What is the management for a newborn with elevated direct bilirubin (hyperbilirubinemia)?

Management of Elevated Direct Bilirubin in Newborns

For newborns with elevated direct bilirubin (14.8 mg/dL), immediate evaluation for underlying causes of cholestasis is essential, while phototherapy can be used if needed, recognizing that direct hyperbilirubinemia should not be considered a contraindication to phototherapy despite reduced efficacy and risk of bronze infant syndrome. 1

Initial Assessment and Diagnosis

• Laboratory measurement of direct bilirubin is not precise, and values between laboratories can vary widely. If the total serum bilirubin (TSB) is at or below 5 mg/dL, a direct or conjugated bilirubin of more than 1.0 mg/dL is considered abnormal. 1

• Direct-reacting bilirubin is not the same as conjugated bilirubin, though the terms are often used interchangeably in clinical practice. Direct-reacting bilirubin reacts directly with diazotized sulfanilic acid, while conjugated bilirubin is bilirubin made water-soluble by binding with glucuronic acid in the liver. 1

• When evaluating a newborn with elevated direct bilirubin, essential laboratory tests include: 1

  • TSB and direct bilirubin levels
  • Blood type (ABO, Rh)
  • Direct antibody test (Coombs')
  • Serum albumin
  • Complete blood cell count with differential and smear for red cell morphology
  • Reticulocyte count
  • G6PD if suggested by ethnic or geographic origin
  • Urine for reducing substances
  • Consider blood, urine, and cerebrospinal fluid cultures if sepsis is suspected

Treatment Approach

Phototherapy Considerations

• The presence of direct hyperbilirubinemia should not be considered a contraindication to phototherapy if treatment is needed, particularly in sick neonates. 1

• When using phototherapy in infants with direct hyperbilirubinemia, be aware that: 1

  • The efficacy of phototherapy is reduced in cholestasis because phototherapy products are excreted in bile
  • These infants may develop the bronze infant syndrome (dark, grayish-brown discoloration of skin, serum, and urine)
  • The bronze infant syndrome occurs exclusively in infants with cholestasis, though not all infants with cholestatic jaundice develop it

• In infants receiving phototherapy who develop the bronze infant syndrome, exchange transfusion should be considered if the TSB is in the intensive phototherapy range and phototherapy does not promptly lower the TSB. 1

Important Treatment Principles

• When making treatment decisions for phototherapy or exchange transfusion, the direct-reacting (or conjugated) bilirubin level should NOT be subtracted from the total bilirubin. 1

• In unusual situations where the direct bilirubin level is 50% or more of the total bilirubin, there are no good data to provide guidance for therapy, and consultation with an expert in the field is recommended. 1

• If the TSB does not fall or continues to rise despite intensive phototherapy, it is very likely that hemolysis is occurring. 1

• For infants with prolonged jaundice beyond 2-3 weeks, evaluation for cholestatic causes is essential, including checking stool color (pale stools suggest cholestasis) and urine color (dark yellow urine suggests cholestasis). 2

Special Considerations for Direct Hyperbilirubinemia

• Unlike physiologic jaundice, direct hyperbilirubinemia at this level requires investigation for underlying pathology such as biliary atresia, metabolic disorders, or infection. 2, 3

• Don't ignore prolonged jaundice. Any infant who is still jaundiced beyond age 3 weeks must have a measurement of direct bilirubin to rule out cholestatic causes. 2

• Rarely, purpura and bullous eruptions have been described in infants with severe cholestatic jaundice receiving phototherapy. Congenital porphyria or a family history of porphyria is an absolute contraindication to phototherapy. 1

Follow-up Recommendations

• All infants should be examined by a qualified healthcare professional in the first few days after discharge to assess infant well-being and the presence or absence of jaundice. 1

• Follow-up timing depends on discharge age: 1

  • Discharge before 24 hours: follow-up by 72 hours
  • Discharge between 24-47.9 hours: follow-up by 96 hours
  • Discharge between 48-72 hours: follow-up by 120 hours

• Earlier or more frequent follow-up should be provided for infants with risk factors for hyperbilirubinemia. 1

• If appropriate follow-up cannot be ensured in the presence of elevated risk for developing severe hyperbilirubinemia, it may be necessary to delay discharge until appropriate follow-up can be ensured or the period of greatest risk has passed (72-96 hours). 1