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Kernicterus Clinical Presentation

  • Author: Shelley C Springer, JD, MD, MSc, MBA, FAAP; Chief Editor: Ted Rosenkrantz, MD  more...
 
Updated: Apr 02, 2014
 

History

When assessing possible kernicterus, remember that a history of risk for hemolytic disease can be an important clue to a neonate's increased risk of pathologic hyperbilirubinemia, particularly Rh antigen incompatibility between mother and baby[13] . ABO incompatibility and a family history of RBC abnormalities (ie, glucose-6-phosphate dehydrogenase deficiency, hereditary spherocytosis) are also concerning. A review of neonatal readmissions in Canada showed that, of 258 infants readmitted for severe hyperbilirubinemia from 2002-2004, 87 (34%) demonstrated one of these hematologic abnormalities.[14]

Certain cultural postnatal practices may also contribute to significant hyperbilirubinemia and should be inquired about if culturally relevant. In the Middle East, Peker et al reported in 2010 a case series of 10 severely hypernatremic babies who also presented with kernicterus, 2 of whom died.[15] Of 112 postpartum women surveyed in Jordan Hospital, Amman, Jordan, almost 50% of them admitted to "salting" their newborns as is the common custom. Women doing this practice broadly represented all socioeconomic and educational strata.[16]

Conversely, if the baby is breastfeeding well and appears healthy and vigorous, this can be reassuring. The mother may have breastfed previous babies who also developed significant jaundice. If so, she may be one of the approximately 20-40% of women who have above-average levels of beta-glucuronidase in their breast milk, which potentiates and prolongs hyperbilirubinemia in their breastfed babies.

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Physical

Bilirubin-induced neurologic dysfunction (BIND) is the term applied to the spectrum of neurologic abnormalities associated with hyperbilirubinemia. It can be further divided into characteristic signs and symptoms that appear in the early stages (acute) and those that evolve over a prolonged period (chronic).

Acute bilirubin encephalopathy

The clinical features of this diagnosis have been well described and can be divided into 3 stages. Of babies with BIND, approximately 55-65% present with these features, 20-30% may display some neurologic abnormalities, and approximately 15% have no neurologic signs.

The 3 stages are as follows:

  • Phase 1 (first few days of life): Decreased alertness, hypotonia, and poor feeding are the typical signs. Obviously, these are quite nonspecific and could easily be indicative of a multitude of neonatal abnormalities. A high index of suspicion of possible BIND at this stage that leads to prompt intervention can halt the progression of the illness, significantly minimizing long-term sequelae. Of note, seizure is not typically associated with acute bilirubin encephalopathy. Among infants reported in the US kernicterus registry, the mean birth weight was 3281 g. [6]
  • Phase 2 (variable onset and duration): Hypertonia of the extensor muscles is a typical sign. Patients present clinically with retrocollis (backward arching of the neck), opisthotonus (backward arching of the back), or both. Infants who progress to this phase develop long-term neurologic deficits.
  • Phase 3 (infants aged >1 wk): Hypotonia is a typical sign.

Chronic bilirubin encephalopathy

The clinical features of chronic bilirubin encephalopathy evolve slowly over the first several years of life in the affected infant. The clinical features can be divided into phases; the first phase occurs in the first year of life and consists of hypotonia, hyperreflexia, and delayed acquisition of motor milestones. The tonic neck reflex can also be observed. In children older than 1 year, the more familiar clinical features develop, which include abnormalities in the extrapyramidal, visual, and auditory systems. Minor intellectual deficits can also occur.

Note the following:

