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Table of Contents
Vol. 100, No. 4, 2011
Issue release date: November 2011
Section title: Review
Free Access
Neonatology 2011;100:354–362
(DOI:10.1159/000330055)

Severe Neonatal Hyperbilirubinemia and Kernicterus: Are These Still Problems in the Third Millennium?

Kaplan M.a, b · Bromiker R.a, b · Hammerman C.a, b
aDepartment of Neonatology, Shaare Zedek Medical Center, and bFaculty of Medicine of the Hebrew University, Jerusalem, Israel
email Corresponding Author

Abstract

Despite efforts to eliminate permanent and irreversible brain damage due to bilirubin encephalopathy and kernicterus, these conditions continue to accompany us into the third millennium. This phenomenon occurs not only in developing countries with emerging medical systems, but in Westernized countries as well. Comprehensive guidelines to detect newborns with jaundice and treat those in whom hyperbilirubinemia has already developed have been formulated in several countries, but have not been successful in completely eliminating the problem. In this appraisal of the situation we review selected aspects of bilirubin encephalopathy and/or kernicterus. We highlight recent reports of severe hyperbilirubinemia and kernicterus, discuss some of the factors responsible for the continuing appearance of these conditions, and briefly review what can be done to decrease bilirubin-related morbidity and mortality to the minimum.

© 2011 S. Karger AG, Basel


  

Key Words

  • Kernicterus
  • Bilirubin encephalopathy
  • Bilirubin
  • Glucose-6-phosphate dehydrogenase deficiency
  • Late prematurity
  • ABO blood group heterospecificity
  • Exchange transfusion
  • Phototherapy

