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Home , Bilirubin, Birth trauma (physical), Cephalohematoma, Hypotonia, Kernicterus, Neonatal jaundice

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Hyperbilirubinemia in the Term Newborn MEREDITH L. PORTER, CPT, MC, USA, and BETH L. DENNIS, MAJ, MC, USA Dewitt Army Community Hospital, Fort Belvoir, Virginia

Hyperbilirubinemia is one of the most common problems encountered in term newborns. Historically, management guidelines were derived from studies on in O A patient informa- with hemolytic disease. More recent recommendations support the use of less tion handout on jaun- intensive in healthy term newborns with . Phototherapy should be insti- dice in infants, written by the authors of this tuted when the total bilirubin level is at or above 15 mg per dL (257 µmol per L) in article, is provided on infants 25 to 48 hours old, 18 mg per dL (308 µmol per L) in infants 49 to 72 hours old, and page 613. 20 mg per dL (342 µmol per L) in infants older than 72 hours. Few term newborns with hyperbilirubinemia have serious underlying . Jaundice is considered pathologic if it presents within the first 24 hours after birth, the total serum bilirubin level rises by more than 5 mg per dL (86 µmol per L) per day or is higher than 17 mg per dL (290 µmol per L), or an has suggestive of serious illness. The management goals are to exclude pathologic causes of hyperbilirubinemia and initiate treatment to prevent bilirubin neurotoxicity. (Am Fam Physician 2002;65:599-606,613-4. Copyright© 2002 Ameri- can Academy of Family Physicians.)

eonatal hyperbilirubin- form of jaundice encountered by family emia, defined as a total physicians. The separate topic of conju- serum bilirubin level gated hyperbilirubinemia is beyond the above 5 mg per dL (86 scope of this article. µmol per L), is a fre- Nquently encountered problem. Although Risk Factors for Hyperbilirubinemia up to 60 percent of term newborns have Infants without identified risk factors clinical jaundice in the first week of life, rarely have total serum bilirubin levels few have significant underlying dis- above 12 mg per dL (205 µmol per L). As ease.1,2 However, hyperbilirubinemia in the number of risk factors increases, the the newborn period can be associated potential to develop markedly elevated with severe illnesses such as hemolytic bilirubin levels also increases.2 disease, metabolic and endocrine disor- Common risk factors for hyper- ders, anatomic abnormalities of the , bilirubinemia include fetal-maternal and . group incompatibility, prematu- Jaundice typically results from the rity, and a previously affected sibling deposition of unconjugated bilirubin (Table 1).2-4 Cephalohematomas, bruis- pigment in the skin and mucus mem- ing, and trauma from instrumented branes. Depending on the underlying delivery may increase the risk for serum etiology, this condition may present bilirubin elevation. Delayed meconium throughout the neonatal period. Uncon- passage also increases the risk. Infants jugated hyperbilirubinemia, the primary with risk factors should be monitored focus of this article, is the most common closely during the first days to weeks of life.

Bilirubin Production and Newborns Up to 60 percent of term newborns have clinical jaundice in the Bilirubin is the final product of first week of life. degradation. At physiologic pH, bilirubin is insoluble in plasma and

