6 Neonatal Hyperbilirubinemia Visible jaundice:Adults: >2mg%Newborns: >6mgUp to 50% of all newborns may develop jaundice
7 Source of BilirubinMetabolism of heme mg/kg/day. (adults 3- 4mg/kg/day)1gr Hemoglobine produces 34mg of bilirubin75%: from old RBCs released from RES25%: from ineffective erythropoyesis, myoglobine, cytochromes, catalase, peroxidase.2
8 Metabolism Heme Biliverdin + CO + Fe Indirect (unconjugated) bilirubin Heme Oxygenase + O2Heme Biliverdin + CO + FeBiliverdin reductaseIndirect (unconjugated) bilirubinBinds to albumin in plasma3
9 Conjugation Indirect bilirubin Liver Gut Liver Uptake (binds to ligandin) Endoplasmic reticullumBilirubin Mono and diconjugated bilirubinUDPG-TLiverExcretionGutEliminationEnterohepatic recirculationUrobilinoidsStoolBeta glucuronidaseBacteria4
10 Jaundice: Physical examination Blanch skin with a finger JaundiceSignificant when appears at palms or below knees.Transcutaneous bilirubinometerBruising, cephalohematoma, others.Organomegaly13
11 Dermal Zones of Jaundice After leaving RES bilirubin binds to albumin, initially with low affinity, thus bilirubin precipitates in the proximal parts of the body before it does it distally. So jaundice appears first proximally, and later distally.
12 Jaundice: Laboratory Total serum bilirubin Blood type, Rh, Coombs infant and motherSmear (morphology and reticulocytes)Hematocrit14
13 Jaundice: Laboratory Antibody identification Direct bilirubin: When more than 2 weeks old or signs of cholestasisIf prolonged:LFT, TORCH, sepsis work-up, metabolic, thyroidG6PD15
14 Non Physiologic Jaundice Onset at < 24 hsBilirubin over levels for phototherapyBilirubin rise > 0.5 mg%/hrSigns of underlying illnessVomiting, lethargy, poor feeding, weightAge > 8 days in term or 15 days in premature9
15 Non Physiologic Jaundice: Anamnesis Familial:G6PD, spherocytosis, metabolic, enzymes.Siblings:Immune, breast milk.Pregnancy:Infections, drugs, diabetes.Delivery:Trauma, cord clumping, asphyxia.10
16 Bilirubin toxicity: Disrupted BB barrier Hyperosmolarity Anoxia Cerebral Penetration:As free indirect bilirubin or bound when disrupted BBBDisrupted BB barrierHyperosmolarityAnoxiaHypercarbiaPrematurity16
17 Bilirubin toxicity: Factors Unbound indirect bilirubin Albumin concentration1gr albumin binds 8.5mg bilirubinDisplacement from albumin siteFFADrugs: SulfonamidesCorrection of acidosis17
18 Bilirubin toxicity: Kernicterus Neuronal injury + yellow staining of brain incidence in hemolytic disease (especially RH)LocalizationBasal gangliaCranial nerve and cerebral nucleiHippocampusAnterior horn of spinal cord18
19 Bilirubin toxicity: Acute encephalopathy I) Hypotonia, lethargy, high pitched cry, poor suckII) Hypertonia of extensor musclesopistotonus, rigidity, oculogyric crises, retrocollisIII) Return of hypotonia after 1 week19
21 Bilirubin toxicity Healthy full-term infants: Abnormality in ABR Hypotony: reverses with bilirubin levelsVery rarely kernicterusLow birth weight infants:Damage most probably due to accompanying factors than to high bilirubin.21
22 Breast Feeding Jaundice Bilirubin after 4 days of age. Healthy infantsResolves after holding breast milk for 1-2 daysPresentationEarly: 2-4 days of ageLate: after 4 days of age11
23 Breast Feeding Jaundice: Mechanism Interference with hepatic conjugationBeta glucuronidase in milkReduced bacterial colonization of gutCaloric intake intestinal motility recirculationFFA suggested to reduce bilirubin metabolism12
24 Treatment Options for Jaundiced Breast-fed Infants
25 Isoimmune hemolytic disease of the newborn Rh , or minor types (Kell, Duffy, E, C,c)15% of people are Rh-Coombs +Maternal sensitization d/t previous pregnancy, transfusion, amniocentesis, abortion
26 IHDN: Pregnancy Management Coombs titers >1/16 or previous history of severe disease Amniocentesis for optical densityHigh levels, and clinical signs of hydrops Intrauterine transfusionIntraperitoneal, intravascular or intracardiacRepeated transfusions switched fetal blood type
27 IHDN: Newborn Management Check immediately after birthHematocritBilirubinBlood type50% will only need phototherapy24% will be anemic and cord bilirubin >4mg% exchange transfusion
28 IHDN: Prevention Anti D (Rh) immune globulin indications At 28 weeks within 72 hours since birth.Procedures or suspected transplacental hemorrhage.
