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  1. Problem. An infant's direct (conjugated) serum bilirubin level is 3 mg/dL. A value >1.5–2.0 mg/dL (or a fraction >10–20% of the total serum bilirubin) is abnormal at any age. Guidelines from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition uses the following definition for abnormal bilirubin: direct bilirubin >1 mg/dL if total bilirubin <5mg/dL or direct bilirubin is >20% of the total if the total bilirubin >5mg/dL. A persistent or increasing elevated direct bilirubin is always pathologic and must be evaluated promptly to minimize long-term sequelae. Conjugated hyperbilirubinemia is never normal or physiologic. It occurs in one in every 2500 infants. Early diagnosis and treatment is essential because it means a better outcome for the infant and can be potentially life saving. The goal is to complete the evaluation by 45 to 60 days of age (surgery for biliary atresia has its best outcome if performed before the age of 45–60 days.)

  2. Immediate questions

      1. Is the urine dark and what color is the stool? Dark urine is a nonspecific indicator of increased conjugated bilirubin. Persistent pale or clay-colored stools occur with cholestasis and obstruction needs to be ruled out.

      1. Is the infant receiving total parenteral nutrition (TPN)? TPN may cause direct hyperbilirubinemia by an unknown mechanism and usually does not occur until the infant has been on TPN for >2 weeks. It is more common in sick premature infants.

      1. Is the infant gaining weight? Failure to gain weight can be seen in neonatal hepatitis and some metabolic diseases.

      1. Does the infant appear sick? Is a bacterial or viral infection present? Infants with cholestatic jaundice caused by bacterial sepsis appear acutely ill. Infection may cause hepatocellular damage, leading to increased direct bilirubin levels. Infants with galactosemia, hypopituitarism, or gallstones with cholestatic jaundice can also appear ill. These disorders require immediate diagnosis and treatment.

      1. Did direct hyperbilirubinemia occur only after feedings had been established? This suggests a metabolic disorder such as galactosemia may be present.

      1. Have any risk factors been identified? The most important risk factors include low gestational age, early or prolonged exposure to parenteral nutrition, lack of enteral feeding, and sepsis. Episodes of sepsis can be associated with an increase of 30% in the bilirubin level. Other risk factors include neonatal hepatitis , ABO incompatibility, and trisomy 21.

      1. Is the infant being treated for jaundice for another condition and not improving? Any infant who is being treated for jaundice and whose jaundice does not resolve or improve needs to be retested and evaluated for cholestasis.

      1. How old is the infant? The Guideline Committee recommends that any infant who has jaundice at 2 weeks of age be evaluated for cholestasis, except for breastfed infants who have a normal history (no light stools or dark urine) and physical examination can be monitored and evaluated at 3 weeks of age.

  3. Differential diagnosis. See also Table 91–1. Bilirubin is the main waste product of hemoglobin breakdown when the liver breaks down old red blood cells. There are two forms of circulating bilirubin: indirect ...

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