Hiperbilirrubinemia neonatal, encefalopatía bilirrubínica aguda y Kernicterus: La secuencia sigue vigente en el siglo XXI
Palabras clave:
Hiperbilirrubinemia neonatal; encefalopatía bilirrubínica; Kernicterus; ictericia.Resumen
Aunque la ictericia afecta a más de la mitad de los neonatos en la primera semana de vida, sólo un grupo de ellos pueden desarrollar hiperbilirrubinemia severa y estar en riesgo de desarrollar encefalopatía bilirrubínica. La afectación neurológica puede presentarse con un cuadro agudo (la encefalopatía bilirrubínica aguda), la cual puede o no progresar a una forma crónica (Kernicterus), o con una constelación de síntomas sensoriales, motores y cognitivos, subagudos o crónicos, dependiendo de la presencia de factores de riesgo que aumentan la susceptibilidad al daño neurológico. La bilirrubina libre interactúa con citoquinas inflamatorias y es la responsable del daño neuronal y de las células de la glía en el sistema nervioso central. A pesar de las diferentes medidas de prevención de hiperbilirrubinemia severa, se siguen reportando casos de Kernicterus sobre todo en países en vías de desarrollo, en algunos de los cuales constituyen un problema de salud pública.
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2. Bhutani VK, Johnson LH, Keren R. Diagnosis and management of hyperbilirubinemia in the term neonate: for a safe first week. Pediatr Clin North Am. 2004;51:843- 61.
3. Watchko JF. Kernicterus and the molecular mechanism of bilirubin induced CNS injury in newborns .Neuromolecular Med. 2006;8:513-29.
4. Mancuso C. Bilirubin and brain: a pharmacological approach. Neuro Pharm. 2017;118:113-123.
5. Docood MJ, McDonagh AF, Watchko JF. Calculates free bilirubin levels and neurotoxicity. J Perinatol. 2009;29 Suppl:S14-S19.
6. Robertson A, Brodersen R. Effect of drug combination on bilirubin –albumin binding. Dev Pharmacol Ther. 1991;17:95-99.
7. Watchko JF, Tiribelli C. Bilirubin –induced neurologic damage-Mechanism and management approaches. N Engl J Med. 2013;369(21):2021-30.
8. Brites D. The evolving landscape of neurotoxicity by uncongugates bilirubin :role of glial cells and inflamation. Front Pharmacol. 2012;29:88.
9. Falcao AS, Silva RF, Vaz AR, Silva SL, Fernandes A, Brites D. Cross – talk between neurons and astrocytes in response to bilirubin: early beneficial effects. Neurochem Res. 2013:38:644-59.
10. Falcao AS, Silva RF, Vaz AR, Gomes C, Fernandes A, Barateiro A, et al. Cross – talk between neurons and astrocytes in response to bilirubin : adverse secundary impacts. Neurotox Res. 2014:26:1-5.
11. From the Centers for Diseases Control and Prevention. Kernicterus in full-term infants—United States, 1994-1998. JAMA. 2001;286:299-300.
12. Johnson L, Bhutyani VK. Guidelines for management of the jaundice in term and near term infants. Clin Perinatol. 1998;25:555-74.
13. Brooks JC, Fisher–Owens SA, Wu YW, Strauss DJ, Newman TB. Evidence suggest there was not a resurgence of Kernicterus in the 1990s. Pediatrics. 2011;127:672-79.
14. American Academy of Pediatrics. Provisional committee for quality improvement and subcommittee on hyperbilirubinemia practice parameter: management of hyperbilirubinemia in the healthy term newborn. Pediatrics. 1994;94:558-65.
15. American Academy of Pediatrics. Subcomittee on hyperbilirubinemia in the newborn infants 35 p more weeks of gestation. Pediatrics. 2004;114:297-16.
16. Bhutani VK, Johnson LH, Maisels MJ, Newman TB, Phibbs C, Stark AR, et al. Kernicterus: epidemiological strategies for the prevention through systems-based approaches. J Perinatol. 2004;24;650-62.
17. Ezechukwu CC, Ugochukwu EF, Egbuonu I, Chkwaka JO. Risk factors from neonatal mortality in regional tertiary hospital in Nigeria. Niger J Clin Pract. 2004;7:50-52.
