Severe neonatal hyperbilirubinemia, defined as total serum bilirubin (TSB) ≥20 mg/dl, is associated with a higher risk of permanent neurological sequelae and death. Jaundice can and should be promptly diagnosed and treated. Reliable methods for TSB assay are not always readily available, particularly in low- and middle-income countries, making the true incidence of severe neonatal jaundice (NNJ) difficult to estimate. To gather a more comprehensive picture, a symposium addressing NNJ worldwide was organized during the 2015 Don Ostrow Trieste Yellow Retreat. Data collected by several researchers in different regions of the world were presented and differences/similarities discussed. This report points out the need for: (1) a coordinated worldwide effort to define the burden and the causes of severe NNJ and its consequences; (2) aggressive educational programs for families and health personnel to facilitate timely care-seeking, and (3) accurate diagnostics and effective phototherapy.

Keywords:
Neonatal jaundice, Severe hyperbilirubinemia, Acute bilirubin encephalopathy, Kernicterus, Low- and middle-income countries
1.
Olusanya BO, Ogunlesi TA, Slusher TM: Why is kernicterus still a major cause of death and disability in low-income and middle-income countries? Arch Dis Child 2014;99:1117-1121.
2.
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.
3.
Young Infants Clinical Signs Study Group: Clinical signs that predict severe illness in children under age 2 months: a multicentre study. Lancet Lond Engl 2008;371:135-142.
4.
Hansen TWR: Mechanisms of bilirubin toxicity: clinical implications. Clin Perinatol 2002;29:765-778, viii.
5.
Newman TB, Maisels MJ: Evaluation and treatment of jaundice in the term newborn: a kinder, gentler approach. Pediatrics 1992;89:809-818.
6.
Volpe JJ: Neurology of the Newborn. Amsterdam, Elsevier Health Sciences, 2008.
7.
Maisels MJ: Managing the jaundiced newborn: a persistent challenge. CMAJ 2015;187:335-343.
8.
Barrington KJ, Sankaran K; Canadian Paediatric Society Fetus and Newborn Committee: 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;12:401-407.
9.
World Health Organization: WHO recommendations on postnatal care of the mother and newborn 2014 (cited December 23, 2015). http://www.who.int/iris/handle/10665/97603.
10.
World Health Organization: Pocket Book of Hospital Care for Children: guidelines for the management of common childhood illnesses. Geneva, World Health Organization, 2013.
11.
NICE/National Institute for Health and Care Excellence: Neonatal jaundice 2010. https://www.nice.org.uk/guidance/cg98/evidence/full-guideline-245411821.
12.
NICE/National Institute for Health and Care Excellence: Updated neonatal jaundice pathway 2014 (cited December 23, 2015). http://pathways.nice.org.uk/pathways/neonatal-jaundice.
13.
NICE/National Institute for Health and Care Excellence: Updated postnatal care 2014 (cited December 23, 2015). https://www.nice.org.uk/guidance/cg37.
14.
Subcommittee on Hyperbilirubinemia: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297-316.
15.
Screening of infants for hyperbilirubinemia to prevent chronic bilirubin encephalopathy: US Preventive Services Task Force recommendation statement. Pediatrics 2009;124:1172-1177.
16.
Bhutani VK; American Academy of Pediatrics Committee on Fetus and Newborn: Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2011;128:e1046-e1052.
17.
Whyte R: Safe discharge of the late preterm infant. Paediatr Child Health 2010;15:655-666.
18.
NANN Board of Directors: Prevention of acute bilirubin encephalopathy and kernicterus in newborns. Position Statement #3049. Adv Neonatal Care 2011;11(suppl):S3-S9.
19.
Queensland Health Statewide Maternity and Neonatal Clinical Guidelines Program: Neonatal jaundice clinical guideline supplement 2012 (cited December 23, 2015). https://www.health.qld.gov.au/qcg/documents/s_jaundice.pdf.
20.
