|
Hyperbilirubinemia
is an elevated serum bilirubin concentration; the threshold for
an abnormal value varies by age and, in preterm infants, by health
status. The primary sign is jaundice, but marked hyperbilirubinemia
can cause kernicterus, a syndrome of neurologic damage. Diagnosis
is obvious by examination and confirmed by measurement of serum
bilirubin. Treatment depends on cause and degree of elevation; definitive treatments
include phototherapy and exchange transfusion.
Etiology
and Pathophysiology
Table 1: Metabolic, Electrolyte, and Toxic Disorders in Neonates: Causes of Neonatal Hyperbilirubinemia  lists the causes of hyperbilirubinemia. In general, hyperbilirubinemia may be physiologic or pathologic and is always caused by increased production, decreased clearance, or increased enterohepatic circulation of bilirubin (see Perinatal Physiology: Bilirubin). Most cases involve unconjugated hyperbilirubinemia, but liver dysfunction (eg, parenteral alimentation causing cholestasis, neonatal sepsis, severe erythroblastosis fetalis) may cause conjugated hyperbilirubinemia.
Physiologic
hyperbilirubinemia occurs in almost all neonates. Shorter neonatal RBC life span increases bilirubin production; deficient conjugation decreases clearance; and low bacterial levels in the intestine combined with increased hydrolysis of conjugated bilirubin increase enterohepatic circulation. Bilirubin levels rise up to 18 mg/dL by 3 to 4 days of life (7 days in Asian infants) and fall thereafter.
Breastfeeding
jaundice develops in 1⁄6 of breastfed infants in the 1st wk of life; breastfeeding increases enterohepatic circulation of bilirubin in some infants who have decreased milk intake and who also have dehydration or low caloric intake.
Pathologic
hyperbilirubinemia in term infants is bilirubinemia > 18 mg/dL that occurs in the 1st day or beyond the 1st wk of life or is caused by an abnormal process. The most common pathologic cause of increased bilirubin production is hemolytic anemia (see Perinatal Hematologic Disorders: Hemolysis), usually from blood type incompatibility; polycythemia (eg, from twin-to-twin transfusion) and hematomas are other causes. Conditions that decrease bilirubin clearance are genetic disorders that impair conjugation such as Crigler-Najjar and Gilbert syndromes (see Approach to the Patient With Liver Disease: Gilbert syndrome).
Symptoms,
Signs, and Diagnosis
Hyperbilirubinemia is asymptomatic but begins to cause jaundice at > 4 to 5 mg/dL (> 68 to 86 μmol/L). With increasing bilirubin levels, visible jaundice advances in a head-to-foot direction. Prolonged hyperbilirubinemia can cause kernicterus (see Metabolic, Electrolyte, and Toxic Disorders in Neonates: Kernicterus).
Diagnosis is suspected by the infant's color and confirmed by measurement of serum bilirubin. A bilirubin concentration > 10 mg/dL (> 170 μmol/L) in preterm infants or > 18 mg/dL (> 308 μmol/L) in term infants warrants additional diagnostic testing, including Hct, blood smear, reticulocyte count, direct Coombs' test, total and direct serum bilirubin concentrations, and blood type and Rh group of the neonate and mother. Other tests, such as blood, urine, and CSF cultures to detect sepsis and measurement of RBC enzyme levels to detect unusual causes of hemolysis, may be indicated by the history, physical examination, or initial laboratory findings or by an initial bilirubin level > 25 mg/dL (428 μmol/L).
Breastfeeding jaundice, though suspected by history, is diagnosed by exclusion; it is important to consider other possible causes of hyperbilirubinemia that may require specific treatment (see also Perinatal Problems: Metabolic problems).
Treatment
Physiologic jaundice usually is not clinically significant and resolves within 1 wk. Frequent formula feedings can reduce the incidence and severity of hyperbilirubinemia by increasing GI motility and frequency of stools, thereby minimizing the enterohepatic circulation of bilirubin. The type of formula does not appear important in increasing bilirubin excretion.
Breastfeeding jaundice may be prevented or reduced by increasing the frequency of feeds and minimizing the use of water to replace breast milk. In a term infant with early breastfeeding jaundice, if the bilirubin level continues to increase > 18 mg/dL, a temporary change from breast milk to formula feedings may be appropriate; phototherapy may also be indicated at higher levels. Stopping breastfeeding is necessary for only 1 or 2 days, and the mother should be encouraged to continue expressing breast milk regularly so she can resume nursing as soon as the neonate's bilirubin level starts to decline. She should also be assured that the hyperbilirubinemia has not caused any harm and that she may safely resume breastfeeding.
Definitive treatment involves phototherapy or exchange transfusion.