FEBRUARY 15, 2002 / VOLUME 65, NUMBER 4 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 599 cally declines to the adult level within 10 to 14 TABLE 1 days after birth.2 Risk Factors for Hyperbilirubinemia in Newborns Bilirubin Toxicity Maternal factors Neonatal factors “” refers to the neurologic con- ABO or : , cutaneous sequences of the deposition of unconjugated Rh incompatibility bruising, instrumented delivery bilirubin in tissue. Subsequent damage : sulfisoxazole acetyl with erythromycin and scarring of the and brain- ethylsuccinate (Pediazole), chloramphenicol Drugs: stem nuclei may occur.5 (Valium), oxytocin (Chloromycetin) (Pitocin) Excessive weight loss after birth The precise role of bilirubin in the develop- Ethnicity: Asian, Infections: TORCH ment of kernicterus is not completely under- Native American Infrequent feedings stood. If the serum unconjugated bilirubin Maternal illness: Male gender level exceeds the binding capacity of , gestational unbound -soluble bilirubin crosses the Prematurity blood-brain barrier. Albumin-bound biliru- Previous sibling with hyperbilirubinemia bin may also cross the blood-brain barrier if damage has occurred because of asphyxia, TORCH = , other viruses, rubella, cytomegalovirus, herpes (sim- acidosis, , hypoperfusion, hyper- plex) viruses. osmolality, or in the newborn.3,8 Information from references 2, 3, and 4. The exact bilirubin concentration associ- ated with kernicterus in the healthy term infant is unpredictable.1 Toxicity levels may requires binding with albumin. vary among ethnic groups, with maturation of After conjugation in the liver, it is excreted an infant, and in the presence of hemolytic in .3,5-7 disease. Although the risk of bilirubin toxicity Newborns produce bilirubin at a rate of is probably negligible in a healthy term new- approximately 6 to 8 mg per kg per day. This born without ,9 the physician is more than twice the production rate in should become concerned if the bilirubin level adults, primarily because of relative poly- is above 25 mg per dL (428 µmol per L).1,3,10 cythemia and increased red turn- In the term newborn with hemolysis, a biliru- over in neonates.7 Bilirubin production typi- bin level above 20 mg per dL (342 µmol per L) is a concern.1,3 The effects of bilirubin toxicity are often devastating and irreversible (Table 2).3,9 TABLE 2 Early signs of kernicterus are subtle and Effects of Bilirubin Toxicity in Newborns nonspecific, typically appearing three to four days after birth. However, hyperbiliru- Early Late Chronic binemia may lead to kernicterus at any time Lethargy Irritability Athetoid during the neonatal period.2 After the first Poor feeding Opisthotonos High-frequency High-pitched cry Paralysis of upward gaze week of life, the affected newborn begins to Apnea Dental dysplasia demonstrate late effects of bilirubin toxicity. Mild mental retardation If the infant survives the initial severe neu- rologic insult, chronic bilirubin enceph- Fever alopathy (evident by three years of age) leads to developmental and motor delays, Information from references 3 and 9. sensorineural deafness, and mild mental retardation.

600 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 65, NUMBER 4 / FEBRUARY 15, 2002 Hyperbilirubinemia

Classification of Neonatal Infants without identified risk factors rarely have total serum Hyperbilirubinemia bilirubin levels above 12 mg per dL (205 µmol per L). The causes of neonatal hyperbilirubinemia can be classified into three groups based on mechanism of accumulation: bilirubin over- production, decreased bilirubin conjugation, over the first week after birth.2 Bilirubin eleva- and impaired bilirubin excretion (Table 3).11 tions of up to 12 mg per dL, with less than 2 mg per dL (34 µmol per L) of the conjugated PHYSIOLOGIC JAUNDICE form, can sometimes occur. Infants with mul- Physiologic jaundice in healthy term new- tiple risk factors may develop an exaggerated borns follows a typical pattern. The average form of physiologic jaundice in which the total serum bilirubin level usually peaks at 5 to total serum bilirubin level may rise as high as 6 mg per dL (86 to 103 µmol per L) on the 17 mg per dL (291 µmol per L).3 third to fourth day of life and then declines Factors that contribute to the development

TABLE 3 Classification of Neonatal Hyperbilirubinemia Based on Mechanism of Accumulation

