Neonatal Hyperbilirubinemia: Diagnosis and Management in the ED
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Neonatal Hyperbilirubinemia: Recommendations for Diagnosis and Management in the Emergency Department

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About This Issue

Hyperbilirubinemia is one the most common reasons for emergency department visits for neonates. Although rare, unrecognized or untreated pathologic unconjugated hyperbilirubinemia can lead to the development of acute bilirubin encephalopathy and, ultimately, kernicterus. This issue reviews the evaluation and management of neonatal hyperbilirubinemia, with an emphasis on utilization of bilirubin nomograms to guide treatment and disposition. You will learn:

The pathophysiology of neonatal hyperbilirubinemia

The most common types of nonpathologic hyperbilirubinemia (physiologic jaundice, breastfeeding jaundice, and breast milk jaundice) and how to differentiate them

Causes of neonatal unconjugated hyperbilirubinemia

Key aspects of the history and physical examination that can help narrow the differential diagnosis

How to use prediction tools such as the hour-specific nomogram, phototherapy nomogram, and exchange nomogram, along with hyperbilirubinemia risk factors and neurotoxicity risk factors, to risk-stratify patients and guide management

Limitations of bilirubin screening devices, and when a confirmatory TSB and conjugated bilirubin level are needed

Strategies for treatment of neonatal hyperbilirubinemia

Which patients need to be admitted and which can be discharged home with appropriate follow-up

Table of Contents
  1. About This Issue
  2. Abstract
  3. Case Presentations
  4. Introduction
  5. Critical Appraisal of the Literature
  6. Etiology and Pathophysiology
    1. Nonpathologic Hyperbilirubinemia
      1. Physiologic Jaundice
      2. Breastfeeding Jaundice
      3. Breast Milk Jaundice
    2. Pathologic Hyperbilirubinemia
  7. Hyperbilirubinemia Prediction Tools
  8. Differential Diagnosis
    1. Pathologic Unconjugated Hyperbilirubinemia
      1. Hemolysis
        • Immune-Mediated Hemolysis
        • Non–Immune-Mediated Hemolysis
      2. Decreased Excretion and/or Conjugation of Bilirubin
      3. Other Causes of Pathologic Unconjugated Hyperbilirubinemia
    2. Pathologic Conjugated Hyperbilirubinemia
  9. Prehospital Care
  10. Emergency Department Evaluation
    1. History
      1. Initial History
      2. Timing and Duration
      3. Risk Factors
        • Severe Hyperbilirubinemia Risk Factors
        • Neurotoxicity Risk Factors
    2. Physical Examination
  11. Diagnostic Studies
    1. Screening tests
      1. Noninvasive Screening Devices
        • Transcutaneous Bilirubinometer Nomograms
    2. Diagnosis
      1. Assessment of Total Serum Bilirubin
      2. Additional Laboratory Testing
      3. Diagnostic Testing for Acute Bilirubin Encephalopathy
      4. Assessment of Patients With Elevated Conjugated Bilirubin
  12. Treatment
    1. Implementation of a Standard Clinical Pathway and Treatment Guidelines
    2. Treatment Strategies
      1. Sunlight
      2. Phototherapy
      3. Exchange Transfusion
      4. Pharmacologic Treatments
  13. Special Considerations
    1. Conjugated Hyperbilirubinemia
  14. Controversies and Cutting Edge
    1. Side Effects of Phototherapy
    2. Intravenous Fluid Supplementation During Phototherapy
    3. Bilirubin Detection Devices
  15. Disposition
  16. Summary
  17. Time- and Cost-Effective Strategies
  18. Risk Management Pitfalls for Neonatal Hyperbilirubinemia in the Emergency Department
  19. Case Conclusions
  20. Clinical Pathway for Management of Neonatal Hyperbilirubinemia in the Emergency Department
  21. Tables, Figures and Appendix
    1. Table 1. Timing and Duration of Neonatal Nonpathologic Hyperbilirubinemia
    2. Table 2. Risk Factors Associated With the Development of Severe Hyperbilirubinemia and Bilirubin Neurotoxicity
    3. Table 3. Differential Diagnosis for Conjugated Hyperbilirubinemia
    4. Figure 1. The Pathophysiology of Neonatal Hyperbilirubinemia
    5. Figure 2. Causes of Neonatal Unconjugated Hyperbilirubinemia
    6. Figure 3. Hour-Specific Nomogram
    7. Figure 4. Phototherapy Nomogram
    8. Figure 5. Exchange Nomogram
    9. Appendix 1. Discharge Follow-up Recommendations Based on Risk Zone and Hyperbilirubinemia Risk Factors
  22. References

Abstract

Hyperbilirubinemia is one the most common reasons for emergency department visits for the neonate. Most cases of unconjugated hyperbilirubinemia are benign. Although rare, unrecognized or untreated pathologic unconjugated hyperbilirubinemia can lead to the development of acute bilirubin encephalopathy and, ultimately, kernicterus. This issue reviews the emergency department evaluation and management of neonatal hyperbilirubinemia and discusses how to recognize acute bilirubin encephalopathy, with the goal of preventing kernicterus. Recommendations are provided for risk stratification and determining the need for phototherapy or exchange transfusion, using nomograms to plot total serum bilirubin levels and taking into consideration hyperbilirubinemia and neurotoxicity risk factors.

