Management of Unconjugated Hyperbilirubinemia

               Vinod K. Bhutani

INDICATION

Reduction of elevated or increasing unconjugated (indirect) bilirubin levels, measured as total plasma bilirubin (TB) or transcutaneous bilirubin (TcB), is key to the prevention of bilirubin toxicity. Preterm and sick infants are at increased risk for hyperbilirubinemia and its sequelae. Factors that place these populations at risk for hyperbilirubinemia include impaired bilirubin-albumin binding, decreased enteral intake, and decreased gastrointestinal activity, resulting in increased enterohepatic circulation. As a result of biological conditions such as vulnerability of the blood-brain barrier, asphyxia, acidosis, and hypoalbuminemia, neurotoxicity may occur at lower bilirubin levels than for term and healthy infants.

Clinical

Levels of Hyperbilirubinemia

1. Newborns 35 weeks’ gestational age (GA) or older

• Significant hyperbilirubinemia: greater than 95th percentile for age hours

• Severe hyperbilirubinemia: hour-specific value at which phototherapy is recommended

• Extreme hyperbilirubinemia: TB greater than 25 mg/dL

2. Newborns less than 35 weeks’ GA

• Significant hyperbilirubinemia: greater than 5 mg/dL (possibly: no consensus opinion)

• Severe hyperbilirubinemia: hour-specific value at which phototherapy is recommended

• Extreme hyperbilirubinemia: TB greater than 20 mg/dL (possibly: no consensus opinion)

Clinical Risk Factors

   1. TB greater than 95th percentile for age in hours (≥35 weeks’ GA)

   2. Neonatal hemolysis (intravascular, extravascular)

   3. Male gender

   4. Asian race

   5. Prematurity (each week)

   6. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (race/ethnicity: African Americans with jaundice, East Asians, Middle Eastern, and Mediterranean)

   7. Maternal diabetes mellitus

   8. Suboptimal breast milk intake

   9. Early discharge (before age 72 hours)

10. Family history (of jaundice or its treatment)

Clinical Manifestations

Jaundice can be detected by blanching the skin with digital pressure to reveal the underlying skin and subcutaneous tissue color at the forehead, sternum, iliac crest, patella, and malleolus. Jaundice should be assessed whenever the infant’s vital signs are measured, but no less than every 8 to 12 hours. The assessment of jaundice must be done in a well-lit room or, preferably, in daylight with ambient sunlight. There is usually a cephalocaudal progression, and sometimes it can fade in and out like a tan. Color varies from lemon yellow to bright orange and sienna. Assessment may be limited by skin pigmentation, plethora, decreased ambient light, and exposure to sun or phototherapy. Absence of jaundice is not an indication of the absence of hyperbilirubinemia; estimating the degree of hyperbilirubinemia can lead to errors, and the absence or severity of jaundice is not predictive of subsequent severe hyperbilirubinemia.

1. Onset of jaundice in the first 24 hours of life should be considered a sign of excessive rate of bilirubin rise and indication for emergency bilirubin testing and further evaluation.

2. Progression of jaundice is usually seen, with appearance first in the face and progressing caudally to the trunk and extremities, but sometimes it appears and fades similar to a tan.

Testing

1. TB is measured in plasma to objectively assess the severity of jaundice. In term and late-preterm infants, this level is plotted on an hour-specific nomogram that identifies risk zones or assessment of clinical risk factors. The hour-specific nomogram provides a more appropriate understanding of the magnitude of hyperbilirubinemia and its projected rate of rise in the contexts of postnatal age in hours and the percentile level as defined for healthy infants.

2. TcB testing is a noninvasive alternative to TB measurement. TcB devices are useful screening tools and provide a valid estimate of the TB level, although data are limited.

    a. Measurements in newborns using the new TcB devices are within 2–3 mg/dL of the TB and are useful to screen for or trend TB levels less than 12 mg/dL.

    b. The use of TcB measurements in sick and preterm infants as well as those undergoing phototherapy has not yet been validated.

    c. Confounding effects of skin melanin content among different races and manufacturing consistency among devices are additional limitations.

Differential Diagnosis

Table 97-1

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