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  1. 1. Neonatal Jaundice Dr Muzammil Koshish DCH, DNB Resident, JLN Hospital and Research Centre, Bhillai.
  2. 2. Neonatal Jaundice Learning Objectives: Define hyperbilirubinemia. Differentiate between physiological and pathological jaundice. Causes of hyperbilirubinemia. Discuss the pathophysiology of hyperbilirubinemia. Complication of hyperbilirubinemia. The three elements of therapeutic management. Plan of care if baby has hyperbilirubinemia. 2
  3. 3. Neonatal Jaundice(Hyperbilirubinemia) Definition: Hyperbilirubinemia refers to an excessive level of accumulated bilirubin in the blood and is characterized by jaundice, a yellowish discoloration of the skin, sclerae, mucous membranes and nails. Unconjugated bilirubin = Indirect bilirubin. Conjugated bilirubin = Direct bilirubin. 3
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  5. 5. Neonatal Jaundice Visible form of bilirubinemia  Newborn skin >5 mg / dl Occurs in 60% of term and 80% of preterm neonates However, significant jaundice occurs in 6 % of term babies 5
  6. 6. Non – heme sourceHb → globin + haem 1 mg / kg1g Hb = 34mg bilirubin Bilirubin Ligandin (Y - acceptor) Intestine Bilirubin glucuronidase Bil Bil glucuronide glucuronide β glucuronidase bacteria Bilirubin Stercobilin Bilirubin metabolism 6
  7. 7. Bilirubin Production & Metabolism 7
  8. 8. Clinical assessment of jaundiceArea of body Bilirubin levels mg/dl (*17=umol)Face 4-8Upper trunk 5-12Lower trunk & thighs 8-16Arms and lower legs 11-18Palms & soles > 15 8
  9. 9. Physiological jaundiceCharacteristics Appears after 24 hours Maximum intensity by 4th-5th day in term & 7th day in preterm Serum level less than 15 mg / dl Clinically not detectable after 14 days Disappears without any treatment Note: Baby should, however, be watched for worsening jaundice. 9
  10. 10. Why does physiologicaljaundice develop? Increased bilirubin load. Defective uptake from plasma. Defective conjugation. Decreased excretion. Increased entero-hepatic circulation. 10
  11. 11. Course of physiologicaljaundice 15 Bilirubin level mg/dl 10 5 Term Preterm 1 2 3 4 5 6 10 11 12 13 14 Age in Days 11
  12. 12. Pathological jaundice Appears within 24 hours of age Increase of bilirubin > 5 mg / dl / day Serum bilirubin > 15 mg / dl Jaundice persisting after 14 days Stool clay / white colored and urine staining clothes yellow Direct bilirubin> 2 mg / dl 12
  13. 13. Causes of jaundiceAppearing within 24 hours of age Hemolytic disease of NB : Rh, ABO Infections: TORCH, malaria, bacterial G6PD deficiency 13
  14. 14. Causes of jaundiceAppearing between 24-72 hours of life Physiological Sepsis Polycythemia Intraventricular hemorrhage Increased entero-hepatic circulation 14
  15. 15. Causes of jaundiceAfter 72 hours of age Sepsis Cephalhaematoma Neonatal hepatitis Extra-hepatic biliary atresia Breast milk jaundice Metabolic disorders. 15
  16. 16. Risk factors for jaundiceJAUNDICE J - jaundice within first 24 hrs of life A - a sibling who was jaundiced as neonate U - unrecognized hemolysis N – non-optimal sucking/nursing D - deficiency of G6PD I - infection C – cephalhematoma /bruising E - East Asian/North Indian 16
  17. 17. Diagnostic evaluation: Normal values of unconjugated B. are 0.2 to 1.4 mg/dL. Investigate the cause of jaundice. 17
  18. 18. Clinical Jaundice Measure BilirubinBilirubin>12mg/dL Bilirubin<12mg/dLAnd Infant <24-h old and Infant >24-h old Coomb’s test Follow BilirubinPositive Coomb’s Negative Coomb’sIdentify Antibody•Rh•ABO•KELL, etc. Direct Bilirubin 18
  19. 19. Direct BilirubinDirect Bilirubin >2; Consider: Direct Bilirubin <2HepatitisIntrauterine, Viral, orToxoplasmic infections HematocritBiliary obstructionSepsisGalactosemiaAlpha-1-antitrypsin deficiency Normal or Low HighCystic fibrosis (Polycythemia)TyrosinosisCholestasisHyperalimentationSyphillis RBC MorphologyHemochromatosis Reticulocyte count 19
  20. 20. RBC Morphology Reticulocyte countAbnormal: Normal:Spherocytosis -Enclosed hemorrhageElliptocytosis -Increased EnterohepaticStomatocytosis CirculationPyknocytosis -Breast Milk JaundiceABO incompatibility -HypothyroidismRed cell enzyme deficiency -Criglar-Najjar SyndromeAlpha Thalassemia -Infant of Diabetic motherDrugs (eg. Penicillin) -RDSDIC -Asphyxia -Infection -Gilbert Syndrome -Drugs (eg. Novobiocin) -Galactosemia (Early) 20
  21. 21.  Medical Care of neonatal jaundice 21
  22. 22. Medical Care Phototherapy Exchange transfusion Drugs Diet 22
  23. 23. Phototherapy Is the primary treatment . Was discovered in England in the 1950s . 23
  24. 24. Why Phototherapy iseffective?Three reactions can occur when bilirubin is exposed to light : Photo-oxidation Photo-isomerization Structural isomerization 24
  25. 25. Factors That Affect the Doseand Efficacy of Phototherapy Wavelength Irradiation level Distance Bilirubin concentration Nature and character of the light source 25
  26. 26. Wavelength Bilirubin absorbs light primarily around 450 nm, typically 425 to 475 nm In practice, light used in wavelengths : white, blue, and green 26
