AUTHOR AND EDITOR INFORMATION

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• Introduction
• Clinical
• Differentials
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• Medication
• Follow-up
• Miscellaneous
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INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Jaundice is the most common condition that requires medical attention in newborns. The yellow coloration of the skin and sclera in newborns with jaundice is the result of accumulation of unconjugated bilirubin. In most infants, unconjugated hyperbilirubinemia reflects a normal transitional phenomenon. However, in some infants, serum bilirubin levels may excessively rise, which can be cause for concern because unconjugated bilirubin is neurotoxic and can cause death in newborns and lifelong neurologic sequelae in infants who survive (kernicterus). For these reasons, the presence of neonatal jaundice frequently results in diagnostic evaluation.

Neonatal jaundice may have first been described in a Chinese textbook 1000 years ago. Medical theses, essays, and textbooks from the 18^th and 19^th centuries contain discussions about the causes and treatment of neonatal jaundice. Several of these texts also describe a lethal course in infants who probably had Rh isoimmunization. In 1875, Orth first described yellow staining of the brain, in a pattern later referred to as kernicterus.

Pathophysiology

Neonatal physiologic jaundice results from simultaneous occurrence of the following 2 phenomena:

• Bilirubin production is elevated because of increased breakdown of fetal erythrocytes. This is the result of the shortened lifespan of fetal erythrocytes and the higher erythrocyte mass in neonates.
• Hepatic excretory capacity is low both because of low concentrations of the binding protein ligandin in the hepatocytes and because of low activity of glucuronyl transferase, the enzyme responsible for binding bilirubin to glucuronic acid, thus making bilirubin water soluble (conjugation).

Bilirubin is produced in the reticuloendothelial system as the end product of heme catabolism and is formed through oxidation-reduction reactions. Approximately 75% of bilirubin is derived from hemoglobin, but degradation of myoglobin, cytochromes, and catalase also contributes. In the first oxidation step, biliverdin is formed from heme through the action of heme oxygenase, the rate-limiting step in the process, releasing iron and carbon monoxide. The iron is conserved for reuse, whereas carbon monoxide is excreted through the lungs and can be measured in the patient's breath to quantify bilirubin production.

Next, water-soluble biliverdin is reduced to bilirubin, which, because of the intramolecular hydrogen bonds, is almost insoluble in water in its most common isomeric form (bilirubin IXá Z,Z). Because of its hydrophobic nature, unconjugated bilirubin is transported in the plasma tightly bound to albumin. Binding to other proteins and erythrocytes also occurs, but the physiologic role is probably limited. Binding of bilirubin to albumin increases postnatally with age and is reduced in infants who are ill.

The presence of endogenous and exogenous binding competitors, such as certain drugs, also decreases the binding affinity of albumin for bilirubin. A minute fraction of unconjugated bilirubin in serum is not bound to albumin. This free bilirubin is able to cross lipid-containing membranes, including the blood-brain barrier, leading to neurotoxicity. In fetal life, free bilirubin crosses the placenta, apparently by passive diffusion, and excretion of bilirubin from the fetus occurs primarily through the maternal organism.

Albumin is bound to a receptor on the cell surface when the bilirubin-albumin complex reaches the hepatocyte, and bilirubin is transported into the cell, where it binds to ligandin. Uptake of bilirubin into hepatocytes increases with increasing ligandin concentrations. Ligandin concentrations are low at birth but rapidly increase over the first few weeks of life. Ligandin concentrations may be increased by the administration of pharmacologic agents such as phenobarbital.

Bilirubin is bound to glucuronic acid (conjugated) in the hepatocyte endoplasmic reticulum in a reaction catalyzed by uridine diphosphoglucuronyltransferase (UDPGT). Monoconjugates are formed first and predominate in the newborn. Diconjugates appear to be formed at the cell membrane and may require the presence of the UDPGT tetramer.

Bilirubin conjugation is biologically critical because it transforms a water-insoluble bilirubin molecule into a water-soluble molecule. Water-solubility allows conjugated bilirubin to be excreted into bile. UDPGT activity is low at birth but increases to adult values by age 4-8 weeks. In addition, certain drugs (phenobarbital, dexamethasone, clofibrate) can be administered to increase UDPGT activity.

Infants who have Gilbert syndrome or who are compound heterozygotes for the Gilbert promoter and structural mutations of the UDPGT1A1 coding region are at an increased risk of significant hyperbilirubinemia. Interactions between the Gilbert genotype and hemolytic anemias such as glucose-6-phosphatase dehydrogenase (G-6-PD) deficiency, hereditary spherocytosis, or ABO hemolytic disease also appear to increase the risk of severe neonatal jaundice.

Once excreted into bile and transferred to the intestines, bilirubin is eventually reduced to colorless tetrapyrroles by microbes in the colon. However, some unconjugation occurs in the proximal small intestine through the action of B-glucuronidases located in the brush border. This unconjugated bilirubin can be reabsorbed into the circulation, increasing the total plasma bilirubin pool. This cycle of uptake, conjugation, excretion, unconjugation, and reabsorption is termed the enterohepatic circulation. The process may be extensive in the neonate, partly because nutrient intake is limited in the first days of life, prolonging the intestinal transit time.
 
Certain factors present in the breast milk of some mothers may also contribute to increased enterohepatic circulation of bilirubin (breast milk jaundice). Data suggest that the risk of breast milk jaundice is significantly increased in infants who have genetic polymorphisms in the coding sequences of the UDPGT1A1 or OATP2 genes. Although the mechanism that causes this phenomenon is not yet agreed upon, evidence suggests that supplementation with certain breast milk substitutes may reduce the degree of breast milk jaundice (see Other therapies).

Neonatal jaundice, although a normal transitional phenomenon in most infants, can occasionally become more pronounced. Blood group incompatibilities (eg, Rh, ABO) may increase bilirubin production through increased hemolysis. Historically, Rh isoimmunization was an important cause of severe jaundice, often resulting in the development of kernicterus. Although this condition has become relatively rare in industrialized countries following the use of Rh prophylaxis in Rh-negative women, Rh isoimmunization remains common in developing countries.

Nonimmune hemolytic disorders (spherocytosis, G-6-PD deficiency) may also cause increased jaundice, although increased hemolysis appears to have been present in some of the infants reported to have developed kernicterus in the United States in the last 10-15 years. The possible interaction between such conditions and genetic variants of the Gilbert and UDPGT1A1 genes is discussed above.