Increased bilirubin load Decreased bilirubin conjugation Impaired bilirubin excretion Hemolytic causes Characteristics: increased Characteristics: increased unconjugated Characteristics: increased unconjugated bilirubin unconjugated bilirubin level, and conjugated bilirubin level, negative level, >6 percent reticulocytes, normal percentage of Coombs’ test, conjugated bilirubin level concentration of <13 g per dL (130 g per L) reticulocytes of >2 mg per dL (34 µmol per L) or Coombs’ test positive: Rh factor incompatibility, Physiologic jaundice >20% of total serum bilirubin level, ABO incompatibility, minor Crigler-Najjar syndrome types 1 conjugated bilirubin in Coombs’ test negative: membrane and 2 Biliary obstruction: , defects (, elliptocytosis), red blood Gilbert syndrome choledochal cyst, primary sclerosing cell defects (G6PD deficiency, pyruvate cholangitis, , neoplasm, kinase deficiency), drugs (e.g., sulfisoxazole acetyl jaundice Dubin-Johnson syndrome, Rotor’s with erythromycin ethylsuccinate (Pediazole), syndrome streptomycin, vitamin K), abnormal red blood : sepsis, , cells (), sepsis syphilis, toxoplasmosis, tuberculosis, Nonhemolytic causes , rubella, herpes Characteristics: increased unconjugated bilirubin : alpha1 antitrypsin level, normal percentage of reticulocytes deficiency, , , Extravascular sources: cephalohematoma, bruising, glycogen storage disease, Gaucher’s hemorrhage, swallowed disease, hypothyroidism, Wilson’s blood disease, Niemann-Pick disease Polycythemia: fetal-maternal transfusion, delayed Chromosomal abnormality: Turner’s cord clamping, -twin transfusion syndrome, trisomy 18 and 21 syndromes Exaggerated enterohepatic circulation: cystic Drugs: , acetaminophen, sulfa, fibrosis, ileal atresia, , alcohol, rifampin (Rifadin), erythromycin, Hirschsprung’s disease, breast milk jaundice corticosteroids, tetracycline

G6PD = glucose-6-phosphate dehydrogenase. Information from Siberry GK, Iannone R, eds. The Harriet Lane handbook: a manual for pediatric house officers. 15th ed. St. Louis: Mosby, 2000:257-8.

FEBRURARY 15, 2002 / VOLUME 65, NUMBER 4 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 601 of physiologic hyperbilirubinemia in the level usually falls continually after the infant is neonate include an increased bilirubin load two weeks old, but it may remain persistently because of relative polycythemia, a shortened elevated for one to three months. erythrocyte life span (80 days compared with If the diagnosis of breast milk jaundice is in the adult 120 days), immature hepatic uptake doubt or the total serum bilirubin level becomes and conjugation processes, and increased markedly elevated, breastfeeding may be tem- enterohepatic circulation.7 porarily interrupted, although the mother should continue to express breast milk to main- JAUNDICE AND BREASTFEEDING tain production. With formula substitution, the Early-Onset Breastfeeding Jaundice. Breast- total serum bilirubin level should decline fed newborns may be at increased risk for rapidly over 48 hours (at a rate of 3 mg per dL early-onset exaggerated physiologic jaundice [51 µmol per L] per day),1 confirming the diag- because of relative caloric deprivation in the nosis. Breastfeeding may then be resumed. first few days of life.12 Decreased volume and frequency of feedings may result in mild dehy- PATHOLOGIC JAUNDICE dration and the delayed passage of meco- All etiologies of jaundice beyond physio- nium. Compared with formula-fed newborns, logic and breastfeeding or breast milk jaun- breastfed infants are three to six times more dice are considered pathologic. Features of likely to experience moderate jaundice (total pathologic jaundice include the appearance of serum bilirubin level above 12 mg per dL) or jaundice within 24 hours after birth, a rapidly severe jaundice (total serum bilirubin level rising total serum bilirubin concentration above 15 mg per dL [257 µmol per L]).12,13 (increase of more than 5 mg per dL per day), In a breastfed newborn with early-onset and a total serum bilirubin level higher than hyperbilirubinemia, the frequency of feedings 17 mg per dL in a full-term newborn.3,5 Other needs to be increased to more than 10 per day. features of concern include prolonged jaun- If the infant has a decline in weight gain, dice, evidence of underlying illness, and eleva- delayed stooling, and continued poor caloric tion of the serum conjugated bilirubin level to intake, formula supplementation may be nec- greater than 2 mg per dL or more than 20 per- essary, but breastfeeding should be continued cent of the total serum bilirubin concentra- to maintain breast milk production. Supple- tion. Pathologic causes include disorders such mental water or dextrose-water administra- as sepsis, rubella, toxoplasmosis, occult hem- tion should be avoided, as it decreases breast orrhage, and erythroblastosis fetalis. milk production and places the newborn at risk for iatrogenic .3,5,11 Diagnosis Late-Onset Breast Milk Jaundice. Breast PHYSICAL EXAMINATION milk jaundice occurs later in the newborn The presence of jaundice can be deter- period, with the bilirubin level usually peak- mined by examining the infant in a well-lit ing in the sixth to 14th days of life. This late- room and blanching the skin with digital onset jaundice may develop in up to one third pressure to reveal the color of the skin and of healthy breastfed infants.1 Total serum subcutaneous tissue. Neonatal dermal icterus bilirubin levels vary from 12 to 20 mg per dL is not noticeable at total serum bilirubin lev- (340 µmol per L) and are nonpathologic. els below 4 mg per dL (68 µmol per L).16 The underlying cause of breast milk jaun- Increasing total serum bilirubin levels are dice is not entirely understood. Substances in accompanied by the cephalocaudal progres- maternal milk, such as -glucuronidases, and sion of dermal icterus, predictably from the nonesterified fatty acids, may inhibit normal face to the trunk and extremities, and finally to bilirubin .5,7,14,15 The bilirubin the palms and soles.16,17 The total serum biliru-