  • Extrapyramidal abnormalities: Athetosis is the most common movement disorder associated with chronic bilirubin encephalopathy, although chorea can also occur. The upper extremities are usually more affected than the lower ones; bulbar functions can also be impacted. The abnormalities result from damage to the basal ganglia, the characteristic feature of chronic bilirubin encephalopathy.
  • Visual abnormalities: Ocular movements are affected, most commonly resulting in upward gaze, although horizontal gaze abnormalities and gaze palsies can also be observed. These deficits result from damage to the corresponding cranial nerve nuclei in the brain stem.
  • Auditory abnormalities: Hearing abnormalities are the most consistent feature of chronic bilirubin encephalopathy and can develop in patients who show none of the other characteristic features. The most common abnormality is high-frequency hearing loss, which can range from mild to severe. These deficits can result from damage both to the cochlear nuclei in the brain stem and to the auditory nerve, which appear to be exquisitely sensitive to the toxic effects of bilirubin, even at relatively low levels. Clinically, this deficit can manifest as delayed language acquisition. Hence, auditory function must be assessed early in any baby at risk for chronic bilirubin encephalopathy.
  • Cognitive deficits: Cognitive function is relatively spared in chronic bilirubin encephalopathy. However, individuals with chronic bilirubin encephalopathy are often mistakenly considered to have mental retardation because of their choreoathetoid movement disorders and hearing deficits. The clinician must emphasize that intellectual functioning is not typically severely affected.
  • Abnormalities of dentition: Some degree of dental enamel hypoplasia can be observed in about three quarters of patients with chronic bilirubin encephalopathy. A smaller number of individuals develop green-stained teeth.
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Causes

Familiarity with bilirubin metabolism leads to an understanding of the factors leading to an increased risk of kernicterus (see image below). Bilirubin is produced during the catabolism of the heme component of RBCs. Red cell destruction is usually increased in the immediate neonatal period; it can be pathologically elevated in the presence of immune-mediated or nonimmune-mediated hemolytic disease. The first enzyme in the catabolic cascade leading to bilirubin is heme oxygenase. A constitutive form and an inducible form are recognized and are induced by physiologic stressors. The creation of bilirubin, a potentially toxic water-insoluble compound, from biliverdin, a nontoxic water-soluble substance, consumes energy.

Overview of bilirubin metabolism. Overview of bilirubin metabolism.

Because of its lipophilic nature, bilirubin must be bound to albumin to travel through the blood stream. In this state, it is not free to cross the blood-brain barrier and cause kernicterus. The albumin-bilirubin complex is carried to the liver, where bilirubin enters the hepatocyte for further metabolism. Once in the liver, bilirubin is conjugated via the action of uridine diphosphate glucuronyl transferase (UDPGT), an enzyme not fully functional until 3-4 months of life.

Conjugated bilirubin is excreted into the intestinal tract via the biliary system. Beta-glucuronidase, present in the intestinal lumen of human neonates, deconjugates the conjugated bilirubin, allowing it to be reabsorbed across the intestinal lipid cell membranes back into the blood stream where it must be re-bound to albumin to repeat the cycle. This process, called enterohepatic recirculation, is a unique neonatal phenomenon and contributes significantly to physiologic jaundice. Feeding and excretion of meconium and stool interrupt the enterohepatic recirculation.

Among infants reported in the US kernicterus registry, 56% had abnormalities known to increase the bilirubin concentration in the blood.[12] Severe hemolytic processes were identified in 25 of 122 babies (20.5%); glucose-6-phosphate dehydrogenase deficiency was diagnosed in 26 babies (21.3%), birth trauma identified in 18 patients (15%), and other causes such as galactosemia, Crigler-Najjar syndrome, and sepsis were diagnosed in 8 babies (7%). In 53 of 122 infants (43.4%), no etiology for the severe hyperbilirubinemia was discovered.

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Increased Bilirubin Production

Most of the circulating bilirubin in the neonate arises from destruction of circulating RBCs. Neonates produce bilirubin at more than double the daily rate of the average adult, primarily because of the larger circulating volume of RBCs and their shorter life span. Any event resulting in increased serum bilirubin load puts the infant at risk for hyperbilirubinemia.

Polycythemia

Prenatal factors, such as maternal smoking, maternal illness, placental insufficiency, and gestation at high altitude, can result in neonatal polycythemia. Obstetric factors, such as delayed clamping of the cord, stripping the cord, or holding the baby below the level of the introitus for a prolonged period, can result in increased RBC mass in the baby. This is particularly true for babies born in the absence of a trained birth attendant.

Hemolysis

Immune hemolytic disease, most often Rh isoimmunization (erythroblastosis fetalis), is the prototype etiology for kernicterus.