References

  1. Maisels MJ: Neonatal hyperbilirubinemia and kernicterus – not gone but sometimes forgotten. Early Hum Dev 2009;85:727–732.
  2. Shapiro SM: Hyperbilirubinemia and the risk for brain injury; in Perlman J, Polin RA (eds): Neurology: Neonatology Questions and Controversies. Philadelphia, Saunders Elsevier, 2008, pp 195–209.
  3. Hansen TW: Kernicterus in term and near-term infants – the specter walks again. Acta Paediatr 2000;89:1155–1157.
  4. Schmorl CG: Zur Kenntnis des Ikterus neonatorum, insbesondere der dabei auftretenden Gehirnveränderungen. Verh Dtsch Pathol Ges 1904;6:109–115.
  5. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297–316.
  6. Horn AR, Kirsten GF, Kroon SM, Henning PA, Möller G, Pieper C, Adhikari M, Cooper P, Hoek B, Delport S, Nazo M, Mawela B: Phototherapy and exchange transfusion for neonatal hyperbilirubinaemia: neonatal academic hospitals’ consensus guidelines for South African hospitals and primary care facilities. S Afr Med J 2006;96:819–824.
  7. Kaplan M, Merlob P, Regev R: Israel guidelines for the management of neonatal hyperbilirubinemia and prevention of kernicterus. J Perinatol 2008;28:389–397.
  8. Bratlid D, Nakstad B, Hansen TW: National guidelines for treatment of jaundice in the newborn. Acta Paediatr 2011;100:499–505.
  9. 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 1999;103:6–14.
  10. Hansen TW: The role of phototherapy in the crash-cart approach to extreme neonatal jaundice. Semin Perinatol 2011;35:171–174.
  11. Slusher TM, Zipursky A, Bhutani VK: A global need for affordable neonatal jaundice technologies. Semin Perinatol 2011;35:185–191.
  12. National Institute for Health and Clinical Excellence: Neonatal jaundice (clinical guideline 98). 2010. www.nice.org.uk/CG98.
  13. Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants (35 or more weeks’ gestation) – summary: Paediatr Child Health 2007;12:401–418.
  14. Maisels MJ, Bhutani VK, Bogen D, Newman TB, Stark AR, Watchko JF: Hyperbilirubinemia in the newborn infant > or = 35 weeks’ gestation: an update with clarifications. Pediatrics 2009;124:1193–1198.
  15. Oh W, Stevenson DK, Tyson JE, Morris BH, Ahlfors CE, Bender GJ, Wong RJ, Perritt R, Vohr BR, Van Meurs KP, Vreman HJ, Das A, Phelps DL, O’Shea TM, Higgins RD, NICHD Neonatal Research Network Bethesda MD: Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants. Acta Paediatr 2010;99:673–678.
  16. Morris BH, Oh W, Tyson JE, Stevenson DK, Phelps DL, O’Shea TM, McDavid GE, Perritt RL, Van Meurs KP, Vohr BR, Grisby C, Yao Q, Pedroza C, Das A, Poole WK, Carlo WA, Duara S, Laptook AR, Salhab WA, Shankaran S, Poindexter BB, Fanaroff AA, Walsh MC, Rasmussen MR, Stoll BJ, Cotten CM, Donovan EF, Ehrenkranz RA, Guillet R, Higgins RD, NICHD Neonatal Research Network: Aggressive versus conservative phototherapy for infants with extremely low birth weight. N Engl J Med 2008;359:1885–1896.
  17. Okumura A, Kidokoro H, Shoji H, Nakazawa T, Mimaki M, Fujii K, Oba H, Shimizu T: Kernicterus in preterm infants. Pediatrics 2009;123:e1052–e1058.
  18. Okumura A, Hayakawa F, Maruyama K, Kubota T, Kato K, Watanabe K: Single photon emission computed tomography and serial MRI in preterm infants with kernicterus. Brain Dev 2006;28:348–352.
  19. Okumura A, Hayakawa F, Kato T, Itomi K, Mimura S, Watanabe K: Preterm infants with athetoid cerebral palsy: kernicterus? Arch Dis Child Fetal Neonatal Ed 2001;84:F136–F137.
  20. Govaert P, Lequin M, Swarte R, Robben S, De Coo R, Weisglas-Kuperus N, De Rijke Y, Sinaasappel M, Barkovich J: Changes in globus pallidus with (pre)term kernicterus. Pediatrics 2003;112:1256–1263.
  21. Moll M, Goelz R, Naegele T, Wilke M, Poets CF: Are recommended phototherapy thresholds safe enough for extremely low birth weight (ELBW) infants? A report on 2 ELBW infants with kernicterus despite only moderate hyperbilirubinemia. Neonatology 2011;99:90–94.
  22. Watchko JF, Claassen D: Kernicterus in premature infants: current prevalence and relationship to NICHD Phototherapy Study exchange criteria. Pediatrics 1994;93:996–999.