Frequency

United States

Neonatal hyperbilirubinemia is extremely common because almost every newborn develops an unconjugated serum bilirubin level of more than 30 µmol/L (1.8 mg/dL) during the first week of life. Incidence figures are difficult to compare because authors of different studies do not use the same definitions for significant neonatal jaundice. In addition, identification of infants to be tested depends on visual recognition of jaundice by health care providers, which is subject to great variability and depends both on observer attention and on infant characteristics such as race and gestational age.

With the above caveats, epidemiologic studies provide a frame of reference for estimated incidence. In 1986, Maisels and Gifford reported 6.1% of infants with serum bilirubin levels greater than 220 µmol/L (12.9 mg/dL).¹ In a 2003 study in the United States, 4.3% of 47,801 infants had total serum bilirubin (TSB) levels in a range in which phototherapy was recommended by the 1994 American Academy of Pediatrics (AAP) guidelines, and 2.9% had values in a range in which the 1994 AAP guidelines suggest considering phototherapy.²

International

Incidence varies with ethnicity and geography. Incidence is higher in East Asians and American Indians and lower in African Americans. Greeks living in Greece have a higher incidence than those of Greek descent living outside of Greece. Incidence is higher in populations living at high altitudes. In 1984, Moore et al reported 32.7% of infants with serum bilirubin levels greater than 205 µmol/L (12 mg/dL) at 3100 m of altitude.³ A study from Turkey reported significant jaundice in 10.5% of term infants and in 25.3% of near-term infants.⁴ Significant jaundice was defined according to gestational and postnatal age and leveled off at 14 mg/dL (240µmol/L) at 4 days in preterm infants and 17 mg/dL (290 µmol/L) in the term infants.

Mortality/Morbidity

• Death from physiologic neonatal jaundice per se should not occur.
• Death from kernicterus may occur, particularly in countries with less developed medical care systems. Mortality figures in this setting are not available.

Race

• The incidence of neonatal jaundice is increased in infants of East Asian, American Indian, and Greek descent, although the latter appears to apply only to infants born in Greece and thus may be environmental rather than ethnic in origin.
• African-American infants are affected less often than white infants. For this reason, significant jaundice in an African-American infant merits a closer evaluation of possible causes, including G-6-PD deficiency.
• In 1985, Linn et al reported on a series in which 49% of East Asian, 20% of white, and 12% of African American infants had serum bilirubin levels greater than 170 µmol/L (10 mg/dL).⁵

Sex

Risk of developing significant neonatal jaundice is higher in male infants. This does not appear to be related to bilirubin production rates, which are similar to those in female infants.

Age

The risk of significant neonatal jaundice is inversely proportional with gestational age.

CLINICAL

Section 3 of 11  

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History

• Presentation and duration
• • Typically, presentation is on the second or third day of life.
  • Jaundice that is visible during the first 24 hours of life is likely to be nonphysiologic; further evaluation is suggested.
  • Infants who present with jaundice after 3-4 days of life may also require closer scrutiny and monitoring.
  • In infants with severe jaundice or jaundice that continues beyond the first 1-2 weeks of life, the results of the newborn metabolic screen should be checked for galactosemia and congenital hypothyroidism, further family history should be explored, the infant's weight curve should be evaluated, the mother's impressions as far as adequacy of breastfeeding should be elicited, and the stool color should be assessed.
• Family history
• • Previous sibling with jaundice in the neonatal period, particularly if the jaundice required treatment
  • Other family members with jaundice or known family history of Gilbert syndrome
  • Anemia, splenectomy, or bile stones in family members or known heredity for hemolytic disorders
  • Liver disease
• History of pregnancy and delivery
• • Maternal illness suggestive of viral or other infection
  • Maternal drug intake
  • Delayed cord clamping
  • Birth trauma with bruising
• Postnatal history
• • Loss of stool color
  • Breastfeeding
  • Greater than average weight loss
  • Symptoms or signs of hypothyroidism
  • Symptoms or signs of metabolic disease (eg, galactosemia)
  • Exposure to total parental nutrition

Physical

• Neonatal jaundice first becomes visible in the face and forehead. Identification is aided by pressure on the skin, since blanching reveals the underlying color. Jaundice then gradually becomes visible on the trunk and extremities. This cephalocaudal progression is well described, even in 19th-century medical texts. Jaundice disappears in the opposite direction. This phenomenon is clinically useful because, independent of other factors, visible jaundice in the feet may be an indication to check the bilirubin level, either in the serum or noninvasively via transcutaneous bilirubinometry.
• In most infants, yellow color is the only finding on physical examination. More intense jaundice may be associated with drowsiness. Brainstem auditory evoked potentials performed at this time may reveal prolongation of latencies, decreased amplitudes, or both.
• Overt neurologic findings, such as changes in muscle tone, seizures, or altered cry characteristics, in a significantly jaundiced infant are danger signs and require immediate attention to prevent kernicterus. In the presence of such symptoms or signs, effective phototherapy should commence immediately without the laboratory test results (see Lab Studies). The potential need for exchange transfusion should not preclude the immediate initiation of phototherapy.
• Hepatosplenomegaly, petechiae, and microcephaly may be associated with hemolytic anemia, sepsis, and congenital infections and should trigger a diagnostic evaluation directed towards these diagnoses. Neonatal jaundice may be exacerbated in these situations.