ABO isoimmunization, as well as minor blood group antigens, can also cause hemolytic disease in the newborn, usually of moderate severity. Infants born to mothers of blood type O negative are at greatest risk, with one series of 249 infants with severe hyperbilirubinemia reporting an odds ratio of 48.6 for infants with Rh incompatibility.[13]

Abnormalities of the red cell itself can also predispose to hemolysis. These can be grouped into membrane defects, such as hereditary spherocytosis and elliptocytosis; enzyme defects, such as glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency; and hemoglobinopathies, such as alpha and beta thalassemias.

Sickle cell disease does not typically cause hemolytic disease in the neonatal period.

Extravasated blood

Significant areas of bruising, such as severe cephalohematoma, subgaleal hemorrhage or peripheral ecchymoses from birth trauma, can result in an increased bilirubin load in the serum as the blood collection resolves. Internal areas of hemorrhage, such as pulmonary or intraventricular bleeds, can also be a significant occult source of serum bilirubin.

Enzyme induction

As mentioned above, heme-oxygenase-one (HO-1) is the inducible form of the first enzyme involved in the creation of bilirubin. This enzyme is activated by physiologic stressors, such as hypothermia, acidosis, hypoxia, and infection (odds ratio 20.6 in sepsis).[13]

Epidemiologic factors

East Asian and Native American babies produce bilirubin at higher rates than do white infants; black infants have lower production rates than do infants of other racial groups. Male infants have higher serum bilirubin levels than females. Hyperbilirubinemia also runs in families; the etiology is unclear but may relate to genetically increased levels of beta-glucuronidase in the infant, in the mother's breast milk, or both (if the infant is breastfed).

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Decreased Elimination

Even with normal bilirubin production, abnormalities in transport, excretion, or both can result in an increased level of free bilirubin in the serum.

Albumin binding

Because of its lipophilic nature, bilirubin must be bound to carrier protein to be transported in the aqueous environment of the serum. Albumin has one primary high-affinity binding site for bilirubin and two lower-affinity sites. At physiologic pH, the amount of free bilirubin (eg, bilirubin not bound to albumin) is very low. This is important because only free bilirubin is available to cross the blood-brain barrier and cause neurotoxicity. Decreased albumin binding capacity, decreased albumin binding affinity, or both can serve to increase the amount of free serum bilirubin. Binding affinity is lower in neonates than in older infants and is lower still in premature and sick infants than in healthy term ones.

Some authors advocate including measures of unbound (ie, free) bilirubin when assessing the risk of bilirubin neurotoxicity,[17] in part because some studies have shown a closer association between the unbound bilirubin concentration and auditory abnormalities than those seen with total serum bilirubin, although identifying the neurotoxic unbound bilirubin concentration threshold remains elusive.[18]

Decreased binding capacity can occur in hypoalbuminemia or if the binding sites are filled with other anions. Whether parenterally administered lipid can displace bilirubin from its albumin-binding site is controversial. If faced with dangerously high levels of serum bilirubin, restricting lipid administration to less than maximal levels may be prudent. Drugs, such as sulfisoxazole and ceftriaxone, can also compete for bilirubin-binding sites on the albumin molecule and must be used with caution or avoided in the neonatal period.

Hepatic uptake and conjugation

Albumin carries bilirubin to the liver, where it is incorporated into the hepatocyte by an acceptor protein called ligandin. Hepatic levels of ligandin do not reach adult values until around age 5 days, but they can be induced by administration of phenobarbital.

Once inside the hepatocyte, bilirubin is conjugated to a sugar moiety, glucuronic acid, via the enzyme UDPGT. Inherent neonatal deficiency of this enzyme is the principal etiology of physiologic jaundice. For the first 10 days of life, UDPGT is present at levels about 0.1% of adult values, and hyperbilirubinemia appears to be the primary stimulus to enzyme production.

Beyond physiologic jaundice, congenital inherited defects in UDPGT cause pathologic hyperbilirubinemia of varying severity. Crigler-Najjar syndrome type I is the virtual absence of UDPGT and is characterized by profound refractory hyperbilirubinemia with the ongoing risk of kernicterus at any point during an individual's lifespan. Currently, liver transplantation is the only definitive therapy, although experimental therapies are under investigation. Patients with Crigler-Najjar syndrome type II (ie, Arias syndrome) have a similar clinical presentation as patients with type I. However, patients with type II dramatically respond to therapy with phenobarbital, which is how the diagnosis is made.