  23. Pearlman MA, Gartner LM, Lee K, Morecki R, Horoupian DS: Absence of kernicterus in low-birth weight infants from 1971 through 1976: comparison with findings in 1966 and 1967. Pediatrics 1978;62:460–464.
  24. Kaplan M, Eidelman AI: Post factum imposition of exchange transfusion criteria: in defence of neonatologists. Acta Paediatr 2011;100:479–481.
  25. Maisels MJ, Watchko JF: Treatment of jaundice in low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2003;88:F459–F463.
  26. Cashore WJ: Bilirubin and jaundice in the micropremie. Clin Perinatol 2000;27:171–179.
  27. Gartner LM, Snyder RN, Chabon RS, Bernstein J: Kernicterus: high incidence in premature infants with low serum bilirubin concentrations. Pediatrics 1970;45:906–917.
  28. Harris RC, Lucey JF, Maclean JR: Kernicterus in premature infants associated with low concentrations of bilirubin in the plasma. Pediatrics 1958;21:875–884.
  29. Bhutani VK, Johnson L: Kernicterus in late preterm infants cared for as term healthy infants. Semin Perinatol 2006;30:89–97.
  30. Watchko JF: Hyperbilirubinemia and bilirubin toxicity in the late preterm infant. Clin Perinatol 2006;33:839–852.
  31. Kaplan M, Hammerman C: Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: biochemical versus genetic technologies. Semin Perinatol 2011;35:155–161.
  32. Kaplan M, Renbaum P, Levy-Lahad E, Hammerman C, Lahad A, Beutler E: Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci USA 1997;94:12128–12132.
  33. Kaplan M, Muraca M, Hammerman C, Vilei MT, Leiter C, Rudensky B, Rubaltelli FF: Bilirubin conjugation, reflected by conjugated bilirubin fractions, in glucose-6-phosphate dehydrogenase-deficient neonates: a determining factor in the pathogenesis of hyperbilirubinemia. Pediatrics 1998;102:E37.
  34. Kaplan M, Rubaltelli FF, Hammerman C, Vilei MT, Leiter C, Abramov A, Muraca M: Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency. J Pediatr 1996;128:695–697.
  35. Zipursky A, Paul VK: The global burden of Rh disease. Arch Dis Child Fetal Neonatal Ed 2011;96:F84–F85.
  36. Jansen PL: Diagnosis and management of Crigler-Najjar syndrome. Eur J Pediatr 1999;158(suppl 2):S89–S94.
  37. Kuzniewicz M, Newman TB: Interaction of hemolysis and hyperbilirubinemia on neurodevelopmental outcomes in the collaborative perinatal project. Pediatrics 2009;123:1045–1050.
  38. Newman TB, Liljestrand P, Jeremy RJ, Ferriero DM, Wu YW, Hudes ES, Escobar GJ, Jaundice and Infant Feeding Study Team: Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more. N Engl J Med 2006;354:1889–1900.
  39. Nilsen ST, Finne PH, Bergsjø P, Stamnes O: Males with neonatal hyperbilirubinemia examined at 18 years of age. Acta Paediatr Scand 1984;73:176–180.
  40. Ozmert E, Erdem G, Topçu M, Yurdakök M, Tekinalp G, Genç D, Renda Y: Long-term follow-up of indirect hyperbilirubinemia in full-term Turkish infants. Acta Paediatr 1996;85:1440–1444.
  41. Watchko JF, Oski FA: Bilirubin 20 mg/dl = vigintiphobia. Pediatrics 1983;71:660–663.
  42. Newman TB, Maisels MJ: Does hyperbilirubinemia damage the brain of healthy full-term infants? Clin Perinatol 1990;17:331–358.
  43. Miwa A, Morioka I, Hisamatsu C, Fujioka K, Morikawa S, Shibata A, Yasufuku M, Yokoyama N, Matsuo M: Hypoalbuminemia following abdominal surgery leads to high serum unbound bilirubin concentrations in newborns soon after birth. Neonatology 2011;99:202–207.
  44. Ahlfors CE: Predicting bilirubin neurotoxicity in jaundiced newborns. Curr Opin Pediatr 2010;22:129–133.
  45. Ahlfors CE, Wennberg RP, Ostrow JD, Tiribelli C: Unbound (free) bilirubin: improving the paradigm for evaluating neonatal jaundice. Clin Chem 2009;55:1288–1299.
  46. Oh W, Stevenson DK, Tyson JE, Morris BH, Ahlfors CE, Bender GJ, Wong RJ, Perritt R, Vohr BR, Van Meurs KP, Vreman HJ, Das A, Phelps DL, O’Shea TM, Higgins RD, NICHD Neonatal Research Network Bethesda MD: Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants. Acta Paediatr 2010;99:673–678.
