New Treatment Options in Neonatal Hyperbilirubinaemia

  • P. T. Pisciotto
Chapter
Part of the Developments in Hematology and Immunology book series (DIHI, volume 39)

Abstract

Jaundice is one of the most common problems encountered in the newborn period. It has been estimated that in the United States over 60% of the 4 million newborns born each year develop clinical jaundice with bilirubin levels greater than 5 mg/dL (86 µmol/L) in the first week of life. Bilirubin encephalopathy, known pathologically as kernicterus for the yellow staining of the subthalmic nuclei (kerns), has been recognized for a long time. The degree to which bilirubin may cause more subtle neurologic abnormalities remains controversial [1]. While clinical jaundice is commonly encountered in the newborn, kernicterus is a rare occurrence. Factors that affect bilirubin toxicity are complex and incompletely understood. These include; the serum albumin concentration and available binding sites on albumin for bilirubin, the integrity of the blood brain barrier and therefore ability for bilirubin to enter the brain, the duration of bilirubin exposure and the type and stage of development of the cells being exposed [2]. The relationship between increasing total serum bilirubin (TSB) levels, particularly greater then 20 mg/dL (344 µmol/L), and the risk of developing kernicterus in infants with Rh haemolytic disease of the newborn (HDN) was observed in the late 1940s and early 1950s [3]. This led to an aggressive approach to the treatment of jaundice in these patients with exchange transfusion being the predominant mode of therapy to maintain bilirubin levels below 20 mg/dL (344 µmol/L). In 1958 it was observed that premature infants exposed to sunlight or blue fluorescent light experienced a decrease in TSB levels [4].

