A mother is concerned that her 4-day-old son’s face and chest are turning yellow
CONJUGATED (DIRECT) BILIRUBIN: Bilirubin chemically attached to a glucuronide by an enzymatic process in the liver; elevated levels are not neurotoxic (do
not cross blood brain barrier) but may be indicative of a more serious underlying
illness.
UNCONJUGATED (INDIRECT) BILIRUBIN: Bilirubin yet to be enzymatically
attached to a glucuronide in the liver; elevated levels can cause neurotoxicity.
ERYTHROBLASTOSIS FETALIS: Increased RBC destruction due to transplacental maternal antibody passage active against the infant’s RBC antigens.
HEMOLYSIS: Rapid breakdown of RBCs. Clinical and laboratory findings might
include a rapid rise of serum bilirubin level (>0.5 mg/dL/h), anemia, pallor, reticulocytosis, and hepatosplenomegaly
KERNICTERUS: A neurologic syndrome resulting from unconjugated bilirubin
deposition in brain cells, especially the basal ganglia, globus pallidus, putamen, and
caudate nuclei. Less mature or sick infants have greater susceptibility. Lethargy,
poor feeding, and loss of Moro reflex are common initial signs.
POLYCYTHEMIA: A central hematocrit of 65% or higher, which can lead to
blood hyperviscosity.
TRANSCUTANEOUS BILIRUBINOMETER (TcB): A device that is placed on
infant’s skin and produces light at several wavelengths that then measures its reflection after interacting with the serum bilirubin in the microcirculation beneath the
skin. The device is used to noninvasively measure serum bilirubin as an alternative
to serum bilirubin measurement.
END-TIDAL CO CONCENTRATION (ETCO): ETCO corrected for ambient
CO; provides a noninvasive assessment of bilirubin production.
CLINICAL APPROACH
Physiologic jaundice comprises primarily unconjugated hyperbilirubinemia observed
during the first week of life in approximately 60% of full-term infants and 80% of
preterm infants. Physiologic jaundice is established by precluding known jaundice
causes through history, clinical and laboratory findings. Newborn infants have a
limited ability to conjugate bilirubin and cannot readily excrete unconjugated
bilirubin. Jaundice usually begins on the face and then progresses to the chest,
abdomen, and feet. Full-term newborns with physiologic jaundice usually have
peak bilirubin concentrations of 5 to 6 mg/dL between the second and fourth
days of life.
Findings suggestive of nonphysiologic jaundice include (1) appearance in the first
24 to 36 hours of life, (2) bilirubin rate of rise greater than 5 mg/dL/24 h,
(3) bilirubin greater than 12 mg/dL in a full-term infant without other physiologic
jaundice risk factors listed, and (4) jaundice that persists after 10 to 14 days of
life. Nonphysiologic etiologies are commonly diagnosed in a jaundiced infant who
has a family history of hemolytic disease or in an infant with concomitant pallor, hepatomegaly, splenomegaly, failure of phototherapy to lower bilirubin, vomiting, lethargy, poor feeding, excessive weight loss, apnea, or bradycardia. Causes of
nonphysiologic jaundice include septicemia, biliary atresia, hepatitis, galactosemia,
hypothyroidism, cystic fibrosis, congenital hemolytic anemia (eg, spherocytosis,
maternal Rh, or blood type sensitization), or drug-induced hemolytic anemia.
Jaundice presenting within the first 24 hours of life requires immediate attention;
causes include erythroblastosis fetalis, hemorrhage, sepsis, cytomegalic inclusion
disease, rubella, and congenital toxoplasmosis. Unconjugated hyperbilirubinemia
can cause kernicterus, the signs of which mimic sepsis, asphyxia, hypoglycemia,
and intracranial hemorrhage. Lethargy and poor feeding are common initial
signs, followed by a gravely ill appearance with respiratory distress and diminished tendon reflexes.
Approximately 2% of breast-fed full-term infants develop significant unconjugated bilirubin elevations (breast milk jaundice) after the seventh day of life; concentrations up to 30 mg/dL during the second to third week can be seen. If breast-feeding
is continued, the levels gradually decrease. Formula substitution for breast milk
for 12 to 24 hours results in a rapid bilirubin level decrease; breast-feeding can be
resumed without return of hyperbilirubinemia.
The American Academy of Pediatrics recommends establishing protocols in all
low-risk nurseries to assess the risk of severe hyperbilirubinemia in all newborns
prior to their discharge home. This assessment can be done by measuring total
serum bilirubin (TsB) levels or by using a noninvasive, TcB. The TcB bilirubin
measured at the newborn’s sternum correlates with serum levels and is reliable in
newborns of different ethnicities and at different gestational ages. The TcB measurements are not reliable after the infant has undergone phototherapy.
The infant’s serum or transcutaneous bilirubin should be charted on a bilirubin
nomogram which plots bilirubin level versus hour of life to assess the patient’s risk
of developing severe hyperbilirubinemia. The nomogram categorizes infant’s bilirubin levels as low risk, low intermediate risk, high intermediate risk, and high risk
to estimate likelihood of bilirubin toxicity and the need for further evaluation or
intervention. Online nomograms, such as BiliTool (www.bilitool.org), are easy to
use for risk designation and to minimize medical error while also considering other
risk factors that lower the threshold for initiating phototherapy.
Significant hyperbilirubinemia requires a diagnostic evaluation, including the measurement of indirect and direct bilirubin concentrations, hemoglobin level, reticulocyte count, blood type, Coombs test, and peripheral blood smear examination.
Phototherapy is often used to treat unconjugated hyperbilirubinemia, with the
unclothed infant placed under a bank of phototherapy lights, the eyes shielded, and
hydration maintained. The phototherapy light converts the skin’s bilirubin isomerization into a more easily excreted form.
Exchange transfusion is needed in a small number of jaundiced infants who do not
respond to conservative measures. Small aliquots of the infant’s blood are removed
via a blood vessel catheter and replaced with similar aliquots of donor blood. Risks
of this procedure include air embolus, volume imbalance, arrhythmias, acidosis,
respiratory distress, electrolyte imbalance, anemia or polycythemia, blood pressure
fluctuation, infection, and necrotizing enterocolitis.