Olusanya BO, Osibanjo FB, Mabogunje CA, Slusher TM, Olowe SA: The burden and management of neonatal jaundice in Nigeria: a scoping review of the literature. Niger J Clin Pract 2016;19:1-17.
21.
Bhutani VK: Editorial: building evidence to manage newborn jaundice worldwide. Indian J Pediatr 2012;79:253-255.
22.
Bhutani VK, Vilms RJ, Hamerman-Johnson L: Universal bilirubin screening for severe neonatal hyperbilirubinemia. J Perinatol 2010;30(suppl):S6-S15.
23.
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.
24.
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.
25.
Sgro M, Campbell D, Shah V: Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ 2006;175:587-590.
26.
Zoubir S, Mieth RA, Berrut S, Roth-Kleiner M; Swiss Paediatric Surveillance Unit: Incidence of severe hyperbilirubinaemia in Switzerland: a nationwide population-based prospective study. Arch Dis Child Fetal Neonatal Ed 2011;96:F310-F311.
27.
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.
28.
McGillivray A, Evans N: Severe neonatal jaundice: is it a rare event in Australia? J Paediatr Child Health 2012;48:801-807.
29.
Gotink MJ, Benders MJ, Lavrijsen SW, Rodrigues Pereira R, Hulzebos CV, Dijk PH: Severe neonatal hyperbilirubinemia in the Netherlands. Neonatology 2013;104:137-142.
30.
Bhutani VK, Johnson L: Kernicterus in the 21st century: frequently asked questions. J Perinatol 2009;29(suppl 1):S20-S24.
31.
Olusanya BO, Imam ZO, Emokpae AA, Iskander IF: Revisiting the criteria for exchange transfusion for severe neonatal hyperbilirubinemia in resource-limited settings. Neonatology 2016;109:97-104.
32.
Bhutani VK, Zipursky A, Blencowe H, Khanna R, Sgro M, Ebbesen F, et al: Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels. Pediatr Res 2013;74(suppl 1):86-100.
33.
Gamaleldin R, Iskander I, Seoud I, Aboraya H, Aravkin A, Sampson PD, et al: Risk factors for neurotoxicity in newborns with severe neonatal hyperbilirubinemia. Pediatrics 2011;128:e925-e931.
34.
Iskander I, Gamaleldin R, El Houchi S, El Shenawy A, Seoud I, El Gharbawi N, et al: Serum bilirubin and bilirubin/albumin ratio as predictors of bilirubin encephalopathy. Pediatrics 2014;134:e1330-e1339.
35.
Simiyu DE: Morbidity and mortality of neonates admitted in general paediatric wards at Kenyatta National Hospital. East Afr Med J 2003;80:611-616.
36.
Mwaniki MK, Gatakaa HW, Mturi FN, Chesaro CR, Chuma JM, Peshu NM, et al: An increase in the burden of neonatal admissions to a rural district hospital in Kenya over 19 years. BMC Public Health 2010;10:591.
37.
Ugwu RO, Eneh AU, Oruamabo RS: Blood transfusion therapy in neonates admitted into the Special Care Baby Unit (SCBU) of University of Port Harcourt Teaching Hospital, Port Harcourt. Niger J Med 2006;15:401-405.
38.
Ojukwu JU, Abonyi LE, Ugwu J, Orji IK: Neonatal septicemia in high risk babies in South-Eastern Nigeria. J Perinat Med 2006;34:166-172.
39.
Owa JA, Osinaike AI: Neonatal morbidity and mortality in Nigeria. Indian J Pediatr 1998;65:441-449.
40.
Okechukwu AA, Achonwa A: Morbidity and mortality patterns of admissions into the Special Care Baby Unit of University of Abuja Teaching Hospital, Gwagwalada, Nigeria. Niger J Clin Pract 2009;12:389-394.
41.
Udo JJ, Anah MU, Ochigbo SO, Etuk IS, Ekanem AD: Neonatal morbidity and mortality in Calabar, Nigeria: a hospital-based study. Niger J Clin Pract 2008;11:285-289.
42.
