Lipid-soluble, unconjugated, indirect bilirubin fraction is toxic to the developing central nervous system, especially when indirect bilirubin concentrations are high and exceed the binding capacity of albumin. Kernicterus results when indirect bilirubin is deposited in brain cells and disrupts neuronal metabolism and function, especially in the basal ganglia. Indirect bilirubin may cross the blood-brain barrier because of its lipid solubility. Other theories propose that a disruption of the blood-brain barrier permits entry of a bilirubin-albumin or free bilirubin–fatty acid complex.
Kernicterus usually is noted when the bilirubin level is excessively high for gestational age. It usually does not develop in term infants when bilirubin levels are less than 20 to
Common Blood group Physiologic jaundice, incompatibility: ABO, Rh, breast milk jaundice, Kell, Duffy infection internal hemorrhage, polycythemia, infant of diabetic mother
Rare Red blood cell enzyme defects: glucose-6-phosphate dehydrogenase, pyruvate kinase Red blood cell membrane disorders: spherocytosis, ovalocytosis Hemoglobinopathy: thalassemia Mutations of glucuronyl transferase enzyme (Crigler-Najjar syndrome, Gilbert disease), pyloric stenosis, hypothyroidism, immune thrombocytopenia
Breast milk jaundice may be associated with unconjugated hyperbilirubinemia without evidence of hemolysis during the first to second week of life. Bilirubin levels rarely increase to more than 20 mg/dL. Interruption of breastfeeding for 1 to 2 days results in a rapid decline of bilirubin levels, which do not increase significantly after breastfeeding resumes. Breast milk may contain an inhibitor of bilirubin conjugation or may increase enterohepatic recirculation of bilirubin because of breast milk glucuronidase.
Jaundice on the first day of life is always pathologic, and immediate attention is needed to establish the cause. Early onset often is a result of hemolysis, internal hemorrhage (cephalhematoma, hepatic or splenic hematoma), or infection (Table 62-1). Infection also is often associated with direct-reacting bilirubin resulting from perinatal congenital infections or from bacterial sepsis.
Physical evidence of jaundice is observed in infants when bilirubin levels reach 5 to 10 mg/dL (versus 2 to 3 mg/dL in adults). When jaundice is observed, the laboratory evaluation for hyperbilirubinemia should include a total bilirubin measurement to determine the magnitude of hyperbilirubinemia. Bilirubin levels greater than 5 mg/dL on the first day of life or greater than 13 mg/dL thereafter in term infants should be evaluated further with measurement of indirect and direct bilirubin levels, blood typing, Coombs test, complete blood count, blood smear, and reticulocyte count. These tests must be performed before treatment of hyperbilirubinemia with phototherapy or exchange transfusion. In the absence of hemolysis or evidence for either the common or the rare causes of nonhemolytic indirect hyperbilirubinemia, the diagnosis is either physiologic or breast milk jaundice. Jaundice present after 2 weeks of age is pathologic and suggests a direct-reacting hyperbilirubinemia.
Etiology of Direct Conjugated Hyperbilirubinemia