  27. 27. Irradiation level A dose-response relationship exists 27
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  29. 29. Distance Distance should not be greater than 50 cm (20 in) Can be less if the infants temperature is monitored. Energy delivered decreases with increasing distance . 29
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  31. 31. Bilirubin concentration The efficiency of phototherapy increases with : - serum bilirubin concentration. - skin surface 31
  32. 32. Nature and character of thelight source Wide Spectrum Quartz halide spotlights Green light Blue fluorescent tubes Narrow-spectrum Ordinary White (daylight) fluorescent tubes White quartz lamps Fiberoptic light 32
  33. 33. Indications for phototherapy In most neonatal wards, total serum bilirubin levels are used as the primary measure of risk for bilirubin encephalopathy. The 2004 AAP guidelines represent a significant change from the 1994 guidelines. The emphasis on preventive action and risk evaluation is much stronger. 33
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  35. 35. Key points in the practice Maximizing energy delivery Maximizing the available surface area. 35
  36. 36. Intermittent VersusContinuous Phototherapy ? Clinical studies have produced conflicting results. Individual judgment should be exercised. If the infant’s bilirubin level is approaching the exchange transfusion zone , phototherapy should be administered continuously until a satisfactory decline in the serum bilirubin level occurs or exchange transfusion is initiated. 36
  37. 37. What about insensible waterloss? New data suggest that if temperature homeostasis is maintained, fluid loss is not increased significantly by phototherapy. In infants who are fed orally, the preferred fluid is milk, since milk serves as a vehicle to transport bilirubin out of the gut. 37
  38. 38. Timing of follow-upserum bilirubin ? In infants admitted with extreme serum bilirubin values ( 30 mg/dL): monitoring should occur every hour or every other hour.--------- Reductions in serum bilirubin values (5 mg/dL/h). In infants with more moderate elevations of serum bilirubin : monitoring every 6-12 hours . 38
  39. 39. Expectations regardingefficacy of phototherapy ? Bilirubin concentrations are still rising----- a significant reduction of the rate of increase . Bilirubin concentrations are close to their peak----- phototherapy should result in measurable reductions in serum bilirubin levels within a few hours. In general, the higher the starting serum bilirubin concentration, the more dramatic the initial rate of decline. 39
  40. 40. When discontinuation ofphototherapy? When serum bilirubin levels fall (1.5-3 mg/dL) below the level that triggered the initiation of phototherapy. Serum bilirubin levels often rebound, and follow-up tests should be obtained within 6-12 hours after discontinuation. 40
  41. 41. What aboutprophylactic Phototherapy ? No purpose In general, the lower the serum bilirubin level, the less efficient the phototherapy. 41
  42. 42. Phototherapy complications Phototherapy is very safe, and it may have no serious long- term effects in neonates . Insensible water loss is not as important as previously believed. Loose stools. Bronze baby syndrome Retinal damage Effects on cellular genetic material in vitro and animal data have not been shown any implication for treatment of human neonates. However, most hospitals use cut-down diapers during phototherapy . 42
  43. 43. Phototherapy complications Skin blood flow is increased-- redistribution of blood flow may occur in small premature infants-- Increased incidence of patent ductus arteriosus (PDA) has been reported But this effect is less pronounced in modern servocontrolled incubators. Hypocalcemia in premature infants . It has been suggested that this is mediated by altered melatonin metabolism. Deterioration of certain amino acids in total parenteral nutrition (TPN) solutions. Shield TPN solutions from light as much as possible. Accidents have been reported, including burns resulting from failure to replace UV filters. 43
  44. 44. Babies under phototherapyBaby under conventional Baby under triple unit intense phototherapy phototherapy
  45. 45.  Exchange transfusion 45
  46. 46. What are indications ofExchange transfusion? Avoiding bilirubin neurotoxicity when other therapeutic modalities have failed. In addition, even in the absence of high serum bilirubin levels, the procedure may be indicated in infants with erythroblastosis . 46
  47. 47. Exchange transfusion hasbeen performed because of : Cord hemoglobin <11 g/dL Cord bilirubin > 4.5 mg/dL Rapid rate of increase in bilirubin >1 mg/dL/h More moderate rate of increase in bilirubin> 0.5 in the presence of moderate anemia Hb=11-13 Hemolytic jaundice with bilirubin > 20 or a rate of increase that predicted this level (fear of 20) . 47
