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  1. Problem. An infant's indirect (unconjugated) serum bilirubin level is 10 mg/dL. The exact definition of a physiologic range and management of indirect hyperbilirubinemia is complex and based on many factors, including gestational age (GA), postnatal age, birthweight, disease state, risk factors, degree of hydration, nutritional status, and ethnicity. Total bilirubin (TSB) (sum of the direct [conjugated] and indirect [unconjugated]) and direct serum bilirubin can be measured in the blood. The indirect bilirubin is calculated by subtracting the direct bilirubin from the total bilirubin. TcB (transcutaneous bilirubin) is a measurement of total serum bilirubin from an instrument that uses reflectance measurements on the skin and correlates well with the laboratory TSB value.

  2. Immediate questions

      1. How old is the infant? High indirect serum bilirubin levels during the first 24 h of life are never physiologic. Hemolytic disease (Rh isoimmunization or ABO incompatibility), congenital infection (eg, rubella, toxoplasmosis), sepsis, occult hemorrhage, and polycythemia are likely causes. The age and gestation of the infant help determine the bilirubin level at which phototherapy should be initiated.

      1. Is the infant being breast-fed? Breast milk jaundice is common and may be present; the cause is unknown and there is a familial association. Peak bilirubin levels usually occur 4–10 days after birth.

      1. What is the family ethnicity? The incidence of neonatal jaundice is increased in infants of American Indian, Greek, and Eastern Asian descent. Greeks who were born in Greece and live there have a higher incidence of hyperbilirubinemia than Greeks living in the United States. Glucose-6-phosphate dehydrogenase (G6PD) deficiency occurs more commonly in people of Mediterranean, African, Arabian Peninsula, Southeast Asian, and Middle Eastern descent. Immigration and intermarriage have increased the incidence of G6PD in the United States. It occurs in 11–13% of African Americans. There is a rapid increase in the total serum bilirubin level after 24–48 h of age.

      1. Is the infant dehydrated? With dehydration (or weight loss from birth is >12%), fluid administration may lower the serum bilirubin level. Additional feedings should be given, if tolerated (milk-based formula is recommended in dehydrated breast-fed infants); otherwise, IV fluids should be given. It is recommended that mothers nurse their infants 8–12 times a day as a minimum for the first few days. For example, a 3-day-old infant is strictly breast-feeding, but his mother's milk has not yet "come in," so he has lost significant weight and becomes dehydrated. Remember that adequate hydration is essential, but excess hydration will not clear the bilirubin any more quickly, prevent hyperbilirubinemia, or decrease TSB.

      1. What is the gestational age of the infant? The risk of unconjugated hyperbilirubinemia is inversely proportional with GA.

  3. Differential diagnosis. Indirect (unconjugated) bilirubin is derived mainly from hemoglobin metabolism and must be conjugated in the liver before it can be excreted in the bile, stool, or urine. It can not be directly measured in the blood and is never present in urine. (See also Chapter 92.)

      1. More common causes of indirect hyperbilirubinemia

          1. Physiologic hyperbilirubinemia.

          1. ABO incompatibility.

          1. Breast-feeding or breast milk jaundice.

          1. Infection...

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