Gilbert syndrome is characterized by a benign chronic indirect hyperbilirubinemia without evidence of liver disease or abnormality. The genetic basis for this syndrome has recently been identified as an amplified triplet repeat in the coding gene for UDPGT, and investigations are continuing to clarify the possible role of Gilbert syndrome in infants with neonatal hyperbilirubinemia.

Excretion

Once conjugated, water-soluble bilirubin is excreted in an energy-dependent manner into the bile canaliculi for ultimate delivery into the small intestine. Disruption in this system or obstruction in the biliary system results in accumulation of conjugated bilirubin in the serum, identified by an elevation in the direct fraction of total bilirubin. Direct hyperbilirubinemia in the neonate (defined as a direct fraction greater than one third of total bilirubin) is always pathologic, and an etiology must be pursued.

In the small intestine, conjugated bilirubin cannot be reabsorbed. Intestinal florae convert it into urobilinogen, which is excreted. In the neonate, the paucity of colonic bacteria impedes this conversion. Furthermore, the neonatal gut (but not that of the adult) produces beta-glucuronidase, an enzyme that acts upon conjugated bilirubin, releasing free bilirubin for potential absorption across the intestinal cell lipid membrane into the blood stream. Breast milk also contains beta-glucuronidase, and breast milk feedings increase the level of this enzyme in the neonatal intestine. Combined with slow intestinal motility in the first few days of life, the above factors result in what is called enterohepatic recirculation of bilirubin back into the blood stream.

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Systemic Factors

Various systemic conditions increase the risk of hyperbilirubinemia and the risk of kernicterus without severe hyperbilirubinemia.

Galactosemia

Patients with this rare inborn error of metabolism may primarily present with hyperbilirubinemia, although the direct fraction typically increases during the second week of life. The baby may manifest other characteristic signs, such as hepatomegaly, poor feeding, or lethargy. Urine for reducing substances, but not glucose, is diagnostic. Many state newborn metabolic screens include a test for this disorder.

Hypothyroidism

Although the etiology is unclear, prolonged indirect hyperbilirubinemia is one of the typical features of congenital hypothyroidism, and this diagnosis must be ruled out in any baby with hyperbilirubinemia persisting after age 2-3 weeks. Most state metabolic screens include an assay of thyroid function, although false-negative results and delayed receipt of results may necessitate individual testing in symptomatic infants.

Drugs

Maternal administration of oxytocin, diazepam, or promethazine may result in increased serum bilirubin in the infant. Similarly, neonatal administration of pancuronium and chloral hydrate increases bilirubin levels. Additionally, some drugs, such as sulfonamides and some penicillins, can displace bilirubin from its albumin-binding site, effectively increasing the serum concentration of free bilirubin available to cross the blood-brain barrier.

Acidosis

Systemic acidosis decreases the binding affinity of albumin for bilirubin, resulting in increased levels of free bilirubin in the blood stream. Ready availability of protons promotes the formation of bilirubin acid (free bilirubin anion plus 2 hydrogen ions); that moiety demonstrates increased binding and transport into neural cell membranes.

Disrupted blood-brain barrier

The neonatal blood-brain barrier is more permeable to substances than is the adult's. Administration of hyperosmolar substances, hypercarbia, asphyxia, infection (particularly meningitis), and impaired autoregulation with variations in blood pressure all may weaken capillary tight junctions, increasing capillary permeability. This, in turn, might lower the concentration at which bilirubin is toxic to the CNS.

Breast milk feedings

The well-described physiologic jaundice observed in the first few days of life, particularly in the breastfed infant, is called breastfeeding jaundice. Breastfeeding jaundice is thought to result from multiple mechanisms, described above, which promote production and inhibit excretion of bilirubin, as well as from insufficient milk intake because of reduced mammary gland milk production in the first few days postpartum. Breastfeeding jaundice should be distinguished from breast milk jaundice.