  48. 48. Why Exchange transfusionbecome a rare procedure ?? Immunotherapy in Rh-negative women So ,ABO incompatibility has become the most frequent cause of hemolytic disease in industrialized countries. Effective phototherapy Recently, immunotherapy has been introduced as treatment in the few remaining sensitized infants. Results are promising 48
  49. 49. When exchange transfusionshould be performed ?  When phototherapy does not significantly lower serum bilirubin levels  Intensive phototherapy is strongly recommended in preparation for an exchange transfusion. do not await laboratory test results in these cases . 49
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  51. 51. Complications of Exchangetransfusion Hypocalcemia and hypomagnesemia Hypoglycemia Acid-base disorder Hyperkalemia Cardiovascular Bleeding Infections Hemolysis Temperature dysreguation 51
  52. 52.  DRUGS 53
  53. 53. What about Phenobarbital ?an inducer of hepatic bilirubinmetabolism  Several studies have shown that phenobarbital is effective .  Phenobarbital may be administered : - pre-natally in the mother or - post-natally in the infant.  However, concerns exist regarding the long-term effects of phenobarbital on these children. 54
  54. 54. What about IV immunoglobulin(500 mg/kg) ?  Significantly reduce the need for exchange transfusions in infants with isoimmune hemolytic disease. 55
  55. 55. New therapy :Mesoporphyrins and Protoporphyrins  Currently under development  Inhibition of bilirubin production through blockage of heme oxygenase.  Apparently, heme can be excreted directly through the bile .  This approach may virtually eliminate neonatal jaundice as a clinical problem. But … 56
  56. 56. Important questionsbefore the treatment can be applied  Long-term safety ?.  Complete understanding of putative role for bilirubin in light of data suggesting that bilirubin may play an important role as a free radical quencher ( anti-oxidant ) ? 57
  57. 57. DIET Temporary interruption of breastfeeding…It is not recommendedunless serum bilirubin levels reach 20 mg/dL 58
  58. 58. Supplementation with dextrosesolution It is not recommended because - it may decrease caloric intake - it may decrease milk production - it may accelerate enterohepatic circulation and consequently delay the drop in serum bilirubin concentration 59
  59. 59. What isthe recommendation ? Increase breastfeeding to 8-12 times per day Breastfeeding can also be supported with manual or electric pumps and the pumped milk given as a supplement to the baby. 60
  60. 60. When infants can bedischarged ? When they are : - feeding adequately and - demonstrating a trend towards lower values. Auditory function tests prior is advisable in infants who have had severe jaundice. 61
  61. 61. How to manage infants releasedwithin the first 48 hours of life ? In the era of early discharge in recent years, a number of infants have developed kernicterus --- Infants need to be reassessed for jaundice within 1-2 days. Use of hour-specific bilirubin nomogram may assist in selecting infants . 62
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  63. 63. Do infants need follow-upobsevation after Bilirubin falls? Infants with hemolytic jaundice require follow-up observation for several weeks because hemoglobin levels may fall lower than seen in physiologic anemia. Erythrocyte transfusions may be required if infants develop symptomatic anemia. 64
  64. 64. Finally…What aboutPrognosis ? Prognosis is excellent if the patient receives treatment according to accepted guidelines. The increased incidence of kernicterus in recent years may be due to the misconception that jaundice in the healthy full-term infant is not dangerous and can be disregarded. 65
  65. 65. The goals of planning Infant should receive appropriate therapy if needed to reduce serum bilirubin levels. Infant should experience no complications from therapy. Family should receive emotional support. Family should be prepared for discharge and home based care. 66
  66. 66. References 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 Johnson LH, Bhutani VK, Brown AK. System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr. 2002;140:396-403 American Academy of Pediatrics, Steering Committee on Quality Improvement and Management. Classification of recommendations for clinical practice guidelines. Pediatrics. 2004;114:874-877 Gartner LM, Herschel M. Jaundice and breastfeeding. Pediatr Clin North Am. 2001;48:389-399 Moyer VA, Ahn C, Sneed S. Accuracy of clinical judgment in neonatal jaundice. Arch Pediatr Adolesc Med. 2000;154:391-394 Ip S, Glicken S, Kulig J, Obrien R, Sege R, Lau J. Management of Neonatal Hyperbilirubinemia. Rockville, MD: US Department of Health and Human Services, Agency for Healthcare Research and Quality; 2003. AHRQ Publication 03-E011 Bhutani VK, Johnson LH, Sivieri EH. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent hyperbilirubinemia in healthy term and near-term newborns. Pediatrics. 1999;103:6-14. American Academy of Pediatrics, Subcommittee on Neonatal Hyperbilirubinemia. Neonatal jaundice and kernicterus. Pediatrics. 67 2001;108:763-765
  67. 67. Thank You! 68