  47. Wennberg RP, Ahlfors CE, Bhutani VK, Johnson LH, Shapiro SM: Toward understanding kernicterus: a challenge to improve the management of jaundiced newborns. Pediatrics 2006;117:474–485.
  48. Hsia DY, Allen FH Jr, Gellis SS, Diamond LK: Erythroblastosis fetalis. VIII. Studies of serum bilirubin in relation to kernicterus. N Engl J Med 1952;247:668–671.
  49. Hansen TW, Nietsch L, Norman E, Bjerre JV, Hascoet JM, Mreihil K, Ebbesen F: Reversibility of acute intermediate phase bilirubin encephalopathy. Acta Paediatr 2009;98:1689–1694.
  50. Harris MC, Bernbaum JC, Polin JR, Zimmerman R, Polin RA: Developmental follow-up of breastfed term and near-term infants with marked hyperbilirubinemia. Pediatrics 2001;107:1075–1080.
  51. Sgro M, Campbell D, Barozzino T, Shah V: Acute neurological findings in a national cohort of neonates with severe neonatal hyperbilirubinemia. J Perinatol 2011;31:392–396.
  52. Bartmann P, Schaaff F: Kernicterus in Germany 2003–2005. Pediatric Academic Societies. E-PAS 2007;617936.24.
  53. Dani C, Poggi C, Barp J, Romagnoli C, Buonocore G: Current Italian practices regarding the management of hyperbilirubinaemia in preterm infants. Acta Paediatr 2011;100:666–669.
  54. Bjerre JV, Petersen JR, Ebbesen F: Surveillance of extreme hyperbilirubinaemia in Denmark. A method to identify the newborn infants. Acta Paediatr 2008;97:1030–1034.
  55. Manning D, Todd P, Maxwell M, Jane Platt M: Prospective surveillance study of severe hyperbilirubinaemia in the newborn in the UK and Ireland. Arch Dis Child Fetal Neonatal Ed 2007;92:F342–F346.
  56. Sgro M, Campbell D, Shah V: Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ 2006;175:587–590.
  57. Raupp P, Hassan JA, Varughese M, Kristiansson B: Henna causes life threatening haemolysis in glucose-6-phosphate dehydrogenase deficiency. Arch Dis Child 2001;85:411–412.
  58. Katar S: Glucose-6-phosphate dehydrogenase deficiency and kernicterus of South-East Anatolia. J Pediatr Hematol Oncol 2007;29:284–286.
  59. Nair PA, Al Khusaiby SM: Kernicterus and G6PD deficiency – a case series from Oman. J Trop Pediatr 2003;49:74–77.
  60. Owa JA, Ogunlesi TA: Why we are still doing so many exchange blood transfusion for neonatal jaundice in Nigeria? World J Pediatr 2009;5:51–55.
  61. Hameed NN, Na’ Ma AM, Vilms R, Bhutani VK: Severe neonatal hyperbilirubinemia and adverse short-term consequences in Baghdad, Iraq. Neonatology 2011;100:57–63.
  62. Brooks JC, Fisher-Owens SA, Wu YW, Strauss DJ, Newman TB: Evidence suggests there was not a ‘resurgence’ of kernicterus in the 1990s. Pediatrics 2011;127:672–679.
  63. Burke BL, Robbins JM, Bird TM, Hobbs CA, Nesmith C, Tilford JM: Trends in hospitalizations for neonatal jaundice and kernicterus in the United States, 1988–2005. Pediatrics 2009;123:524–532.
  64. Ebbesen F, Andersson C, Verder H, Grytter C, Pedersen-Bjergaard L, Petersen JR, Schaarup J: Extreme hyperbilirubinaemia in term and near-term infants in Denmark. Acta Paediatr 2005;94:59–64.
  65. Ebbesen F: Recurrence of kernicterus in term and near-term infants in Denmark. Acta Paediatr 2000;89:1213–1217.
  66. Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM: Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). J Perinatol 2009;29(suppl 1):S25–S45.
  67. Bhutani VK, Johnson LH, Jeffrey Maisels M, Newman TB, Phibbs C, Stark AR, Yeargin-Allsopp M: Kernicterus: epidemiological strategies for its prevention through systems-based approaches. J Perinatol 2004;24:650–662.
  68. Penn AA, Enzmann DR, Hahn JS, Stevenson DK: Kernicterus in a full term infant. Pediatrics 1994;93:1003–1006.
  69. Maisels MJ, Newman TB: Kernicterus in otherwise healthy, breast-fed term newborns. Pediatrics 1995;96:730–733.
  70. MacDonald MG: Hidden risks: early discharge and bilirubin toxicity due to glucose 6-phosphate dehydrogenase deficiency. Pediatrics 1995;96:734–738.
  71. Kaplan M, Hammerman C: Glucose-6-phosphate dehydrogenase deficiency and severe neonatal hyperbilirubinemia: a complexity of interactions between genes and environment. Semin Fetal Neonatal Med 2010;15:1448–1456.

