Neonatal Jaundice Questions & Answers

1. Huang MJ, Kua KE, Teng HC, Tang KS, Weng HW, Huang CS. Risk factors for severe hyperbilirubinemia in neonates. Pediatr Res. 2004 Nov. 56(5):682-9. [QxMD MEDLINE Link].

2. Christensen RD, Yaish HM. Hemolytic disorders causing severe neonatal hyperbilirubinemia. Clin Perinatol. 2015 Sep. 42 (3):515-27. [QxMD MEDLINE Link].

3. Woodgate P, Jardine LA. Neonatal jaundice: phototherapy. BMJ Clin Evid. 2015 May 22. 2015:[QxMD MEDLINE Link].

4. Macias RI, Marin JJ, Serrano MA. Excretion of biliary compounds during intrauterine life. World J Gastroenterol. 2009 Feb 21. 15(7):817-28. [QxMD MEDLINE Link]. [Full Text].

5. Yusoff S, Van Rostenberghe H, Yusoff NM, et al. Frequencies of A(TA)7TAA, G71R, and G493R mutations of the UGT1A1 gene in the Malaysian population. Biol Neonate. 2006. 89(3):171-6. [QxMD MEDLINE Link]. [Full Text].

6. Memon N, Weinberger BI, Hegyi T, Aleksunes LM. Inherited disorders of bilirubin clearance. Pediatr Res. 2015 Nov 23. [QxMD MEDLINE Link].

7. Watchko JF, Lin Z. Genetics of neonatal jaundice. Stevenson DK, Maisels MJ, Watchko JF. Care of the jaundiced neonate. New York: McGraw-Hill; 2012. 1-27.

8. Fujiwara R, Maruo Y, Chen S, Tukey RH. Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia. Toxicol Appl Pharmacol. 2015 Nov 15. 289 (1):124-32. [QxMD MEDLINE Link].

9. 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. 2005 Nov. 58(5):881-4. [QxMD MEDLINE Link].

10. 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. 2002 Aug. 48(3-4):73-7. [QxMD MEDLINE Link].

11. Kumral A, Ozkan H, Duman N, Yesilirmak DC, Islekel H, Ozalp Y. Breast milk jaundice correlates with high levels of epidermal growth factor. Pediatr Res. 2009 Aug. 66(2):218-21. [QxMD MEDLINE Link].

12. Maisels MJ, Newman TB. The epidemiology of neonatal hyperbilirubinemia. Stevenson DK, Maisels MJ, Watchko JF. Care of the jaundiced neonate. New York: McGraw-Hill; 2012. 97-113.

13. Maisels MJ, Gifford K. Normal serum bilirubin levels in the newborn and the effect of breast- feeding. Pediatrics. 1986 Nov. 78(5):837-43. [QxMD MEDLINE Link].

14. [Guideline] 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. [QxMD MEDLINE Link]. [Full Text].

15. Slusher TM, Olusaniya BO. Neonatal jaundice in low- and middle-income countries. Stevenson DK, Maisels MJ, Watchko JF. Care of the jaundiced neonate. New York: McGraw-Hill; 2012. 263-73.

16. Moore LG, Newberry MA, Freeby GM, Crnic LS. Increased incidence of neonatal hyperbilirubinemia at 3,100 m in Colorado. Am J Dis Child. 1984 Feb. 138(2):157-61. [QxMD MEDLINE Link].

17. 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. [QxMD MEDLINE Link]. [Full Text].

18. 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. 2005 Jan. 94(1):59-64. [QxMD MEDLINE Link].

19. Linn S, Schoenbaum SC, Monson RR, Rosner B, Stubblefield PG, Ryan KJ. Epidemiology of neonatal hyperbilirubinemia. Pediatrics. 1985 Apr. 75(4):770-4. [QxMD MEDLINE Link].

20. Maisels MJ, Newman TB. Prevention, screening and postnatal management of neonatal hyperbilirubinemia. Stevenson DK, Maisels MJ, Watchko JF. Care of the jaundiced neonate. New York: McGraw-Hill; 2012. 175-94.