Causes

• Physiologic jaundice is caused by a combination of increased bilirubin production secondary to accelerated destruction of erythrocytes, decreased excretory capacity secondary to low levels of ligandin in hepatocytes, and low activity of the bilirubin-conjugating enzyme UDPGT.
• Pathologic neonatal jaundice occurs when additional factors accompany the basic mechanisms described above. Examples include immune or nonimmune hemolytic anemia, polycythemia, and the presence of bruising or other extravasation of blood.
• Decreased clearance of bilirubin may play a role in breast milk jaundice and in several metabolic and endocrine disorders.
• Risk factors include the following:
• • Race: Incidence is higher in East Asians and American Indians and is lower in African Americans.
  • Geography: Incidence is higher in populations living at high altitudes. Greeks living in Greece have a higher incidence than those living outside of Greece.
  • Genetics and familial risk: Incidence is higher in infants with siblings who had significant neonatal jaundice and particularly in infants whose older siblings were treated for neonatal jaundice. Incidence is also higher in infants with mutations in the gene that codes for the UDPGT promoter (Gilbert syndrome), as well as in the UDPGT-coding region and in infants with homozygous or heterozygous G-6-PD deficiency and other hereditary hemolytic anemias.
  • Nutrition: Incidence is higher in infants who are breastfed or who receive inadequate nutrition.
  • Maternal factors: Infants of mothers with diabetes have higher incidence. Use of some drugs may increase the incidence, whereas others decrease the incidence.
  • Birthweight and gestational age: Incidence is higher in premature infants and in infants with low birthweight.
  • Congenital infection

DIFFERENTIALS

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Other Problems to be Considered

Certain conditions may cause nonphysiologic jaundice. In these infants, a baseline physiologic jaundice most likely occurs, which is then exaggerated, for example, by increased enterohepatic circulation in bowel atresia, bile stasis in choledochal cyst, or increased bilirubin production in hemolytic anemias. Such conditions include the following:

• Bowel atresia
• Choledochal cyst
• Conjugated hyperbilirubinemia
• Crigler-Najjar syndrome
• Arias syndrome
• Gilbert syndrome
• Immune hemolytic anemia
• Nonimmune hemolytic anemia

WORKUP

Section 5 of 11  

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Lab Studies

• Bilirubin measurement may include the following:
• • Transcutaneous bilirubinometry can be performed using handheld devices that incorporate sophisticated optical algorithms. However, such devices cannot be used to monitor the progress of phototherapy.
  • In infants with mild jaundice, transcutaneous bilirubinometry may be all that is needed to assure that total bilirubin levels are safely below those requiring intervention.
  • In infants with moderate jaundice, transcutaneous bilirubinometry may be useful in selecting patients who require phlebotomy for serum bilirubin measurement.
  • In infants with extreme jaundice, transcutaneous bilirubinometry may be a useful tool to fast-track such infants to early and aggressive therapy.
  • Usually, a total serum bilirubin level is the only testing required in an infant with moderately jaundice who presents on the typical second or third day of life without a history and physical findings suggestive of a pathologic process.
• Additional studies may be indicated in the following situations:
• • Infants who present with jaundice on the first or after the third day of life
  • Infants who are anemic at birth
  • Infants who otherwise appear ill
  • Infants in whom serum bilirubin levels are elevated enough to trigger treatment
  • Infants in whom significant jaundice persists beyond the first 2 weeks of life
  • Infants in whom family, maternal, pregnancy, or case histories suggest the possibility of a pathologic process
  • Infants in whom physical examination reveals findings not explained by simple physiologic hyperbilirubinemia
• In addition to total serum bilirubin levels, other suggested studies may include the following, particularly if the rate of rise in the bilirubin concentration is approaching the need for phototherapy:
• • Blood type and Rh determination in mother and infant
  • Direct Coombs testing in the infant
  • Hemoglobin and hematocrit values
  • Serum albumin levels: This appears to be a useful adjunct in evaluating risk of toxicity levels because albumin binds bilirubin in a ratio of 1:1 at the primary high-affinity binding site.
  • Nomogram for hour-specific bilirubin values: This may be a useful tool for predicting, either before or at the time of hospital discharge, which infants are likely to develop high serum bilirubin values. Infants identified in this manner require close follow-up monitoring and repeated bilirubin measurements. The predictive ability has been shown both for bilirubin values measured in serum and for values measured transcutaneously.
  • Measurement of end-tidal carbon monoxide in breath: End-tidal carbon monoxide in breath (ETCO) may be used as an index of bilirubin production. Measurement of ETCO may assist in identifying individuals with increased bilirubin production and, thus, at increased risk of developing high bilirubin levels. An apparatus has been developed that makes measuring ETCO simple (CO-Stat End Tidal Breath Analyzer; Natus Medical Inc).
  • Peripheral blood film for erythrocyte morphology
  • Reticulocyte count
  • Conjugated bilirubin: Note that direct bilirubin measurements are often inaccurate, are subject to significant interlaboratory and intralaboratory variation, and generally are not a sensitive tool for diagnosing cholestasis unless repeated measurements confirm the presence of an elevated conjugated bilirubin.
  • Liver function tests: Aspartate aminotransferase (ASAT or SGOT) and alanine aminotransferase (ALAT or SGPT) levels are elevated in hepatocellular disease. Alkaline phosphatase and g-glutamyltransferase (GGT) levels are often elevated in cholestatic disease. A GGT/ALAT ratio of more than 1 is strongly suggestive of biliary obstruction.
  • Tests for viral and/or parasitic infection: These may be indicated in infants with hepatosplenomegaly or other evidence of hepatocellular disease.
  • Reducing substance in urine: This is a useful screening test for galactosemia, provided the infant has received sufficient quantities of milk.
  • Blood gas measurements: The risk of bilirubin CNS toxicity is increased in acidosis, particularly respiratory acidosis.
  • Bilirubin-binding tests: Although they are interesting research tools, these tests have not found widespread use in clinical practice. Although elevated levels of unbound bilirubin are associated with an increased risk of bilirubin encephalopathy, unbound bilirubin is but one of several factors that mediate/modulate bilirubin toxicity.
  • Thyroid function tests

Imaging Studies

• Ultrasonography: Ultrasonography of the liver and bile ducts is warranted in infants with laboratory or clinical signs of cholestatic disease.
• Radionuclide scanning: A radionuclide liver scan for uptake of hepatoiminodiacetic acid (HIDA) is indicated if extrahepatic biliary atresia is suspected. At the author's institution, patients are pretreated with phenobarbital 5 mg/kg/d for 3-4 days before performing the scan.

Other Tests

• Auditory and visually evoked potentials are affected during ongoing significant jaundice; however, no criteria have been established that allow extrapolation from evoked potential findings to the risk of kernicterus. Brainstem auditory-evoked potentials should be obtained in the aftermath of severe neonatal jaundice to exclude sensorineural hearing loss. In physiologic jaundice, the auditory-evoked potential returns to normal with the resolution of hyperbilirubinemia. However, in patients with significant neonatal jaundice or kernicterus, the auditory-evoked potential and functional hearing may remain abnormal.
• The phonetic characteristics of the infant's cry are changed in significant neonatal jaundice; however, computerized analyses of these phonetic characteristics are not used in clinical practice.