602 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 65, NUMBER 4 / FEBRUARY 15, 2002 Laboratory Evaluation of Term Newborn with Jaundice

Age of newborn

<24 hours 24 hours to 2 weeks >2 weeks

Evaluate for pathologic cause: Fractionated bilirubin level Fractionated bilirubin level Sepsis Urine bilirubin level Rubella Thyroid studies Toxoplasmosis Conjugated bilirubin level Evaluation for sepsis Occult hemorrhage Tests for metabolic disorders Erythroblastosis fetalis

>2mg per dL (34 µmol per L) < 2mg per dL

Evaluate for causes of direct hyperbilirubinemia Normal or low High hemoglobin (see Table 3, impaired hemoglobin concentration bilirubin excretion concentration column). Polycythemia Reticulocyte count Peripheral blood smear

Abnormal Normal

Evaluate for hemolytic Evaluate for nonhemolytic causes (see Table 3, causes (see Table 3, increased bilirubin increased bilirubin load load column). and decreased bilirubin conjugation columns).

FIGURE 1. Algorithm for the suggested evaluation of a term newborn with hyperbilirubinemia. Information from jaundice and hyperbilirubinemia in the newborn. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of . 16th ed. Philadelphia: Saunders, 2000:511-28. bin level can be estimated clinically by the levels, interobserver variability, and other fac- degree of caudal extension: face, 5 mg per dL; tors contribute to the difficulty of accurately upper chest, 10 mg per dL (171 µmol per L); predicting the total serum bilirubin concentra- abdomen, 12 mg per dL; palms and soles, tion based on caudal progression alone.18 greater than 15 mg per dL. The physical examination should focus on The only consistently reliable estimation of identifying one of the known causes of patho- total serum bilirubin occurs when dermal logic jaundice. The infant should be assessed icterus is confined to above the nipple line. In for pallor, petechiae, extravasated blood, ex- this situation, the bilirubin level is invariably cessive bruising, , weight below 12 mg per dL.As jaundice extends below loss, and evidence of . the middle of the chest, the correlation between physical signs and measured bilirubin LABORATORY EVALUATION levels becomes increasingly unreliable. Differ- The initial evaluation of jaundice depends ences in skin color among races, delays in der- on the age of the newborn (Figure 1).2 If the mal deposition with rapidly rising bilirubin serum conjugated bilirubin level is above