21. Slusher TM, Vreman HJ, McLaren DW, Lewison LJ, Brown AK, Stevenson DK. Glucose-6-phosphate dehydrogenase deficiency and carboxyhemoglobin concentrations associated with bilirubin-related morbidity and death in Nigerian infants. J Pediatr. 1995 Jan. 126(1):102-8. [QxMD MEDLINE Link].

22. Knudsen A. The influence of the reserve albumin concentration and pH on the cephalocaudal progression of jaundice in newborns. Early Hum Dev. 1991 Jan-Feb. 25(1):37-41. [QxMD MEDLINE Link].

23. Purcell N, Beeby PJ. The influence of skin temperature and skin perfusion on the cephalocaudal progression of jaundice in newborns. J Paediatr Child Health. 2009 Oct. 45(10):582-6. [QxMD MEDLINE Link].

24. [Guideline] 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. [QxMD MEDLINE Link].

25. Bhutani VK, Johnson LH, Maisels MJ, et al. Kernicterus: epidemiological strategies for its prevention through systems-based approaches. J Perinatol. 2004. 24:650-62. [QxMD MEDLINE Link]. [Full Text].

26. Mishra S, Chawla D, Agarwal R, Deorari AK, Paul VK, Bhutani VK. Transcutaneous bilirubinometry reduces the need for blood sampling in neonates with visible jaundice. Acta Paediatr. 2009 Dec. 98(12):1916-9. [QxMD MEDLINE Link].

27. 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. 2000 Aug. 106(2):E17. [QxMD MEDLINE Link]. [Full Text].

28. Keren R, Tremont K, Luan X, Cnaan A. Visual assessment of jaundice in term and late preterm infants. Arch Dis Child Fetal Neonatal Ed. 2009 Sep. 94(5):F317-22. [QxMD MEDLINE Link].

29. Riskin A, Tamir A, Kugelman A, Hemo M, Bader D. Is visual assessment of jaundice reliable as a screening tool to detect significant neonatal hyperbilirubinemia?. J Pediatr. 2008 Jun. 152(6):782-7, 787.e1-2. [QxMD MEDLINE Link].

30. Schutzman DL, Sekhon R, Hundalani S. Hour-specific bilirubin nomogram in infants with ABO incompatibility and direct Coombs-positive results. Arch Pediatr Adolesc Med. 2010 Dec. 164(12):1158-64. [QxMD MEDLINE Link].

31. Ahlfors CE, Parker AE. Unbound bilirubin concentration is associated with abnormal automated auditory brainstem response for jaundiced newborns. Pediatrics. 2008 May. 121(5):976-8. [QxMD MEDLINE Link].

32. Mreihil K, Madsen P, Nakstad B, Benth JS, Ebbesen F, Hansen TW. Early formation of bilirubin isomers during phototherapy for neonatal jaundice: effects of single vs. double fluorescent lamps vs. photodiodes. Pediatr Res. 2015 Jul. 78 (1):56-62. [QxMD MEDLINE Link].

33. Vandborg PK, Hansen BM, Greisen G, Ebbesen F. Dose-response relationship of phototherapy for hyperbilirubinemia. Pediatrics. 2012 Aug. 130(2):e352-7. [QxMD MEDLINE Link].

34. Kumar P, Chawla D, Deorari A. Light-emitting diode phototherapy for unconjugated hyperbilirubinaemia in neonates. Cochrane Database Syst Rev. 2011 Dec 7. 12:CD007969. [QxMD MEDLINE Link].

35. Tridente A, De Luca D. Efficacy of light-emitting diode versus other light sources for treatment of neonatal hyperbilirubinemia: a systematic review and meta-analysis. Acta Paediatr. 2012 May. 101(5):458-65. [QxMD MEDLINE Link].

36. Gottstein R, Cooke RW. Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed. 2003 Jan. 88(1):F6-10. [QxMD MEDLINE Link]. [Full Text].