Histologic Findings

Organs, including the brain, are yellow in any individual with significant jaundice; however, the yellow color does not always indicate CNS toxicity. This distinction was not always clearly understood in older descriptions of low-bilirubin kernicterus. At present, this has contributed to confusion and uncertainty regarding therapeutic guidelines and intervention levels. See Kernicterus for a more detailed description.

TREATMENT

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Medical Care

Phototherapy, intravenous immune globulin, and exchange transfusion are the most widely used therapeutic modalities in infants with neonatal jaundice.

Phototherapy

Phototherapy is the primary treatment in neonates with unconjugated hyperbilirubinemia. This therapeutic principle was discovered rather serendipitously in England in the 1950s and now is arguably the most widespread therapy of any kind (excluding prophylactic treatments) used in newborns.

Phototherapy is effective because 3 reactions can occur when bilirubin is exposed to light, as follows:

• Initially, photooxidation was believed to be responsible for the beneficial effect of phototherapy. However, although bilirubin is bleached through the action of light, the process is slow and is now believed to contribute only minimally to the therapeutic effect of phototherapy.
• Configurational isomerization is a very rapid process that changes some of the predominant 4Z,15Z bilirubin isomers to water-soluble isomers in which one or both of the intramolecular bonds are opened (E,Z; Z,E; or E,E). In human infants, the 4Z,15E isomer predominates, and, at equilibrium conditions, the isomer constitutes about 20% of circulating bilirubin after a few hours of phototherapy. This proportion is not significantly influenced by the intensity of light.
• Structural isomerization consists of intramolecular cyclization, resulting in the formation of lumirubin. This process is enhanced by increasing the intensity of light. During phototherapy, lumirubin may constitute 2-6% of the total serum bilirubin concentration.

The photoisomers of bilirubin are excreted in bile and, to some extent, in urine. The half-life of lumirubin in serum is much shorter than that in E isomers, and lumirubin is the primary pigment found in bile during phototherapy. Thus, although the E isomers predominate in serum, lumirubin is mostly responsible for the therapeutic effect of phototherapy of lowering the serum bilirubin level.

Bear in mind when initiating phototherapy that lowering of the total serum bilirubin concentration is only part of the therapeutic benefit. Because photoisomers, by virtue of their water-soluble nature, should not be able to cross the blood-brain barrier, phototherapy reduces the risk of bilirubin-induced neurotoxicity as soon as the lights are turned on. At any given total serum bilirubin concentration, the presence of 20-25% of photoisomers means that only 75-80% of the total bilirubin is present in a form that can enter the brain.

Phototherapy can be administered in a number of ways. To understand the benefits and limitations of the various approaches, some basic principles regarding wavelength and types of light are discussed below with comments and suggestions regarding each system.

First, wavelength must be considered. Bilirubin absorbs light primarily around 450 nm. However, the ability of light to penetrate skin is also important; longer wavelengths penetrate better. In practice, light is used in the white, blue, and green wavelengths.

Second, a dose-response relationship exists between the amount of irradiation and reduction in serum bilirubin up to an irradiation level of 30-40 µW/cm²/nm. Many older phototherapy units deliver much less energy, some at or near the minimally effective level, which appears to be approximately 6 µW/cm²/nm. On the other hand, newer phototherapy units, when properly configured and with the use of reflecting blanket and curtains may deliver light energy up to the 40 µW/cm²/nm suggested to be the saturation level.

Third, the energy delivered to the infant's skin decreases with increasing distance between the infant and the light source. This distance should not be greater than 50 cm (20 in) and can profitably be less (down to 10 cm) provided the infant's temperature is monitored.

Fourth, the efficiency of phototherapy depends on the amount of bilirubin that is irradiated. Irradiating a large skin surface area is more efficient than irradiating a small area, and the efficiency of phototherapy increases with serum bilirubin concentration.

Fifth, the nature and character of the light source may affect energy delivery. Irradiation levels using quartz halide spotlights are maximal at the center of the circle of light and decrease sharply towards the perimeter of the circle. Large infants and infants who can move away from the circle's center may receive less efficient phototherapy.

Although green light theoretically penetrates the skin better, it has not been shown unequivocally to be more efficient in clinical use than blue or white light. Because green light makes babies look sick and is unpleasant to work in, green light has not gained widespread acceptance.

Blue fluorescent tubes are widely used for phototherapy. Narrow-spectrum blue lamps (special blue) appear to work best, while ordinary blue fluorescent lamps are probably equivalent to standard white daylight lamps. Blue lights may cause discomfort in hospital staff members, which can be ameliorated by mixing blue and white tubes in the phototherapy unit.

White (daylight) fluorescent tubes are less efficient than special blue lamps; however, decreasing the distance between infants and lamps can compensate for the lower efficiency. Use of reflecting materials also helps. Thus, in developing countries where the cost of special blue lamps may be prohibitive, efficient phototherapy is accomplished with white lamps.

White quartz lamps are an integral part of some radiant warmers and incubators. They have a significant blue component in the light spectrum. When used as spotlights, the energy field is strongly focused towards the center, with significantly less energy delivered at the perimeter, as discussed above.

Quartz lamps also are used in single or double banks of 3-4 bulbs attached to the overhead heat source of some radiant warmers. The energy field delivered by these is much more homogeneous than that of spotlights, and the energy output is reasonably high. However, because the lamps are fixed to the overhead heater unit, the ability to increase energy delivery by moving lights closer to infants is limited.

Fiberoptic light is also used in phototherapy units. These units deliver high energy levels, but to a limited surface area. Efficiency may be comparable to that of conventional low-output overhead phototherapy units but not to that of overhead units used with maximal output. Drawbacks of fiberoptic phototherapy units include noise from the fan in the light source and decrease of delivered energy with aging and/or breakage of the optic fibers. Advantages include the following:

• Low risk of overheating the infant
• No need for eye shields
• Ability to deliver phototherapy with the infant in a bassinet next to the mother's bed
• Simple deployment for home phototherapy
• The possibility of irradiating a large surface area when combined with conventional overhead phototherapy units (double/triple phototherapy)

"Double" and "triple" phototherapy, which implies the concurrent use of 2 or 3 phototherapy units to treat the same patient, has often been used in the treatment of infants with very high levels of serum bilirubin. The studies that appeared to show a benefit with this approach were performed with old, relatively low-yield phototherapy units. Newer phototherapy units provide much higher levels of irradiance, which may in fact be close to the apparent saturation level of bilirubin photoisomerization. Whether double or triple phototherapy also confers a benefit with the newer units, has not been tested in systematic trials.

