What is neonatal jaundice? |

Causes and Symptoms

Most jaundice found in children is neonatal nonhemolytic
jaundice, a yellowish pigmentation of the skin of some infants. The term
“nonhemolytic” is used to differentiate this condition from jaundice caused by
blood group incompatibilities (such as Rh or ABO groups) or other enzyme
abnormalities of the red blood cells.

Neonatal nonhemolytic jaundice is the result of an excess of serum
bilirubin called hyperbilirubinemia. The pigment bilirubin
is derived from two major sources. One source is the normal destruction of
circulating red blood cells (erythrocytes). The normal life span of the
erythrocytes varies from 80 to 120 days. Old erythrocytes are removed and
destroyed in specific tissues in the spleen and liver, where the hemoglobin of the
red blood cells is broken down and converted to bilirubin. This accounts for about
75 percent of the daily production of bilirubin. The remaining 25 percent of
bilirubin is derived from ineffective erythropoiesis (red blood cell formation) in
the bone marrow and other tissue heme or heme proteins from the liver.

The bilirubin formed is transported in the plasma of the blood and bound
reversibly to albumin, a protein in the blood and tissues. This bilirubin-albumin
complex is then transported to the liver, where it is converted into a
water-soluble compound (or conjugated) by the enzyme glucuronyl transferase in the
interior of the liver cells. The conjugated bilirubin is excreted into the bile
capillaries and then into the intestine. Once in the small intestine, the
conjugated bilirubin is converted by bacteria in the colon into a colorless
compound known as urobilinogen. In the newborn infant, because of the lack of
bacteria in the colon and the presence of the enzyme
B-glucuronidase in the gut wall, a significant amount of the conjugated bilirubin
is deconjugated and reabsorbed back into the plasma pool, a process known as the
enterohepatic shunt.

Chemical hyperbilirubinemia can be defined as a serum concentration of bilirubin
that exceeds 1.5 milligrams per 100 milliliters. Visible yellowing (icterus) of
the skin is caused by the combination of normal skin color, bilirubin-albumin
complexes located outside the blood vessels, and precipitated bilirubin acid in
the membranes of the cell walls. It first becomes visible when serum bilirubin
reaches from 3 to 6 milligrams per deciliter, depending on the infant’s skin
texture and pigmentation and on the observer. Jaundice is first seen in the face
and eyes and then progresses toward the trunk and extremities.

In general, infants whose jaundice is restricted to the face and trunk and does
not extend below the umbilicus have serum bilirubin levels of about 12 milligrams
per deciliter or less, while those whose hands and feet are jaundiced have serum
bilirubin levels in excess of 15 milligrams per deciliter. A more objective way to
estimate the depth of jaundice in neonates is with the use of an icterometer, a
strip of transparent plastic with five transverse yellow strips in different
shades. The baby’s skin is blanched using pressure, and the resulting shade of
yellow is matched against a color scale. In recent years, a transcutaneous
bilirubinometer has been developed, which provides an electronic readout of an
index that corresponds with a serum bilirubin concentration. A more precise way to
judge jaundice is to draw a small amount of blood from the baby and to measure its
serum concentration in a laboratory.

A transient rise in serum bilirubin concentration is almost universally seen in
healthy newborns between one to seven days old. This type of jaundice, called
physiologic jaundice, may be attributable to several factors. First, this
condition may result from increased bilirubin load on liver cells caused by
increased red
blood cell volume, decreased red blood cell survival time,
increased heme from muscles, or increased enterohepatic circulation of bilirubin.
Second, the condition may result from decreased liver uptake of bilirubin from
plasma caused by a decrease in specific proteins in liver cells (termed Y and Z
proteins) for the transport of bilirubin. Third, it may result from defective
bilirubin conjugation caused by decreased enzyme activity. Fourth, physiologic
jaundice can result from defective bilirubin excretion.

The serum bilirubin level in newborns reaches its peak between three and five days
after birth and then decreases, so that the yellowish pigmentation may not be
visible by the fifth to seventh day. The peak level of serum bilirubin in
physiologic jaundice varies from a mean of 5 to 15 milligrams per 100 milliliters.
A number of factors will confound the level of serum bilirubin present with this
condition. They include maternal pregnancy history, complications, drugs,
gestational age, early initiation of feeding, type of feeding (breast milk or
formula), and ethnicity. The heterogeneity of the human population makes it
difficult to apply a particular serum bilirubin level to the definition of
physiologic jaundice. No jaundice should be dismissed as physiologic, however,
without at least a review of maternal and neonatal history, an examination of the
infant for signs of illness, and further laboratory investigation when
indicated.