37. Rubo J, Albrecht K, Lasch P, et al. High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease. J Pediatr. 1992 Jul. 121(1):93-7. [QxMD MEDLINE Link].

38. Huizing K, Roislien J, Hansen T. Intravenous immune globulin reduces the need for exchange transfusions in Rhesus and AB0 incompatibility. Acta Paediatr. 2008 Oct. 97(10):1362-5. [QxMD MEDLINE Link].

39. Hansen TW. Therapeutic approaches to neonatal jaundice: an international survey. Clin Pediatr (Phila). 1996 Jun. 35(6):309-16. [QxMD MEDLINE Link].

40. [Guideline] American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004 Jul. 114(1):297-316. [QxMD MEDLINE Link]. [Full Text].

41. Maisels MJ, Watchko JF, Bhutani VK, Stevenson DK. An approach to the management of hyperbilirubinemia in the preterm infant less than 35 weeks of gestation. J Perinatol. 2012 Sep. 32(9):660-4. [QxMD MEDLINE Link].

42. Morris BH, Oh W, Tyson JE, et al. Aggressive vs. conservative phototherapy for infants with extremely low birth weight. N Engl J Med. 2008 Oct 30. 359(18):1885-96. [QxMD MEDLINE Link]. [Full Text].

43. Hintz SR, Stevenson DK, Yao Q, et al. Is phototherapy exposure associated with better or worse outcomes in 501- to 1000-g-birth-weight infants?. Acta Paediatr. 2011 Jul. 100(7):960-965. [QxMD MEDLINE Link].

44. Tyson JE, Pedroza C, Langer J, et al. Does aggressive phototherapy increase mortality while decreasing profound impairment among the smallest and sickest newborns?. J Perinatol. 2012 Sep. 32(9):677-84. [QxMD MEDLINE Link]. [Full Text].

45. Hansen TW. Let there be light-but should there be less?. J Perinatol. 2012 Sep. 32(9):649-51. [QxMD MEDLINE Link].

46. Madan JC, Kendrick D, Hagadorn JI, Frantz ID 3rd. Patent ductus arteriosus therapy: impact on neonatal and 18-month outcome. Pediatrics. 2009 Feb. 123(2):674-81. [QxMD MEDLINE Link].

47. Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM. Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). J Perinatol. 2009 Feb. 29 Suppl 1:S25-45. [QxMD MEDLINE Link].

48. Hansen TW, Nietsch L, Norman E, et al. Reversibility of acute intermediate phase bilirubin encephalopathy. Acta Paediatr. 2009 Oct. 98(10):1689-94. [QxMD MEDLINE Link].

49. Calado CS, Pereira AG, Santos VN, Castro MJ, Maio JF. What brings newborns to the emergency department?: a 1-year study. Pediatr Emerg Care. 2009 Apr. 25(4):244-8. [QxMD MEDLINE Link].

50. Newman TB, Liljestrand P, Escobar GJ. Combining clinical risk factors with serum bilirubin levels to predict hyperbilirubinemia in newborns. Arch Pediatr Adolesc Med. 2005 Feb. 159(2):113-9. [QxMD MEDLINE Link].

51. Bhutani VK, Johnson LH, Keren R. Diagnosis and management of hyperbilirubinemia in the term neonate: for a safer first week. Pediatr Clin North Am. 2004 Aug. 51(4):843-61, vii. [QxMD MEDLINE Link].

52. 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. 2006 May. 117(5):e855-62. [QxMD MEDLINE Link].

53. 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. 2004 Oct. 114(4):1015-22. [QxMD MEDLINE Link].

54. Suresh GK, Clark RE. Cost-effectiveness of strategies that are intended to prevent kernicterus in newborn infants. Pediatrics. 2004 Oct. 114(4):917-24. [QxMD MEDLINE Link].

55. [Guideline] 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 Oct. 124(4):1193-8. [QxMD MEDLINE Link].

56. 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. 2008 May. 167(5):501-7. [QxMD MEDLINE Link].