Indications for phototherapy are discussed as follows:

• The purpose of treating neonatal jaundice is to avoid neurotoxicity. Thus, indications for treatment have been based on clinical studies of infants who developed kernicterus. Historical data, much of which was derived from infants with hemolytic jaundice, appeared to suggest that total serum bilirubin levels greater than 350 µmol/L (20 mg/dL) were associated with increased risk of neurotoxicity, at least in full-term infants.
• As treatment of premature infants became more widespread and increasingly successful during the last half of the 20th century, autopsy findings and follow-up data suggested that immature infants were at risk of bilirubin encephalopathy at lower total serum bilirubin levels than mature infants. Treatment was initiated at lower levels for these infants.
• Until the 1940s, a truly effective treatment was not available. At that time, exchange transfusion was shown to be feasible and was subsequently used in the treatment of Rh-immunized infants with severe anemia, hyperbilirubinemia, or hydrops. However, exchange transfusion is not without risk for the infant, and only with the discovery of phototherapy did neonatal jaundice start to become an indication for treatment on a wider scale. Once phototherapy was shown to be a rather innocuous treatment, lights were turned on at lower serum bilirubin values than those that had triggered exchange transfusion.
• Exchange transfusion became the second-line treatment when phototherapy failed to control serum bilirubin levels. However, recent data have shown that treatment with intravenous immune globulin (IVIG) in infants with Rh or ABO isoimmunization can significantly reduce the need for exchange transfusions. At the author's institution, a tertiary center where exchange transfusions used to be frequent, only 0-2 such procedures per year are performed, and IVIG has replaced exchange transfusion as the second-line treatment in infants with isoimmune jaundice.
• Clearly, the scientific data on which current therapeutic guidelines are based have very significant shortcomings. Unfortunately, because the endpoint of bilirubin neurotoxicity is permanent brain damage, a randomized study to reassess the guidelines is ethically unthinkable.
• In most neonatal wards, total serum bilirubin levels are used as the primary measure of risk for bilirubin encephalopathy. Numerous people would prefer to add a test for serum albumin at higher bilirubin levels because bilirubin entry into the brain, a sine qua non for bilirubin encephalopathy, increases when the bilirubin-albumin ratio exceeds unity. Tests for bilirubin-albumin binding or unbound bilirubin levels are used by some but have failed to gain widespread acceptance. New analytical tools for measurement of unbound bilirubin have greatly simplified the process, but the effect on clinical practice remains to be seen.
• A number of guidelines for the management of neonatal jaundice have been published, and even more appear to be in local use without submission for critical review. In a survey published in 1996, the author analyzed clinical practices in this field based on responses from 108 neonatal intensive care units (NICUs) worldwide.⁷ The survey revealed a significant disparity in guidelines.
• • Media file 1 shows a box-and-whisker plot of the range of serum bilirubin values that trigger phototherapy and exchange transfusion, respectively, in these NICUs. Evidently, an infant might receive an exchange transfusion in one NICU for a serum bilirubin level that would not trigger phototherapy in many other NICUs. This disparity illustrates how difficult it has been to translate clinical data into sensible treatment guidelines.
  • In 2004, the AAP published new guidelines for the management of hyperbilirubinemia in healthy full-term newborns.⁶ These guidelines have been plotted on Media file 1.
  • The 2004 AAP guidelines represent a significant change from the 1994 guidelines.⁶ Thus, the emphasis on preventive action and risk evaluation is much stronger. An algorithm aids in the assessment of risk and the decision about further management and follow-up (see Media file 2). The committee that wrote the guidelines has carefully assessed the strength of the scientific evidence on which the guidelines are based.
  • Practitioners in North America are advised to follow the 2004 AAP guidelines. However, physicians in different ethnic or geographic regions should tailor these guidelines as pertinent to their own populations and must consider factors that are unique to their medical practice settings. Such factors may include racial characteristics, prevalence of congenital hemolytic disorders, and environmental concerns. At present, the wisest course of action may be to apply local guidelines that have been successful in the prevention of kernicterus.
  • With this background and the clear understanding that this is meant only as an example, Media file 3 shows the chart currently in use in most pediatric departments in Norway. These guidelines are the result of a 2006 consensus in the Neonatal Subgroup of the Norwegian Pediatric Society. The similarity between the Norwegian chart and the 2004 AAP guidelines are apparent.

Key points in the practical execution of phototherapy are maximizing energy delivery and the available surface area.

• The infant should be naked except for diapers (use these only if deemed absolutely necessary and cut them to minimum workable size), and the eyes should be covered to reduce risk of retinal damage.
• Check the distance between the infant's skin and the light source. With fluorescent lamps, the distance should be no greater than 50 cm (20 in). This distance may be reduced down to 10-20 cm if temperature homeostasis is monitored to reduce the risk of overheating. Note that this does not apply to quartz lamps.
• Cover the inside of the bassinet with reflecting material; white linen works well. Hang a white curtain around the phototherapy unit and bassinet. These simple expedients can multiply energy delivery by several fold.
• When using spotlights, ensure that the infant is placed at the center of the circle of light, since photoenergy drops off towards the circle's perimeter. Observe the infant closely to ensure that the infant doesn't move away from the high-energy area. Spotlights are probably more appropriate for small premature infants than for larger near-term infants.
• Older data suggested that phototherapy was associated with increased insensible water loss; therefore, many clinicians have routinely added a certain percentage to the infant's estimated basic fluid requirements. Newer data suggest that if temperature homeostasis is maintained, fluid loss is not significantly increased by phototherapy. At the author's institution, routine fluid supplementation for infants under phototherapy is no longer recommended. Rather, the infant is monitored for weight loss, urine output, and urine specific gravity. Fluid intake is adjusted accordingly. In infants who are orally fed, the preferred fluid is milk because it serves as a vehicle to transport bilirubin out of the gut.
• Timing of follow-up serum bilirubin testing must be individualized. In infants admitted with extreme serum bilirubin values (>500 µmol/L or 30 mg/dL), monitoring should occur every hour or every other hour. Reductions in serum bilirubin values of 85 µmol/L/h (5 mg/dL/h) have been documented under such circumstances. In infants with more moderate elevations of serum bilirubin, monitoring every 6-12 hours is probably adequate.
• Expectations regarding efficacy of phototherapy must be tailored to the circumstances. In infants in whom serum bilirubin concentrations are still rising, a significant reduction of the rate of increase may be satisfactory. In infants in whom serum bilirubin concentrations are close to their peak, phototherapy should result in measurable reductions in serum bilirubin levels within a few hours. In general, the higher the starting serum bilirubin concentration, the more dramatic the initial rate of decline.
• Discontinuation of phototherapy is a matter of judgment, and individual circumstances must be taken into consideration. In practice, phototherapy is discontinued when serum bilirubin levels fall 25-50 µmol/L (1.5-3 mg/dL) below the level that triggered the initiation of phototherapy. Serum bilirubin levels often rebound after treatment has been discontinued, and follow-up tests should be obtained within 6-12 hours after discontinuation.
• Indications for prophylactic phototherapy are debatable. Phototherapy serves no purpose in an infant who is not clinically jaundiced. In general, the lower the serum bilirubin level, the less efficient the phototherapy. It seems more rational to apply truly effective phototherapy once serum (and skin) bilirubin has reached levels at which photons may do some good.
• Wherever phototherapy is offered as a therapeutic modality, a device for measuring the irradiance delivered by the equipment used should be readily at hand. This assist sin configuring the phototherapy set-up to deliver optimal efficiency.

