Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Kernicterus Treatment & Management

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

Medical Care

The cornerstone of management of hyperbilirubinemia is prevention of neurotoxicity. The definitive method of removing bilirubin from the blood is via exchange transfusion. This is currently the indicated approach in the presence of clinical bilirubin-induced neurologic dysfunction (BIND) when the bilirubin level has reached dangerous levels despite preventive efforts. Phototherapy is the most common method aimed at prevention of bilirubin toxicity. Clinical research efforts evaluating the use of metalloporphyrins to block bilirubin formation by competing with the enzyme heme oxygenase have not yielded a clinically useful intervention to date.

Exchange transfusion

This definitive therapy is used to mechanically remove already-formed bilirubin from the blood. It is indicated whenever clinical signs of acute bilirubin encephalopathy are present in patients who present with critically high serum bilirubin levels that continue to rise despite attempts to reduce it.

This procedure is not without risk. Whereas exchange transfusion remains the definitive therapy, as recommended in the AAP's Clinical Practice Guideline “Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation” published in 2004, all babies should undergo a trial of phototherapy, if only while the blood is being prepared, prior to initiating exchange transfusion.[23] In the presence of Rh isoimmunization, a cord bilirubin level of more than 5 mg/dL or a rate of rise in serum bilirubin of more than 0.5-1 mg/dL/h is predictive of the ultimate need for exchange transfusion. This relationship has not been demonstrated in hyperbilirubinemia of other etiologies. A report of supplemental intravenous fluid administration in 74 term babies with nonhemolytic severe hyperbilirubinemia (total serum bilirubin level, 18-25 mg/dL) demonstrated a decreased rate of exchange transfusion in babies receiving the extra fluid (16%) compared with controls (54%).[27]

The procedure involves removing the baby's native blood and replacing it with citrate phosphate dextrose (CPD) banked blood that does not contain bilirubin. Obviously, this must be performed gradually. Using an estimate of 80-90 mL/kg total blood volume, double this amount is usually removed and replaced sequentially in aliquots (10-15 mL in term babies; 5-10 mL in smaller preterm babies) over several hours. This approach, called a double volume exchange transfusion, harvests the most efficient amount of bilirubin from the blood for the amount of intervention and results in a decrease in total serum bilirubin levels by about 40%.

Because of ongoing pathology and equilibrium between the intravascular and extravascular spaces, having to repeat the procedure at least once is not uncommon.

Using O negative blood rather than the baby's blood type is important because not all circulating antibodies may be removed. Packed RBCs resuspended in fresh frozen plasma must be used for this procedure. Irradiated RBCs are used to decrease the risk of graft-versus-host reaction.

This procedure carries both inherent risks and iatrogenic ones and should be carefully performed. The reported overall mortality rate is about 3:1000; the risk of significant morbidity has been reported at about 5:100. In babies who were very ill, the risks are higher. One series of 25 infants who were ill reported a mortality rate of 20%. As exchange transfusion is becoming an increasingly rare intervention, iatrogenic complications can be expected to increase.

A review of 183 exchange transfusions performed in 165 neonates in Bangkok, Thailand, from 1994-2003 reported an overall morbidity of 15.3%, of which 67% was attributed to infection associated with the procedure.[28] Infants who were sick at the time of the procedure (31.3%) were more likely to develop complications than were infants who were basically healthy but hyperbilirubinemic (6.8%). Preterm infants who required exchange transfusion also developed procedure-related complications of anemia, apnea, and cardiac arrest; overall, basically healthy preterm infants were more likely to develop some morbidity than were similarly treated full-term infants. Morbidities were identified in infants at the same rate regardless of gestational age (preterm vs term). No mortalities were reported. In Iran, exchange transfusions performed from 2001-2004 in 68 infants for hyperbilirubinemia resulted in one death directly related to complications from the procedure.[29]

Transfusing with banked blood products carries a risk of infection. Currently, the risk of infection with known pathogens is exceedingly small. However, a risk of infection with pathogens that have not yet been discovered (ie, most recently hepatitis C) continues.

During the procedure, continually monitor for attendant physiologic aberrations, such as hypoglycemia, thrombocytopenia (reported in 6% of patients in the Iranian series[29] ), hyperkalemia (particularly if the banked blood is >5 d), and hypocalcemia (if ethylenediamine tetra-acetic acid [EDTA] preservative is used in the banked blood).

Mechanical issues can contribute to the overall mortality and morbidity of the procedure. The need for central access, catheter-related and infusion-related problems, and human error during infusion are all areas that can pose potentially significant risk. Since the advent of phototherapy and obstetric treatment of Rh disease, the need for exchange transfusion has diminished. As fewer contemporary clinicians are familiar with exchange transfusion, the risk of iatrogenic complications increases.

As mentioned above, no clear-cut level of bilirubin above which encephalopathy is assured and below which neurologic safety is assured has been determined. Birthweight, gestational age, and chronologic age are all important, as are a baby's systemic condition, fluid and nutritional status, acid-base status, and the presence or absence of known pathology.