18. Olusanya BO, Ogunlesi TA, Slusher TM. Why is Kernicterus still a mayor cause of death and disability in low – income and middle-income countries. Arch Dis Child. 2014;99:1117-21.
19. Lopez M, Mesquita M, Casartelli M, Bordon L. Kernicterus; encefalopatía crónica secundaria a hiperbilirrubinemia severa: presentación de una serie de casos con seguimiento neurológico. Pediatr (Asunción). 2014;41(Supl):84.
20. Wolff M, Aronson S. Chinase D, Lavelle D, Boorstein D, Zorc JJ. Management of neonates with hyperbilirubinemia improving timeliness of care using a clinical pathway. Pediatrics. 2012;130:e1688-e1694.
21. Romagnoli CB, Arone G, Pratesi S, Raimondi F, Capasso L, Zecca E, et al. Italian guidelines for management and treatment of hyperbilirubinemia of newborn infants => 34 gestational ages. Ital J Pediar. 2014;40:11.
22. Bratlid D, Nakstad B, Hansen TWR. National guidelines for treatment of jaundice in the newborn. Acta Paediatrica. 2011:100:499-505.
23. 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 newborn. Pediatrics. 1999;103:493-95.
24. Fay DL, Schellhase KG, Suresh GK. Bilirubin screening for normal newborn: a critique of the hour specific bilirubin nomogram. Pediatrics. 2009;124:1203-1206.
25. US Preventive Services Task Force. Prevent chronic bilirubin encephalopathy. Pediatrics. 2009;124;1172-1177.
26. Macedo de Lima G, Campos Porto MAS, Alves da Cunha AL. Medical education required for Kernicterus risk recognition. Iran J Pediatr. 2012;22:163-170.
27. Johnson L, Bhutani VK, Karp K, Siviere EM, Shapiro SM. Clinical report from the pilot USA Kernicterus Registry (1992 – 2004). J Perinatol. 2009;29:S25- 45.
28. Bhutani VK, Jhonson L. Sinopsis report from the pilot USA Kernicterus Registry. J Perinatol. 2009;29:S4-7.
29. Bhutani VK, Maisels MJ, Stark AR, Buonocore G. Management of jaundice and prevention of severe neonatal hyperbilirubinemia in infants ≥ 35 weeks gestations. Neonatology. 2008;94:63 -67.
30. Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemiain Canada. CMAJ. 2006;175:587- 90.
31. Ebbesen F, Andreson C, Verder H, Grytter C, Pedersen–Bjergaard L, et al. Extreme hyperbilirubinemia in term and near term infants in Denmark. Acta Paediatr. 2005;94:59-64.
32. Vandborg PK, Hansen BM, Greisen G, Jepsen M, Ebbesen F. Follow-up of neonates with total serum bilirubin level≥25 mg/dl: a danish population –based study. Pediatrics. 2012;130:61-66.
33. Hansen TWR. Prevention of neurodevelopmental sequelae of jaundice in the newborn. Dev Med Child Neurol. 2011;53(Suppl.4):24-28.
34. Mezzacappa MA, Fracchi FP, Pinto AC, Cassone AEL, Souza DS, Bezerra MAC, et al. Clinical and genetic risk factors for moderate hyperbilirubinemia in Brazilian newborn infants. J Perinatol. 2010;30:819-826.
35. Besa S, Calvo CI, Harris PR. Evolucion prolongada en síndrome de Crigler –Najar tipo I. Rev Med Chile. 2014;142:109-113.
36. Shapiro SM. Chronic bilirubin encephalopathy: diagnosis and outcome. Sem Fetal Neonatal Med. 2010;15:157-163.
37. Shapiro SM, Popelka GR. Auditory impairment in infants at risk for bilirubin –induced neurologic dysfunction. Sem Perinatol. 2011;35:162-170.
38. Bhutani VK, Johnson L. Kernicterus en the 21st century: frequently asked questions. J Perinatol. 2009;29:S20-S24.
39. Nuñez –Batalla F, Carro-Fernandez P, Antuña-Leon ME, Gonzalez- Trellez T. Incidence of hipoacusia secundary ti hyperbilirubinaemia in a universal neonatal auditory screening programme base don otoacusticemission and evoked auditory potentials. Acta Otorrinolaringol Esp. 2008;59:108-13.
