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Clinical report from the pilot USA Kernicterus Registry (1992 to 2004)

Abstract

To identify antecedent clinical and health services events in infants (35 weeks gestational age (GA)) who were discharged as healthy from their place of birth and subsequently sustained kernicterus. We conducted a root-cause analysis of a convenience sample of 125 infants 35 weeks GA cared for in US healthcare facilities (including off-shore US military bases). These cases were voluntarily reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric sequelae. Multiple providers at multiple sites managed this cohort of infants for their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE, verbalized by parents, were often inadequately elicited or recorded and often not recognized as an emergency. Clinical signs of ABE were reported in 7 of 125 infants with a subsequent diagnosis of kernicterus who were not re-evaluated or treated for hyperbilirubinemia, although jaundice was noted at outpatient visits. The remaining infants (n=118) had total serum bilirubin (TSB) levels >20 mg per 100 ml (342 μmol l−1; range: 20.7 to 59.9 mg per 100 ml). No specific TSB threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus, 34.9% were LGA (large for gestational age) as compared with 24.7% of term infants (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of milk transfer and lactation support was suboptimal in most. Mortality was 4% (5 of 125) in infants readmitted at age 1 week. Along with a rapid rise of TSB (>0.2 mg per 100 ml per hour), contributing factors, alone or in combination, included undiagnosed hemolytic disease, excessive bilirubin production related to extra-vascular hemolysis and delayed bilirubin elimination (including increased enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase deficiency, infection and dehydration. Readmission was at age 5 days in 81 of 118 (69%) infants and <10 days in 101 of 118 (86%) infants. TSB levels were 35 mg per 100 ml (598 μmol l−1) in 46 (39%) infants, of whom one died before exchange transfusion, one was untreated and one was lost to follow-up. Timely and efficacious bilirubin reduction interventions defined by ‘crash-cart’ initiation of immediate intensive phototherapy and urgent exchange transfusion were accomplished in 11 of 43 infants, which were compared with 12 of 43 infants in whom a timely exchange sometimes could not be accomplished. No overt sequelae were found in 8 of 11 infants (73%) treated with a ‘crash-cart’ approach compared with none without sequelae when exchange was delayed by pre-admission delays, technical factors or need to transfer to a tertiary facility. None of the remaining 20 of 43 infants treated only with phototherapy escaped sequelae. Regardless of age at readmission and intervention, infants with peak measured TSB >35 mg per 100 ml had post-icteric sequelae (n=73). There was a narrow margin of safety between birthing hospital discharge or home birth and readmission to a tertiary neonatal/pediatric facility. Progression of hyperbilirubinemia to hazardous levels and onset of neurological signs were often not identified as infant's care and medical supervision transitioned during the first week after birth. The major underlying root cause for kernicterus was systems failure of services by multiple providers at multiple sites and inability to identify the at-risk infant and manage severe hyperbilirubinemia in a timely manner.

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References

  1. Van Praagh R . Diagnosis of kernicterus in the neonatal period. Pediatrics 1961; 28: 870–874.

    CAS  PubMed  Google Scholar 

  2. Jones MH, Sands R, Hyman CB, Sturgeon P, Koch FP . Longitudinal study of the incidence of central nervous system damage following erythroblastosis fetalis. Pediatrics 1954; 14: 346.

    CAS  PubMed  Google Scholar 

  3. Perlstein M . Neurologic sequelae of erythroblastosis fetalis. Am J Dis Child 1950; 79: 605–606.

    Google Scholar 

  4. Volpe JJ . Bilirubin and brain injury. In: Volpe JJ (ed). Neurology of the Newborn, 4th edn. 2001.

  5. Johnson L, Brown AK, Bhutani V . BIND—a clinical score for bilirubin induced neurologic dysfunction in newborns. Pediatrics 1999; 104: 746.

    Google Scholar 

  6. Bhutani VK, Johnson L, Keren R . Acute bilirubin encephalopathy… before it is too late. Contemporary Pediatr 2005; 54–74. http://www.modernmedicine.com/modernmedicine/Features/Treating-acute-bilirubin-encephalopathy--before-it/ArticleStandard/Article/detail/161379.

  7. Shapiro SM . Definition of the clinical spectrum of kernicterus and bilirubin-induced neurologic dysfunction (BIND). J Perinatol 2005; 25 (1): 54–59.

    Article  CAS  Google Scholar 

  8. Shapiro SM, Bhutani VK, Johnson L . Hyperbilirubinemia and kernicterus. Clin Perinatol 2006; 33 (2): 387–410.

    Article  Google Scholar 

  9. Odell GB, Storey GNB, Rosenberg LA . Studies in kernicterus. III. The saturation of serum proteins with bilirubin during neonatal life and its relationship to brain damage at five years. J Pediatr 1970; 76: 12–21.