FEBRURARY 15, 2002 / VOLUME 65, NUMBER 4 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 603 TABLE 4 Management of Hyperbilirubinemia in Healthy Term Newborns

The rightsholder did not grant rights to reproduce hyperbilirubinemia. More recently, term in- fants without hemolysis have been found to this item in electronic tolerate higher total serum bilirubin levels,21 media. For the missing and management guidelines now focus pri- item, see the original print marily on phototherapy as initial treatment.1 version of this publication. Recommendations for the management of hyperbilirubinemia in healthy term newborns have been outlined by the American Academy of Pediatrics (Table 4).1 Jaundice in a term newborn fewer than 24 hours old is always pathologic: it should be investigated thor- oughly and treated appropriately. Depending on the rate at which the bilirubin level rises, a newborn’s risk of developing significant hyperbilirubinemia can be classified as low, intermediate, or high (Figure 2).22 With the assumption that the bilirubin level will con- tinue to rise at the same rate, the physician can 2 mg per dL, the infant should be evaluated predict the potential further progression of for possible hepatocellular disease or biliary the rise and calculate the number of days that obstruction. the infant may be at risk for bilirubin toxicity. Conjugated hyperbilirubinemia is never Management physiologic, and it may indicate the presence of Studies on the toxic effects of hyperbiliru- a potentially serious underlying disorder. How- binemia historically involved infants with ever, elevated conjugated bilirubin levels are hemolytic disease. An increased incidence of not directly toxic to brain cells in the neonate.2 kernicterus was found to be associated with If jaundice persists for more than two total serum bilirubin levels above 20 mg per weeks in a formula-fed infant and more than dL in the presence of hemolysis.19,20 This three weeks in a breastfed infant, further eval- observation was the basis for aggressive guide- uation is warranted.1,7 Laboratory studies lines recommending the use of exchange should include a fractionated bilirubin level, transfusion in all infants with significant thyroid studies, evaluations for metabolic dis- orders or hemolytic disease, and an assess- ment for intestinal obstruction.

The Authors Treatment MEREDITH L. PORTER, CPT, MC, USA, is a staff family physician at Vicencza Army Before treatment is initiated, the minimum Health Clinic, Italy. Dr. Porter received her medical degree from Virginia Common- evaluation should include the infant’s age and wealth University School of Medicine, Richmond, and completed a family practice res- postnatal course, a maternal and gestational idency at Dewitt Army Community Hospital, Fort Belvoir, Va. history, physical examination of the infant, and BETH L. DENNIS, MAJ, MC, USA, is a staff family physician and clinic director at Dewitt Army Community Hospital. She also serves as assistant professor of medicine at the determination of the total serum bilirubin level Uniformed Services University of Health Sciences F. Edward Hébert School of Medicine, and the rate at which it is rising (Figure 2).22 Bethesda, Md. Dr. Dennis received her medical degree from the University of Virginia School of Medicine, Charlottesville, and completed a family practice residency at PHOTOTHERAPY Tripler Army Medical Center, Honolulu. Address correspondence to Meredith L. Porter, CMR 427, Box 3389, APO, Phototherapy employs blue wavelengths of AE 09630 (e-mail: [email protected]). Reprints are not avail- light to alter unconjugated bilirubin in the able from the authors. skin. The bilirubin is converted to less toxic

604 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 65, NUMBER 4 / FEBRUARY 15, 2002 Bilirubin Levels and Risk of Significant Hyperbilirubinemia

25 (428)