Etuk SJ, Etuk IS, Ekott MI, Udoma EJ: Perinatal outcome in pregnancies booked for antenatal care but delivered outside health facilities in Calabar, Nigeria. Acta Trop 2000;75:29-33.
43.
Omoigberale AI, Sadoh WE, Nwaneri DU: A 4-year review of neonatal outcome at the University of Benin Teaching Hospital, Benin City. Niger J Clin Pract 2010;13:321-325.
44.
Ezeaka VC, Iroha EO: Physical health status of pupils in a school for the mentally disabled in Lagos. Niger Postgrad Med J 2003;10:238-242.
45.
Owa JA, Adebami OJ, Fadero FF, Slusher TM: Irradiance readings of phototherapy equipment: Nigeria. Indian J Pediatr 2011;78:996-998.
46.
Eneh AU, Ugwu RO: Perception of neonatal jaundice among women attending children out-patient and immunization clinics of the UPTH Port Harcourt. Niger J Clin Pract 2009;12:187-191.
47.
Wei K-L, Yang Y-J, Yao Y-J, Du L-Z, Wang Q-H, Wang R-H, et al: Epidemiologic survey on hospitalized neonates in China. Transl Pediatr 2012;1:15-22.
48.
Rasul CH, Hasan MA, Yasmin F: Outcome of neonatal hyperbilirubinemia in a tertiary care hospital in Bangladesh. Malays J Med Sci 2010;17:40-44.
49.
Islam MN, Siddika M, Hossain MA, Bhuiyan MK, Ali MA: Morbidity pattern and mortality of neonates admitted in a tertiary level teaching hospital in Bangladesh. Mymensingh Med J 2010;19:159-162.
50.
Dutta D, Bhattacharya MK, Bhattacharya SK, Chaudhuri A, Lahiri M, Mitra U, et al: Influence of admission weight on neonatal mortality amongst hospitalised neonates in Calcutta. J Indian Med Assoc 1992;90:308-309.
51.
Bang AT, Bang RA, Baitule S, Deshmukh M, Reddy MH: Burden of morbidities and the unmet need for health care in rural neonates - a prospective observational study in Gadchiroli, India. Indian Pediatr 2001;38:952-965.
52.
Myanmar Department of Health: Annual hospital statistics 2010-2011, 2013 (cited December 23, 2015). http://www.moh.gov.mm/file/Annual%20Hospital%20Statistics%20Report%202010-2011.pdf.
53.
Arnolda G, Nwe HM, Trevisanuto D, Thin AA, Thein AA, Defechereux T, et al: Risk factors for acute bilirubin encephalopathy on admission to two Myanmar national paediatric hospitals. Matern Health Neonatol Perinatol 2015. DOI: 10.1186/s40748-015-0024-3.
54.
Selvaraju S: Preliminary report: a survey on severe neonatal jaundice cases admitted to selected hospitals in Malaysia. Proc Natl Perinat Health Conf, 1999, pp 70-79.
55.
Crowther C, Middleton P: Anti-D administration after childbirth for preventing Rhesus alloimmunisation. Cochrane Database Syst Rev 2000;CD000021.
56.
Malla T, Singh S, Poudyal P, Sathian B, Bk G, Malla KK: A prospective study on exchange transfusion in neonatal unconjugated hyperbilirubinemia - in a tertiary care hospital, Nepal. Kathmandu Univ Med J 2015;13:102-108.
57.
Louis D, More K, Oberoi S, Shah PS: Intravenous immunoglobulin in isoimmune haemolytic disease of newborn: an updated systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2014;99:F325-F331.
58.
Izetbegovic S: Occurrence of ABO and RhD incompatibility with Rh negative mothers. Mater Sociomed 2013;25:255-258.
59.
Bhutani VK, Wong RJ: Bilirubin neurotoxicity in preterm infants: risk and prevention. J Clin Neonatol 2013;2:61-69.
60.
Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bull World Health Organ 1989;67:601-611.
61.