    Article  CAS  Google Scholar 

  10. Johnson L, Boggs Jr TR . Bilirubin-dependent brain damage: incidence and indication for treatment. In: Odell GB, Schaffer R, Simopoulous AP (eds). Phototherapy in the Newborn: An Overview. National Academy of Sciences: Washington, DC, 1974, pp 122–149.

    Google Scholar 

  11. Diamond I . Kernicterus: revised concepts of pathogenesis and management. Pediatrics 1966; 38: 539–542.

    CAS  PubMed  Google Scholar 

  12. Zuelzer WW, Mudgett RT . Kernicterus; etiologic study based on an analysis of 55 cases. Pediatrics 1950; 6 (1:3): 452–474.

    CAS  PubMed  Google Scholar 

  13. American Academy of Pediatrics, Provisional Committee for Quality Improvement. Practice parameter: management of hyperbilirubinemia in the healthy term newborn. Pediatrics 1994; 94: 558–565.

    Google Scholar 

  14. Palmer RH, Ezhuthachan S, Newman C, Maisels MJ, Testa MA . Management of hyperbilirubinemia in newborns: measuring performance using a benchmarking model. Pediatrics 2004; 114 (3): 902.

    PubMed  Google Scholar 

  15. Johnson LH, Bhutani VK . Guidelines for management of the jaundiced term and near-term infant. Clin Perinatol 1998; 25: 555–574.

    Article  CAS  Google Scholar 

  16. Johnson L, Brown AK, Bhutani VK . System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr 2002; 93: 488–494.

    Google Scholar 

  17. American Academy of Pediatrics Clinical Practice Guideline: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114: 297–316.

  18. Hansen TW . Acute management of extreme neonatal jaundice—the potential benefits of intensified phototherapy and interruption of enterohepatic bilirubin circulation. Acta Paediatr 1997; 86 (8): 843–846.

    Article  CAS  Google Scholar 

  19. Ip S, Chung M, Kulig J, O’Brien R, Sege R, Glicken S, et al., Subcommittee on Hyperbilirubinemia. An evidence-based review of important issues concerning neonatal hyperbilirubinemia. Pediatrics 2004; 114: e130–e153.

    Article  Google Scholar 

  20. Raju TN, Higgins RD, Stark AR, Leveno KJ . Optimizing care and outcome for late-preterm (near-term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics 2006; 118 (3): 1207–1214.

    Article  Google Scholar 

  21. Palmer RH, Keren R, Maisels MJ, Yeargin-Allsopp M . National Institute of Child Health and Human Development (NICHD) conference on kernicterus: a population perspective on prevention of kernicterus. J Perinatol 2004; 24 (11): 723–725.

    Article  Google Scholar 

  22. Stevenson DK, Wong RJ, Vreman HJ, McDonagh AF, Maisels MJ, Lightner DA . NICHD Conference on Kernicterus: research on prevention of bilirubin-induced brain injury and kernicterus: bench-to-bedside—diagnostic methods and prevention and treatment strategies. J Perinatol 2004; 24: 521–525.

    Article  Google Scholar 

  23. Sheridan SE . Parents of infants and children with kernicterus. J Perinatol 2005; 25 (4): 227–228.

    Article  Google Scholar 

  24. Bhutani VK, Johnson LH, Maisels MJ, 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 

  25. Bhutani VK, Johnson L, Sivieri EM . Predictive ability of a pre-discharge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999; 103 (1): 6–14.

    Article  CAS  Google Scholar 

  26. Stevenson DK, Fanaroff AA, Maisels MJ, Young BW, Wong RJ, Vreman HJ et al. Prediction of hyperbilirubinemia in term and near-term newborn infants. Pediatrics 2001; 108: 31–39.

    Article  CAS  Google Scholar 

  27. 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; 51 (4): 843–861.

    Article  Google Scholar 

  28. Institute of Medicine. To err is human: building a safer health system. 1 November 1999. http://www.iom.edu/?id=12735.

  29. Joint Commission Accrediting Hospital Organizations (JCAHO). Revised guidance to help prevent kernicterus. Sentinel Event Alert 2004; 31 (31): 1–2.

    Google Scholar 

  30. Bhutani VK, Johnson L . Kernicterus in late preterm infants cared for as term healthy infants. Semin Perinatol 2006; 30 (2): 89–97.

    Article  Google Scholar 

  31. Ebbesen F, Nyboe J . Postnatal changes in the ability of plasma albumin to bind bilirubin. Acta Paediatr Scand 1983; 72: 665–670.

