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 18th and 19th 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.
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 IX α 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.
In the liver, 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.
Further, the observation of jaundice in some infants with hypertrophic pyloric stenosis may also be related to a Gilbert-type variant. Genetic polymorphism for the organic anion transporter protein OATP-2 correlates with a 3-fold increased risk for developing marked neonatal jaundice. Combination of the OATP-2 gene polymorphism with a variant UDPGT1A1 gene further increases this risk to 22-fold. Studies also suggest that polymorphisms in the gene for glutathione-S-transferase (ligandin) may contribute to higher levels of total serum bilirubin.
Thus, some interindividual variations in the course and severity of neonatal jaundice may be explained genetically. As the impact of these genetic variants is more fully understood, development of a genetic test panel for risk of severe or prolonged neonatal jaundice may become feasible.
Once excreted into bile and transferred to the intestines, bilirubin is eventually reduced to colorless tetrapyrroles by microbes in the colon. However, some deconjugation 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, deconjugation, 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.
In mother-infant dyads who are experiencing difficulties with the establishment of breast feeding, inadequate fluid and nutrient intake often leads to significant postnatal weight loss in the infant. Such infants have an increased risk of developing jaundice through increased enterohepatic circulation, as described above. This phenomenon is often referred to as breastfeeding jaundice and is different from the breast milk jaundice described below.
Certain factors present in the breast milk of some mothers may also contribute to increased enterohepatic circulation of bilirubin (breast milk jaundice). β -glucuronidase may play a role by uncoupling bilirubin from its binding to glucuronic acid, thus making it available for reabsorption. 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 on, 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, and increased hemolysis appears to have been present in some of the infants reported to have developed kernicterus in the United States in the past 10-15 years. The possible interaction between such conditions and genetic variants of the Gilbert and UDPGT1A1 genes, as well as genetic variants of several other proteins and enzymes involved in bilirubin metabolism, is discussed above.
- Maisels MJ, Gifford K. Normal serum bilirubin levels in the newborn and the effect of breast- feeding. Pediatrics. Nov 1986;78(5):837-43. [Medline].
- Atkinson LR, Escobar GJ, Takyama JI, Newman TB. Phototherapy use in jaundiced newborns in a large managed care organization: do clinicians adhere to the guideline?. Pediatrics. 2003;111:e555. [Medline]. [Full Text].
- Moore LG, Newberry MA, Freeby GM, Crnic LS. Increased incidence of neonatal hyperbilirubinemia at 3,100 m in Colorado. Am J Dis Child. Feb 1984;138(2):157-61. [Medline].
- Sarici SU, Serdar MA, Korkmaz A, et al. Incidence, course, and prediction of hyperbilirubinemia in near-term and term newborns. Pediatrics. 2004;113:775-80. [Medline]. [Full Text].
- Linn S, Schoenbaum SC, Monson RR, Rosner B, Stubblefield PG, Ryan KJ. Epidemiology of neonatal hyperbilirubinemia. Pediatrics. Apr 1985;75(4):770-4. [Medline].
- Ahlfors CE, Parker AE. Unbound bilirubin concentration is associated with abnormal automated auditory brainstem response for jaundiced newborns. Pediatrics. May 2008;121(5):976-8. [Medline].
- Hansen TW. Therapeutic approaches to neonatal jaundice: an international survey. Clin Pediatr (Phila). Jun 1996;35(6):309-16. [Medline].
- American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. Jul 2004;114(1):297-316. [Medline]. [Full Text].
- [Best Evidence] Madan JC, Kendrick D, Hagadorn JI, Frantz ID 3rd. Patent ductus arteriosus therapy: impact on neonatal and 18-month outcome. Pediatrics. Feb 2009;123(2):674-81. [Medline].
- Huizing K, Roislien J, Hansen T. Intravenous immune globulin reduces the need for exchange transfusions in Rhesus and AB0 incompatibility. Acta Paediatr. Oct 2008;97(10):1362-5. [Medline].