    External Resources

  72. Beutler E: G6PD deficiency. Blood 1994;84:3613–3636.
  73. Davidson L, Thilo EH: How to make kernicterus a ‘never event’. NeoReviews 2003;4:e308–e314.

    External Resources

  74. Johnson L, Bhutani VK: Guidelines for management of the jaundiced term and near-term infant. Clin Perinatol 1998;25:555–574.
  75. Shapiro SM: Bilirubin toxicity in the developing nervous system. Pediatr Neurol 2003;29:410–421.

  

Author Contacts

Prof. Michael Kaplan
Department of Neonatology, Shaare Zedek Medical Center
PO Box 3235
Jerusalem 91031 (Israel)
Tel. +972 2 655 5643, E-Mail kaplan@cc.huji.ac.il

  

Article Information

Presented at the International Symposium ‘Recent Advances in Neonatal Medicine’, Würzburg, 2011.

Published online: October 3, 2011
Number of Print Pages : 9
Number of Figures : 0, Number of Tables : 0, Number of References : 75

  

Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 100, No. 4, Year 2011 (Cover Date: November 2011)

Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661-7800 (Print), eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Despite efforts to eliminate permanent and irreversible brain damage due to bilirubin encephalopathy and kernicterus, these conditions continue to accompany us into the third millennium. This phenomenon occurs not only in developing countries with emerging medical systems, but in Westernized countries as well. Comprehensive guidelines to detect newborns with jaundice and treat those in whom hyperbilirubinemia has already developed have been formulated in several countries, but have not been successful in completely eliminating the problem. In this appraisal of the situation we review selected aspects of bilirubin encephalopathy and/or kernicterus. We highlight recent reports of severe hyperbilirubinemia and kernicterus, discuss some of the factors responsible for the continuing appearance of these conditions, and briefly review what can be done to decrease bilirubin-related morbidity and mortality to the minimum.

© 2011 S. Karger AG, Basel


  

Author Contacts

Prof. Michael Kaplan
Department of Neonatology, Shaare Zedek Medical Center
PO Box 3235
Jerusalem 91031 (Israel)
Tel. +972 2 655 5643, E-Mail kaplan@cc.huji.ac.il

  

Article Information

Presented at the International Symposium ‘Recent Advances in Neonatal Medicine’, Würzburg, 2011.

Published online: October 3, 2011
Number of Print Pages : 9
Number of Figures : 0, Number of Tables : 0, Number of References : 75

  

Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 100, No. 4, Year 2011 (Cover Date: November 2011)

Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661-7800 (Print), eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Article / Publication Details