57. Cremer RJ, Perryman PW. Influence of light on the hyperbilirubinemia of infants. Lancet. 1958. 1:1094-7.

58. Gourley GR, Li Z, Kreamer BL, Kosorok MR. A controlled, randomized, double-blind trial of prophylaxis against jaundice among breastfed newborns. Pediatrics. 2005 Aug. 116(2):385-91. [QxMD MEDLINE Link]. [Full Text].

59. Grohmann K, Roser M, Rolinski B, et al. Bilirubin measurement for neonates: comparison of 9 frequently used methods. Pediatrics. 2006 Apr. 117(4):1174-83. [QxMD MEDLINE Link].

60. Hansen TW. Acute management of extreme neonatal jaundice--the potential benefits of intensified phototherapy and interruption of enterohepatic bilirubin circulation. Acta Paediatr. 1997 Aug. 86(8):843-6. [QxMD MEDLINE Link].

61. Hansen TW. Recent advances in the pharmacotherapy for hyperbilirubinaemia in the neonate. Expert Opin Pharmacother. 2003. 4(11):1939-48. [QxMD MEDLINE Link]. [Full Text].

62. 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. [QxMD MEDLINE Link].

63. Hart C, Cameron R. The importance of irradiance and area in neonatal phototherapy. Arch Dis Child Fetal Neonatal Ed. 2005. 90:F437-F440. [QxMD MEDLINE Link]. [Full Text].

64. Hervieux, J. De l'ictere des nouveau-nes. Paris: These med. 1847.

65. Ho HT, Ng TK, Tsui KC, Lo YC. Evaluation of a new transcutaneous bilirubinometer in Chinese newborns. Arch Dis Child Fetal Neonatal Ed. 2006 Nov. 91(6):F434-8. [QxMD MEDLINE Link].

66. 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 Apr. 150(4):412-7. [QxMD MEDLINE Link].

67. 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. 2007 Apr 5. [QxMD MEDLINE Link].

68. Kaplan M, Shchors I, Algur N, Bromiker R, Schimmel MS, Hammerman C. Visual screening versus transcutaneous bilirubinometry for predischarge jaundice assessment. Acta Paediatr. 2008 Jun. 97(6):759-63. [QxMD MEDLINE Link].

69. 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. 2005 Apr. 90(4):415-21. [QxMD MEDLINE Link].

70. 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. 2008 Aug. 153(2):234-40. [QxMD MEDLINE Link].

71. Lin Z, Fontaine J, Watchko JF. Coexpression of gene polymorphisms involved in bilirubin production and metabolism. Pediatrics. 2008 Jul. 122(1):e156-62. [QxMD MEDLINE Link].

72. Maisels MJ, McDonagh AF. Phototherapy for neonatal jaundice. N Engl J Med. 2008 Feb 28. 358(9):920-8. [QxMD MEDLINE Link].

73. Maisels MJ, Newman TB, Watchko JF. Effect of predischarge bilirubin screening on subsequent hyperbilirubinemia. Pediatrics. 2006 Oct. 118(4):1796; author reply 1976-7. [QxMD MEDLINE Link].

74. 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. 2008 Jan. 167(1):57-61. [QxMD MEDLINE Link].

75. 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. 2006 May 4. 354(18):1889-900. [QxMD MEDLINE Link].

76. Ostrow JD, Jandl JH, Schmid R. The formation of bilirubin from hemoglobin in vivo. J Clin Invest. 1962 Aug. 41:1628-37. [QxMD MEDLINE Link]. [Full Text].

77. Seidman DS, Moise J, Ergaz Z. A new blue light-emitting phototherapy device: a prospective randomized controlled study. J Pediatr. 2000. 136:771-4. [QxMD MEDLINE Link]. [Full Text].

78. Smitherman H, Stark AR, Bhutan VK. Early recognition of neonatal hyperbilirubinemia and its emergent management. Semin Fetal Neonatal Med. 2006 Jun. 11(3):214-24. [QxMD MEDLINE Link].