In some cases, excess bilirubin can cause neurotoxicity leading to brain damage
known as bilirubin encephalopathy or kernicterus. This damage can result in either
neonatal death or the development of long-term abnormal neurologic findings, such
as cerebral
palsy, a low intelligence quotient (IQ), lower
school achievement, hyperactivity, and deafness. The identification of jaundiced
newborn infants at risk for kernicterus is difficult. The data suggest that
healthy infants with serum bilirubin levels as high as 25 to 30 milligrams per 100
milliliters may not have adverse neurologic effects, since the bilirubin is bound
to adequate albumin and the blood-brain barrier formed by cerebral blood vessels
is intact in these infants. Early hospital discharge policies practiced in many
maternity centers, however, make it difficult to assess the evolution of
physiologic as well as pathologic jaundice, or confounding factors such as
infection. Clinicians, practitioners, and home health visitors need to pay special
attention to the degree of jaundice and when it is associated with danger signs
such as sleepiness, lethargy, irritability, poor feeding, vomiting, fever,
high-pitched or shrill cry, hypertonia or hypotonia (depending on whether the
infant is asleep or awake), neck and trunk arching, dark urine, or light
stools.

Treatment and Therapy

The treatment of jaundice depends on the underlying pathology. For clinical
purposes, the two major types need to be separated: jaundice resulting from
hemolytic disease (Rh, ABO, and other blood group incompatibilities) and
nonhemolytic jaundice. Nonhemolytic jaundice may be physiologic or an accentuation
of physiologic jaundice, such as jaundice caused by polycythemia (an increased
number of red blood cells), cephalhematoma (the collection of blood in the scalp
between the bone and bone lining), bruising, cerebral or other hemorrhages,
swallowed blood, increased enterohepatic shunting (because of breastfeeding,
delayed passage of stools, or gastrointestinal tract obstruction), and infection
or sepsis.

Although no general consensus exists concerning the management of nonhemolytic
jaundice, infants with this condition are generally treated with phototherapy.
Phototherapy consists of exposure of the baby’s skin to light energy from a bank
of fluorescent, other special lamps, or sunlight. The light converts the
fat-soluble bilirubin, which cannot be excreted, into a water-soluble bilirubin,
which can be easily excreted in the bile, thus lowering the serum concentration of
bilirubin.

When the serum bilirubin level reaches between 20 and 25 milligrams per 100
milliliter—some clinicians advocate between 25 and 30 milligrams per 100
milliliters—exchange transfusion is generally recommended. In this method, all of
the baby’s bilirubin-containing blood is removed and exchanged with compatible
blood, without bilirubin, from a donor. Both forms of treatment, phototherapy and
exchange transfusion, aim to reduce or remove bilirubin from the baby’s system,
thereby preventing brain injury.

Perspective and Prospects

Jaundice was identified as a major problem in newborn infants in the nineteenth
century. Its association with brain injury was first described by German
pathologist Johannes J. Orth in 1875. Fifty years later, brain damage was further
identified with increased destruction of red blood cells because of
hemolysis caused by Rh and ABO blood group
incompatibilities.

It was also realized, however, that jaundice is encountered in healthy newborn
infants. The major problem has been to identify which infants are at risk for
brain damage when bilirubin is at a particular level. Since there are multiple
confounding factors, better means are being developed for identifying risks, such
as laboratory methods to identify free (unbound) bilirubin and noninvasive
clinical methods such as auditory evoked potential to measure brain waves in
response to sound and nuclear magnetic resonance to measure the energy metabolism
of brain cells. In addition, methods to prevent the formation of bilirubin or to
reduce its levels by decreasing the activity of the enzyme heme oxygenase are
being studied.

Bibliography

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Robert M. Kliegman, and Hal B. Jenson, eds. Nelson Textbook of
Pediatrics. 19th ed. Philadelphia: Saunders/Elsevier, 2011.
Print.

Kirchner, Jeffrey T.
“Clinical Assessment of Neonatal Jaundice.” American Family
Physician 62.8 (2000): 1880. Print.

MacDonald, Mhairi G.,
Mary M. K. Seshia, and Martha D. Mullett, eds. Avery’s Neonatology:
Pathophysiology and Management of the Newborn. 6th ed.
Philadelphia: Lippincott, 2005. Print.

Martin, Richard J.,
Avroy A. Fanaroff, and Michele C. Walsh, eds. Fanaroff and Martin’s
Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 2
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