20 (342) High-risk zone 95th percentile

75th percentile 15 (257) 40th percentile

High-intermediate-risk zone 10 (171) Low-intermediate-risk zone

Low-risk zone 5 (86) Total serum bilirubin level, mg per dL (µmol L) Total

0 0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 Age in hours

FIGURE 2. Risk for significant hyperbilirubinemia in healthy term and near-term well newborns. Based on age-specific total serum bilirubin levels, the risk can be classified as high (above 95th percentile), intermediate (40th to 95th percentile), or low (below 40th percentile). Adapted with permission from Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-spe- cific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999;103:6-14. water-soluble photoisomers that are excreted oration of the skin (bronze baby syndrome).2 in the bile and urine without conjugation. Potential problems that may occur with The decision to initiate phototherapy is based phototherapy include burns, retinal damage, on the newborn’s age and total serum biliru- thermoregulatory instability, loose stools, bin level (Table 4).1 dehydration, skin rash, and tanning of the The efficacy of phototherapy depends on sev- skin. Because phototherapy is continuous, eral important factors. The ideal configuration treatment also involves significant separation is four special blue bulbs (F20T12/BB) placed of the infant and parents. centrally, with two daylight fluorescent tubes on With intensive phototherapy, the total serum either side. The power output of the lights (irra- bilirubin level should decline by 1 to 2 mg per diance) is directly related to the distance dL (17 to 34 µmol per L) within four to six between the lights and the newborn.23 Ideally, hours.1,5 The bilirubin level may decline more all lights should be 15 to 20 cm from the infant.2 slowly in breastfed infants (rate of 2 to 3 mg To expose the greatest surface area, the newborn per dL per day) than in formula-fed infants.3 should be naked except for eye shields. For dou- Phototherapy usually can be discontinued ble phototherapy, a fiber-optic pad can be when the total serum bilirubin level is below placed under the newborn. This method is 15 mg per dL.1 The average rebound bilirubin twice as effective as standard phototherapy.5 level after phototherapy is below 1 mg per dL. The only contraindication to the use of Therefore, hospital discharge of most infants phototherapy is conjugated hyperbilirubine- does not have to be delayed to monitor for mia, as occurs in patients with and rebound elevation.24,25 hepatic disease. In this setting, phototherapy If the total serum bilirubin level remains ele- may cause a dark grayish- discol- vated after intensive phototherapy or if the ini-

FEBRURARY 15, 2002 / VOLUME 65, NUMBER 4 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 605 Hyperbilirubinemia

