1. Dr.AbdulRahman Al-nemri Ass. Professor Consultant neonatologist Hyperbilirubineamia New Guidelines AAP - 2004

2. Early History of Neonatal Jaundice The concept of a relationship between severe neonatal hyperbilirubinemia and kernicterus evolved slowly the first record concerning jaundice of the newborn appears to be by Barthomomaeus Metlinger in 1473 in his book Ein Regiment der Jungen Kinder. An early description of icterus neonatorum was published in 1742 in London by John Burton Johannes Orth is credited with publication of the first description of the characteristic pathoanatomic findings in kernicterus in 1875 in Berlin In 1904, Christian Georg Schmorl was the first to use the term kernicterus (nuclear jaundice) Diamond LK. A history of jaundice. In: Bergsma D, Hsia DYY, eds. Bilirubin Metabolism in the Newborn. Birth Defects Original Article Series VI. Baltimore, Md: Williams and Wilkins;1970

3. 1956 -Phototherapy Begins Rochford General Hospital in Essex, England,

4. Is Kernicterus Preventable? Baby Hisham borne to a 32 year old Saudi, G3 P3 mother Birth-weight was 3500 grams; GA was 38 weeks: The routine examination was normal Discharge after 24 hours on breast feeding 2 nd day notice to be jaundice

5. Follow up At about 48 hours of age, seen by pediatric emergency Total serum bilirubine was 14 mg/dl Admitted to Pediatric ward, Phototherapy started with IV fluid and antibiotics

6. 3th day recorded progression of jaundice At night nurse had noted he had “breast feeding difficulties”. 2 AM The total serum bilirubin was 35.6 mg/dL. After 18 hrs of phototherapy Transfer to NICU, DV exchange transfusion Developed respiratory distress connected to MV for 5 days CT and MRI Follow up choreo-athedoid CP Case of Kernicterus

7. NEONATAL JAUNDICE IN AL-HOFUF AREA Abbas Al-Omran, MD; Fouad Al-Ghazal, MD; Samir Gupta, MD; Over the study period, (May 1996 to May 1997) a total of 4388 children were admitted to the pediatric ward. Of these, 365 (8%) were neonates and 218 admissions were for neonatal jaundice. (60% of all neonatal admissions) Annals of Saudi Medicine, Vol 19, No 2, 1999

8. TABLE 1. The causes of jaundice. Cause Number (%) G6PD deficiency 64 (30.3) ABO incompatibility 21 (10) Breast milk 11 (5.2) Sepsis 4 (1.9) Rh incompatibility 2 (0.9) Other (elliptocytosis) 1 (0.5) Undetermined 108 (51.2) Total 211 (100)

10. Hour-specific Bilirubin load Bilirubin production Entero-hepatic circulation Bilirubin Elimination MINUS PLUS

16. kernicterus basal ganglia hippocampus cranial nerve nuclei geniculate bodies

17. Pathophysiology Bilirubin staining in the regions of the basal ganglia, hippocampus, substantia nigra, and brainstem nuclei staining can occur in the absence of severe hyperbilirubinemia Characteristic patterns of neuronal necrosis

18. This coronal section shows yellow discoloration of subcortical gray structures, globus pallidus, subthalamic nucleus and hippocampus

19. Incidence Do we have any registry in Saudi Arabia?? All reported cases from Saudi literatures were secondary to Crigler Najjarr syndrome All reported cases from Saudi literatures were secondary to Crigler Najjarr syndrome Am J Med Genet. 1998 Aug 27;79(1):12-5

20. Prevalent in the 1950s and 1960s, kernicterus had virtually disappeared from the clinical scene (In the 1970s, the combination of advances in management (ie, use of phototherapy and exchange transfusion and the use of Rhogam to prevent Rh erythroblastosis offered the promise of a major reduction in the occurrence of kernicterus ) Only to reappear during the 1990s. Johnson L, Brown AK: A pilot registry for acute and chronic kernicterus in term and near-term infants. Pediatrics 1999 Sep; 104:(3): 736.

21. A pilot kernicterus registry following the cases of babies with kernicterus in the United States reports 80 babies with chronic kernicterus enrolled in the registry in the last 12 years Johnson L, Brown AK: A pilot registry for acute and chronic kernicterus in term and near-term infants. Pediatrics 1999 Sep; 104:(3): 736.