Keywords

Total Serum Bilirubin Total Serum Bilirubin Level Total Serum Bilirubin Concentration Bilirubin Production Bilirubin Exposure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Maisels MJ, Newman TB. Bilirubin and neurological dysfunction — do we need to change what we are doing? Pediatr Res 2001;50:677–678.CrossRefPubMedGoogle Scholar
  2. 2.
    Dennery PA, Seidman DS, Stevenson DK. Drug therapy: Neonatal hyperbilirubinemia. N Engl J Med 2001:344:581–590.CrossRefPubMedGoogle Scholar
  3. 3.
    Hsia DYY, Allen FH, Gellis SS, Diamond LK. Erythroblastosis fetalis. VIII. Studies of serum bilirubin in relation to kernicterus. N Engl J Med 1952;247:668–671.PubMedGoogle Scholar
  4. 4.
    Cremer RJ, Perryman PW, Richards DH. Influence of light on the hyperbilirubinemia of infants. Lancet 1958;1:1094–1097.CrossRefPubMedGoogle Scholar
  5. 5.
    Maisels MJ. Phototherapy — Traditional and nontraditional. J Perinatol 2001;21(suppl):93–97.CrossRefGoogle Scholar
  6. 6.
    Soorani-Lunsing I, Woltil HA, Hadders-Algra M. Are moderate degrees of hyperbilirubinemia in healthy term neonates really safe for the brain? Pediatr Res 2001;50:701–705.CrossRefPubMedGoogle Scholar
  7. 7.
    Newman TB, Maisels MJ. Evaluation and treatment of jaundice in the term newborn. A kinder, gentler approach. Pediatrics 1992;89:809–818.PubMedGoogle Scholar
  8. 8.
    AAP Provisional committee for Quality Improvement and Subcommittee on Hyperbilirubinemia. Practice parameter: Management of hyperbilirubinemia in the healthy term newborn. Pediatrics 1994;94:558–562.Google Scholar
  9. 9.
    Hanson TWR. Fetal and neonatal bilirubin metabolism. In Maisels MJ, Watchko JF, eds. Neonatal Jaundice. London: Harwood Academic, 2000 pp3–22.Google Scholar
  10. 10.
    Cashore WJ. Bilirubin and jaundice in the micropremie. Clin Perinatol 2000;27:171–179.CrossRefPubMedGoogle Scholar
  11. 11.
    Seideman DS, Stevenson DK, Ergaz Z, Gale R. Hospital readmission due to neonatal hyperbilirubinemia. Pediatrics 1995;96:727–729.Google Scholar
  12. 12.
    Maisels MJ, King E. Length of stay, jaundice, and hospital readmission. Pediatrics 1998;101:995–998.CrossRefPubMedGoogle Scholar
  13. 13.
    Johnson L, Brown AK. A pilot registry for acute and chronic kernicterus in term and near-term infants. Pediatrics 1999;104:(suppl):736a.Google Scholar
  14. 14.
    Ebbesen F. Recurrence of kernicterus in term and near-term infants in Denmark. Acta Paediatr 2000;89:1–5.CrossRefGoogle Scholar
  15. 15.
    AAP Subcommittee on Neonatal Hyperbilirubinemia. Neonatal jaundice and kernicterus. Pediatrics 2001;108:763–765.CrossRefGoogle Scholar
  16. 16.
    Maisels MJ, Pathak A, Nelson NM, et al. Endogenous production of carbon monoxide in normal and erythroblastotic newborn infants. J Clin Invest 1971;50:1–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Bosma PJ, Seppen J, Goldhoorn B, et al. Bilirubin UDP-glucuronyl transferase 1 is the only relevant bilirubin glucuronodating isoform in man J Biol Chem 1994;269:17960–17964.PubMedGoogle Scholar
  18. 18.
    Maisels MJ. Neonatal hyperbilirubinemia. In Klaus MH, Fanaroff AA, eds. Care of the high risk neonate. Philadelphia: WB Saunders, 2001 pp324–362.CrossRefGoogle Scholar
  19. 19.
    Hardy JB, Drage JS, Jackson EC. The first year of life: The Collaborative Perinatal Project of the National Institutes of Neurologic and Communicative Disorders and Stroke. Baltimore; Johns Hopkins University Press 1979.Google Scholar
  20. 20.
    Bhutani VK, Johnson L, Siveri 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.CrossRefPubMedGoogle Scholar
  21. 21.
    Ryan AS. The resurgence of breastfeeding in the United States. Pediatrics 99:E12, 1997.CrossRefPubMedGoogle Scholar
  22. 22.
    Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyl transferase (UGT 1A1) promotor: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci USA 1998;95:8170–8174.CrossRefPubMedGoogle Scholar
  23. 23.
    Bhutani VK, Johnson LH. Jaundice technologies: Prediction of hyperbilirubinemia in term and near-term newborns. J Perinatol 2001;21:(suppl):76–82.CrossRefGoogle Scholar
  24. 24.
    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 2000;154:1140–1147.PubMedGoogle Scholar
  25. 25.
    Stevenson DK, Fanaroff A, Maisels J. et al. Prediction of hyperbilirubinemia in term and near-term newborn infants. Pediatrics 2001;108:31–39.CrossRefPubMedGoogle Scholar
  26. 26.
    Lucey J, Ferreiro M, Hewitt J. Prevention of hyperbilirubinemia of prematurity by phototherapy. Pediatrics 1968;41:1047–1054.PubMedGoogle Scholar
  27. 27.
    Brown AK, Kim MH, Wu PYK, et al. Efficacy of phototherapy in prevention and management of hyperbilirubinemia. Pediatrics 1985;75:393–400.PubMedGoogle Scholar
  28. 28.
    Maurer HM, Kirpatrick BV, McWilliams NB et al. Phototherapy for hyperbilirubinemia of hemolytic disease of the newborn. Pediatrics 1985;75:68–76.Google Scholar
  29. 29.