- Bhutani VK, Maisels MJ, Stark AR, Buonocore G. Management of jaundice and prevention of severe neonatal hyperbilirubinemia in infants >or=35 weeks gestation. Neonatology. 2008;94(1):63-7. [Medline].
- [Best Evidence] Newman TB, Liljestrand P, Escobar GJ. Combining clinical risk factors with serum bilirubin levels to predict hyperbilirubinemia in newborns. Arch Pediatr Adolesc Med. Feb 2005;159(2):113-9. [Medline].
- Bhutani VK, Johnson LH, Keren R. Diagnosis and management of hyperbilirubinemia in the term neonate: for a safer first week. Pediatr Clin North Am. Aug 2004;51(4):843-61, vii. [Medline].
- Eggert LD, Wiedmeier SE, Wilson J, Christensen RD. The effect of instituting a prehospital-discharge newborn bilirubin screening program in an 18-hospital health system. Pediatrics. May 2006;117(5):e855-62. [Medline].
- Paul IM, Phillips TA, Widome MD, Hollenbeak CS. Cost-effectiveness of postnatal home nursing visits for prevention of hospital care for jaundice and dehydration. Pediatrics. Oct 2004;114(4):1015-22. [Medline].
- Suresh GK, Clark RE. Cost-effectiveness of strategies that are intended to prevent kernicterus in newborn infants. Pediatrics. Oct 2004;114(4):917-24. [Medline].
- Alcock GS, Liley H. Immunoglobulin infusion for isoimmune haemolytic jaundice in neonates. Cochrane Database Syst Rev. 3:CD003313. [Medline]. [Full Text].
- Bartoletti AL, Stevenson DK, Ostrander CR, Johnson JD. Pulmonary excretion of carbon monoxide in the human infant as an index of bilirubin production. I. Effects of gestational and postnatal age and some common neonatal abnormalities. J Pediatr. Jun 1979;94(6):952-5. [Medline].
- Bhutani VK, Gourley GR, Adler S, et al. Noninvasive measurement of total serum bilirubin in a multiracial predischarge newborn population to assess the risk of severe hyperbilirubinemia. Pediatrics. Aug 2000;106(2):E17. [Medline]. [Full Text].
- Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics. Jan 1999;103(1):6-14. [Medline]. [Full Text].
- Bhutani VK, Johnson LH, Maisels MJ, et al. Kernicterus: epidemiological strategies for its prevention through systems-based approaches. J Perinatol. 2004;24:650-62. [Medline]. [Full Text].
- Buiter HD, Dijkstra SS, Oude Elferink RF, Bijster P, Woltil HA, Verkade HJ. Neonatal jaundice and stool production in breast- or formula-fed term infants. Eur J Pediatr. May 2008;167(5):501-7. [Medline].
- Carbonell X, Botet F, Figueras J, Riu-Godo A. Prediction of hyperbilirubinaemia in the healthy term newborn. Acta Paediatr. Feb 2001;90(2):166-70. [Medline].
- Cremer RJ, Perryman PW. Influence of light on the hyperbilirubinemia of infants. Lancet. 1958;1:1094-7.
- De Carvalho M, De Carvalho D, Trzmielina S, et al. Intensified phototherapy using daylight fluorescent lamps. Acta Paediatr. Jul 1999;88(7):768-71. [Medline].
- Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. NEJM. 2001;344:581-90. [Medline]. [Full Text].
- Ebbesen F, Andersson C, Verder H, Grytter C, Pedersen-Bjergaard L, Petersen JR. Extreme hyperbilirubinaemia in term and near-term infants in Denmark. Acta Paediatr. Jan 2005;94(1):59-64. [Medline].
- Gibbs WN, Gray R, Lowry M. Glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Jamaica. Br J Haematol. Oct 1979;43(2):263-74. [Medline].