22. Copyright ©2004 American Academy of Pediatrics Ip, S. et al. Pediatrics 2004;114:e130-e153 Geographic distribution of reported kernicterus cases

23. Alert in 2001 The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) issued a Sentinel Event Alert in 2001 notifying all hospitals that kernicterus does threaten healthy newborns. Laura Davidson, MD*ElizabethH.How to Make Kernicterus a "Never Event" NeoReviews Vol.4 No.11 2003 e308

24. Causes Severe hemolytic processes were identified in 19 out of 80 babies glucose-6-phosphate dehydrogenase (G6PD) deficiency was diagnosed in 18 out of 80 galactosemia occurred in 2 out of 80 Crigler-Najjar syndrome type I occurred in 1 NO etiology in 73% of cases Johnson L, Brown AK: A pilot registry for acute and chronic kernicterus in term and near-term infants. Pediatrics 1999 Sep; 104:(3): 736.

25. Fourteen cases of kernicterus were seen during a time period of 6 years, 71 per cent of them had G6PD deficiency, 1% Crigler-Najjar syndrome 23 % un determine Journal of Tropical Pediatrics 2003 49(2):74-77; doi:10.1093/tropej/49.2.74 Department of Child Health, Royal Hospital, Oman

26. Collaborative Perinatal Project (review of an old study: done before phototherapy was available) Number of Infants by Bilirubin Category with Abnormal Seven Year Neurologic Exam * u M/L mg/dl Number % < 171< 10.01090 3.7 171-25510-14.9 116 4.0 256-34115-19.8 43 4.9 > 342 > 20 12 4.5 P (trend, unadjusted)................................................. 0.06 Adjusted odds ratio (OR) per bilirubin category......... 1.10 95% confidence interval.............................................. 0.98, 1.23 * 1261 / 34299 (3.7%) of those examined (~50% exchange)

27. Collaborative Perinatal Project (cont’d) Number of Infants by Bilirubin Category with Abnormal or Suspicious 7 Year Neurologic Exam * u M/L Mg/dl Number % < 171<10.0 4346 14.9 10-14.9 472 16.9 15-19.8 157 18.0 > 342 > 20.0 60 22.4 P (trend, unadjusted).................................................. <0.001 Adjusted odds ratio per bilirubin category.............. 1.12 95% confidence limits................................................ 1.06, 1.20 * 5035 / 34299 (14.7%) of those examined

28. Phase 1 (first few days of life): Acute Bilirubin Encephalopathy (ABE) Decreased alertness Hypotonia are the typical signs Poor feeding. These are quite nonspecific A high index of suspicion of possible bilirubin encephalopathy Seizure is not typically associated with acute bilirubin encephalopathy.

29. Phase 11 Acute Bilirubin Encephalopathy (ABE) Phase 11 Acute Bilirubin Encephalopathy (ABE) Hypertonia Retrocolis Arching Ophisthonus Fever High pitched cry Regardless of TSB level [rising or falling] TSB = 22.7 mg/dL

30. Clinical Spectrum: Adverse Effects of Newborn Jaundice Bilirubin Induced Neurologic Dysfunction (BIND) Acute Bilirubin Encephalopathy Chronic Post-icteric Sequelae (Kernicterus) Auditory Neuropathy (isolated) Subtle manifestations (extra-pyramidal and central posturing disorders) suspected but not yet proven Death: respiratory failure Outcome influenced by timely intervention

31. Collaborative Perinatal Project (cont’d) Suspicious neurologic findings with stepwise increase in peak serum bilirubin levels (likely signs of extra-pyramidal damage) Gait abnormalities Awkwardness Equivocal Babinski Failure at fine stereognosis Questionable hypotonia Gaze abnormalities Vasomotor abnormalities Abnormal abdominal reflexes Abnormal cremasteric reflexes <0.001 0.008 0.005 to 0.07 0.001 to 0.05 0.005 0.008 0.001 Probability

32. Condition1 Point2Points3 Points Mental StatusSleepy, poor feeding Lethargy, irritability Semicoma, seizures Muscle ToneSlight decreaseHyper- or hypotonia, mild arching Markedly increased or decreased, opishotonus, bicycling CryHigh-pitchedShrill or too infrequent Inconsolable or only with stimulation Pediatrics. 1999;104(suppl):746–747 Bilirubin neurologic dysfunction (BIND) score

33. Management of Severe Hyperbilirubinemia Decrease entero-hepatic circulation  Increase enteral milk intake  Promote breast feeding and milk transfer  Supplement enteral intake Phototherapy Exchange transfusion Immunoglobulin With Increasing hyperbilirubinemia MRI evidence of Kernicterus

34. Management of Hyperbilirubinemia AAP Alerts: Clinical Overview: Usually benign; but potential of bilirubin toxicity Focus: Reduce incidence of severe hyperbilirubinemia Recommend: Promote and support successful breastfeeding. Universal systematic pre-discharge assessment. Provide targeted follow-up based on the risk. Track outcome for timely treatment to prevent excessive hyperbilirubinemia and possibly, kernicterus.