First-Page Preview
Abstract of Review

Published online: 10/3/2011
Issue release date: November 2011

Number of Print Pages: 9
Number of Figures: 0
Number of Tables: 0

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Maisels MJ: Neonatal hyperbilirubinemia and kernicterus – not gone but sometimes forgotten. Early Hum Dev 2009;85:727–732.
  2. Shapiro SM: Hyperbilirubinemia and the risk for brain injury; in Perlman J, Polin RA (eds): Neurology: Neonatology Questions and Controversies. Philadelphia, Saunders Elsevier, 2008, pp 195–209.
  3. Hansen TW: Kernicterus in term and near-term infants – the specter walks again. Acta Paediatr 2000;89:1155–1157.
  4. Schmorl CG: Zur Kenntnis des Ikterus neonatorum, insbesondere der dabei auftretenden Gehirnveränderungen. Verh Dtsch Pathol Ges 1904;6:109–115.
  5. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297–316.
  6. Horn AR, Kirsten GF, Kroon SM, Henning PA, Möller G, Pieper C, Adhikari M, Cooper P, Hoek B, Delport S, Nazo M, Mawela B: Phototherapy and exchange transfusion for neonatal hyperbilirubinaemia: neonatal academic hospitals’ consensus guidelines for South African hospitals and primary care facilities. S Afr Med J 2006;96:819–824.
  7. Kaplan M, Merlob P, Regev R: Israel guidelines for the management of neonatal hyperbilirubinemia and prevention of kernicterus. J Perinatol 2008;28:389–397.
  8. Bratlid D, Nakstad B, Hansen TW: National guidelines for treatment of jaundice in the newborn. Acta Paediatr 2011;100:499–505.
  9. 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 1999;103:6–14.
  10. Hansen TW: The role of phototherapy in the crash-cart approach to extreme neonatal jaundice. Semin Perinatol 2011;35:171–174.
  11. Slusher TM, Zipursky A, Bhutani VK: A global need for affordable neonatal jaundice technologies. Semin Perinatol 2011;35:185–191.
  12. National Institute for Health and Clinical Excellence: Neonatal jaundice (clinical guideline 98). 2010. www.nice.org.uk/CG98.
  13. Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants (35 or more weeks’ gestation) – summary: Paediatr Child Health 2007;12:401–418.
  14. Maisels MJ, Bhutani VK, Bogen D, Newman TB, Stark AR, Watchko JF: Hyperbilirubinemia in the newborn infant > or = 35 weeks’ gestation: an update with clarifications. Pediatrics 2009;124:1193–1198.
  15. Oh W, Stevenson DK, Tyson JE, Morris BH, Ahlfors CE, Bender GJ, Wong RJ, Perritt R, Vohr BR, Van Meurs KP, Vreman HJ, Das A, Phelps DL, O’Shea TM, Higgins RD, NICHD Neonatal Research Network Bethesda MD: Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants. Acta Paediatr 2010;99:673–678.
  16. Morris BH, Oh W, Tyson JE, Stevenson DK, Phelps DL, O’Shea TM, McDavid GE, Perritt RL, Van Meurs KP, Vohr BR, Grisby C, Yao Q, Pedroza C, Das A, Poole WK, Carlo WA, Duara S, Laptook AR, Salhab WA, Shankaran S, Poindexter BB, Fanaroff AA, Walsh MC, Rasmussen MR, Stoll BJ, Cotten CM, Donovan EF, Ehrenkranz RA, Guillet R, Higgins RD, NICHD Neonatal Research Network: Aggressive versus conservative phototherapy for infants with extremely low birth weight. N Engl J Med 2008;359:1885–1896.
  17. Okumura A, Kidokoro H, Shoji H, Nakazawa T, Mimaki M, Fujii K, Oba H, Shimizu T: Kernicterus in preterm infants. Pediatrics 2009;123:e1052–e1058.
  18. Okumura A, Hayakawa F, Maruyama K, Kubota T, Kato K, Watanabe K: Single photon emission computed tomography and serial MRI in preterm infants with kernicterus. Brain Dev 2006;28:348–352.
  19. Okumura A, Hayakawa F, Kato T, Itomi K, Mimura S, Watanabe K: Preterm infants with athetoid cerebral palsy: kernicterus? Arch Dis Child Fetal Neonatal Ed 2001;84:F136–F137.
  20. Govaert P, Lequin M, Swarte R, Robben S, De Coo R, Weisglas-Kuperus N, De Rijke Y, Sinaasappel M, Barkovich J: Changes in globus pallidus with (pre)term kernicterus. Pediatrics 2003;112:1256–1263.
  21. Moll M, Goelz R, Naegele T, Wilke M, Poets CF: Are recommended phototherapy thresholds safe enough for extremely low birth weight (ELBW) infants? A report on 2 ELBW infants with kernicterus despite only moderate hyperbilirubinemia. Neonatology 2011;99:90–94.
  22. Watchko JF, Claassen D: Kernicterus in premature infants: current prevalence and relationship to NICHD Phototherapy Study exchange criteria. Pediatrics 1994;93:996–999.
  23. Pearlman MA, Gartner LM, Lee K, Morecki R, Horoupian DS: Absence of kernicterus in low-birth weight infants from 1971 through 1976: comparison with findings in 1966 and 1967. Pediatrics 1978;62:460–464.
  24. Kaplan M, Eidelman AI: Post factum imposition of exchange transfusion criteria: in defence of neonatologists. Acta Paediatr 2011;100:479–481.
  25. Maisels MJ, Watchko JF: Treatment of jaundice in low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2003;88:F459–F463.
  26. Cashore WJ: Bilirubin and jaundice in the micropremie. Clin Perinatol 2000;27:171–179.
  27. Gartner LM, Snyder RN, Chabon RS, Bernstein J: Kernicterus: high incidence in premature infants with low serum bilirubin concentrations. Pediatrics 1970;45:906–917.
  28. Harris RC, Lucey JF, Maclean JR: Kernicterus in premature infants associated with low concentrations of bilirubin in the plasma. Pediatrics 1958;21:875–884.
  29. Bhutani VK, Johnson L: Kernicterus in late preterm infants cared for as term healthy infants. Semin Perinatol 2006;30:89–97.
  30. Watchko JF: Hyperbilirubinemia and bilirubin toxicity in the late preterm infant. Clin Perinatol 2006;33:839–852.
  31. Kaplan M, Hammerman C: Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: biochemical versus genetic technologies. Semin Perinatol 2011;35:155–161.
  32. Kaplan M, Renbaum P, Levy-Lahad E, Hammerman C, Lahad A, Beutler E: Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci USA 1997;94:12128–12132.
  33. Kaplan M, Muraca M, Hammerman C, Vilei MT, Leiter C, Rudensky B, Rubaltelli FF: Bilirubin conjugation, reflected by conjugated bilirubin fractions, in glucose-6-phosphate dehydrogenase-deficient neonates: a determining factor in the pathogenesis of hyperbilirubinemia. Pediatrics 1998;102:E37.
  34. Kaplan M, Rubaltelli FF, Hammerman C, Vilei MT, Leiter C, Abramov A, Muraca M: Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency. J Pediatr 1996;128:695–697.
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