours if <20 mg/dL 1
- TSB should decrease within 4-6 hours of initiating effective phototherapy in infants without hemolysis 1
- Discontinue phototherapy when TSB falls to <13-14 mg/dL (239 μmol/L) 1
Exchange Transfusion
Exchange transfusion is indicated when 1:
- TSB reaches exchange transfusion threshold levels (varies by age and risk factors, typically 25-30 mg/dL) 1
- TSB continues to rise despite intensive phototherapy 1
- Immediate exchange transfusion is required for any jaundiced infant manifesting intermediate to advanced acute bilirubin encephalopathy signs (hypertonia, arching, retrocollis, opisthotonos, fever, high-pitched cry), even if TSB is falling 1
Exchange transfusion protocol 1:
- Perform only in neonatal intensive care units by trained personnel with full monitoring and resuscitation capabilities 1
- Use modified whole blood (red cells and plasma) crossmatched against mother and compatible with infant 1
- Send blood for immediate type and crossmatch when TSB approaches exchange level 1
- Consider albumin level and bilirubin/albumin ratio in conjunction with TSB when determining need for exchange transfusion 1
Adjunctive Therapy for Isoimmune Hemolytic Disease
Intravenous immunoglobulin (IVIG) 0.5-1 g/kg over 2 hours should be administered if TSB is rising despite intensive phototherapy or is within 2-3 mg/dL (34-51 μmol/L) of exchange transfusion level in cases of Rh or ABO hemolytic disease 1
- IVIG reduces the need for exchange transfusions in isoimmune hemolytic disease 1
Laboratory Evaluation
Initial workup for pathologic jaundice (presenting <24 hours, rising >5 mg/dL/day, or TSB >17 mg/dL) 1, 2:
- TSB and direct bilirubin levels
- Blood type (ABO, Rh) and direct antibody test (Coombs')
- Complete blood count with differential and red cell morphology
- Reticulocyte count
- Serum albumin
- G6PD if suggested by ethnicity/geography or poor phototherapy response
- End-tidal carbon monoxide (ETCOc) if available to confirm hemolysis 1
- Sepsis workup if clinically indicated 1
Follow-Up After Discharge
Structured follow-up is critical to identify delayed hyperbilirubinemia 1:
- Infants discharged <24 hours: seen by 72 hours
- Infants discharged 24-47.9 hours: seen by 96 hours
- Infants discharged 48-72 hours: seen by 120 hours
- Earlier or more frequent follow-up for infants with risk factors 1
- Delay discharge if appropriate follow-up cannot be ensured in presence of elevated risk until 72-96 hours 1
Emergency Management
TSB ≥25 mg/dL (428 μmol/L) is a medical emergency requiring immediate direct admission to hospital pediatric service for intensive phototherapy—do not refer to emergency department as this delays treatment 1
Adult Hyperbilirubinemia
Treatment of hyperbilirubinemia in adults is directed at the underlying cause, with specific interventions for cholestatic disease and biliary obstruction. 3
Diagnostic Approach
- Measure direct (conjugated) bilirubin fraction; >35% suggests hepatocellular or cholestatic etiology (including drug-induced liver injury) 3
- If etiology uncertain with prolonged hyperbilirubinemia, breakdown direct bilirubin into conjugated and delta bilirubin fractions 3
- Use CT or MRI if ultrasonography is inconclusive for evaluating biliary obstruction 3
Treatment by Etiology
Gilbert's Syndrome: No treatment required—this is a benign condition with conjugated bilirubin <20-30% of total bilirubin in absence of hemolysis 3
Cholestatic liver diseases (primary biliary cholangitis, primary sclerosing cholangitis) 3:
- Ursodeoxycholic acid is first-line therapy
- Monitor for fat-soluble vitamin deficiencies
- Attempt parenteral vitamin K supplementation to correct prolonged INR before attributing coagulopathy to liver failure
- Note: Non-adherence to ursodeoxycholic acid can cause abrupt liver test elevations mimicking drug-induced liver injury
Biliary obstruction 3:
- Malignant obstruction may require stent placement or surgical intervention depending on location and nature