Management of infants with extreme jaundice includes the following:

• Numerous cases have been reported in which infants have been readmitted to hospitals with extreme jaundice. In some cases, significant delays have occurred between the time the infant was first seen by medical personnel and the actual commencement of effective therapy.
• Any infant who returns to the hospital with significant jaundice within the first 1-2 weeks of birth should be immediately triaged with measurement of transcutaneous bilirubin. High values should result in immediate initiation of treatment. If such a measuring device is not available, or if the infant presents with any kind of neurological symptoms, the infant should be put in maximally efficient phototherapy as an emergency procedure, preferably by fast-tracking the infant to a NICU. Waiting for laboratory results is not necessary before instituting such therapy because no valid contraindications to phototherapy are possible in this scenario. Plans for an exchange transfusion do not constitute an argument for delaying or not performing phototherapy. Immediate benefit is obtained within minutes, as soon as conversion of bilirubin into water-soluble photoisomers is measurable.
• Every hospital in which babies are delivered, or which has an emergency department in which infants may be seen, should consider developing a protocol and triage algorithm for rapid evaluation and management of jaundiced infants. The objective of such a protocol should be rapid recognition of risk severity and reduction in the time to initiate appropriate treatment.

Generally, phototherapy is very safe and may have no serious long-term effects in neonates; however, the following adverse effects and complications have been noted:

• Insensible water loss may occur, but newer data suggest that this issue is not as important as previously believed. Rather than instituting blanket increases of fluid supplements to all infants receiving phototherapy, the author recommends fluid supplementation tailored to the infant's individual needs, as measured through evaluation of weight curves, urine output, urine specific gravity, and fecal water loss.
• Phototherapy may be associated with loose stools. Increased fecal water loss may create a need for fluid supplementation.
• Retinal damage has been observed in some animal models during intense phototherapy. In an NICU environment, infants exposed to higher levels of ambient light were found to have an increased risk of retinopathy. Therefore, covering the eyes of infants undergoing phototherapy with eye patches is routine. Care must be taken lest the patches slip and leave the eyes uncovered or occlude one or both nares.
• The combination of hyperbilirubinemia and phototherapy can produce DNA-strand breakage and other effects on cellular genetic material. In vitro and animal data have not demonstrated any implication for treatment of human neonates. However, because most hospitals use cut-down diapers during phototherapy, the issue of gonad shielding may be moot.
• Skin blood flow is increased during phototherapy, but this effect is less pronounced in modern servocontrolled incubators. However, redistribution of blood flow may occur in small premature infants. An increased incidence of patent ductus arteriosus (PDA) has been reported in these circumstances.
• Hypocalcemia appears to be more common in premature infants under phototherapy lights. This has been suggested to be mediated by altered melatonin metabolism. Concentrations of certain amino acids in total parenteral nutrition solutions subjected to phototherapy may deteriorate. Shield total parenteral nutrition solutions from light as much as possible.
• Regular maintenance of the equipment is required because accidents have been reported, including burns resulting from a failure to replace UV filters.

Exchange transfusion

Exchange transfusion is indicated for avoiding bilirubin neurotoxicity when other therapeutic modalities have failed or are not sufficient. In addition, the procedure may be indicated in infants with erythroblastosis who present with severe anemia, hydrops, or both, even in the absence of high serum bilirubin levels.

Exchange transfusion was once a common procedure. A significant proportion was performed in infants with Rh isoimmunization. Immunotherapy in Rh-negative women at risk for sensitization has significantly reduced the incidence of severe Rh erythroblastosis. Therefore, the number of infants requiring exchange transfusion is now much smaller, and even large NICUs may perform only a few procedures per year. ABO incompatibility has become the most frequent cause of hemolytic disease in industrialized countries.

Recently, immunotherapy has been introduced as treatment in the few remaining sensitized infants. Results are promising and suggest that the number of infants requiring exchange transfusion may be reduced further.