In 2004, the AAP published revised practice parameters for the management of hyperbilirubinemia in healthy infants aged 35 weeks' gestation or older.[23] In this document, the AAP presented recommendations for exchange transfusion for serum bilirubin levels greater than 20-25 mg/dL, depending on the postconceptional age of the infant and the bilirubin-to-albumin ratio, a tool that is not widely incorporated into the decision algorithm. The series by Gamaleldin et al of 249 infants with severe hyperbilirubinemia (≥25 mg/dL) suggested that when neurotoxicity risk issues such as Rh incompatibility or sepsis were present, 90% of infants who developed BIND manifested total serum bilirubin levels of greater than 25.4 mg/dL. However, in the 111 infants without risk factors, neurotoxicity was first observed with total serum bilirubin levels greater than 31.5 mg/dL.[13]

Studies have reported neurologically normal outcomes in healthy term infants with histories of serum bilirubin levels as high as 46 mg/dL. However, kernicterus has been reported to occur in near-term infants with serum bilirubin levels as low as 20.7 mg/dL and, more recently, in preterm infants with peak total serum bilirubin as low as 13.1 mg/dL.[18] The level at which to intervene is a clinical question that remains to be answered. A survey answered by 163 hospitals in the United Kingdom in 2009 yielded a range of 20-30 mg/dL as thresholds for exchange transfusion in otherwise healthy term infants.[19] The procedure should be strongly considered in babies with significant risk factors predisposing for kernicterus (eg, sepsis, acidosis, hemolytic disease) if the bilirubin level has approached the range of 20-25 mg/dL.

Enteral interventions

Administration of agar has been tried in an attempt to decrease the enterohepatic recirculation of conjugated bilirubin. It has not proved to be clinically useful and may cause intestinal obstruction.

Parenteral administration of immunoglobulin G (IgG) has been shown in controlled clinical trials to reduce the need for exchange transfusion in both Rh and ABO immune-mediated hemolytic disease. Its mechanism of action is not entirely clear.

Administration in hyperbilirubinemia resulting from isoimmune hemolytic disease that is unresponsive to phototherapy and/or is approaching exchange level has been recommended by the AAP in its 2004 revised clinical practice guideline.

Accelerated meconium evacuation

Administration of glycerin suppositories to facilitate stooling has been evaluated as a potential method of ameliorating hyperbilirubinemia. Although a controlled trial demonstrated earlier passage of meconium, no effect was demonstrated on total serum bilirubin levels, except for a small statistically significant effect identified in males with blood type A positive. Whether this was a statistical aberration or a true treatment effect is unclear.

Enteral prebiotics

Enterohepatic recirculation and delayed stooling contribute to perpetuation of hyperbilirubinemia. Recent investigation has focused on the role of oligosaccharides (galactose and fructose) naturally occurring in breastmilk as a modulator of intestinal flora and function. As a result, major infant formula manufacturers are now adding these so-called prebiotics to their formulations. A randomized, double-blind trial of formula and prebiotics versus formula and maltodextrine placebo was examined the effect of the investigational formula on stooling frequency. For the first 28 days of life, 76 newborns were randomly assigned to receive one of the formulations. Transcutaneous bilirubin measurements and number of stools per day were recorded. Infants in the prebiotic group showed significantly more stools per day for the duration of the trial period, as well as lower transcutaneous bilirubin levels (p< 0.05).[30]

Beta-glucuronidase inhibition

L-aspartic acid and enzymatically hydrolyzed casein (EHC) are known inhibitors of beta glucuronidase, the enzyme that promotes enterohepatic recirculation of conjugated bilirubin in the neonatal intestine. A randomized controlled trial of enteral administration of these substances (2 treatment groups) compared with babies who received nothing (group 3) or enteral whey/casein (no known enzymatic activity, group 4) showed significantly lower transcutaneous bilirubin measurements in breastfed babies aged 3-7 days who received the enzyme inhibitors when compared with the controls.[31] However, a similar treatment effect observed in group 4 raises some questions regarding the value of these therapies.

Sn-mesoporphyrin

Experimental therapy with Sn-mesoporphyrin inhibits bilirubin production by interfering with heme-oxygenase, an essential enzyme in the catabolic pathway of hemoglobin. This therapy is in clinical trials but has not been approved for use by the Food and Drug Administration (FDA). A report of a single case of compassionate use in the United States in a very low birth weight infant with severe growth restriction who was not a candidate for exchange transfusion showed a more than 25% reduction in total serum bilirubin levels after administration of a single dose at 46 hours of life.[32] Although more extensively studied in other countries, the safety and possible long-term sequelae of this therapeutic modality remain to be elucidated.

Consultations

Obtaining input from a pediatric neurologist during the acute presentation of BIND may be useful. However, the history and clinical presentation may make the diagnosis apparent.

In the chronic phase, involving neurodevelopmental specialists in the care and evaluation of the infant is important. Developmental potential can be maximized by early identification of and intervention for neurologic deficits.

If the patient develops hydrocephalus, consultation with a neurosurgeon is recommended.

Next

Surgical Care

Stable central venous access is required to successfully perform an exchange transfusion. Surgical placement of appropriate lines may be required to facilitate this procedure if a catheter cannot be placed into the umbilical vein.

Previous
Next

Diet

Depending on the degree of neurologic impairment, infants or children may have limitations in their ability to eat normally. Diet and nutrition must be individualized with the help of the neurodevelopmental team caring for the patient.

Previous
Next

Activity

Some neurologic deficits typically appear during the phase of motor skill acquisition by the infant. Motor deficits should be identified early, and appropriate intervention should be initiated to maximize the infant's ability in this critical area.

Previous
 
 
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].

 
Previous
Next
 
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.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.