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Israel guidelines for the management of neonatal hyperbilirubinemia and prevention of kernicterus

Abstract

Despite publication of guidelines for the prevention and management of hyperbilirubinemia in term and late-preterm newborn infants, kernicterus, although rare, continues to occur. Guidelines written for use in one country may not always be universally appropriate. Bearing this in mind, a committee appointed by the Israel Neonatal Society has formulated a set of guidelines, based on those of the American Academy of Pediatrics (2004), but adapted to the realities of the Israeli scene. The guidelines include methods of surveillance of jaundice, prediction of jaundice, assessment of risk factors, discharge planning and post-discharge follow-up, in addition to therapeutic guidelines including indications for phototherapy, exchange transfusion and the use of intravenous immune globulin. Availability of these guidelines to the international community may offer direction to physicians of other countries who may be setting up guidelines for use in their own communities.

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References

  1. Maisels MJ . Epidemiology of neonatal jaundice. In: Maisels MJ, Watchko JF (eds). Neonatal Jaundice. Harwood Academic Publishers: Amsterdam, 2000, pp 37–49.

    Google Scholar 

  2. Kaplan M, Muraca M, Hammerman C, Rubaltelli FF, Vilei MT, Vreman HJ et al. Imbalance between production and conjugation of bilirubin: a fundamental concept in the mechanism of neonatal jaundice. Pediatrics 2002; 110: e47.

    Article  Google Scholar 

  3. 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.

    Article  Google Scholar 

  4. Shapiro SM, Bhutani VK, Johnson L . Hyperbilirubinemia and kernicterus. Clin Perinatol 2006; 33: 387–410.

    Article  Google Scholar 

  5. Bhutani VK, Johnson LH, Jeffrey Maisels M, Newman TB, Phibbs C, Stark AR et al. Kernicterus: epidemiological strategies for its prevention through systems-based approaches. J Perinatol 2004; 24: 650–662.

    Article  Google Scholar 

  6. Johnson LH, Bhutani VK, Brown AK . System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr 2002; 140: 396–403.

    Article  Google Scholar 

  7. American Academy of Pediatrics, Subcommittee on Neonatal Hyperbilirubinemia. Neonatal jaundice and kernicterus. Pediatrics 2001; 108: 763–765.

    Article  Google Scholar 

  8. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Clinical practice guideline: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114: 297–316.

    Article  Google Scholar 

  9. AlOtaibi SF, Blaser S, MacGregor DL . Neurological complications of kernicterus. Can J Neurol Sci 2005; 32: 311–315.

    Article  Google Scholar 

  10. Sgro M, Campbell D, Shah V . Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ 2006; 175: 587–590.

    Article  Google Scholar 

  11. Govaert P, Lequin M, Swarte R, Robben S, De Coo R, Weisglas-Kuperus N et al. Changes in globus pallidus with (pre)term kernicterus. Pediatrics 2003; 112: 1256–1263.

    Article  Google Scholar 

  12. Ebbesen F, Andersson C, Verder H, Grytter C, Pedersen-Bjergaard L, Petersen JR et al. Extreme hyperbilirubinaemia in term and near-term infants in Denmark. Acta Paediatr 2005; 94: 59–64.

    Article  CAS  Google Scholar 

  13. Bertini G, Dani C, Fonda C, Zorzi C, Rubaltelli FF . Bronze baby syndrome and the risk of kernicterus. Acta Paediatr 2005; 94: 968–971.

    Article  Google Scholar 

  14. 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.

    Article  Google Scholar 

  15. Stanley TV . A case of kernicterus in New Zealand: a predictable tragedy? J Paediatr Child Health 1997; 33: 451–453.

    Article  CAS  Google Scholar 

  16. Bartmann P, Schaaf F . Kernicterus in Germany 2003–2005. Pediatric Academic Societies. Online abstract number: E-PAS2007:7936. 23.

  17. Grobler JM, Mercer MJ . Kernicterus associated with elevated predominantly direct-reacting bilirubin. S Afr Med J 1997; 87: 1146.