Some breastfed infants, although clinically thriving, continue to manifest an indirect hyperbilirubinemia of unidentifiable etiology for several months. If this is witnessed in a breastfed infant, the exclusion diagnosis of breast milk jaundice may be made. Such hyperbilirubinemia is thought to be caused by persistently high levels of as-yet-unidentified components in some women's breast milk, which result in persistence of the infant's hyperbilirubinemia. One clue may be a history of similar hyperbilirubinemia in other breastfed siblings. This entity is benign.

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Contributor Information and Disclosures
Author

Shelley C Springer, JD, MD, MSc, MBA, FAAP Professor, University of Medicine and Health Sciences, St Kitts, West Indies; Clinical Instructor, Department of Pediatrics, University of Vermont College of Medicine; Clinical Instructor, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health

Shelley C Springer, JD, MD, MSc, MBA, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

David J Annibale, MD Professor of Pediatrics, Director of Neonatology, Director of Fellowship Training Program in Neonatal-Perinatal Medicine, Department of Pediatrics, Medical University of South Carolina

David J Annibale, MD is a member of the following medical societies: American Academy of Pediatrics, National Perinatal Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David A Clark, MD Chairman, Professor, Department of Pediatrics, Albany Medical College

David A Clark, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Pediatric Society, Christian Medical and Dental Associations, Medical Society of the State of New York, New York Academy of Sciences, Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Oussama Itani, MD, FAAP, FACN Clinical Associate Professor of Pediatrics and Human Development, Michigan State University; Medical Director, Department of Neonatology, Borgess Medical Center

Oussama Itani, MD, FAAP, FACN is a member of the following medical societies: American Academy of Pediatrics, American Association for Physician Leadership, American Heart Association, American College of Nutrition

Disclosure: Nothing to disclose.

References
  1. Brooks JC, Fisher-Owens SA, Wu YW, Strauss DJ, Newman TB. Evidence suggests there was not a "resurgence" of kernicterus in the 1990s. Pediatrics. 2011 Apr. 127(4):672-9. [Medline].

  2. Moll M, Goelz R, Naegele T, Wilke M, Poets CF. Are recommended phototherapy thresholds safe enough for extremely low birth weight (ELBW) infants? A report on 2 ELBW infants with kernicterus despite only moderate hyperbilirubinemia. Neonatology. 2011. 99(2):90-4. [Medline].

  3. Dogan M, Peker E, Kirimi E, Sal E, Akbayram S, Erel O, et al. Evaluation of oxidant and antioxidant status in infants with hyperbilirubinemia and kernicterus. Hum Exp Toxicol. 2011 Nov. 30(11):1751-60. [Medline].

  4. Gkoltsiou K, Tzoufi M, Counsell S, Rutherford M, Cowan F. Serial brain MRI and ultrasound findings: relation to gestational age, bilirubin level, neonatal neurologic status and neurodevelopmental outcome in infants at risk of kernicterus. Early Hum Dev. 2008 Dec. 84(12):829-38. [Medline].

  5. Johnson L, Brown AK. A pilot registry for acute and chronic kernicterus in term and near-term infants. Pediatrics. 1999 Sept. 104:(3):736.

  6. Johnson LH, Bhutani VK, Brown AK. System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr. 2002 Apr. 140(4):396-403. [Medline].

  7. Ebbesen F. Recurrence of kernicterus in term and near-term infants in Denmark. Acta Paediatr. 2000 Oct. 89(10):1213-7. [Medline].

  8. 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 Jan. 94(1):59-64. [Medline].

  9. British Paediatric Surveillance Unit. Surveillance of severe hyperbilirubinaemia in the newborn commenced the May. BPSU Quarterly Bulletin. 2003. 11(2):2.

  10. Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ. 2006 Sep 12. 175(6):587-90. [Medline].

  11. Bhutani VK, Johnson L. Kernicterus in the 21st century: frequently asked questions. J Perinatol. 2009 Feb. 29 Suppl 1:S20-4. [Medline].

  12. Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM. Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). J Perinatol. 2009 Feb. 29 Suppl 1:S25-45. [Medline].

  13. Gamaleldin R, Iskander I, Seoud I, Aboraya H, Aravkin A, Sampson PD. Risk factors for neurotoxicity in newborns with severe neonatal hyperbilirubinemia. Pediatrics. 2011 Oct. 128(4):e925-31. [Medline].