• Early exchange transfusion has usually been performed because of anemia (cord hemoglobin <11 g/dL), elevated cord bilirubin (level >70 µmol/L or 4.5 mg/dL), or both. A rapid rate of increase in the serum bilirubin level (>15-20 µmol/L /h or 1 mg/dL/h) was an indication for exchange transfusion, as was a more moderate rate of increase (>8-10 µmol/L/h or 0.5 mg/dL/h) in the presence of moderate anemia (11-13 g/dL).
• The serum bilirubin level that triggered an exchange transfusion in infants with hemolytic jaundice was 350 µmol/L (20 mg/dL) or a rate of increase that predicted this level or higher. Strict adherence to the level of 20 mg/dL has been jocularly referred to as vigintiphobia (fear of 20).
• Currently, most experts encourage an individualized approach, recognizing that exchange transfusion is not a risk-free procedure, that effective phototherapy converts 15-25% of bilirubin to nontoxic isomers, and that transfusion of a small volume of packed red cells may correct anemia. Administration of IVIG (500 mg/kg) has been shown to reduce red cell destruction and to limit the rate of increase of serum bilirubin levels in infants with Rh and ABO isoimmunization. The 2004 AAP guidelines suggest a dose range for IVIG of 500-1000 mg/kg.⁶ The author has used the 500-mg/kg dose but has, on occasion, repeated the dose 2-3 times. In the author's own institution, with about 750 NICU admissions per year, the use of exchange transfusions has decreased to 0-2 per year following the implementation of IVIG therapy for Rh and AB0 isoimmunization.
• Current AAP guidelines distinguish between 3 risk categories: low, intermediate, and high.⁶ These correspond to 3 levels of suggested intervention, which increase from birth and plateau at age 4 days. Naturally, intervention levels associated with exchange transfusion are higher than those of phototherapy. Intensive phototherapy is strongly recommended in preparation for an exchange transfusion. In fact, intensive phototherapy should be performed on an emergency basis in any infant admitted for pronounced jaundice; do not await laboratory test results in these cases. Phototherapy has minimal side effects, whereas the waiting period for laboratory test results and blood for exchange can take hours and could constitute the difference between intact survival and survival with kernicterus. If phototherapy does not significantly lower serum bilirubin levels, exchange transfusion should be performed.
• Many physicians believe that hemolytic jaundice represents a greater risk for neurotoxicity than nonhemolytic jaundice, although the reasons for this belief are not intuitively obvious, assuming that total serum bilirubin levels are equal. In animal studies, bilirubin entry into or clearance from the brain was not affected by the presence of hemolytic anemia.
• The technique of exchange transfusion, including adverse effects and complications, is discussed extensively elsewhere. For more information, please consult Hemolytic Disease of Newborn.

Other therapies

In infants with breast milk jaundice, interruption of breastfeeding for 24-48 hours and feeding with breast milk substitutes often helps to reduce the bilirubin level. Evidence suggests that the simple expedient of supplementing feeds of breast milk with 5 mL of a breast milk substitute reduces the level and duration of jaundice in breast milk–fed infants.

Oral bilirubin oxidase can reduce serum bilirubin levels, presumably by reducing enterohepatic circulation; however, its use has not gained wide popularity. The same may be said for agar or charcoal feeds, which act by binding bilirubin in the gut. Bilirubin oxidase is not available as a drug, and for this reason, its use outside an approved research protocol probably is proscribed in many countries.

Prophylactic treatment of Rh-negative women with Rh immunoglobulin has significantly decreased the incidence and severity of Rh-hemolytic disease.

Surgical Care

• Surgical care is not indicated in infants with physiologic neonatal jaundice.
• Surgical therapy is indicated in infants in whom jaundice is caused by bowel or external bile duct atresia.

Consultations

• For infants with physiologic neonatal jaundice, no consultation is required.
• Gastroenterologists and surgeons may be consulted regarding infants with jaundice resulting from hepatobiliary or bowel disease.

Diet

Breastfeeding concerns associated with neonatal jaundice are as follows:

• Incidence and duration of jaundice have increased as breastfeeding has become more popular. The factors in breast milk that contribute to this phenomenon are unclear. In selected infants, interruption of breastfeeding and its replacement for 24-48 hours by a breast milk substitute may be indicated. This decision should always be discussed in person with the mother before implementation.
• With increasing emphasis on breastfeeding, some new mothers may have difficulty admitting (even to themselves) to a lack of success in establishing lactation. Occasionally, infants of breastfeeding mothers are admitted to hospitals with severe jaundice. They typically weigh significantly less than their birthweight at a time when they should have regained and surpassed that weight. Presumably, the process is one of increased enterohepatic circulation, as bilirubin is left longer in the proximal gut for lack of milk to bind it and carry it onward and out. The author refers to this condition as lack-of-breast-milk jaundice. These infants may respond dramatically to phototherapy plus oral feedings of milk ad libitum.

MEDICATION

Section 7 of 11  

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• Differentials
• Workup
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medications are not usually administered in infants with physiologic neonatal jaundice. However, in certain instances, phenobarbital, an inducer of hepatic bilirubin metabolism, has been used to enhance bilirubin metabolism. Several studies have shown that phenobarbital is effective in reducing mean serum bilirubin values during the first week of life. Phenobarbital may be administered prenatally in the mother or postnatally in the infant.

In populations in which the incidence of neonatal jaundice or kernicterus is high, this type of pharmacologic treatment may warrant consideration. However, concerns surround the long-term effects of phenobarbital on these children. Therefore, this treatment is probably not justified in populations with a low incidence of neonatal jaundice. Other drugs can induce bilirubin metabolism, but lack of adequate safety data prevents their use outside research protocols.

IVIG (500 mg/kg) has been shown to significantly reduce the need for exchange transfusions in infants with isoimmune hemolytic disease. The mechanism is unknown but may be related to the way the immune system handles red cells that have been coated by antibodies. Published experience is still somewhat limited, but administration of immunoglobulin does not appear to be likely associated with greater risks for the infant than an exchange transfusion.

A new therapy currently under development consists of inhibition of bilirubin production through blockage of heme oxygenase. This can be achieved through the use of metal mesoporphyrins and protoporphyrins. Apparently, heme can be directly excreted through the bile; thus, inhibition of heme oxygenase does not result in accumulation of unprocessed heme. This approach may virtually eliminate neonatal jaundice as a clinical problem. However, before the treatment can be applied on a wide scale, important questions regarding the long-term safety of the drugs must be answered. Also, in light of data suggesting that bilirubin may play an important role as a free radical quencher, a more complete understanding of this putative role for bilirubin is required before wholesale inhibition of its production is contemplated.

FOLLOW-UP

Section 8 of 11  

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• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Infants who have been treated for jaundice can be discharged when they are adequately feeding and have had 2 successive serum bilirubin levels demonstrating a trend towards lower values.
• If the hospital does not routinely screen newborns for auditory function, ordering such tests prior to discharge is advisable in infants who have had severe jaundice.
• The 2004 AAP guideline recommends a systematic risk assessment for hyperbilirubinemia risk in all infants before discharge.⁶ Parents should be provided with verbal and written information about jaundice.