40. Radmacher PG, Groves FD, Owa JA, Otovwe GE, Amuabunos EA, Olusanya BO, et al. A modified bilirubin-induced neurologic dysfunction (BIND-M) algorithmis useful in evaluating severity of jaundice in resource limited setting. BMC Pediatrics. 2015;15:28.
41. Hansen TWR, Niestsch L, Norman E. Apparent reversibility of acute intermédiate phase bilirubin encephalopathy. Acta Pediatr. 2009;98:1689-94.
42. Saluja S, Agaru A, Kler N, Amin S. Auditory neuropaty spectrum disorder in late preterm and term infants with severe jaudice. Int J Otorhinolaryngol. 2010;74:1292-1297.
43. Manchanda S, Prasad A, Baruah BP. MRI findings in Kernicterus. Ind J Pediatr. 2013;80:181- 82.
44. Yilmaz Y, Ekinci G. Thalamic involvement in a patient with kernicterus. Eur Radiol. 2002;12:1837 -39.
45. Parashari UC, Singh R, Yadav R, Aga P. Changes in the globus pallidus in chronic kernicterus. J Pediatr Neurosci. 2009;4:117- 119.
46. Lawn JE, Blencowe H, Oza S, You D, Lee C, Waiswa P, et al. Every newborn: progress, priorities and potential beyond survival. Lancet. 2014;384:189- 205.
47. Olusanya BO, Osiban JO, Slusher TM. Risk factors for severe neonatal hyoperbilirubinemia in low and middle income countries: a systematic review and Meta – analysis. PLoS One. 2015;10:e 0117229.
48. Bhutani VK, Zipursky A, Blencowe H, Khanna R, Sgro M. Neonatal hyperbilirubinemia and rhesus diseases of the newborn: incidencia and impairment estimates for 2010 regional and global levels. Pediatr Res. 2013;74(Suppl 1):80-100.
49. Benitez Leite S, Mesquita M, Macchi ML. Manejo de la hiperbilirrubinemia neonatal por pediatras que realizan atención inmediata del recién nacido. Pediatr (Asunción). 2005;32:23-33.
50. Dominguez Ch, Godoy L, Mesquita M. Niveles de bilirrubina en neonatos que consultan en el departamento de urgencias de un hospital pediátrico. Pediatr (Asunción). 2016;43(Suppl):97.
2. Bhutani VK, Johnson LH, Keren R. Diagnosis and management of hyperbilirubinemia in the term neonate: for a safe first week. Pediatr Clin North Am. 2004;51:843- 61.
3. Watchko JF. Kernicterus and the molecular mechanism of bilirubin induced CNS injury in newborns .Neuromolecular Med. 2006;8:513-29.
4. Mancuso C. Bilirubin and brain: a pharmacological approach. Neuro Pharm. 2017;118:113-123.
5. Docood MJ, McDonagh AF, Watchko JF. Calculates free bilirubin levels and neurotoxicity. J Perinatol. 2009;29 Suppl:S14-S19.
6. Robertson A, Brodersen R. Effect of drug combination on bilirubin –albumin binding. Dev Pharmacol Ther. 1991;17:95-99.
7. Watchko JF, Tiribelli C. Bilirubin –induced neurologic damage-Mechanism and management approaches. N Engl J Med. 2013;369(21):2021-30.
8. Brites D. The evolving landscape of neurotoxicity by uncongugates bilirubin :role of glial cells and inflamation. Front Pharmacol. 2012;29:88.
9. Falcao AS, Silva RF, Vaz AR, Silva SL, Fernandes A, Brites D. Cross – talk between neurons and astrocytes in response to bilirubin: early beneficial effects. Neurochem Res. 2013:38:644-59.
10. Falcao AS, Silva RF, Vaz AR, Gomes C, Fernandes A, Barateiro A, et al. Cross – talk between neurons and astrocytes in response to bilirubin : adverse secundary impacts. Neurotox Res. 2014:26:1-5.