    Valaes T, Koliopoulos C, Koiopoulos A. The impact of phototherapy in the management of neonatal hyperbilirubinemia. Comparison of historical cohorts. Acta Paediatr 1996;85:273–276.CrossRefPubMedGoogle Scholar
  30. 30.
    Scheidt PC, Bryla DA, Nelson KB, Hirtz DG, Hoffman HJ. Phototherapy for neonatal hyperbilirubinemia; six year follow-up of the national institute of child health and human development clinical trial. Pediatrics 1990;85:455–463.PubMedGoogle Scholar
  31. 31.
    McDonagh AF. Phototherapy: From ancient Egypt to the new millennium. J Perinatol 2001;21:(suppl):7–12.CrossRefGoogle Scholar
  32. 32.
    Ennever JF, Costarino AT, Polin RA, Speck WT. Rapid clearance of a structural isomer of bilirubin during phototherapy. J Clin Invest 1987;79:1674–1678.CrossRefPubMedGoogle Scholar
  33. 33.
    Hanson TWR. Therapeutic approaches to neonatal jaundice: an international survey. Clin Pediatr 1996;75:393–400.Google Scholar
  34. 34.
    Tan KL. The pattern of bilirubin response to phototherapy for neonatal hyperbilirubinemia. Pediatr Res 1982;16:670–674.CrossRefPubMedGoogle Scholar
  35. 35.
    Tan KL. Efficacy of fluorescent daylight, blue, and green lamps in the management of nonhemolytic hyperbilirubinemia. J Pediatr 1989;114:132–137.CrossRefPubMedGoogle Scholar
  36. 36.
    Mills JF, Tudehope D. Fiberoptic phototherapy for neonatal jaundice. In: The Cochrane Library, Issue 1. Oxford: Update Software; 2001.Google Scholar
  37. 37.
    Holtrop PC, Madison K, Maisels MJ. A clinical trial of fiberoptic phototherapy vs conventional phototherapy. AJDC 1992;146:235–237.PubMedGoogle Scholar
  38. 38.
    Tan KL. Comparison of the efficacy of fiberoptic and conventional phototherapy for neonatal hyperbilirubinemia. J Pediatr 1994;125:607–612.CrossRefPubMedGoogle Scholar
  39. 39.
    Tan KL. Efficacy of bi-directional fiber-optic phototherapy for neonatal hyperbilirubinemia. Pediatrics 1997;99:e13.CrossRefPubMedGoogle Scholar
  40. 40.
    Holtrop PC, Ruedisueli K, Maisels MJ. Double versus single phototherapy in low birth weight newborns. Pediatric 1992;90:674–677.Google Scholar
  41. 41.
    Seidman DS, Moise J, Ergaz Z et al. A new blue light-emitting phototherapy device: A prospectiverandomized controlled study. J Pediatr 2000;136:771–774.CrossRefPubMedGoogle Scholar
  42. 42.
    Garg AK, Prasad RS, Hifzi IA. A controlled trial of high-intensity doublesurface phototherapy on a fluid bed versus conventional phototherapy in neonatal jaundice. Pediatrics 1995;95:914–916.PubMedGoogle Scholar
  43. 43.
    Yetman RJ, Parks D, Huseby V, Mistry K, Garcia J. Rebound bilirubin levels in infants receiving phototherapy. J Pediatr 1998;133:705–707.CrossRefPubMedGoogle Scholar
  44. 44.
    Maisels MJ, Kring E. Rebound in serum bilirubin level following intensive phototherapy. Arch Pediatr Adolesc Med. 2002;669–672.Google Scholar
  45. 45.
    Benders MJNL, van Bel F, van de Bor. The effect of photottherapy of cerebral blood flow velocity in preterm infants. Acta Paediatr 1998;87:786–791CrossRefPubMedGoogle Scholar
  46. 46.
    Valaes, T. Bilirubin distribution and dynamics of bilirubin removal by exchange transfusion. Acta. Paediatr. Scand. 1963;52(suppl 149).Google Scholar
  47. 47.
    Diamond LK, Allen FH, Thomas WO Erythroblastosis fetalis. VII. Treatment with exchange transfusion. N Engl J Med. 1951;244:39.PubMedCrossRefGoogle Scholar
  48. 48.
    Keenen WJ, Novak KK, Sutheralns JM, Bryla DA, Fetterly KL. Morbidity and mortality associated with exchange transfusion. Pediatrics 1985;75:(suppl):422–426.Google Scholar
  49. 49.
    Jackson JC. Adverse events associated with exchange transfusion in healthy and ill newborns. Pediatrics 1997;99:e7.CrossRefPubMedGoogle Scholar
  50. 50.
    Vreman HJ, Wong RJ, Stevenson DK. Alternative metalloporphyrins for the treatment of neonatal jaundice. J Perinatol 2001;21:(suppl):108–113.CrossRefGoogle Scholar
  51. 51.
    Whitington PF et al The effect of tine (IV)-protoporphyrin-IX on bilirubin production and excretion in the rat. Pediatr Res 1987;21:487–491.CrossRefPubMedGoogle Scholar
  52. 52.
    Valaes T, Petmezaki, S, Henschke C, Drummond GS, Kappas A. Control of jaundice in preterm newborns by an inhibitor of bilirubin production: Studies with tin-mesoporphyrin. Pediatrics 1994;93:1–11.PubMedGoogle Scholar
  53. 53.
    Kappas A, Drummond GS, Henschke C, Valaes T. Direct comparison of Sn-Mesoprphorin, an inhibitor of bilirubin production and phototherapy in controlling hyperbilirubinemia in term and near-term newborns. Pediatrics 1995;95:468–474.PubMedGoogle Scholar
  54. 54.
    Martinez JC, Garcia HO, Otheguy LE, Drummonds GS, Kappas A. Control of severe hyperbilirubinemia in full-term newborns with the inhibitor of bilirubin production Sn-mesoporphyrin. Pediatrics 1999;103:1–5.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • P. T. Pisciotto
    • 1
  1. 1.Department of Laboratory MedicineUniversity of Connecticut Health CenterFarmingtonUSA

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