35. AAP 2004: Recommendations AAP 2004: Recommendations I. Primary Prevention: lactation support II. Risk assessment for severe hyperbilirubinemia:: III. Interpretation of TSB values IV. Cause of jaundice/hyperbilirubinemia. V. Pre-discharge risk assessment VI. Hospital policies and procedures VII. Treatment

36. RECOMMENDATION 1.0: Clinicians should advise mothers to nurse their infants at least 8 to 12 times per day for the first several days (evidence quality C: benefits exceed harms).

37. RECOMMENDATION 1.1: The AAP recommends against routine supplementation of non-dehydrated breastfed infants with water or dextrose water evidence quality B and C: harms exceed benefits). RECOMMENDATION 1.1: The AAP recommends against routine supplementation of non-dehydrated breastfed infants with water or dextrose water evidence quality B and C: harms exceed benefits).

38. SECONDARY PREVENTION All pregnant women should be tested for ABO and Rh (D) blood types and have a serum screen for unusual iso-immune antibodies (evidence quality B: benefits exceed harms). If a mother has not had prenatal blood grouping or is Rh-negative, a direct antibody test (or Coombs’ test), blood type, and an Rh (D) type on the infant’s (cord) blood are strongly recommended (evidence quality B: benefits exceed harms).

39. Mother is O +ve If the maternal blood is group O, Rh-positive, it is an option to test the cord blood for the infant’s blood type and direct antibody test, but it is not required provided that there is appropriate surveillance, risk assessment before discharge, and follow-up (evidence quality C: benefits exceed harms).

40. Clinical Assessment Clinicians should ensure that all infants are routinely monitored for the development of jaundice, and nurseries should have established protocols for the assessment of jaundice Jaundice should be assessed whenever the infant’s vital signs are measured but no less than every 8 to 12 hours

41. Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316 Algorithm for the management of jaundice in the newborn nursery

42. Measurement of Bilirubin TcB: BiliChek ® TSB: at individual hospital laboratories TSB: Inter-and intra- institution calibration CAP Variance Actual variance values: are usually 2 to 3%. * Bhutani et al: Pediatrics. 2000;106:1-6; Rubaltelli et al: Pediatrics. 2001;107:1264 A

43. Accuracy, Precision and Performance of TcB Measurements in Term and near-term Infants (BiliChek TM device) A

44. Monitor for Jaundice progression every 8 to 12 hours [recommendation 2.2] Jaundice ProgressionZone None0 Face and neck1 Umbilicus2 Knees3 Ankles4 Toes5 Kramer LI. Am J Dis Child. 1969;118:454-458 D

45. Zone(n)Mean ± SDMedianRanges 04105.0 ± 1.75.20.0 to 11.2 13276.4 ± 1.66.12.3 to 13.8 21467.8 ± 1.57.64.3 to 14.2 32210.2 ± 2.710.06.1 to 18.4 4910.9 ± 2.810.07.2 to 16.2 5111.6 Correlation of Jaundice Zone Distribution to TcB (mg/ d L) values at Age <36 hrs (n=916)

46. RECOMMENDATION 4.1 Cause of Jaundice RECOMMENDATION 4.1 The possible cause of jaundice should be sought in an infant receiving phototherapy or whose TSB level is rising rapidly (ie, crossing percentiles and is not explained by the history and physical examination D: benefits versus harms exceptional).