    CAS  PubMed  Google Scholar 

  18. Maisels MJ, Newman TB . Kernicterus in otherwise healthy, breast-fed term newborns. Pediatrics 1995; 96: 730–733.

    CAS  Google Scholar 

  19. Bhutani VK, Johnson L . Kernicterus in late preterm infants cared for as term healthy infants. Semin Perinatol 2006; 30: 89–97.

    Article  Google Scholar 

  20. Kaplan M, Hammerman C . American Academy of Pediatrics guidelines for detecting neonatal hyperbilirubinaemia and preventing kernicterus. Arch Dis Child Fetal Neonatal Ed 2005; 90: F448–F449.

    Article  CAS  Google Scholar 

  21. Sheba C, Szeinberg A, Ramot B, Adam A, Ashkenazi I . Epidemiologic surveys of deleterious genes in different population groups in Israel. Am J Public Health Nations Health 1962; 52: 1101–1106.

    Article  CAS  Google Scholar 

  22. Kaplan M, Hammerman C, Kvit R, Rudensky B, Abramov A . Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: sex distribution. Arch Dis Child Fetal Neonatal Ed 1994; 71: F59–F60.

    Article  CAS  Google Scholar 

  23. Kaplan M, Abramov A . Neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency in Sephardic-Jewish neonates: incidence, severity, and the effect of phototherapy. Pediatrics 1992; 90: 401–405.

    CAS  Google Scholar 

  24. Schreiber RA, Barker CC, Roberts EA, Martin SR, Alvarez F, Smith L, et al., Canadian Pediatric Hepatology Research Group. Biliary atresia: the Canadian experience. J Pediatr 2007; 151: 659–665.

    Article  Google Scholar 

  25. Kelly DA, Davenport M . Current management of biliary atresia. Arch Dis Child 2007; 92: 1132–1135.

    Article  Google Scholar 

  26. 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.

    Article  CAS  Google Scholar 

  27. Blanchette V, Dror Y, Chan A . Hematology. In: MacDonald MG, Mullet MD, Seshia MMK (eds). Avery's Neonatology: Pathophysiology and Management of the Newborn. Lippincott, Williams and Wilkins: Philadelphia, 2005, pp 1169–1234.

    Google Scholar 

  28. Kaplan M, Hammerman C, Vreman HJ, Wong RJ, Stevenson DK . Severe hemolysis with normal blood count in a glucose-6-phosphate dehydrogenase deficient neonate. J Perinatol 2008, In press.

  29. Kaplan M, Hammerman C . Glucose-6-phosphate dehydrogenase deficiency: a hidden risk for kernicterus. Semin Perinatol 2004; 28: 356–364.

    Article  Google Scholar 

  30. Doxiadis SA, Karaklis A, Valaes T, Stavrakakis D . Risk of severe jaundice in glucose-6-phosphate-dehydrogenase deficiency of the newborn. Differences in population groups. Lancet 1964; 2: 1210–1212.

    Article  CAS  Google Scholar 

  31. Katar S . Glucose-6-phosphate dehydrogenase deficiency and kernicterus of South-East Anatolia. J Pediatr Hematol Oncol 2007; 29: 284–286.

    Article  CAS  Google Scholar 

  32. Kaplan M, Vreman HJ, Hammerman C, Schimmel MS, Abrahamov A, Stevenson DK . Favism by proxy in nursing glucose-6-phosphate dehydrogenase-deficient neonates. J Perinatol 1998; 18: 477–479.

    CAS  Google Scholar 

  33. Kaplan M, Hammerman C, Vreman HJ, Stevenson DK, Beutler E . Acute hemolysis and severe neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes. J Pediatr 2001; 139: 137–140.

    Article  CAS  Google Scholar 

  34. WHO Working Group. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ 1989; 67: 601–611.

    Google Scholar 

  35. Kaplan M, Leiter C, Hammerman C, Rudensky B . Comparison of commercial screening tests for glucose-6-phosphate dehydrogenase deficiency in the neonatal period. Clin Chem 1997; 43: 1236–1237.

    CAS  Google Scholar 

  36. Newman TB, Easterling MJ, Goldman ES, Stevenson DK . Laboratory evaluation of jaundice in newborns. Frequency, cost, and yield. Am J Dis Child 1990; 144: 364–368.