11. From the Centers for Diseases Control and Prevention. Kernicterus in full-term infants—United States, 1994-1998. JAMA. 2001;286:299-300.
12. Johnson L, Bhutyani VK. Guidelines for management of the jaundice in term and near term infants. Clin Perinatol. 1998;25:555-74.
13. Brooks JC, Fisher–Owens SA, Wu YW, Strauss DJ, Newman TB. Evidence suggest there was not a resurgence of Kernicterus in the 1990s. Pediatrics. 2011;127:672-79.
14. American Academy of Pediatrics. Provisional committee for quality improvement and subcommittee on hyperbilirubinemia practice parameter: management of hyperbilirubinemia in the healthy term newborn. Pediatrics. 1994;94:558-65.
15. American Academy of Pediatrics. Subcomittee on hyperbilirubinemia in the newborn infants 35 p more weeks of gestation. Pediatrics. 2004;114:297-16.
16. Bhutani VK, Johnson LH, Maisels MJ, Newman TB, Phibbs C, Stark AR, et al. Kernicterus: epidemiological strategies for the prevention through systems-based approaches. J Perinatol. 2004;24;650-62.
17. Ezechukwu CC, Ugochukwu EF, Egbuonu I, Chkwaka JO. Risk factors from neonatal mortality in regional tertiary hospital in Nigeria. Niger J Clin Pract. 2004;7:50-52.
18. Olusanya BO, Ogunlesi TA, Slusher TM. Why is Kernicterus still a mayor cause of death and disability in low – income and middle-income countries. Arch Dis Child. 2014;99:1117-21.
19. Lopez M, Mesquita M, Casartelli M, Bordon L. Kernicterus; encefalopatía crónica secundaria a hiperbilirrubinemia severa: presentación de una serie de casos con seguimiento neurológico. Pediatr (Asunción). 2014;41(Supl):84.
20. Wolff M, Aronson S. Chinase D, Lavelle D, Boorstein D, Zorc JJ. Management of neonates with hyperbilirubinemia improving timeliness of care using a clinical pathway. Pediatrics. 2012;130:e1688-e1694.
21. Romagnoli CB, Arone G, Pratesi S, Raimondi F, Capasso L, Zecca E, et al. Italian guidelines for management and treatment of hyperbilirubinemia of newborn infants => 34 gestational ages. Ital J Pediar. 2014;40:11.
22. Bratlid D, Nakstad B, Hansen TWR. National guidelines for treatment of jaundice in the newborn. Acta Paediatrica. 2011:100:499-505.
23. 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 newborn. Pediatrics. 1999;103:493-95.
24. Fay DL, Schellhase KG, Suresh GK. Bilirubin screening for normal newborn: a critique of the hour specific bilirubin nomogram. Pediatrics. 2009;124:1203-1206.
25. US Preventive Services Task Force. Prevent chronic bilirubin encephalopathy. Pediatrics. 2009;124;1172-1177.
26. Macedo de Lima G, Campos Porto MAS, Alves da Cunha AL. Medical education required for Kernicterus risk recognition. Iran J Pediatr. 2012;22:163-170.
27. Johnson L, Bhutani VK, Karp K, Siviere EM, Shapiro SM. Clinical report from the pilot USA Kernicterus Registry (1992 – 2004). J Perinatol. 2009;29:S25- 45.
28. Bhutani VK, Jhonson L. Sinopsis report from the pilot USA Kernicterus Registry. J Perinatol. 2009;29:S4-7.
29. Bhutani VK, Maisels MJ, Stark AR, Buonocore G. Management of jaundice and prevention of severe neonatal hyperbilirubinemia in infants ≥ 35 weeks gestations. Neonatology. 2008;94:63 -67.
30. Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemiain Canada. CMAJ. 2006;175:587- 90.
31. Ebbesen F, Andreson C, Verder H, Grytter C, Pedersen–Bjergaard L, et al. Extreme hyperbilirubinemia in term and near term infants in Denmark. Acta Paediatr. 2005;94:59-64.
32. Vandborg PK, Hansen BM, Greisen G, Jepsen M, Ebbesen F. Follow-up of neonates with total serum bilirubin level≥25 mg/dl: a danish population –based study. Pediatrics. 2012;130:61-66.