  14. Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ. 2006 Sep 12. 175(6):587-90. [Medline].

  15. Peker E, Kirimi E, Tuncer O, Ceylan A. Severe hypernatremia in newborns due to salting. Eur J Pediatr. 2010 Jul. 169(7):829-32. [Medline].

  16. Abu-Osba YK, Jarad RA, Zainedeen KH, Khmour AY. Salting Newborns: Pickling Them or Killing Them? A practice that should be stopped. powerpoint file. Available at http://medical.abu-osba.com/PublishedPapers/20091514331.ppt. Accessed: March 31, 2012.

  17. Ahlfors CE. Predicting bilirubin neurotoxicity in jaundiced newborns. Curr Opin Pediatr. 4/2010. 22(2):129-33. [Medline].

  18. Watchko JF, Jeffrey Maisels M. Enduring controversies in the management of hyperbilirubinemia in preterm neonates. Semin Fetal Neonatal Med. 2010 Jun. 15(3):136-40. [Medline].

  19. Rennie JM, Sehgal A, De A, Kendall GS, Cole TJ. Range of UK practice regarding thresholds for phototherapy and exchange transfusion in neonatal hyperbilirubinaemia. Arch Dis Child Fetal Neonatal Ed. 2009 Sep. 94(5):F323-7. [Medline].

  20. McDonagh AF. Ex uno plures: the concealed complexity of bilirubin species in neonatal blood samples. Pediatrics. 2006 Sep. 118(3):1185-7. [Medline].

  21. Ahlfors CE. Predicting bilirubin neurotoxicity in jaundiced newborns. Curr Opin Pediatr. 2010 Apr. 22(2):129-33. [Medline].

  22. Daood MJ, McDonagh AF, Watchko JF. Calculated free bilirubin levels and neurotoxicity. J Perinatol. 2009 Feb. 29 Suppl 1:S14-9. [Medline].

  23. AAP. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004 Jul. 114(1):297-316. [Medline].

  24. Yu ZB, Dong XY, Han SP, Chen YL, Quiu YF, Sha L, et al. Transcutaneous bilirubine nomogram for predicting neonatal hyperbilirubinemia in healthy term and late-preterm Chinese infants. Eur J Pediatr. 2/2011. 170(2):185-91. [Medline].

  25. Screening of infants for hyperbilirubinemia to prevent chronic bilirubin encephalopathy: US Preventive Services Task Force recommendation statement. Pediatrics. 2009 Oct. 124(4):1172-7. [Medline].

  26. Bental YA, Shiff Y, Dorsht N, Litig E, Tuval L, Mimouni FB. Bhutani-based nomograms for the prediction of significant hyperbilirubinaemia using transcutaneous measurements of bilirubin. Acta Paediatr. 2009 Dec. 98(12):1902-8. [Medline].

  27. Mehta S, Kumar P, Narang A. A randomized controlled trial of fluid supplementation in term neonates with severe hyperbilirubinemia. J Pediatr. 2005. 147 (6):781 - 5. [Medline].

  28. Sanpavat S. Exchange transfusion and its morbidity in ten-year period at King Chulalongkorn Hospital. J Med Assoc Thai. 2005 May. 88(5):588-92. [Medline].

  29. Badiee Z. Exchange transfusion in neonatal hyperbilirubinaemia: experience in Isfahan, Iran. Singapore Med J. 2007 May. 48(5):421-3. [Medline].

  30. Bisceglia M, Indrio F, Riezzo G, Poerio V, Corapi U, Raimondi F. The effect of prebiotics in the management of neonatal hyperbilirubinaemia. Acta Paediatr. 2009 Oct. 98(10):1579-81. [Medline].

  31. Gourley GR, Li Z, Kreamer BL, Kosorok MR. A controlled, randomized, double-blind trial of prophylaxis against jaundice among breastfed newborns. Pediatrics. 2005 Aug. 116(2):385-91. [Medline].

  32. Dennery PA. Metalloporphyrins for the treatment of neonatal jaundice. Curr Opin Pediatr. 2005 Apr. 17(2):167-9. [Medline].

