From the Guidelines
Indirect bilirubin levels should be managed with phototherapy to prevent severe neonatal hyperbilirubinemia, especially in newborns at high risk, as it reduces the risk of bilirubin neurotoxicity and the need for exchange transfusions 1. Indirect bilirubin is the unconjugated form of bilirubin that circulates in the bloodstream bound to albumin. It is formed when hemoglobin from old red blood cells is broken down into heme, which is then converted to bilirubin. This form is fat-soluble and cannot be excreted in urine. The liver is responsible for converting indirect bilirubin to direct (conjugated) bilirubin through a process called glucuronidation, making it water-soluble for excretion. Some key points to consider when managing indirect bilirubin levels include:
- Elevated indirect bilirubin levels can indicate conditions like hemolytic anemia, where red blood cells break down too quickly, or liver disorders such as Gilbert's syndrome, which affects the enzyme needed for bilirubin processing 1.
- Normal indirect bilirubin levels are typically 0.1-1.0 mg/dL.
- When measuring bilirubin, doctors often look at total bilirubin (both direct and indirect forms) and the proportion of each to help diagnose the underlying cause of jaundice or other symptoms.
- Phototherapy is an essential intervention for severe hyperbilirubinemia, especially in neonates at high risk, and its effectiveness depends on the efficacy of the device used and the net gradient between an infant’s rates of bilirubin production and elimination 1.
- The timing of intervention is guided by performing serial measurements of total serum/plasma bilirubin concentrations and screening for the presence of intrinsic risk factors for bilirubin neurotoxicity 1.
- Although clinical trial data that show that phototherapy directly prevents kernicterus are scant, there is sufficient evidence that its use reduces the risk of bilirubin neurotoxicity as well as the use of exchange transfusions 1.
- Failure of response to phototherapy is unusual unless complicated by an increased rate of bilirubin production attributable to the presence of hemolysis or use of phototherapy devices 1.
From the Research
Indirect Bilirubin
- Indirect bilirubin is a yellow compound that occurs in the normal catabolic pathway that breaks down heme in red blood cells 2
- Elevated levels of indirect bilirubin can be caused by excess bilirubin production, impaired liver uptake, or impaired conjugation 2
- In newborns, indirect hyperbilirubinemia can be treated with intensive phototherapy, which has been shown to decrease the need for exchange transfusion and shorten the duration of phototherapy 3
- Phenobarbitone has also been used to prevent and treat unconjugated hyperbilirubinemia in preterm neonates, and has been shown to reduce peak serum bilirubin, duration of phototherapy, and need for exchange transfusion 4
- The combination of phenobarbital and phototherapy has been shown to enhance the decline of total serum bilirubin and may decrease the need for blood exchange transfusion in newborns with isoimmune hemolytic disease 5
Measurement and Clinical Usefulness
- Bilirubin levels can be measured using various analytical methods, including diazo transfer reaction, high-performance liquid chromatography, and direct spectrophotometry 2
- Serum bilirubin is an important marker of liver function, but it does not always identify a lesion in the liver, and alterations in bilirubin concentrations should be assessed in relation to patient anamnesis and concurrent biochemical alterations 2
- In adults, jaundice is typically apparent when serum bilirubin levels exceed 3 mg/dL, and can indicate serious underlying disease of the liver or biliary tract 6
- Initial laboratory evaluation for jaundice should include assays for bilirubin, complete blood cell count, liver enzymes, and other tests to determine the underlying cause of hyperbilirubinemia 6