of The Newborn Khalid Altirkawi MD Assistant Professor Pediatrics College of Medicine King Saud University Riyadh Saudi Arabia 2016 Disclaimer This presentation is meant to guide students when rotating in the NICU ID: 1044723
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1. NEONATAL JAUNDICEHyperbilirubinemia of The NewbornKhalid Altirkawi, M.DAssistant Professor, PediatricsCollege of MedicineKing Saud UniversityRiyadh, Saudi Arabia 2016
2. Disclaimer This presentation is meant to guide students when rotating in the NICU. It is not to replace the recommended textbooks. Khalid Altirkawi, MD
3. Objectives By the end of this presentation, the student should be able to:Describe the metabolic pathways of bilirubin.Differentiate between physiological and pathological types of neonatal jaundice.Tell the appropriate diagnostic tests for evaluating jaundiced infants.Mention the strategies for prevention and treatment of neonatal jaundice.
4. Introduction Neonatal Jaundice:A yellow discoloration of skin and sclera due to an increased concentration of serum bilirubin. Usually appears in the newborn infant when serum bilirubin concentration > 85 mol/L.Occurs in the majority of infantsTerm: >50%.Preterm: 80%
5. Metabolic Pathways
6. Bilirubin MetabolismSynthesis From the breakdown of the heme molecule:The hemoglobin … … ... ... ... ... ... ... ... … … ... (80%)Nonerytheroid heme (cytochrome, myoglobin..) (20%)Bilirubin produced isUnconjugated (indirect).Lipid soluble (pass through BBB) but not water soluble.
7. Bilirubin MetabolismTransportUnconjugated bilirubin is bound to albumin and carried via blood stream to liver.Hepatocytes uptake this Bilirubin and transport it intracellular where it is metabolized
8. Bilirubin Metabolism
9. Bilirubin Metabolism Conjugation Bilirubin is conjugated to glucoronic acid by the enzyme glucoronyl transferaseConjugated bilirubin (Direct) is water-soluble (pass in urine) but not lipid soluble
10. Bilirubin Metabolism ExcretionConjugated Bilirubin is excreted into the bileUnder the effect of the intestinal flora Enzyme glucouronidase unconjugates it. Bilirubin urobilinogin stercobilin (~85%, in the stool) Urobilin (reabsorbed into blood) (~1% in the urine)Some is reabsorbed and transported back to liver (~15%, Enterohepatic circulation)
11. BILIRUBIN Metabolism Pathway
12. Pathogenesis
13. PathogenesisUnconjugated hyperbilirubinemia:Defective conjugationIncreased production (e.g. hemolysis)Increased bilirubin load (e.g. cephalhematoma)Other unidentified mechanisms
14. PathogenesisDefective conjugationPhysiological JaundiceCongenital hypothyroidismEnzyme deficiency (e.g. Crigler-Najjar syndrome)
15. PathogenesisIncreased production (Hemolysis) Immune Iso-immune (hemolytic disease of the newborn)Auto-immune (Maternal auto-antibodies): e.g. SLENon immuneInherited hemolytic anemias (e.g. hemoglobinopathies, G6PD, Spherocytosis)Others: Vitamin E deficiency, Drugs, Infections, sepsis, DIC.
16. PathogenesisIncreased bilirubin loadExtravascular blood collectionPolycythemiaDehydration Increased enterohepatic circulationParalytic ileusHirschsprung’s diseaseIntestinal stenosis or atresia
17. PathogenesisUncertain mechanismsBreast milk jaundiceBreast feeding jaundiceSome ethnic groups
18. Pathogenesis Conjugated hyperbilirubinemia Decreased excretion rateObstructive lesions Congenital biliary atresia Tumors or cystInspissated bileMetabolic and endocrine abnormalities HypothyroidismGalactosemia
19. Pathogenesis Mixed hyperbilirubinemia Hepatocyte abnormalitiesSepsisIntrauterine infectionsNeonatal hepatitisHepatitis virusesTORCHIdiopathic hepatitisHypoxic insult
20. Clinical Presentations
21. Severe hemolysisPhysiological DehydrationSepsisCephalohematomaPolycythemiaCrigler-NajjarPrematurityInfectionHypothyroidism Breast milk jaundiceCrigler-NajjarObstructive lesionBiliary atresiaNeonatal hepatitisPatterns of neonatal jaundice
22. Causes by the age of onsetAt Birth or Within 24hHemolysis (Blood group incompatibility)Congenital infection (TORCH)SepsisWithin The 1st WeekPhysiological jaundiceCongenital infection (TORCH)SepsisConcealed hemorrhage Crigler-Najjar syndrome
23. Causes by the age of onsetAfter The 1st WeekBreast milk jaundiceSepsisHepatitisBiliary atresiaHypothyroidismGalactosemiaInherited hemolytic anemia Persistent After 2nd WeekNeonatal hepatitisBiliary atresiaInspissated bile syndrome
24. Physiological vs. PathologicalPhysiologicalPathological Onset2nd-3rd day of lifeAt any timeLevel of BilirubinUsually lowerUsually higherType of BilirubinUnconjugated AnyRate of increaseSlow increase(usually <85mol/L/24h)May be faster (usually >85mol/L/24h)DurationShorter (7-10 days in the term & 14 days in the Preterm)May be longerPhysical Exam and Lab. testsNormal, healthy infantAbnormal
25. Unconjugated Hyperbilirubinemia
26. Physiological jaundiceDue to:Increased synthesis (excessive RBCs load)Relative immaturity of hepatic glucoronyl transferaseOnset usually on 2nd-3rd dayDisappear around day 7-10Infant is usually healthy