29 ABO hemolytic disease of the newborn 15% of pregnancies mother O infant A or B20% will develop significant jaundice10% will need phototherapy.Presentation:Early jaundice (<24hs of life)Many times Combs -, but there are antibodiesBlood smear: spherocytes
30 Treatment: Phototherapy Bilirubin best absorbs light at 450 hm.The best is to provide it with blue light.White range: hm also adequate.Irradiation generates photochemical reaction in the extravascular space of the skinA higher illuminated area increases effectiveness22
31 Treatment: Phototherapy Mechanism Photoisomerization:Natural Isomer 4Z,15Z 4Z,15E hydrosoluble blood biliar secretion (unconjugated)Slow excretion and fast reisomerization reabsorbed.Photooxydation: Small polar products. Slow23
32 Treatment: Phototherapy mechanism Structural isomerization:Ciclization to lumirubin (irreversible) bile and urineFast excretion not reabsorption.Related to dose of phototherapy (intensity of light)23
33 Treatment: Phototherapy mechanism Main PathwayBilirubinLumirubin24
34 Phototherapy: Technique Fluorescents ,spots or biliblanketsMore than 5mw/cm2 at hmNaked , covering eyesIncrease fluids 10-20%Check bilirubin every 12-24hsStop: 13±1mg% in term, 10±1mg% in pretermCheck 12-24hs later for rebound
35 Phototherapy: Side effects Increased water lossDiarrheaRetinal damageBronze baby, tanningMutations in DNA? shield scrotumDisturb of mother-infant interaction.
36 Exchange transfusion: Technique Irradiated PC < 7 days + FFP. WarmedDouble of blood volume.Open incubator, monitorsRouteUV: push-pull, over > 1hrArtery-vein: Isovolumetric
37 Exchange transfusion: Complications Hypocalcemia-hypomagnesemia (CPD)Hypoglycemia (monitor Dx after exchange)Acid base disturbancesHyperkalemiaCardiovascular:Embolizations, arrhythmia, perforation, arrest.
38 Exchange transfusion: Complications BleedingThrombocytopenia, loss of factors.InfectionsHemolysisGVHDOtherFever, hypothermia, NEC?
39 Neonatal Jaundice: Other treatments Phenobarbital: conjugationOral agar: enterohepatic circulationMetalloporphyrins: inhibit bilirubin production.Competitors of heme oxygenaseIVIGg: inhibits hemolysis.Binds to FC receptor of reticuloendothelial cells
40 Management of Hyperbilirubinemia in the Healthy Term Newborn*
41 Diagnostic approach to neonatal jaundice Measure BilirubinNon physiologicBlood type, Rh, CoombsHematocrit, Smear, ReticulocytesIncreased direct biliIncreased indirect biliCoombs +SepsisTORCHBiliary AtresiaCholestasisInspissated BiHepatitisCFTyrosinosisGalactosemiaCoombs -HematocritABORhminor groupPolycytemiaN or ¯HematocritRC shapeNormalBleedingsEnterohepaticMetabolicDrugsOtherAbnormalSpecific and non specificAbnormalities