47. Hour-specific values clinically more relevant than day- specific values Percentile based assessment rather than arbitrarily defined criteria Clinical Assessment: Hour- specific Serum Bilirubin

48. Hour-Specific Bilirubin Nomogram 95th %ile 75th %ile 40th %ile High-Risk Zone Low-Risk Zone A

49. RECOMMENDATION 4.1.1 Cause of Jaundice RECOMMENDATION 4.1.1 Infants who have an elevation of direct- reacting or conjugated bilirubin should have a urinalysis and urine culture. Additional laboratory evaluation for sepsis should be performed if indicated by history and physical examination (evidence quality C: benefits exceed harms). Additional laboratory evaluation for sepsis should be performed if indicated by history and physical examination (evidence quality

50. Crigler Najjarr syndrome Crigler Najjarr syndrome G6PD deficiency is widespread and frequently unrecognized

51. Bilirubin levels (mg/dL)* Percentile for age in hours AdjectiveEstimated known Incidence (with current strategy) 17.0~95 th Significant1 : 10 20.0~98 th Severe1 : 70 25.0~99 th Extreme1 : 700 30.0~99.99 th Hazardous1 : 10,000 > 30.0> 99.99 th DangerousShould not happen Defining Severity of Hyperbilirubinemia * When measured at > 72 hours age Bhutani et al. Journal of Perinatology: 2004 (NIHCD Report)

52. RECOMMENDATION 5.1: Risk Assessment Before Discharge RECOMMENDATION 5.1: Before discharge, every newborn should be assessed for the risk of developing severe hyperbilirubinemia The best documented method for assessing the risk of subsequent hyperbilirubinemia is to measure the TSB or TcB level and plot the results on a nomogram The best documented method for assessing the risk of subsequent hyperbilirubinemia is to measure the TSB or TcB level and plot the results on a nomogram Stevenson DK, Fanaroff AA, Maisels MJ, et al. Prediction of hyperbilirubinemia in near-term and term infants. Pediatrics. 2001;108:31–39

53. Major Clinical Risk Factors for Hyperbilirubinemia Pre-discharge TSB or TcB level plotted in the high-risk zone (>95 th percentile) of the hour- specific bilirubin nomogram Jaundice observed in the first 24 hours Blood group incompatibility Gestational age 35–36 wks Previous sibling received phototherapy Cephalhematoma or significant bruising Exclusive breastfeeding Subcommittee on Hyperbilirubinemia: Pediatrics 2004 C

54. Minor Clinical Risk Factors Pre-discharge TSB or TcB plotted in the >75 th percentile; high intermediate-risk zone Gestational age 37–38 wks Jaundice observed before discharge Previous sibling with jaundice Macrosomic infant of a diabetic mother Maternal age ≥25 years Male gender Subcommittee on Hyperbilirubinemia: Pediatrics 2004 C

55. Decreased risk (these factors are associated with decreased risk of significant jaundice, listed in order of decreasing importance) TSB or TcB level in the low-risk zone Gestational age 41 wk Exclusive bottle feeding Black race* Discharge from hospital after 72 h40,44 Newman TB, Xiong B, Gonzales VM, Escobar GJ. Prediction and prevention of extreme neonatal hyperbilirubinemia in a mature health maintenance organization. Arch Pediatr Adolesc Med. 2000;154:1140–1147

56. Pre-discharge Risk Assessment: [Recommendation: 5.1.1] Clinical Risk Factors Present Exclusive Breast Feeding…..…… 6 fold Lower Gestation…………….……. 2 fold Maternal Age……………………… 3 fold Cephalhematoma………………… 3 fold Early Jaundice……………………. 7 fold Pre-discharge TcB/TSB (estimate: 14.0 at 52 hours age)  A C

57. 95th %ile 75th %ile 40th %ile  35.4 mg/dL at 130 hrs age 14.0 mg/dL at 48 hrs age   Cord TSB Clinical Case: Window of opportunity B

58. Recommendation 6:1 System Policies and Procedures Each hospital should provide written and oral information for parents at the time of discharge. Each hospital should provide written and oral information for parents at the time of discharge. This should include an explanation of jaundice: its potential risk the need to monitor infants for jaundice advice on how to monitor the progress of jaundice and hyperbilirubinemia. D

59. Recommendation 6.1.1: Follow-up Every infant should be examined by a qualified health care professional in the first few days following discharge to assess infant well-being and the presence or absence of jaundice. The timing and location of this assessment will be determined by the length of stay in the nursery presence or absence of risk factors for hyperbilirubinemia C

60. When Discharged with a pre-discharge Should be seen Age <24 hoursBy age 72 hours Age: 24 to 47.9 hoursBy age 96 hours Age: 48 to 72 hoursBy age 120 hours 6.1.2: Timing of Follow-up Clinical judgment should be used in determining follow-up. Earlier or more frequent follow-up should be provided for those who have risk factors for hyperbilirubinemia while those discharged with few or no risk factors can be seen after later intervals. C