27. Physiological jaundiceExacerbating FactorsPrematurityPolycythemiaDehydrationBreast feeding (usually higher by 50-65 mol/L than formula fed)LaboratoryRate of accumulation is < 85mol/L/day
28. Physiological jaundiceTreatment: Maintain sufficient feedingSerial measurements of serum bilirubin Look for pathological causes if bilirubin level exceeds the expected for age Phototherapy if needed
29. Management
30. PhototherapyIndicated if bilirubin level exceeds a set pointExposure of infant to light with wave length around 450 nmIsomerization of bilirubin to nontoxic water soluble formEyes should be protectedControl for temperature and fluid balance is important
31. Phototherapy
32. Breast MILK JaundiceUnconjugated hyperbilirubineamia beyond 2nd week of life Disappears within 2 days of breast feeding discontinuationMay take up to 3 months to resolve completelyDue to (?) a substance in human milk that inhibits the activity of glucoronyl transferaseTreatment: Reassurance after exclusion of other pathologiesStoppage of breast feeding is NOT recommended
33. Breast FEEDING JaundiceMay be related to decreased amount of milk consumed by the infant (breast-feeding failure )More effective nursing may prevent early “starvation” in breastfed newborns and reduce the incidence of this type of jaundice
34. Hemolytic Disease of TheNewborn
35. Hemolytic disease of the newbornRh isoimmunization Mother is Rh–ve abd the fetus is Rh+veFirst pregnancy usually goes with no fetal problemsMother is sensitized by fetal Rh+ve RBCsAntibodies to Rh+ve RBCs is formed and it is transmitted to the fetus during second pregnancy~ 1/100 pregnancies and not in every Rh-ve motherMay be prevented by Anti-D administered to the mother
36. Hemolytic disease of the newbornPathogenesis of Hemolytic Disease of The Newborn
37. Hemolytic disease of the newbornABO incompatibility (milder disease)The anti-A or Anti-B hemolysins (antibodies) present in a mother with blood group O is transferred to the fetus of A or B blood groupThis results in hemolysis (most transferred antibodies can be neutralized by the baby)1 in every 200 births The first baby can be affected
38. Hemolytic disease of the newbornSevere hemolysis manifestations Hydrops fetalisThe most severe formOften still birth with severe anemia and massive edema and ascitis Icterus gravis neonatorumJaundice in the first 24hr, not at birthVariable degree of hemolytic anemiaHepatosplenomegaly
39. Hemolytic disease of the newbornPreventionAnti-D within 72 hrs after delivery of Rh+ve child or abortion.Management:Life support Establish diagnosisEarly phototherapyTransfusion to restore normal hemoglobin levelExchange transfusion if needed.
40. Exchange transfusionIndicated inKernictrus Cord bilirubin >85mol/L orCord hemoglobin <100 g/LRate of bilirubin rise > 8.5 mol/L/hourUnconjugated bilirubin level > 340 mol/L at any age (at a lower level in presence of risk factor such as sepsis)Double volume exchange transfusion
41. Exchange transfusion
42. ConjugatedHyperbilirubinemia
43. Conjugated hyperbilirubinemiaAlways pathologicalDirect bilirubin >34mol/L Evaluation Serum bilirubinLiver function testsCultures (blood, urine,….)Abdominal ultra soundIsotopic scan (scintegraphy)Liver biopsy
44. Conjugated hyperbilirubinemiaNeonatal hepatitisBiliary atresiaStool colorIntermittent palePersistent paleSerum BilirubinBiphasicMainly conjugatedALT, ASTMarked increaseMild increaseAlk. PhosphataseMild increaseMarked increaseLiver scintegraphyUptake: Sluggish Excretion of isotope: happens eventually Uptake: Intact Excretion of Isotope into intestine is absentLiver biopsyInflammatory Infiltration.Distorted lobular archit-ecture.Focal necrosisIntact lobular architecture.Bile ductular proliferation or paucity.Perilobular edema & fibrosis
45. Conjugated hyperbilirubinemiaTreatment of chronic cholestasisTreatment of the causeSupportiveFat soluble vitaminsUse of MCT-containing formulaAttention to micronutrients as Ca, Ph, ZincSurgical interferenceBiliary atresia: Kasai operation, Liver transplantation
46. BilirubinNeurotoxicity
47. Bilirubin neurotoxicityCause: Crossing of unconjugated bilirubin to the brain.The level at which injury happens depends on:Maturity/Postnatal ageBinding capacity in the blood (S. Albumin)Associated risk factors (acidosis, infection, asphyxia…)
48. Bilirubin neurotoxicityAcute Encephalopathy Three phasesHypotonia, lethargy, high pitched cry and poor suckingExtensors hypertonia, opithotonus, fever and seizuresHypotonia replaces hypertonia in a weekDeath may occur up the second phaseChronic Encephalopathy AthetosisSensorineural hearing deficitLimited upward gazeDental dysplasiaIntellectual deficit
49. KernicterusNotice:Opithotonus position and fisted hands
50. Bilirubin neurotoxicityKernicterus:Yellowish staining of the brain tissue by bilirubin deposition Associated with evidence of neuronal injuryMostly affects basal ganglia, brain stem and cerebellar nuclei and anterior horn cells
51. Bilirubin neurotoxicity / Kernicterus
52. Please send your feedback to:kaltirkawi@ksu.edu.sa