Phototherapy:
Phototherapy is the use of light to photoisomerize bilirubin into forms that are more water-soluble and can be excreted rapidly by the liver without glucuronidation. It provides definitive treatment of hyperbilirubinemia and prevention of kernicterus. Phototherapy is an option when unconjugated bilirubin is > 12 mg/dL and may be indicated when unconjugated bilirubin is > 15 mg/dL at 25 to 48 h; 18 mg/dL at 49 to 72 h; and 20 mg/dL at > 72 h; it is not indicated for conjugated hyperbilirubinemia.
A standard phototherapy light configuration consists of overhead centrally placed blue bulbs and daylight fluorescent bulbs on each side of the infant. A double phototherapy light configuration consists of the same light configuration described above and a fiberoptic pad beneath the infant. Blue light is more effective than white, but blue light complicates detection of cyanosis, so broad-spectrum white light is also used. A clear acrylic shield placed between the phototherapy lights and the neonate screens out ultraviolet radiation, and the neonate is blindfolded to prevent eye damage (being cautious not to cause nasal obstruction). The light should be turned off and the blindfold removed during feedings. Because visible jaundice may disappear during phototherapy while serum bilirubin remains elevated, skin color cannot be used to evaluate jaundice severity. Blood taken for bilirubin determinations should be shielded from bright light, because bilirubin in the collection tubes may rapidly photo-oxidize.
Exchange
transfusion:
Exchange transfusion is indicated for severe hyperbilirubinemia, which most often occurs with hemolysis. Small amounts of blood are withdrawn and replaced through an umbilical vein catheter to remove partially hemolyzed and antibody-coated RBCs and replace them with uncoated donor RBCs. Only unconjugated hyperbilirubinemia can cause kernicterus, so if conjugated bilirubin is elevated, the level of unconjugated rather than total bilirubin is used to determine the need for exchange transfusion.
Specific indications are serum bilirubin ≥ 20 mg/dL at 24 to 48 h or ≥ 25 mg/dL at > 48 h, failure of phototherapy to result in a 1- to 2-mg/dL decrease within 4 to 6 h of initiation, or at the 1st clinical signs of kernicterus regardless of bilirubin levels. If the serum bilirubin level is > 25 mg/dL when the infant is initially examined, preparation for an exchange transfusion should be made in case intensive phototherapy fails to lower the bilirubin level. An alternative approach uses the weight of the infant in grams divided by 100 to determine the bilirubin level (in mg/dL) at which exchange transfusion is indicated. Thus, a 1000- to 1500-g neonate would receive an exchange transfusion at a bilirubin level of 10 to 15 mg/dL, and a 1500- to 2000-g neonate at 15 to 20 mg/dL.
Most often, an exchange volume of 10 to 15 mL/kg of packed RBCs given over 2 to 4 h is used; an alternate is to give 2 successive aliquots of 10 mL/kg each over 1 to 2 h, for a total of 20 mL/kg. Goal is to reduce bilirubin by nearly 50%, with the knowledge that hyperbilirubinemia may rebound to about 60% of pretransfusion level within 1 to 2 h. It is also customary to lower the target level by 1 to 2 mg/dL in conditions that increase the risk of kernicterus (eg, fasting, sepsis, acidosis). Exchange transfusions may need to be repeated if bilirubin levels remain high.
Overall mortality is < 1% when performed by experienced personnel.
Kernicterus
(Bilirubin Encephalopathy)
Kernicterus
is brain damage caused by unconjugated bilirubin deposition in basal
ganglia and brain stem nuclei.
Normally, bilirubin bound to serum albumin stays in the intravascular space. However, bilirubin can cross the blood-brain barrier and cause kernicterus when serum bilirubin concentration is markedly elevated; serum albumin concentration is markedly low (eg, in preterm infants); or bilirubin is displaced from albumin by competitive binders (eg, sulfisoxazole , ceftriaxone , and aspirin ; free fatty acids and hydrogen ions in fasting, septic, or acidotic infants).
In preterm infants, kernicterus may not produce recognizable clinical symptoms or signs. Early symptoms in term infants are lethargy, poor feeding, and vomiting. Opisthotonos, oculogyric crisis, seizures, and death may follow. Kernicterus may result in mental retardation, choreoathetoid cerebral palsy, sensorineural hearing loss, and paralysis of upward gaze later in childhood. It is unknown if minor degrees of kernicterus can produce less severe neurologic impairment (eg, perceptual-motor handicaps and learning disorders).
There is no reliable test to determine the risk of kernicterus, and the diagnosis is made presumptively. A definite diagnosis can be made only by autopsy.
There is no treatment once kernicterus develops; it can be prevented by treatment of hyperbilirubinemia (see Metabolic, Electrolyte, and Toxic Disorders in Neonates: Treatment).
Last full review/revision November 2005
Content last modified November 2005
| 