33. Hansen TWR. Prevention of neurodevelopmental sequelae of jaundice in the newborn. Dev Med Child Neurol. 2011;53(Suppl.4):24-28.
34. Mezzacappa MA, Fracchi FP, Pinto AC, Cassone AEL, Souza DS, Bezerra MAC, et al. Clinical and genetic risk factors for moderate hyperbilirubinemia in Brazilian newborn infants. J Perinatol. 2010;30:819-826.
35. Besa S, Calvo CI, Harris PR. Evolucion prolongada en síndrome de Crigler –Najar tipo I. Rev Med Chile. 2014;142:109-113.
36. Shapiro SM. Chronic bilirubin encephalopathy: diagnosis and outcome. Sem Fetal Neonatal Med. 2010;15:157-163.
37. Shapiro SM, Popelka GR. Auditory impairment in infants at risk for bilirubin –induced neurologic dysfunction. Sem Perinatol. 2011;35:162-170.
38. Bhutani VK, Johnson L. Kernicterus en the 21st century: frequently asked questions. J Perinatol. 2009;29:S20-S24.
39. Nuñez –Batalla F, Carro-Fernandez P, Antuña-Leon ME, Gonzalez- Trellez T. Incidence of hipoacusia secundary ti hyperbilirubinaemia in a universal neonatal auditory screening programme base don otoacusticemission and evoked auditory potentials. Acta Otorrinolaringol Esp. 2008;59:108-13.
40. Radmacher PG, Groves FD, Owa JA, Otovwe GE, Amuabunos EA, Olusanya BO, et al. A modified bilirubin-induced neurologic dysfunction (BIND-M) algorithmis useful in evaluating severity of jaundice in resource limited setting. BMC Pediatrics. 2015;15:28.
41. Hansen TWR, Niestsch L, Norman E. Apparent reversibility of acute intermédiate phase bilirubin encephalopathy. Acta Pediatr. 2009;98:1689-94.
42. Saluja S, Agaru A, Kler N, Amin S. Auditory neuropaty spectrum disorder in late preterm and term infants with severe jaudice. Int J Otorhinolaryngol. 2010;74:1292-1297.
43. Manchanda S, Prasad A, Baruah BP. MRI findings in Kernicterus. Ind J Pediatr. 2013;80:181- 82.
44. Yilmaz Y, Ekinci G. Thalamic involvement in a patient with kernicterus. Eur Radiol. 2002;12:1837 -39.
45. Parashari UC, Singh R, Yadav R, Aga P. Changes in the globus pallidus in chronic kernicterus. J Pediatr Neurosci. 2009;4:117- 119.
46. Lawn JE, Blencowe H, Oza S, You D, Lee C, Waiswa P, et al. Every newborn: progress, priorities and potential beyond survival. Lancet. 2014;384:189- 205.
47. Olusanya BO, Osiban JO, Slusher TM. Risk factors for severe neonatal hyoperbilirubinemia in low and middle income countries: a systematic review and Meta – analysis. PLoS One. 2015;10:e 0117229.
48. Bhutani VK, Zipursky A, Blencowe H, Khanna R, Sgro M. Neonatal hyperbilirubinemia and rhesus diseases of the newborn: incidencia and impairment estimates for 2010 regional and global levels. Pediatr Res. 2013;74(Suppl 1):80-100.
49. Benitez Leite S, Mesquita M, Macchi ML. Manejo de la hiperbilirrubinemia neonatal por pediatras que realizan atención inmediata del recién nacido. Pediatr (Asunción). 2005;32:23-33.
50. Dominguez Ch, Godoy L, Mesquita M. Niveles de bilirrubina en neonatos que consultan en el departamento de urgencias de un hospital pediátrico. Pediatr (Asunción). 2016;43(Suppl):97.
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2017-11-09
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Mesquita, M., & Casartelli, M. (2017). Hiperbilirrubinemia neonatal, encefalopatía bilirrubínica aguda y Kernicterus: La secuencia sigue vigente en el siglo XXI. Pediatría (Asunción), 44(2), 153-158. Recuperado a partir de https://revistaspp.org/index.php/pediatria/article/view/164
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