- Glass P, Avery GB, Subramanian KN, et al. Effect of bright light in the hospital nursery on the incidence of retinopathy of prematurity. N Engl J Med. Aug 15 1985;313(7):401-4. [Medline].
- Gottstein R, Cooke RW. Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed. Jan 2003;88(1):F6-10. [Medline]. [Full Text].
- [Best Evidence] Gourley GR, Li Z, Kreamer BL, Kosorok MR. A controlled, randomized, double-blind trial of prophylaxis against jaundice among breastfed newborns. Pediatrics. Aug 2005;116(2):385-91. [Medline]. [Full Text].
- Grohmann K, Roser M, Rolinski B, et al. Bilirubin measurement for neonates: comparison of 9 frequently used methods. Pediatrics. Apr 2006;117(4):1174-83. [Medline].
- Hansen TW. Acute management of extreme neonatal jaundice–the potential benefits of intensified phototherapy and interruption of enterohepatic bilirubin circulation. Acta Paediatr. Aug 1997;86(8):843-6. [Medline].
- Hansen TW. Recent advances in the pharmacotherapy for hyperbilirubinaemia in the neonate. Expert Opin Pharmacother. 2003;4(11):1939-48. [Medline]. [Full Text].
- Hansen TW, Allen JW. Hemolytic anemia does not increase entry into, nor alter rate of clearance of bilirubin from rat brain. Biol Neonate. 1996;69(4):268-74. [Medline].
- Hart C, Cameron R. The importance of irradiance and area in neonatal phototherapy. Arch Dis Child Fetal Neonatal Ed. 2005;90:F437-F440. [Medline]. [Full Text].
- Hervieux, J. De l’ictere des nouveau-nes. Paris: These med. 1847.
- Ho HT, Ng TK, Tsui KC, Lo YC. Evaluation of a new transcutaneous bilirubinometer in Chinese newborns. Arch Dis Child Fetal Neonatal Ed. Nov 2006;91(6):F434-8. [Medline].
- Hua L, Shi D, Bishop PR, Gosche J, May WL, Nowicki MJ. The role of UGT1A1*28 mutation in jaundiced infants with hypertrophic pyloric stenosis. Pediatr Res. Nov 2005;58(5):881-4. [Medline].
- Huang MJ, Kua KE, Teng HC, Tang KS, Weng HW, Huang CS. Risk factors for severe hyperbilirubinemia in neonates. Pediatr Res. Nov 2004;56(5):682-9. [Medline].
- Ip S, Chung M, Kulig J, et al. An Evidence-Based Review of Important Issues Concerning Neonatal Hyperbilirubinemia. Pediatrics. 2004;114:e130-e153. [Medline]. [Full Text].
- Kapitulnik J, Horner-Mibashan R, Blondheim SH, et al. Increase in bilirubin-binding affinity of serum with age of infant. J Pediatr. Mar 1975;86(3):442-5. [Medline].
- Kaplan M, Bromiker R, Schimmel MS, Algur N, Hammerman C. Evaluation of discharge management in the prediction of hyperbilirubinemia: the Jerusalem experience. J Pediatr. Apr 2007;150(4):412-7. [Medline].
- Kaplan M, Hammerman C, Rubaltelli FF, et al. Hemolysis and bilirubin conjugation in association with UDP-glucuronosyltransferase 1A1 promoter polymorphism. Hepatology. Apr 2002;35(4):905-11. [Medline]. [Full Text].
- Kaplan M, Renbaum P, Vreman HJ, Wong RJ, Levy-Lahad E, Hammerman C. (TA)n UGT 1A1 Promoter Polymorphism: A Crucial Factor in the Pathophysiology of Jaundice in G-6-PD Deficient Neonates. Pediatr Res. Apr 5 2007;[Medline].
- Kaplan M, Shchors I, Algur N, Bromiker R, Schimmel MS, Hammerman C. Visual screening versus transcutaneous bilirubinometry for predischarge jaundice assessment. Acta Paediatr. Jun 2008;97(6):759-63. [Medline].
