Neonatal jaundice

Also known as: Newborn jaundice

Anatomy or system affected: Blood, bones, brain, liver, spleen

Definition: A yellowish coloration visible on the skin and in the eyes of newborn infants

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 it progresses to 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. 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. A noninvasive technique, the transcutaneous bilirubinometer, provides an electronic readout of an index that corresponds with a serum bilirubin concentration. However, a more precise way to judge jaundice is to draw a small amount of blood from the baby and 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. Several 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 and lead 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.

Infants with nonhemolytic jaundice 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 milliliters—some clinicians advocate between 25 and 30 milligrams per 100 milliliters—exchange transfusion is generally recommended. In this method, all 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

Behrman, Richard E., Robert M. Kliegman, and Hal B. Jenson, eds. Nelson Textbook of Pediatrics. 21st ed. Saunders/Elsevier, 2020.

Kirchner, Jeffrey T. “Clinical Assessment of Neonatal Jaundice.” American Family Physician, vol. 62, no. 8, 2000, p. 1880.

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

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 vols. 11th ed., Mosby/Elsevier, 2020.