Published online February 1, 2006
PEDIATRICS Vol. 117 No. 2 February 2006, pp. 474-485 (doi:10.1542/peds.2005-0395)
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (21)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wennberg, R. P.
Right arrow Articles by Shapiro, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wennberg, R. P.
Right arrow Articles by Shapiro, S. M.
Related Collections
Right arrow Premature & Newborn

REVIEW ARTICLE

Toward Understanding Kernicterus: A Challenge to Improve the Management of Jaundiced Newborns

Richard P. Wennberg, MDa, Charles E. Ahlfors, MDb, Vinod K. Bhutani, MDc, Lois H. Johnson, MDd and Steven M. Shapiro, MDe

a Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, Washington
b LW Ligand, LLC, Vashon, Washington
c Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California
d Section on Newborn Pediatrics, Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania
e Department of Neurology, Medical College of Virginia, Richmond, Virginia

PURPOSE. We sought to evaluate the sensitivity and specificity of total serum bilirubin concentration (TSB) and free (unbound) bilirubin concentration (Bf) as predictors of risk for bilirubin toxicity and kernicterus and to examine consistency between these findings and proposed mechanisms of bilirubin transport and brain uptake.

METHODS. A review of literature was undertaken to define basic principles of bilirubin transport and brain uptake leading to neurotoxicity. We then reviewed experimental and clinical evidence that relate TSB or Bf to risk for bilirubin toxicity and kernicterus.

RESULTS. There are insufficient published data to precisely define sensitivity and specificity of either TSB or Bf in determining risk for acute bilirubin neurotoxicity or chronic sequelae (kernicterus). However, available laboratory and clinical evidence indicate that Bf is better than TSB in discriminating risk for bilirubin toxicity in patients with severe hyperbilirubinemia. These findings are consistent with basic pharmacokinetic principles involved in bilirubin transport and tissue uptake.

CONCLUSIONS. Experimental and clinical data strongly suggest that measurement of Bf in newborns with hyperbilirubinemia will improve risk assessment for neurotoxicity, which emphasizes the need for additional clinical evaluation relating Bf and TSB to acute bilirubin toxicity and long-term outcome. We speculate that establishing risk thresholds for neurotoxicity by using newer methods for measuring Bf in minimally diluted serum samples will improve the sensitivity and specificity of serum indicators for treating hyperbilirubinemia, thus reducing unnecessary aggressive intervention and associated cost and morbidity.


Key Words: bilirubin–albumin binding • brainstem auditory evoked potentials • bilirubin • hyperbilirubinemia • kernicterus

Abbreviations: TSB—total serum bilirubin concentration • AAP—American Academy of Pediatrics • BBB—blood-brain barrier • Bf—free bilirubin concentration • AB—albumin-bound bilirubin concentration • A—serum albumin concentration • ABR—brainstem auditory evoked response • AN—auditory neuropathy • AD—auditory dyssynchrony • G6PD—glucose-6-phosphate dehydrogenase


Accepted May 31, 2005.




This article has been cited by other articles:


Home page
NEJMHome page
R. Kapoor, Z. Csoma, L. Kemeny, J. Olah, J. D. Ostrow, R. P. Wennberg, C. Tiribelli, M. J. Maisels, and A. F. McDonagh
Phototherapy for Neonatal Jaundice
N. Engl. J. Med., June 5, 2008; 358(23): 2522 - 2525.
[Full Text] [PDF]


Home page
Clin. Chem.Home page
R. Wennberg
Unbound Bilirubin: A Better Predictor of Kernicterus?
Clin. Chem., January 1, 2008; 54(1): 207 - 208.
[Full Text] [PDF]


Home page
PediatricsHome page
G. J. Bender, W. J. Cashore, and W. Oh
Ontogeny of Bilirubin-Binding Capacity and the Effect of Clinical Status in Premature Infants Born at Less Than 1300 Grams
Pediatrics, November 1, 2007; 120(5): 1067 - 1073.
[Abstract] [Full Text] [PDF]


Home page
NeoReviewsHome page
R. J. Wong, D. K. Stevenson, C. E. Ahlfors, and H. J. Vreman
Neonatal Jaundice: Bilirubin Physiology and Clinical Chemistry
NeoReviews, February 1, 2007; 8(2): e58 - e67.
[Abstract] [Full Text] [PDF]


Home page
PediatricsHome page
F. Raimondi, L. Capasso, F. Migliaro, A. Romano, and R. Paludetto
Prenatal Exposure to Conjugated Bilirubin
Pediatrics, November 1, 2006; 118(5): 2265 - 2265.
[Full Text] [PDF]


Home page
PediatricsHome page
R. P. Wennberg and C. E. Ahlfors
A Different View on Bilirubin Binding
Pediatrics, August 1, 2006; 118(2): 846 - 847.
[Full Text] [PDF]


Home page
PediatricsHome page
A. F. McDonagh and M. J. Maisels
Bilirubin Unbound: Deja Vu All Over Again?
Pediatrics, February 1, 2006; 117(2): 523 - 525.
[Full Text] [PDF]


Home page
PediatricsHome page
E. Hanko
Unbound Bilirubin and Risk Assessment in the Jaundiced Newborn: Possibilities and Limitations
Pediatrics, February 1, 2006; 117(2): 526 - 527.
[Full Text] [PDF]