- Kappas A, Drummond GS, Henschke C, Valaes T. Direct comparison of Sn-mesoporphyrin, an inhibitor of bilirubin production, and phototherapy in controlling hyperbilirubinemia in term and near-term newborns. Pediatrics. Apr 1995;95(4):468-74. [Medline].
- Kawade N, Onishi S. The prenatal and postnatal development of UDP-glucuronyltransferase activity towards bilirubin and the effect of premature birth on this activity in the human liver. Biochem J. Apr 15 1981;196(1):257-60. [Medline]. [Full Text].
- Keren R, Bhutani VK, Luan X, Nihtianova S, Cnaan A, Schwartz JS. Identifying newborns at risk of significant hyperbilirubinaemia: a comparison of two recommended approaches. Arch Dis Child. Apr 2005;90(4):415-21. [Medline].
- Kjartansson S, Hammarlund K, Sedin G. Insensible water loss from the skin during phototherapy in term and preterm infants. Acta Paediatr. Oct 1992;81(10):764-8. [Medline].
- Kuzniewicz MW, Escobar GJ, Wi S, Liljestrand P, McCulloch C, Newman TB. Risk factors for severe hyperbilirubinemia among infants with borderline bilirubin levels: a nested case-control study. J Pediatr. Aug 2008;153(2):234-40. [Medline].
- Lin Z, Fontaine J, Watchko JF. Coexpression of gene polymorphisms involved in bilirubin production and metabolism. Pediatrics. Jul 2008;122(1):e156-62. [Medline].
- Litwack G, Ketterer B, Arias IM. Ligandin: a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature. Dec 24 1971;234(5330):466-7. [Medline].
- Maisels MJ, McDonagh AF. Phototherapy for neonatal jaundice. N Engl J Med. Feb 28 2008;358(9):920-8. [Medline].
- Maisels MJ, Newman TB. Predicting hyperbilirubinemia in newborns: the importance of timing. Pediatrics. Feb 1999;103(2):493-5. [Medline].
- Maisels MJ, Newman TB, Watchko JF. Effect of predischarge bilirubin screening on subsequent hyperbilirubinemia. Pediatrics. Oct 2006;118(4):1796; author reply 1976-7. [Medline].
- Muslu N, Dogruer ZN, Eskandari G, Atici A, Kul S, Atik U. Are glutathione S-transferase gene polymorphisms linked to neonatal jaundice?. Eur J Pediatr. Jan 2008;167(1):57-61. [Medline].
- Newman TB, Liljestrand P, Escobar GJ. Infants with bilirubin levels of 30 mg/dL or more in a large managed care organization. Pediatrics. Jun 2003;111(6 Pt 1):1303-11. [Medline].
- [Best Evidence] Newman TB, Liljestrand P, Jeremy RJ, Ferriero DM, Wu YW, Hudes ES. Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more. N Engl J Med. May 4 2006;354(18):1889-900. [Medline].
- Newman TB, Xiong B, Gonzales VM, Escobar GJ. Prediction and prevention of extreme neonatal hyperbilirubinemia in a mature health maintenance organization. Arch Pediatr Adolesc Med. Nov 2000;154(11):1140-7. [Medline].
- Nielsen HE, Haase P, Blaabjerg J, et al. Risk factors and sib correlation in physiological neonatal jaundice. Acta Paediatr Scand. May 1987;76(3):504-11. [Medline].
- Odell GB, Cukier JO, Seungdamrong S, Odell JL. The displacement of bilirubin from albumin. Birth Defects Orig Artic Ser. 1976;12(2):192-204. [Medline].
- Ostrow JD, Jandl JH, Schmid R. The formation of bilirubin from hemoglobin in vivo. J Clin Invest. 1962;41:1628-37.
- Palmer DC, Drew JH. Jaundice: a 10 year review of 41,000 live born infants. Aust Paediatr J. Jun 1983;19(2):86-9. [Medline].
