Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Quantitative estimation of pre-exchange tissue bilirubin load in neonates who have undergone an exchange transfusion

Journal of Perinatology (2024)Cite this article

Subjects

The pathogenesis of kernicterus, although complex and multifactorial, is ultimately dependent on a central nervous system tissue bilirubin exposure capable of inducing neurotoxicity and resultant bilirubin encephalopathy [1]. The risk of bilirubin encephalopathy, in turn, is driven by the magnitude of the total body (i.e., intravascular plus extravascular) bilirubin load (TBBL) and the level of diffusible unbound bilirubin available to enter the central nervous system [2, 3]. As highlighted by Ahlfors “The greater the bilirubin load, the higher the total and unbound bilirubin levels, tissue bilirubin level, and likelihood of toxicity” [2].

However, a quantitative analysis of the relationship between the TBBL and its tissue bilirubin component to the risk of bilirubin encephalopathy is difficult to carry out in clinical practice. This is because although the total serum bilirubin (TSB), unbound bilirubin level, and the intravascular component (plasma volume x TSB) of TBBL can be measured, the extravascular tissue bilirubin fraction (Tissue B) of TBBL cannot. For infants who have undergone an exchange transfusion (ET), however, the pre-exchange Tissue B can be estimated. The mathematical equations to make this estimate were worked out decades ago in the independent exchange transfusion studies on neonates of Valaes [4], and Sproul and Smith [5]. Both studies detailed bilirubin clearance during ET in hyperbilirubinemic human neonates including bilirubin equilibration between intravascular and extravascular compartments [4, 5]. Sproul and Smith used tracer dilution techniques (Cr51-labeled red blood cells and I131-labeled human serum albumin) in their investigation [5]. However, the relatedness of their individual insights has been overlooked. We show that when combined their heretofore separate equations provide a method to quantitatively estimate the pre-exchange Tissue B and TBBL in neonates who have undergone an ET.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Watchko JF, Inder TE, Volpe JJ. Bilirubin and Brain Injury. In: Volpe JJ, Inder TE (ed). Volpe’s Neurology of the Newborn. 7th Edition. Elsevier: Philadelphia, 2024. p. 878–911.

  2. Ahlfors CE. Criteria for exchange transfusion in jaundiced newborns. Pediatrics. 1994;93:488–94.

    Article  CAS  PubMed  Google Scholar 

  3. Ahlfors CE. Predicting bilirubin neurotoxicity in jaundiced newborns. Curr Opin Pediatr. 2010;22:129–33.

    Article  PubMed  Google Scholar 

  4. Valaes T. Bilirubin distribution and dynamics of bilirubin removal by exchange transfusion. Acta Paediatr. 1963;52:1–117.

    Google Scholar 

  5. Sproul A, Smith L. Bilirubin equilibration during exchange transfusion in hemolytic disease of the newborn. J Pediatr. 1964;65:12–26.

    Article  CAS  PubMed  Google Scholar 

  6. Odell GB, Cohen SN, Gordes EH. Administration of albumin in the management of hyperbilirubinemia by exchange transfusions. Pediatrics. 1962;30:613.

    Article  CAS  PubMed  Google Scholar 

  7. Odell GB. Neonatal Hyperbilirubinemia. Grune & Stratton: New York, 1980. p. 90.

  8. Robinson PJ, Rapoport SI. Binding effect of albumin on uptake of bilirubin by brain. Pediatrics. 1987;79:553–8.

    Article  CAS  PubMed  Google Scholar 

  9. Watchko JF, Tiribelli C. Bilirubin-Induced neurological damage: mechanisms and management approaches. N Engl J Med. 2013;369:2021–30.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Professor Emeritus, Division of Newborn Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Jon F. Watchko

  2. Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, The Netherlands

    Christian V. Hulzebos

Authors
  1. Jon F. Watchko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian V. Hulzebos
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JFW conceived the methodological approach and drafted the initial manuscript. CVH critically reviewed the manuscript. JFW and CVH wrote, edited and approved the final version of the manuscript.

Corresponding author

Correspondence to Jon F. Watchko.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Watchko, J.F., Hulzebos, C.V. Quantitative estimation of pre-exchange tissue bilirubin load in neonates who have undergone an exchange transfusion. J Perinatol (2024). https://doi.org/10.1038/s41372-024-02004-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41372-024-02004-3

Search

Advanced search

Quick links