61. 6.1.3: Inability to Ensure a Follow-up If appropriate follow-up cannot be ensured, scheduled or, there is a concern of parental ability to keep appointment: in the presence of elevated risk for developing severe hyperbilirubinemia:  it may be necessary to delay discharge –until appropriate follow-up can be ensured and assured – or the period of greatest risk has passed when the infant is 72 to 96 hours age. D

62. 6.1.4: Follow-up Assessment The follow-up assessment should document: infant’s weight and percent change from birth weight adequacy of intake, BM or formula pattern of voiding and stooling presence or absence of jaundice. C

63. Follow- up Clinical judgment should be used to determine the need for a bilirubin measurement.  Any doubt about the degree or progression of jaundice: a TSB or TcB should be measured.  Visual estimation of bilirubin levels can lead to errors, particularly in darkly pigmented infants

64. Key Hospital Policies and Procedures: Establish of standing protocols such as: nursing assessment of jaundice, including testing TcB and TSB, with-out requiring physician orders. Use checklists or reminders: Clinical risk factors Age at discharge (in hours) TSB / TcB plotted on hour-specific bilirubin nomogram Risk-based follow-up guidelines. Explicit educational materials for parents concerning the identification and risks of newborns with jaundice.

65. Skill and training Unfettered ability to measure TcB / TSB without MD order for any suspicion of jaundice in first 36 hours after birth Policy to document jaundice, its location and TcB / TSB (when needed) as a vital sign (every 8 hrs after initial evaluation within 4 to 6 hours after birth Consistent resources for parent and family education Ensure timely counseling, follow-up and intervention Nursing Assessment for Newborn Jaundice C

66. Outcome Assessment: Performance standards Hazardous level Extreme level Pre-discharge screening for all infants At-Risk Population “Close Call” Never Event Based on TSB thresholds for phototherapy (at-risk) and exchange transfusion (“close call”) for infants high, medium or low risk for bilirubin neurotoxicity D

67. TREATMENT Phototherapy and Exchange Transfusion Use intensive phototherapy and/or exchange transfusion as indicated Use intensive phototherapy and/or exchange transfusion as indicated In using the guidelines for phototherapy and exchange transfusion direct-reacting (or conjugated) bilirubin level should not be subtracted from the tota

68. Management of the Breastfed Jaundiced In breastfed infants who require phototherapy the AAP recommends that, if possible, breastfeeding should be continued It is also an option to interrupt temporarily breastfeeding and substitute formula. In breastfed infants receiving phototherapy, supplementation with expressed breast milk or formula is appropriate if the infant’s intake seems inadequate, weight loss is excessive, or the infant seems dehydrated.

69. Copyright ©2004 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316 Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation

70. Copyright ©2004 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316 Guidelines for exchange transfusion in infants 35 or more weeks' gestation

71. 71 Can sunlight replace phototherapy units in the treatment of neonatal jaundice? Can sunlight replace phototherapy units in the treatment of neonatal jaundice? Photodermatology Photoimmunology & Photomedicine Volume 17 Issue 6 Page 272 - December 2001 doi:10.1034/j.1600-0781.2001.170605.x

72. AAP Although sunlight provides sufficient irradiance in the 425- to 475-nm band to provide phototherapy, the practical difficulties involved in safely exposing a naked newborn to the sun either inside or outside(and avoiding sunburn) preclude the use of sunlight as a reliable therapeutic tool, and it therefore is not recommended.

73. Acute Bilirubin Encephalopathy : Immediate exchange transfusion is recommended in any infant who is jaundiced and manifests the signs of the intermediate to advanced stages of acute bilirubin encephalopathy (hypertonia, arching, retrocollis, opisthotonos, fever, high-pitched cry) even if the TSB is falling (evidence quality D: benefits versus risks exceptional ). Volpe JJ. Neurology of the Newborn. 4th ed. Philadelphia, PA: W. B. Saunders; 2001

74. RECOMMENDATION 7.1.3 Exchange transfusions should be performed only by trained personnel in a neonate intensive care unit with full monitoring and resuscitation capabilities (evidence quality D: benefits versus harms exceptional).