  33. Kaplan M, Kaplan E, Hammerman C, et al. Post-phototherapy neonatal bilirubin rebound: a potential cause of significant hyperbilirubinaemia. Arch Dis Child. 2006 Jan. 91(1):31-4. [Medline].

  34. Newman TB, Kuzniewicz MW, Liljestrand P, Wi S, McCulloch C, Escobar GJ. Numbers needed to treat with phototherapy according to American Academy of Pediatrics guidelines. Pediatrics. 2009 May. 123(5):1352-9. [Medline]. [Full Text].

  35. Martins BM, de Carvalho M, Moreira ME, Lopes JM. Efficacy of new microprocessed phototherapy system with five high intensity light emitting diodes (Super LED). J Pediatr (Rio J). 2007 May-Jun. 83(3):253-8. [Medline].

  36. Romagnoli C, Zecca E, Papacci P, Vento G, Girlando P, Latella C. Which phototherapy system is most effective in lowering serum bilirubin in very preterm infants?. Fetal Diagn Ther. 2006. 21(2):204-9. [Medline].

  37. van Kaam AH, van Beek RH, Vergunst-van Keulen JG, et al. Fibre optic versus conventional phototherapy for hyperbilirubinaemia in preterm infants. Eur J Pediatr. 1998 Feb. 157(2):132-7. [Medline].

  38. Keren R, Bhutani VK, Luan X, Nihtianova S, Cnaan A, Schwartz JS. Identifying newborns at risk of significant hyperbilirubinaemia: a comparison of two recommended approaches. Arch Dis Child. 2005 Apr. 90(4):415-21. [Medline].

  39. 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 Jan. 121(1):e170-9. [Medline].

  40. Csoma Z, Toth-Molnar E, Balogh K, et al. Neonatal blue light phototherapy and melanocytic nevi: a twin study. Pediatrics. 2011 Oct. 128(4):e856-64. [Medline].

  41. Raghavan K, Thomas E, Patole S, Muller R. Is phototherapy a risk factor for ileus in high-risk neonates?. J Matern Fetal Neonatal Med. 2005 Aug. 18(2):129-31. [Medline].

  42. Chen J, Sadakata M, Ishida M, Sekizuka N, Sayama M. Baby massage ameliorates neonatal jaundice in full-term newborn infants. Tohoku J Exp Med. 2011. 223(2):97-102. [Medline].

  43. Lazarus C, Avchen RN. Neonatal hyperbilirubinemia management: a model for change. J Perinatol. 2009 Feb. 29 Suppl 1:S58-60. [Medline].

  44. Bhutani VK, Johnson L. A proposal to prevent severe neonatal hyperbilirubinemia and kernicterus. J Perinatol. 2009 Feb. 29 Suppl 1:S61-7. [Medline].

  45. Ahlfors CE, Wennberg RP. Bilirubin-albumin binding and neonatal jaundice. Semin Perinatol. 2004 Oct. 28(5):334-9. [Medline].

  46. AlOtaibi SF, Blaser S, MacGregor DL. Neurological complications of kernicterus. Can J Neurol Sci. 2005 Aug. 32(3):311-5. [Medline].

  47. Bader D, Yanir Y, Kugelman A, et al. Induction of early meconium evacuation: is it effective in reducing the level of neonatal hyperbilirubinemia?. Am J Perinatol. 2005 Aug. 22(6):329-33. [Medline].

  48. Barefield ES, Dwyer MD, Cassady G. Association of patent ductus arteriosus and phototherapy in infants weighting less than 1000 grams. J Perinatol. 1993 Sep-Oct. 13(5):376-80. [Medline].

  49. Bhutani VK, Donn SM, Johnson LH. Risk management of severe neonatal hyperbilirubinemia to prevent kernicterus. Clin Perinatol. 2005. 32 (1):125 - 39, vii. [Medline].

  50. Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics. 1999 Jan. 103(1):6-14. [Medline]. [Full Text].

  51. Bhutani VK, Johnson LH, Jeffrey Maisels M, et al. Kernicterus: epidemiological strategies for its prevention through systems-based approaches. J Perinatol. 2004 Oct. 24(10):650-62. [Medline].