- Rubo J, Albrecht K, Lasch P, et al. High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease. J Pediatr. Jul 1992;121(1):93-7. [Medline].
- Seidman DS, Moise J, Ergaz Z. A new blue light-emitting phototherapy device: a prospective randomized controlled study. J Pediatr. 2000;136:771-4. [Medline]. [Full Text].
- Slusher TM, Angyo IA, Bode-Thomas F, Akor F, Pam SD, Adetunji AA. Transcutaneous bilirubin measurements and serum total bilirubin levels in indigenous African infants. Pediatrics. Jun 2004;113(6):1636-41. [Medline].
- Smitherman H, Stark AR, Bhutan VK. Early recognition of neonatal hyperbilirubinemia and its emergent management. Semin Fetal Neonatal Med. Jun 2006;11(3):214-24. [Medline].
- Stevenson DK, Vreman HJ. Carbon monoxide and bilirubin production in neonates. Pediatrics. Aug 1997;100(2 Pt 1):252-4. [Medline]. [Full Text].
- Stevenson DK, Wong RJ, Vreman HJ, et al. NICHD Conference on Kernicterus: Research on Prevention of Bilirubin-Induced Brain Injury and Kernicterus: Bench-to-Bedside–Diagnostic Methods and Prevention and Treatment Strategies. J Perinatol. Aug 2004;24(8):521-5. [Medline]. [Full Text].
- Sun G, Wu M, Cao J, Du L. Cord blood bilirubin level in relation to bilirubin UDP-glucuronosyltransferase gene missense allele in Chinese neonates. Acta Paediatr. Nov 2007;96(11):1622-5. [Medline].
- Tan KL. Glucose-6-phosphate dehydrogenase status and neonatal jaundice. Arch Dis Child. Nov 1981;56(11):874-7. [Medline].
- Tan KL, Lim GC, Boey KW. Efficacy of “high-intensity” blue-light and “standard” daylight phototherapy for non-haemolytic hyperbilirubinaemia. Acta Paediatr. Nov 1992;81(11):870-4. [Medline].
- Tayaba R, Gribetz D, Gribetz I, Holzman IR. Noninvasive estimation of serum bilirubin. Pediatrics. Sep 1998;102(3):E28. [Medline]. [Full Text].
- Valaes T, Petmezaki S, Doxiadis SA. Effect on neonatal hyperbilirubinemia of phenobarbital during pregnancy or after birth: practical value of the treatment in a population with high risk of unexplained severe neonatal jaundice. Birth Defects Orig Artic Ser. Jun 1970;6(2):46-54. [Medline].
- Vander Jagt DL, Garcia KB. Immunochemical comparisons of proteins that bind heme and bilirubin: human serum albumin, alpha-fetoprotein and glutathione S-transferases from liver, placenta and erythrocyte. Comp Biochem Physiol B. 1987;87(3):527-31. [Medline].
- Vreman HJ, Wong RJ, Stevenson DK, et al. Light-emitting diodes: a novel light source for phototherapy. Pediatr Res. 1998;44:804-9. [Medline]. [Full Text].
- Watchko JF. Vigintiphobia revisited. Pediatrics. Jun 2005;115(6):1747-53. [Medline]. [Full Text].
- Yamamoto A, Nishio H, Waku S, Yokoyama N, Yonetani M, Uetani Y. Gly71Arg mutation of the bilirubin UDP-glucuronosyltransferase 1A1 gene is associated with neonatal hyperbilirubinemia in the Japanese population. Kobe J Med Sci. Aug 2002;48(3-4):73-7. [Medline].
- Yusoff S, Van Rostenberghe H, Yusoff NM, Talib NA, Ramli N, Ismail NZ. Frequencies of A(TA)7TAA, G71R, and G493R mutations of the UGT1A1 gene in the Malaysian population. Biol Neonate. 2006;89(3):171-6. [Medline].
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