    Article  CAS  Google Scholar 

  37. Moyer VA, Ahn C, Sneed S . Accuracy of clinical judgment in neonatal jaundice. Arch Pediatr Adolesc Med 2000; 154: 391–394.

    Article  CAS  Google Scholar 

  38. Madlon-Kay DJ . Recognition of the presence and severity of newborn jaundice by parents, nurses, physicians, and icterometer. Pediatrics 1997; 100: e3.

    Article  CAS  Google Scholar 

  39. Maisels MJ . Transcutaneous bilirubinometery. NeoReviews 2006; 7: e217–e225.

    Article  Google Scholar 

  40. Maisels MJ, Ostrea Jr EM, Touch S, Clune SE, Cepeda E, Kring E et al. Evaluation of a new transcutaneous bilirubinometer. Pediatrics 2004; 113: 1628–1635.

    Article  Google Scholar 

  41. Bertini G, Rubaltelli FF . Non-invasive bilirubinometry in neonatal jaundice. Semin Neonatol 2002; 7: 129–133.

    Article  Google Scholar 

  42. Kaplan M, Bromiker R, Schimmel MS, Algur N, Hammerman C . Evaluation of discharge management in the prediction of hyperbilirubinemia: the Jerusalem experience. J Pediatr 2007; 150: 412–417.

    Article  CAS  Google Scholar 

  43. Lazar L, Litwin A, Merlob P . Phototherapy for neonatal nonhemolytic hyperbilirubinemia. Analysis of rebound and indications for discontinuing therapy. Clin Pediatr 1993; 32: 264–267.

    Article  CAS  Google Scholar 

  44. Kaplan M, Kaplan E, Hammerman C, Algur N, Bromiker R, Schimmel MS et al. Post-phototherapy neonatal bilirubin rebound: a potential cause of significant hyperbilirubinaemia. Arch Dis Child 2006; 91: 31–34.

    Article  CAS  Google Scholar 

  45. Maisels MJ, Kring E . Rebound in serum bilirubin level following intensive phototherapy. Arch Pediatr Adolesc Med 2002; 156: 669–672.

    Article  Google Scholar 

  46. Hammerman C, Vreman HJ, Kaplan M, Stevenson DK . Intravenous immune globulin in neonatal immune hemolytic disease: does it reduce hemolysis? Acta Paediatr 1996; 85: 1351–1353.

    Article  CAS  Google Scholar 

  47. Rubo J, Albrecht K, Lasch P, Laufkotter E, Leititis J, Marsan D et al. High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease. J Pediatr 1992; 121: 93–97.

    Article  CAS  Google Scholar 

  48. Steiner LA, Bizzarro MJ, Ehrenkranz RA, Gallagher PG . A decline in the frequency of neonatal exchange transfusions and its effect on exchange-related morbidity and mortality. Pediatrics 2007; 120: 27–32.

    Article  Google Scholar 

  49. Patra K, Storfer-Isser A, Siner B, Moore J, Hack M . Adverse events associated with neonatal exchange transfusion in the 1990s. J Pediatr 2004; 144: 626–631.

    Article  Google Scholar 

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Acknowledgements

We thank Cathy Hammerman, MD, Michael S Schimmel, MD and Ruben Bromiker, MD, for their patience in the practical evaluation of these guidelines while they were being formulated, and the members of the Israel Neonatal Departments Directors Forum for their useful comments and suggestions. Cathy Hammerman, MD, provided invaluable assistance in the preparation of this manuscript. The following international bilirubin experts reviewed drafts of the guidelines and provided valuable input: M Jeffrey Maisels, MB BCh, David K Stevenson, MD, Vinod K Bhutani, MD, Ann Stark, MD, Jon F Watchko, MD, Thor Hansen, MD, Firmino F Rubaltelli, MD.

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Kaplan, M., Merlob, P. & Regev, R. Israel guidelines for the management of neonatal hyperbilirubinemia and prevention of kernicterus. J Perinatol 28, 389–397 (2008). https://doi.org/10.1038/jp.2008.20

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