  52. Cashore WJ. Bilirubin and jaundice in the micropremie. Clin Perinatol. 2000 Mar. 27(1):171-9, vii. [Medline].

  53. Drummond GS, Kappas A. Chemoprevention of severe neonatal hyperbilirubinemia. Semin Perinatol. 2004 Oct. 28(5):365-8. [Medline].

  54. Gartner LM. Neonatal jaundice. Pediatr Rev. 1994 Nov. 15(11):422-32. [Medline].

  55. Juretschke LJ. Kernicterus: still a concern. Neonatal Netw. 2005 Mar-Apr. 24(2):7-19. [Medline].

  56. Kaplan M, Hammerman C. Understanding severe hyperbilirubinemia and preventing kernicterus: adjuncts in the interpretation of neonatal serum bilirubin. Clin Chim Acta. 2005 Jun. 356(1-2):9-21. [Medline].

  57. Kumral A, Genc S, Genc K, et al. Hyperbilirubinemic serum is cytotoxic and induces apoptosis in murine astrocytes. Biol Neonate. 2005. 87(2):99-104. [Medline].

  58. MacMahon JR, Stevenson DK, Oski FA. Physiologic jaundice. Taeusch, Ballards, eds. Avery's Disease of the Newborn. 7th ed. Philadelphia, PA: Saunders; 1998. 1003-7.

  59. Maisels MJ. Jaundice. Avery, Fletcher, eds. Neonatology, Pathophysiology and Management of the Newborn. 5th ed. Philadelphia, PA: Lippincott; 1999. 765-819.

  60. Petersen JR, Okorodudu AO, Mohammad AA, et al. Association of transcutaneous bilirubin testing in hospital with decreased readmission rate for hyperbilirubinemia. Clin Chem. 2005. 51 (3):481 - 2. [Medline]. [Full Text].

  61. Pezzati M, Biagiotti R, Vangi V, et al. Changes in mesenteric blood flow response to feeding: conventional versus fiber-optic phototherapy. Pediatrics. 2000 Feb. 105(2):350-3. [Medline]. [Full Text].

  62. Rubegni P, Cevenini G, Sbano P, et al. Cutaneous colorimetric evaluation of serum concentrations of bilirubin in healthy term neonates: a new methodological approach. Skin Res Technol. 2005 Feb. 11(1):70-5. [Medline].

  63. Sanpavat S, Nuchprayoon I. Noninvasive transcutaneous bilirubin as a screening test to identify the need for serum bilirubin assessment. J Med Assoc Thai. 2004 Oct. 87(10):1193-8. [Medline].

  64. Shapiro SM. Definition of the clinical spectrum of kernicterus and bilirubin-induced neurologic dysfunction (BIND). J Perinatol. 2005 Jan. 25(1):54-9. [Medline].

  65. Taketomo CK, Hodding JH, Draus DM. Pediatric Dosage Handbook. 10th ed. Cleveland, OH: Lexi-Comp, Inc; 2003.

  66. Volpe JJ. Bilirubin and Brain Injury: Neurology of the Newborn. 3rd ed. Philadelphia, PA: WB Saunders; 1995. 490-514.

  67. Watchko JF. Vigintiphobia revisited. Pediatrics. 2005 Jun. 115(6):1747-53. [Medline].

  68. Willems WA, van den Berg LM, de Wit H, Molendijk A. Transcutaneous bilirubinometry with the Bilicheck in very premature newborns. J Matern Fetal Neonatal Med. 2004 Oct. 16(4):209-14. [Medline].

 
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Typical patterns of total serum bilirubin levels in neonates of different racial origins. Used with the permission of the Academy of Pediatrics.
Overview of bilirubin metabolism.
Hour-specific nomogram for total serum bilirubin and attendant risk of subsequent severe disease in term and preterm infants. Used with the permission of the Academy of Pediatrics.
Magnetic resonance image of 21-month-old with kernicterus. Area of abnormality is the symmetric high-intensity signal in the area of the globus pallidus (arrows). Courtesy of M.J. Maisels.
Neuronal changes observed in kernicterus. Courtesy of J.J. Volpe.
 
 
 
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