tial bilirubin level is meets defined critical levels 6. Wintrobe MM, Lee GR. Wintrobe’s Clinical hema- 1 tology. 10th ed. Baltimore: Williams & Wilkins, based on the infant’s age (Table 4), prepara- 1999:267-89. tions should be made for . 7. Gartner LM, Herschel M. Jaundice and breastfeed- ing. Pediatr Clin North Am 2001;48:389-99. EXCHANGE TRANSFUSION 8. Ravel R. Clinical laboratory medicine: clinical appli- cation of laboratory data. 6th ed. St. Louis: Mosby, Exchange transfusion is the most rapid 1999:309-27. method for lowering serum bilirubin concen- 9. Maisels MJ, Newman TB. Kernicterus in otherwise healthy, breast-fed term newborns. Pediatrics trations. This treatment is rarely needed 1995;96(4 pt 1):730-3. 1,26,27 when intensive phototherapy is effective. 10. Newman TB, Maisels MJ. Evaluation and treatment The procedure removes partially hemolyzed of jaundice in the term newborn: a kinder, gentler approach. Pediatrics 1992;89(5 pt 1):809-18. and -coated erythrocytes and 11. Siberry GK, Iannone R, eds. The Harriet Lane hand- replaces them with uncoated donor red blood book: a manual for pediatric house officers. 15th cells that lack the sensitizing . ed. St. Louis: Mosby, 2000:257-8. 12. Osborn LM, Reiff MI, Bolus R. Jaundice in the full- In the presence of hemolytic disease, severe term neonate. Pediatrics 1984;73:520-5. , or a rapid rise in the total serum biliru- 13. Schneider AP II. Breast milk jaundice in the new- bin level (greater than 1 mg per dL per hour in born. A real entity. JAMA 1986;255:3270-4. 14. Poland RL. Breast-milk jaundice. J Pediatr 1981;99: less than six hours), exchange transfusion is the 86-8. recommended treatment. Exchange transfu- 15. Brodersen R, Herman LS. Intestinal reabsorption of sion should be considered in a newborn with unconjugated bilirubin. Lancet 1963;1:1242. 16. Kramer LI. Advancement of dermal icterus in the nonhemolytic jaundice if intensive photother- jaundiced newborn. Am J Dis Child 1969;118:454-8. 1 apy fails to lower the bilirubin level. 17. Knudsen A, Ebbesen F. Cephalocaudal progression Complications of exchange transfusion can of jaundice in newborns admitted to neonatal intensive care units. Biol Neonate 1997;71:357-61. include air embolism, vasospasm, infarction, 18. Moyer VA, Ahn C, Sneed S. Accuracy of clinical infection, and even death. Because of the poten- judgment in . Arch Pediatr Ado- tial seriousness of these complications, intensive lesc Med 2000;154:391-4. 19. Hsai DY, Allen FH, Gellis SS, Diamond LK. Erythro- phototherapy efforts should be exhausted blastosis fetalis. VIII. Studies of serum bilirubin in rela- 26 before exchange transfusion is initiated. tion to kernicterus. N Engl J Med 1952;247:668-71. 20. Gartner LM, Herrarias CT, Sebring RH. Practice pat- The authors indicate that they do not have any con- terns in neonatal hyperbilirubinemia. Pediatrics flicts of interest. Sources of funding: none reported. 1998;101(1 pt 1):25-31. 21. Newman TB, Maisels MJ. Does hyperbilirubinemia damage the brain of healthy full-term infants? Clin The opinions and assertions contained herein are the Perinatol 1990;17:331-58. private views of the authors and are not to be con- 22. Bhutani VK, Johnson L, Sivieri EM. Predictive ability strued as official or as reflecting the views of the U.S. of a predischarge hour-specific serum bilirubin for Army Medical Department or the U.S. Army at large. subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics REFERENCES 1999;103:6-14. 23. Maisels MJ. Why use homeopathic doses of pho- 1. Practice parameter: management of hyperbiliru- totherapy? Pediatrics 1996;98(2 pt 1):283-7. binemia in the healthy term newborn. Pediatrics 24. Yetman RJ, Parks DK, Huseby V, Mistry K, Garcia J. 1994;94(4 pt 1):558-62. Rebound bilirubin levels in infants receiving pho- 2. Jaundice and hyperbilirubinemia in the newborn. totherapy. J Pediatr 1998;133:705-7. In: Behrman RE, Kliegman RM, Jenson HB, eds. 25. Lazar L, Litwin A, Merlob P. Phototherapy for Nelson Textbook of pediatrics. 16th ed. Philadel- neonatal nonhemolytic hyperbilirubinemia. Clin phia: Saunders, 2000:511-28. Pediatr [Phila] 1993;32:264-7. 3. Dennery PA, Seidman DS, Stevenson DK. Neonatal 26. Jackson JC. Adverse events associated with hyperbilirubinemia. N Engl J Med 2001;344:581-90. exchange transfusion in healthy and ill newborns. 4. Clemons RM. Issues in newborn care. Prim Care Pediatrics 1997;99:E7. 2000;27:251-67. 27. Brown AK, Kim MH, Wu YK, Bryla DA. Efficacy of 5. Melton K, Akinbi HT. Neonatal jaundice. Strategies phototherapy in prevention and management of to reduce bilirubin-induced complications. Post- neonatal hyperbilirubinemia. Pediatrics 1985;75(2 grad Med 1999;106:167-8,171-4,177-8. pt 2):393-400.

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