The clinical pattern of physiologic jaundice in term infantsincludes a peak indirect-reacting bilirubin level of no morethan 12 mg/dL on day 3 of life. In premature infants, the peakis higher (15 mg/dL) and occurs later (fifth day). The peak levelof indirect bilirubin during physiologic jaundice may be higherin breast milk–fed infants than in formula-fed infants (15 to17 mg/dL versus 12 mg/dL). This higher level may be partly aresult of the decreased fluid intake of infants fed breast milk. Jaundice is unphysiologic or pathologic if it is clinically evidenton the first day of life, if the bilirubin level increases more than 0.5 mg/dL/hr, if the peak bilirubin is greater than 13 mg/dLin term infants, if the direct bilirubin fraction is greater than 1.5 mg/dL, or if hepatosplenomegaly and anemia are present.
Crigler-Najjar syndrome is a serious, rare, autosomal recessive, permanent deficiency of glucuronosyltransferase that results in severe indirect hyperbilirubinemia. Type II responds to enzyme induction by phenobarbital, producing an increase in enzyme activity and a reduction of bilirubin levels. Type I does not respond to phenobarbital and manifests as persistent indirect hyperbilirubinemia, often leading to kernicterus. Gilbert disease is caused by a mutation of the promoter region of glucuronosyltransferase and results in a mild indirect hyperbilirubinemia. In the presence of another icterogenic factor (hemolysis), more severe jaundice may develop.
Hepatic infarction Inborn errors of metabolism (galactosemia, tyrosinemia) Cystic fibrosis Biliary atresia Choledochal cyst α1-Antitrypsin deficiency Neonatal iron storage disease Alagille syndrome (arteriohepatic dysplasia) Byler disease
CMV, Cytomegalovirus; TORCH, toxoplasmosis, other, rubella, cytomegalovirus, herpes simplex.
Direct-reacting hyperbilirubinemia (defined as a direct bilirubin level >2 mg/dL or >20% of the total bilirubin) is never physiologic and should always be evaluated thoroughly according to the diagnostic categories (Table 62-2). Direct-reacting bilirubin (composed mostly of conjugated bilirubin) is not neurotoxic to the infant but signifies a serious underlying disorder involving cholestasis or hepatocellular injury. The diagnostic evaluation of patients with direct-reacting hyperbilirubinemia involves the determination of the levels of liver enzymes (aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, and γ-glutamyl transpeptidase), bacterial and viral cultures, metabolic screening tests, hepatic ultrasound, sweat chloride test, and occasionally liver biopsy. In addition, the presence of dark urine and gray-white (acholic) stools with jaundice after the second week of life strongly suggests biliary atresia. The treatment of disorders manifested by direct bilirubinemia is specific for the diseases that are listed in Table 62-2. These diseases do not respond to phototherapy or exchange transfusion.