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Clinical Chemistry 50: 477-480, 2004. First published January 15, 2004; 10.1373/clinchem.2003.024489
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(Clinical Chemistry. 2004;50:477-480.)
© 2004 American Association for Clinical Chemistry, Inc.

Current Issues in Laboratory Medicine

Urgent Clinical Need for Accurate and Precise Bilirubin Measurements in the United States to Prevent Kernicterus

Vinod K. Bhutania,1 and Lois H. Johnson1

1 Department of Pediatrics, Pennsylvania Hospital, University of Pennsylvania School of Medicine, Philadelphia, PA.

aAddress correspondence to this author at: Department of Pediatrics/ Center for Reproduction Research and Women’s Health (CRRWH), University of Pennsylvania, 1315 Biomedical Research Bldg. II/III, 421 Curie Blvd., Philadelphia, PA 19104. E-mail bhutani2@mail.med.upenn.edu.

The first 300 words of the full text of this article appear below.

Kernicterus, a preventable brain injury resulting from severe neonatal jaundice, has reemerged in the US (1)(2)(3). Newborn jaundice, a usually benign condition that typically resolves with supervision and appropriate nutritional intake, can progress to severe hyperbilirubinemia in ~8–10% of healthy newborn infants. Severe hyperbilirubinemia may need treatment with phototherapy. Some newborns discharged as healthy have developed severe hyperbilirubinemia after discharge and succumbed to serious and often irreversible posticteric sequelae.

Kernicterus, as described in neonates, refers to the icteric (yellow) staining of the basal ganglia, specifically the globus pallidus (4). The voluntary Pilot Kernicterus Registry now recognizes a syndrome of bilirubin-induced neurologic dysfunction (BIND), which includes kernicterus in its most severe acute and chronic forms. Using the Registry eligibility criteria, Johnson et al. (1) have documented the reemergence of kernicterus in a population of term and near-term "healthy" infants after its near eradication following prevention of Rh sensitization and widespread availability of phototherapy.

The common insult in all cases of BIND results from a total serum bilirubin (TSB) concentration that exceeds the infant’s neuroprotective defenses and leads to neuronal injury, primarily in the basal ganglia, central and peripheral auditory pathways, hippocampus, diencephalon, subthalamic nuclei, midbrain, cerebellum and pontine and brain-stem nuclei for oculomotor function and for respiratory, neurohumoral, and electrolyte control. The manifestations of acute bilirubin encephalopathy and chronic kernicteric sequelae may be minimal to severe and occur as various combinations (or possibly, isolated findings) of extrapyramidal disorders, neuromotor abnormalities, sensorineural hearing loss, and visual disability. Although not yet demonstrated, some experts believe that milder and subtler neurologic manifestations of BIND exist.

The current reemergence of kernicterus in babies discharged as healthy from US hospitals represents a crisis of credibility and calls into question our ability to measure TSB with accuracy . . . [Full Text of this Article]


Hyperbilirubinemia in Healthy Newborns


Relationship between Hyperbilirubinemia and Kernicterus


Incidence of Severe and Extreme Hyperbilirubinemia


BIND in Sick and Preterm Newborns




The following articles in journals at HighWire Press have cited this article:


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J. M Kirk
Neonatal jaundice: a critical review of the role and practice of bilirubin analysis
Ann Clin Biochem, September 1, 2008; 45(5): 452 - 462.
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 Arch. Dis. Child. Fetal Neonatal Ed.Home page
C V Hulzebos, D E van Imhoff, A F Bos, C E Ahlfors, H J Verkade, and P H Dijk
Usefulness of the bilirubin/albumin ratio for predicting bilirubin-induced neurotoxicity in premature infants
Arch. Dis. Child. Fetal Neonatal Ed., September 1, 2008; 93(5): F384 - F388.
[Abstract] [Full Text] [PDF]

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 CMAJHome page
M. Sgro, D. Campbell, and V. Shah
Incidence and causes of severe neonatal hyperbilirubinemia in Canada.
Can. Med. Assoc. J., September 12, 2006; 175(6): 587 - 590.
[Abstract] [Full Text] [PDF]

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 PediatricsHome page
R. H. Palmer, S. Ezhuthachan, C. Newman, M. J. Maisels, and M. A. Testa
Hyperbilirubinemia Benchmarking
Pediatrics, September 1, 2004; 114(3): 902 - 904.
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