Case Presentations

CASE 1
A 4-day-old boy born at 39 weeks’ gestation presents for evaluation of jaundice…
  • The jaundice was first noticed 2 days ago. The birth was unremarkable, with a birth weight of 2.4 kg. The baby has been exclusively breast-fed and has 2 wet diapers/day.
  • On examination, the patient has scleral icterus and generalized jaundice. His vital signs reveal a temperature of 37.2°C and a heart rate of 168 beats/min.
  • You consider the diagnosis of neonatal hyperbilirubinemia, but how do you differentiate nonpathologic from pathologic causes of hyperbilirubinemia? Based on the visual diagnosis of jaundice, should you start treatment immediately with phototherapy? What additional laboratory testing is needed to determine the need for treatment and the disposition for this neonate?
CASE 2
A 7-day-old boy is referred by his primary care physician for jaundice...
  • The mother states that the infant is exclusively formula-fed and is having up to 10 wet diapers/day.
  • On examination, the patient has generalized jaundice, and the liver edge is palpable approximately 4 cm below the costal margin. A transcutaneous bilirubin screen is 12.5 mg/dL.
  • What is the most likely diagnosis for this patient? Should you start phototherapy while awaiting laboratory testing results? What is the most appropriate disposition for this patient?
CASE 3
A 5-day-old girl presents with irritability...
  • The parents state that the girl was born full-term to a gravida 3, para 2 mother with blood type O negative. The patient was kept in the newborn nursery after birth for phototherapy and discharged after 2 days. The baby had been doing well, but now has been crying excessively and is difficult to console.
  • On examination, the baby is crying, with a high-pitched cry, with back-arching.
  • You suspect possible acute bilirubin encephalopathy. Should you start phototherapy while awaiting laboratory testing? What are the indications for exchange transfusion?

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Clinical Pathway for Management of Neonatal Hyperbilirubinemia in the Emergency Department

Clinical Pathway for Management of Neonatal Hyperbilirubinemia in the Emergency Department

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Tables, Figures and Appendix

Table 3. Differential Diagnosis for Conjugated Hyperbilirubinemia

Table 1. Timing and Duration of Neonatal Nonpathologic Hyperbilirubinemia
Table 2. Risk Factors Associated With the Development of Severe Hyperbilirubinemia and Bilirubin Neurotoxicity
Figure 1. The Pathophysiology of Neonatal Hyperbilirubinemia
Figure 2. Causes of Neonatal Unconjugated Hyperbilirubinemia

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Key References

Following are the most informative references cited in this paper, as determined by the authors.

17. * American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114(1):297-316. (Clinical practice guideline) DOI: 10.1542/peds.114.1.297

26. * Lauer BJ, Spector ND. Hyperbilirubinemia in the newborn. Pediatr Rev. 2011;32(8):341-349. (Review) DOI: 10.1542/pir.32-8-341

27. * Maisels MJ. Neonatal jaundice. Pediatr Rev. 2006;27(12):443-454. (Case reports) DOI: 10.1542/pir.27-12-443

54. * Maisels MJ, Bhutani VK, Bogen D, et al. Hyperbilirubinemia in the newborn infant > or =35 weeks’ gestation: an update with clarifications. Pediatrics. 20 09;124(4):1193-1198. (Commentary on clinical guideline) DOI: 10.1542/peds.2009-0329

91. * Bhutani VK, Committee on Fetus and Newborn American Academy of Pediatrics. Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2011;128(4):e1046-e1052. (Technical report) DOI: 10.1542/peds.2011-1494

Subscribe to get the full list of 123 references and see how the authors distilled all of the evidence into a concise, clinically relevant, practical resource.

Keywords: neonatal hyperbilirubinemia, neonatal jaundice, unconjugated hyperbilirubinemia, conjugated hyperbilirubinemia, acute bilirubin encephalopathy, ABE, bilirubin-induced neurologic dysfunction, BIND, kernicterus, nonpathologic hyperbilirubinemia, physiologic jaundice, breastfeeding jaundice, breast milk jaundice, pathologic hyperbilirubinemia, hour-specific nomogram, phototherapy nomogram, exchange nomogram, total serum bilirubin, TSB, transcutaneous bilirubinometers, TcB, hyperbilirubinemia risk factors, neurotoxicity risk factors, exchange transfusion, phototherapy

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Publication Information
Authors

Abdullah Khan, MD; Tommy Y. Kim, MD

Peer Reviewed By

Jennifer Bellis, MD, MPH; Mary Jane Piroutek, MD

Publication Date

January 2, 2022

CME Expiration Date

February 1, 2025

Pub Med ID: 34919365

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CME Information

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