Further Outpatient Care

• In the era of early discharge, newborns released within the first 48 hours of life need to be reassessed for jaundice within 1-2 days. Use of the hour-specific bilirubin nomogram (see Nomogram) may assist in selecting infants with a high likelihood of developing significant hyperbilirubinemia. The 2004 AAP guidelines emphasize the importance of universal systematic assessment for the risk of severe hyperbilirubinemia.⁶
• Telephone consultations are not recommended because parental reports cannot be gauged appropriately. In recent years, a number of infants have developed kernicterus, resulting, at least in part, from inadequate communication between physicians or their representatives and parents.
• The availability of new devices for transcutaneous measurement of bilirubin levels should facilitate follow-up evaluations of infants discharged before 48 hours of life.
• Home phototherapy
• • Home phototherapy is used in an effort to limit the high cost of applying such therapy in hospitals. Home treatment can avoid or limit parent-child separation. Home treatment should be used with caution, since prevention of neurotoxicity is the goal. Some physicians argue that an infant at risk for neurologic damage should not be at home.
  • With effective treatment strategies, the average duration of phototherapy in the regular neonatal nursery at the author's institution is less than 17 hours. Whether the effort and cost to set up home therapy is worthwhile is debatable. This assessment may be different in different socioeconomic and health financing circumstances.
• Infants who have been treated for hemolytic jaundice require follow-up observation for several weeks because hemoglobin levels may fall lower than seen in physiologic anemia. Erythrocyte transfusions may be required if infants develop symptomatic anemia.

In/Out Patient Meds

Although drugs which impact on bilirubin metabolism have been used in studies, drugs are not ordinarily used in unconjugated neonatal hyperbilirubinemia.

Transfer

Infants in need of exchange transfusion born at or admitted to facilities not capable of performing this procedure should be transferred to the nearest facility with such capability. In addition to complete records, the infant should be accompanied by a sample of maternal blood because this is needed by the blood bank to match blood.

However, in determining the best use of time before transfer, as well as the timing of the transfer, the following factors should be considered:  

• If the infant is in imminent danger of kernicterus, or is already exhibiting signs of neurological compromise, the most efficient phototherapy possible under the circumstances should be immediately initiated and should be continued until transfer commences. If fiberoptic or any other kind of phototherapy is technically feasible during transport, it should be continued throughout the duration of the transport.
• If the hyperbilirubinemia is due to blood group isoimmunization, an infusion of IVIG (500 mg/kg) should be immediately started and continued before and during transfer until completed (2 h).

Even if the receiving hospital determines that an exchange transfusion should be performed, continuing optimal phototherapy until the actual exchange procedure can commence is important. If fiberoptic phototherapy is available, the infant may be left on a fiberoptic mattress while the exchange is carried out. Oral hydration with a breast milk substitute may aid the clearance of bilirubin from the gut, thus inhibiting enterohepatic circulation of bilirubin, and should be given unless clearly contraindicated by the clinical state of the infant. Although none of these suggestions have been tested in randomized controlled trials, case reports, bilirubin photobiology, and expert opinion suggest that they may be beneficial and, at the very least, are unlikely to be harmful.

Deterrence/Prevention

Prevention of severe neonatal jaundice is best achieved through attention to the risk status of the infant prior to discharge from the birth hospital, through parent education, and through careful planning of post-discharge follow-up. A predischarge bilirubin measurement, obtained by transcutaneous or serum measurement and plotted into an hour-specific nomogram, has been shown to be a useful tool in distinguishing infants with a low risk of subsequently developing high bilirubin values. Clinical risk factors include gestational age of less than 38 weeks, the use of oxytocin or vacuum during delivery, and breast feeding. Birth weight is also associated with risk of developing significant jaundice; the higher the birthweight, the higher the risk.

Complications

• Kernicterus

Prognosis

• Prognosis is excellent if the patient receives treatment according to accepted guidelines.
• Brain damage due to kernicterus remains a true risk, and the increased incidence of kernicterus in recent years may be due to the misconception that jaundice in the healthy full-term infant is not dangerous and can be disregarded.

Patient Education

• Parents should be educated about neonatal jaundice and receive written information prior to discharge from the birth hospital. The parent information leaflet should preferably be available in several languages.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to recognize the potential of significant jaundice to cause brain damage, even in the healthy full-term neonate
• Failure to assess whether a "healthy full-term neonate" is both healthy and was really delivered at term
• Failure of the physician to personally examine an infant reported by parents or other caregivers to be significantly jaundiced
• Failure to consider risk factors for significant jaundice when an infant is prepared for early discharge from the birth hospital and failure to factor such risk into the plan for follow-up of the baby

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  The graph represents indications for phototherapy and exchange transfusion in infants (with a birthweight of 3500 g) in 108 neonatal ICUs. The left panel shows the range of indications for phototherapy, whereas the right panel shows the indications for exchange transfusion. Numbers on the vertical axes are serum bilirubin concentrations in mg/dL (lateral) and mmol/L (middle). In the left panel, the solid line refers to the current recommendation of the American Academy of Pediatrics (AAP) for low-risk infants, the line consisting of long dashes (- - - - -) represents the level at which the AAP recommends phototherapy for infants at intermediate risk, and the line with short dashes (-----) represents the suggested intervention level for infants at high risk. In the right panel, the dotted line (......) represents the AAP suggested intervention level for exchange transfusion in infants considered at low risk, the line consisting of dash-dot-dash (-.-.-.-.) represents the suggested intervention level for exchange transfusion in infants at intermediate risk, and the line consisting of dash-dot-dot-dash (-..-..-..-) represents the suggested intervention level for infants at high risk. Intensive phototherapy is always recommended while preparations for exchange transfusion are in progress. The box-and-whisker plots show the following values: lower error bar = 10th percentile; lower box margin = 25th percentile; line transecting box = median; upper box margin = 75th percentile; upper error bar = 90th percentile; and lower and upper diamonds = 5th and 95th percentiles, respectively.
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Media type:  Graph

Media file 2:  Algorithm for the management of jaundice in the newborn nursery.6
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Media type:  Chart

Media file 3:  Guidelines for management of neonatal jaundice currently in use in most pediatric departments in Norway. The guidelines were based on previously used charts and were created through a consensus process in the Neonatal Subgroup of the Norwegian Pediatric Society. These guidelines were adopted as national at the fall meeting of the Norwegian Pediatric Society. The reverse side of the chart contains explanatory notes to help the user implement the guidelines. A separate information leaflet for parents was also created.
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Media type:  Chart

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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