79. 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. 2007 Nov. 96(11):1622-5. [QxMD MEDLINE Link].

80. Watchko JF. Vigintiphobia revisited. Pediatrics. 2005 Jun. 115(6):1747-53. [QxMD MEDLINE Link]. [Full Text].

81. Taylor JA, Stout JW, de Greef L, et al. Use of a smartphone app to assess neonatal jaundice. Pediatrics. 2017 Sep. 140 (3):[QxMD MEDLINE Link].

82. Olusanya BO, Slusher TM, Imosemi DO, Emokpae AA. Maternal detection of neonatal jaundice during birth hospitalization using a novel two-color icterometer. PLoS One. 2017. 12 (8):e0183882. [QxMD MEDLINE Link]. [Full Text].

83. Chen Z, Zhang L, Zeng L, et al. Probiotics supplementation therapy for pathological neonatal jaundice: a systematic review and meta-analysis. Front Pharmacol. 2017. 8:432. [QxMD MEDLINE Link]. [Full Text].

84. Yang L, Wu, Wang B, Bu X, Tang J. The influence of zinc sulfate on neonatal jaundice: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2017 Apr 24. 1-7. [QxMD MEDLINE Link].

85. Barekatain B, Badiea Z, Hoseini N. The effect of head covering in prevention of phototherapy-induced hypocalcemia in icterus newborns with gestational age less than 35 weeks. Adv Biomed Res. 2016. 5:176. [QxMD MEDLINE Link]. [Full Text].

86. Chaudhari H, Goyal S, Patil C. Neonates with sickle cell disease are vulnerable to blue light phototherapy-induced oxidative stress and proinflammatory cytokine elevations. Med Hypotheses. 2016 Nov. 96:78-82. [QxMD MEDLINE Link].

87. Christensen RD, Agarwal AM, Yaish HM, Reading NS, O'Brien EA, Prchal JT. Three novel spectrin variants in jaundiced neonates. Clin Pediatr (Phila). 2018 Jan. 57 (1):19-26. [QxMD MEDLINE Link].

88. Keahey PA, Simeral ML, Schroder KJ, et al. Point-of-care device to diagnose and monitor neonatal jaundice in low-resource settings. Proc Natl Acad Sci U S A. 2017 Dec 19. 114 (51):E10965-E10971. [QxMD MEDLINE Link].

89. Mitra S, Rennie J. Neonatal jaundice: aetiology, diagnosis and treatment. Br J Hosp Med (Lond). 2017 Dec 2. 78 (12):699-704. [QxMD MEDLINE Link].

Thor WR Hansen, MD, PhD, MHA, FAAP Professor, Department of Neonatology, Women and Children's Division, Director of Clinical Ethics, Oslo University Hospital HC, Rikshospitalet; Director of Pediatric Education, Faculty of Medicine, University of Oslo, Norway

Thor WR Hansen, MD, PhD, MHA, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the History of Medicine, American Pediatric Society, European Society for Paediatric Research, New York Academy of Sciences, Perinatal Research Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Brian S Carter, MD, FAAP Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Attending Physician, Division of Neonatology, Children's Mercy Hospital and Clinics; Faculty, Children's Mercy Bioethics Center

Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Pediatric Society, American Society for Bioethics and Humanities, American Society of Law, Medicine & Ethics, Society for Pediatric Research, National Hospice and Palliative Care Organization

Disclosure: Nothing to disclose.

Muhammad Aslam, MD Professor of Pediatrics, University of California, Irvine, School of Medicine; Neonatologist, Division of Newborn Medicine, Department of Pediatrics, UC Irvine Medical Center

Muhammad Aslam, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Oussama Itani, MD, FAAP, FACN Clinical Associate Professor of Pediatrics and Human Development, Michigan State University; Medical Director, Department of Neonatology, Borgess Medical Center

Oussama Itani, MD, FAAP, FACN is a member of the following medical societies: American Academy of Pediatrics, American Association for Physician Leadership, American Heart Association, American College of Nutrition

Disclosure: Nothing to disclose.

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