Introduction to Infantile Hyperbilirubinemia

Hyperbilirubinemia, also known as jaundice, is a common clinical condition seen in both term and pre-term infants. Clinically jaundice, is a yellowing of the skin and the whites of the eyes as the result of increased serum bilirubin levels, and can be recognized in up to 60% of healthy infants within the first week of life. Jaundice generally peaks between 4 and 5 days age.¹ . All infants have some degree of jaundice (total serum bilirubin > 2mg /dl) and most have a benign outcome. Bilirubin, which causes the yellow coloring of the skin, is known to be a potential toxin to the brain.² With increasing levels of bilirubin brain dysfunction begins to appear. This change is known as Bilirubin Induced Neurologic Dysfunction or acute bilirubin encephalopathy. The infant becomes drowsy, muscle tone fluctuates from floppy to stiff, and there is decreased feeding and irritability. If left untreated the changes may progress to permanent brain injury with bilirubin staining of the brain, known as kernicterus. Clinically, infants with kernicterus present cerebral palsy, unsteady gait, mental retardation, and hearing loss. Although kernicterus is rare, it is a devastating preventable disorder with lifelong consequences for the infant and family.³

Bilirubin is formed from the breakdown of the heme component of hemoglobin. Infants with hemolytic disease, such as ABO incompatibility or Rh incompatibility between mother and child, have an increased rate of red cell destruction and thus an increase in bilirubin production. Since newborn infants have relatively immature livers they do not clear bilirubin well. Thus for infants with hemolytic disease bilirubin levels may rise rapidly and treatment to prevent excessive levels in the blood may be required in the first 24 hours of life.

At present phototherapy, utilizing blue light, is the most frequently used treatment for hyperbilirubinemia. The blue light employed in phototherapy systems converts bilirubin to less toxic water soluble form, that is then excreted in the urine. Thus, phototherapy enhances the excretion of bilirubin but has no impact on the production of bilirubin.

Since production of bilirubin is significantly increased in infants with hemolytic disease, bilirubin levels may continue to increase despite phototherapy. Infants who do not respond to PT are treated with exchange transfusion; however exchange transfusion is considered a therapy of last resort because of the associated morbidity and mortality.
Stanate® is a heme oxygenase inhibitor that inhibits the breakdown of heme to bilirubin. Previous clinical studies demonstrate that a single IM injection of Stanate^® can eliminate the need for phototherapy when administered prior to reaching the threshold for PT.

InfaCare is developing Stanate® as the first pharmacological treatment for HB. It will be the first treatment of HB that is directed at inhibiting the formation of bilirubin.

References

1. Bhutani VK, Johnson L. A proposal to prevent severe neonatal hyperbilirubinemia and kernicterus. Journal of Perinatology 2009; 29: S61-S67.
2. Brites D, Fernandes A, Falcao AS, et al. Biological risks for neurological abnormalities associated with hyperbilirubinemia. Journal of Perinatology 2009; 29: S8-S13.
3. Bhutani VK, Johnson L. Kernicterous in the 21st Century: frequently asked questions. . Journal of Perinatology 2009; 29: S20-S24

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