75. RECOMMENDATION 7.1.4 In isoimmune hemolytic disease, administration of intravenous Ý-globulin (0.5-1 g/kg over 2 hours) is recommended if the TSB is rising despite intensive phototherapy or the TSB level is within 2 to 3 mg/dL (34-51 mol/L) of the exchange level If necessary, this dose can be repeated in 12 hours Gottstein R, Cooke R. Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn. Arch Dis Child Fetal NeonatalEd. 2003;88:F6–F10

76. Serum Albumin Levels & Bilirubin/Albumin Ratio It is an option to measure the serum albumin level and consider an albumin level of less than 3.0 g/dL as one risk factor for lowering the threshold for phototherapy use If an exchange transfusion is being considered, the serum albumin level should be measured and the bilirubin/albumin (B/A) ratio used in conjunction with the TSB level and other factors in determining the need for exchange transfusion

77. The following B/A ratios can be used together with but in not in lieu of the TSB level as an additional factor in determining the need for exchange transfusion (Pediatrics. 1992;90 :707 –715) Risk Category TSB mg/dL/Alb, g/dLTSB mol/L/Alb, mol/L Infants 38 wk 80.94 Infants 35 –36 and well or 38 wk if higher risk or isoimmune hemolytic disease 7.20.84 Infants 35 0/7–37 6/7 wk if higher risk or isoimmune hemolytic disease or G6PD deficiency 6.80.80

78. Five Key Areas for Improvement in the Management of Neonatal Jaundice Level of concern: neurotoxic potential of bilirubin Limitations on visual recognition of jaundice as index to initiate evaluation or estimate severity Recognize severity of hyperbilirubinemia corrected for age in hours Ensure targeted follow-up within 12 to 48 hours after discharge Quick intensive or timely intervention for severe hyperbilirubinemia. Need for systems-approach to manage jaundice for prevention of kernicterus

79. Root Cause for Kernicterus Failure to recognize the clinical significance of jaundice within the first 24 hours after birth. Failure to recognize the limitations of visual recognition of jaundice. Failure to recognize clinical jaundice and document its severity by bilirubin measurement before discharge from the hospital. Complied from AAP reports, JCAHO Alerts and CDC Report

80. Failure to ensure post-discharge follow-up based on the severity of pre-discharge hyperbilirubinemia. Failure to respond to parental concerns of newborn jaundice, poor feeding, lactational difficulties and change in newborns behavior and activity.

81. Failure to provide ongoing lactational support in breast-feeding babies to ensure adequacy of intake. Failure to recognize the impact of race, ethnicity and family history on severity newborn jaundice and risk of brain damage. Failure to diagnose the cause of hyperbilirubinemia..

82. Failure to institute interventional strategies to prevent severe hyperbilirubinemia when bilirubin is rising more rapidly than expected. Failure to aggressively treat severe hyperbilirubinemia with intensive phototherapy or exchange transfusion for “hazardous” bilirubin levels. Failure to educate parents and health care providers about the potential irreversible risks of jaundice during newborn period and infancy

83. Implementation of these guidelines The establishment of standing protocols for nursing assessment of jaundice, including testing TcB and TSB levels, without requiring physician orders. Checklists or reminders associated with risk factors, age at discharge, and laboratory test results that provide guidance for appropriate follow-up. Explicit educational materials for parents (a key component of all AAP guidelines) concerning the identification of newborns with jaundice.

84. CONCLUSIONS Kernicterus is still occurring but should be largely preventable if health care personnel follow this recommendations These recommendations emphasize the importance of universal, systematic assessment for the risk of severe hyperbilirubinemia, close follow-up, and prompt intervention, when necessary.

85. FUTURE RESEARCH Epidemiology of Bilirubin-Induced Central Nervous System Damage

86. Best Practice Models Pennsylvania Hospital, PA Bhutani V. K., Johnson L.H., Schwoebel, A. William Beaumont Hospital, MI Maisels M. J. and colleagues Henry Ford Hospital, MI Palmer R.H., Ezhuthachan S, Newman C. et al Lucile Packard Children’s Hospital, CA Stevenson D. K. and Burgos A. Hospital Corporation of America, USA Rodriguez M., Bhutani V.K. and Maisels M. J. and the HCA Perinatal Safety Initiative for “Kernicterus As A Never Event” [a 124 hospital-wide initiative]

87. Sentinel References AAP: American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114:297-316. AHRQ: Ip S, et al. and the American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. An evidence-based review of important issues concerning neonatal hyperbilirubinemia. Pediatrics. 2004;114:e130-53. JCAHO: Revised guidance to help prevent kernicterus. Sentinel Event Alert. 2004 31(31):1-2.