What is the treatment for hyperbilirubinemia?

Treatment of Hyperbilirubinemia

For neonates ≥35 weeks gestation with hyperbilirubinemia, initiate intensive phototherapy based on hour-specific nomograms that account for gestational age and risk factors, with immediate exchange transfusion reserved for TSB ≥25 mg/dL or signs of acute bilirubin encephalopathy. 1, 2

Immediate Assessment and Risk Stratification

When evaluating a jaundiced infant, measure total serum bilirubin (TSB) immediately and interpret it according to the infant's exact age in hours (not days) using hour-specific nomograms. 2 Visual estimation is unreliable, particularly in darkly pigmented infants. 2

Critical risk factors that lower treatment thresholds include: 1, 2

• Gestational age <38 weeks
• Hemolytic disease (ABO/Rh incompatibility, positive Coombs test, G6PD deficiency—especially in Mediterranean, Middle Eastern, African, or Asian descent)
• Serum albumin <3.0 g/dL
• Exclusive breastfeeding with poor intake or weight loss >12%

Laboratory Workup

Obtain the following tests: 2

• TSB and direct (conjugated) bilirubin
• Blood type (ABO, Rh) and direct antibody test (Coombs')
• Complete blood count with differential and peripheral smear
• Reticulocyte count
• G6PD testing (particularly for at-risk ethnic groups, as G6PD deficiency accounts for 31.5% of kernicterus cases) 3
• Serum albumin if levels approach exchange transfusion thresholds 1, 2

Do not subtract direct bilirubin from total bilirubin when making treatment decisions. 2

Phototherapy Protocol

Initiate intensive phototherapy when TSB exceeds hour-specific thresholds. 1, 2 For a term infant (≥38 weeks) without risk factors at 120 hours of age (5 days), phototherapy typically begins around 15-18 mg/dL, but thresholds are lower for infants with risk factors. 2

Intensive phototherapy specifications: 1

• Blue-green spectrum wavelengths (430-490 nm)
• Irradiance ≥30 μW/cm²/nm measured at infant's skin
• Maximum surface area exposure
• Line bassinet/incubator with aluminum foil or white material if TSB approaches exchange transfusion levels 1

During phototherapy: 1, 2

• Feed every 2-3 hours (breast milk or formula) to maintain hydration and promote bilirubin excretion
• Continue breastfeeding if possible; interrupting increases risk of early discontinuation 2
• Supplement with formula or expressed breast milk if weight loss exceeds 12% or dehydration is present 1, 2
• Provide IV fluids if oral intake is inadequate 2

Monitoring frequency based on TSB levels: 1

• TSB ≥25 mg/dL: repeat within 2-3 hours
• TSB 20-25 mg/dL: repeat within 3-4 hours
• TSB <20 mg/dL: repeat in 4-6 hours
• If TSB continues to fall: repeat in 8-12 hours

Discontinue phototherapy when TSB falls below 13-14 mg/dL. 1, 2 Consider rebound check 24 hours after discontinuation, particularly for hemolytic disease. 1, 2

Emergency Interventions

TSB ≥25 mg/dL (428 μmol/L) is a medical emergency requiring immediate hospital admission for intensive evaluation and treatment. 3, 2 Obtain type and crossmatch for possible exchange transfusion. 2

For isoimmune hemolytic disease with TSB rising despite intensive phototherapy or within 2-3 mg/dL of exchange level, administer intravenous immunoglobulin 0.5-1 g/kg over 2 hours. 2

Immediate exchange transfusion is indicated for: 1

• Any infant manifesting signs of intermediate to advanced acute bilirubin encephalopathy (hypertonia, arching, retrocollis, opisthotonos, fever, high-pitched cry) even if TSB is falling
• TSB levels exceeding hour-specific exchange transfusion thresholds on nomograms 1, 2

Exchange transfusion should only be performed by trained personnel in a neonatal intensive care unit with full monitoring and resuscitation capabilities. 2 Thresholds are based on hour-specific nomograms, gestational age, and bilirubin/albumin ratio. 1, 2

Special Considerations

Common pitfall: The American Academy of Pediatrics guidelines apply specifically to infants ≥35 weeks gestation. 1 Preterm infants <35 weeks require different, more aggressive thresholds not covered by these recommendations.

For conjugated hyperbilirubinemia (direct bilirubin ≥50% of total): Obtain abdominal ultrasonography to differentiate extrahepatic biliary obstruction from intrahepatic parenchymal disease, and consult hepatology. 3