    Article  CAS  Google Scholar 

  32. Ebbesen F . Recurrence of kernicterus in term and near-term infants in Denmark. Acta Paediatr 2000; 89: 1213–1217.

    Article  CAS  Google Scholar 

  33. 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 

  34. Manning DJ, Maxwell MJ, Todd PJ, Platt MJ . Prospective surveillance study of severe hyperbilirubinaemia in the newborn in the United Kingdom and Ireland. Arch Dis Child. Fetal Neonatal Ed. Online publication. 0.1136/adc.2006.105361. http://fn.bmj.com/cgi/rapidpdf/adc.2006.105361v1.

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

    Article  Google Scholar 

  36. Facchini FP, Mezzacappa MA, Rosa IR, Mezzacappa Filho F, Aranha-Netto A, Marba ST . Follow-up of neonatal jaundice in term and late premature newborns. J Pediatr (Rio J) 2007; 83 (4): 313–322.

    Google Scholar 

  37. 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 (4): 412–417.

    Article  CAS  Google Scholar 

  38. Bhutani VK, Johnson LH, Schwoebel A, Gennaro S . A systems approach for neonatal hyperbilirubinemia in term and near-term newborns. J Obstet Gynecol Neonatal Nurs 2006; 35 (4): 444–455.

    Article  Google Scholar 

  39. 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; 117: e855–e862.

    Article  Google Scholar 

  40. Bhutani VK, Donn SM, Johnson LH . Risk management of severe neonatal hyperbilirubinemia: to prevent kernicterus. Clin Perinatol 2005; 32 (1): 125–139.

    Article  Google Scholar 

  41. Susan E . Sheridan, consumer, Testimony to the National Summit on Medical Errors and Patient Safety Research, Washington, DC, 11 September 2000, www.quic.gov/summit/wsheridan.htm (accessed 21 March 2003).

  42. Newman TB, Liljestrand P, Escobar GJ . Infants with bilirubin levels of 30 mg/dl or more in a large managed care organization. Pediatrics 2003; 111 (6 Pt 1): 1303–1311.

    Article  Google Scholar 

  43. Lucey JE . Kernicterus: revised concepts of pathogenesis and management. Commentary. Pediatrics 1966; 38: 545–546.

    Google Scholar 

  44. 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 

  45. Lannon C, Stark AR . Closing the gap between guidelines and practice: ensuring safe and healthy beginnings. Pediatrics 2004; 114: 494–496.

    Article  Google Scholar 

  46. Center for Disease Control and Prevention. http://www.cdc.gov/ncbddd/dd/kernichome.htm.

  47. Association of Women's Health, Obstetrics and Neonatal Nurses. http://www.awhonn.org/awhonn/product.detail.do?productCode=HNPP-CD-2NDI.

  48. Smitherman H, Stark AR, Bhutani VK . Early recognition of neonatal hyperbilirubinemia and its emergent management. Semin Fetal Neonatal Med 2006; 11: 214–224.

    Article  Google Scholar 

  49. California Perinatal Quality Care Collaborative. http://www.cpqcc.org/quality_improvement.htm.

  50. Keren R, Luan X, Friedman S, Saddlemire S, Cnaan A, Bhutani VK . A comparison of alternative risk-assessment strategies for predicting significant neonatal hyperbilirubinemia in term and near-term infants. Pediatrics 2008; 121 (1): e170–e179.

    Article  Google Scholar 

  51. Lazarus C, Avchen RN . Neonatal hyperbilirubinemia management: a model for change. J Perinatol 2009; 29 (Suppl 1): S58–S60.

    Article  Google Scholar 

  52. Stark AR, Lannon CM . Systems changes to prevent severe hyperbilirubinemia and promote breastfeeding: pilot approaches. J Perinatol 2009; 29 (Suppl 1): S53–S57.

    Article  Google Scholar 

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Acknowledgements

This work was supported in part by AAMC/CDC PERT Grant MM-0448. This research was also supported in part by funds from the Sandy Eglin Fund and her generous support of the Pilot USA Kernicterus Registry at Pennsylvania Hospital, Philadelphia. We remember the late Audrey K Brown, MD, and value her immeasurable contributions to the initiation and maintenance of the Pilot USA Kernicterus Registry. We thank the parents logged on the newborn jaundice list-serve as well as our colleagues who contributed their experiences to the Registry. We also appreciate the administrative support of Donna Spitz (Philadelphia) and Stella Dina-Gengania (Stanford).

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Correspondence to V K Bhutani.

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The authors have declared no financial interests.

Appendix 1

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Table 10 Table a1

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Johnson, L., Bhutani, V., Karp, K. et al. Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). J Perinatol 29 (Suppl 1), S25–S45 (2009). https://doi.org/10.1038/jp.2008.211

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Keywords

  • newborn jaundice
  • kernicterus
  • bilirubin
  • hyperbilirubinemia
  • well babies
  • bilirubin-induced neurological dysfunction

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