Olusanya BO, Neumann KJ, Saunders JE: The global burden of disabling hearing impairment: a call to action. Bull World Health Organ 2014;92:367-373.
62.
Thaddeus S, Maine D: Too far to walk: maternal mortality in context. Soc Sci Med 1994;38:1091-1110.
63.
Johnson LH, Bhutani VK, Brown AK: System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr 2002;140:396-403.
64.
Kumar K, Sohaila A, Tikmani SS, Khan IA, Zafar A: Screening for G6PD deficiency among neonates with neonatal jaundice admitted to tertiary care center: a need in disguise. J Coll Physicians Surg Pak 2015;25:625-626.
65.
M Abo El Fotoh WM, Rizk MS: Prevalence of glucose -6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates. J Matern Fetal Neonatal Med 2016;3:1-4.
66.
Goyal M, Garg A, Goyal MB, Kumar S, Ramji S, Kapoor S: Newborn screening for G6PD deficiency: A 2-year data from North India. Indian J Public Health 2015;59:145-148.
67.
Boo NY, Gan CY, Gian YW, Lim KSL, Lim MW, Krishna-Kumar H: Malaysian mothers' knowledge and practices on care of neonatal jaundice. Med J Malaysia 2011;66:239-243.
68.
Ng SY, Chong SY: What do mothers know about neonatal jaundice? Knowledge, attitude and practice of mothers in Malaysia. Med J Malaysia 2014;69:252-256.
69.
Ogunlesi TA, Abdul AR: Maternal knowledge and care-seeking behaviors for newborn jaundice in Sagamu, southwest Nigeria. Niger J Clin Pract 2015;18:33-40.
70.
Slusher TM, Olusanya BO, Vreman HJ, Brearley AM, Vaucher YE, Lund TC, et al: A randomized trial of phototherapy with filtered sunlight in African neonates. N Engl J Med 2015;373:1115-1124.
71.
Poon WB, Ho WLC, Yeo CL: Survey on parenting practices among Chinese in Singapore. Singapore Med J 2007;48:1006-1011.
72.
Ogunfowora OB, Adefuye PO, Fetuga MB: What do expectant mothers know about neonatal jaundice? Int Electron J Health Educ 2006;9:134-140.
73.
Khalesi N, Rakhshani F: Knowledge, attitude and behaviour of mothers on neonatal jaundice. J Pak Med Assoc 2008;58:671-674.
74.
Amirshaghaghi A, Ghabili K, Shoja MM, Kooshavar H: Neonatal jaundice: knowledge and practice of Iranian mothers with icteric newborns. Pak J Biol Sci 2008;11:942-945.
75.
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;153:234-240.
76.
Rylance S, Yan J, Molyneux E: Can transcutaneous bilirubinometry safely guide phototherapy treatment of neonatal jaundice in Malawi? Paediatr Int Child Health 2014;34:101-107.
77.
National Neonatology Forum of India: Management of neonatal hyperbilirubinemia (cited January 3, 2016). http://www.nnfi.org.
78.
Coda Zabetta CD, Iskander IF, Greco C, Bellarosa C, Demarini S, Tiribelli C, et al: Bilistick: a low-cost point-of-care system to measure total plasma bilirubin. Neonatology 2013;103:177-181.
79.
Thairu L, Wirth M, Lunze K: Innovative newborn health technology for resource-limited environments. Trop Med Int Health 2013;18:117-128.
80.
Arnolda G, Thein AA, Trevisanuto D, Aung N, Nwe HM, Thin AA, et al: Evaluation of a simple intervention to reduce exchange transfusion rates among inborn and outborn neonates in Myanmar, comparing pre- and post-intervention rates. BMC Pediatr 2015;15:216.
81.
Ngerncham S, Jirapaet K, Suvonachai R, Chaweerat R, Wongsiridej P, Kolatat T: Effectiveness of conventional phototherapy versus Super light-emitting diodes phototherapy in neonatal hyperbilirubinemia. J Med Assoc Thai 2012;95:884-889.
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