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Neonatal Jaundice

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Neonatal Jaundice. Ruben Bromiker Department of Neonatology Shaare Zedek Medical Center. Physiologic Jaundice. Healthy infants up to 12mg% in 3rd day; in premature, 5th day. No hemolysis or bleedings No underlying metabolic disease. Mechanism. Production: Volemia, - PowerPoint PPT Presentation
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Neonatal Neonatal Jaundice Jaundice Ruben Bromiker Ruben Bromiker Department of Neonatology Department of Neonatology Shaare Zedek Medical Center Shaare Zedek Medical Center
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Page 1: Neonatal Jaundice

Neonatal JaundiceNeonatal Jaundice

Ruben BromikerRuben Bromiker

Department of NeonatologyDepartment of Neonatology

Shaare Zedek Medical CenterShaare Zedek Medical Center

Page 2: Neonatal Jaundice

Physiologic JaundicePhysiologic JaundiceHealthy infantsHealthy infants

up to 12mg% in 3rd day; in up to 12mg% in 3rd day; in premature, 5th day.premature, 5th day.

No hemolysis or bleedingsNo hemolysis or bleedings

No underlying metabolic diseaseNo underlying metabolic disease

Page 3: Neonatal Jaundice

MechanismMechanism

Production:Production: Volemia,Volemia, RBC span (90 days)RBC span (90 days) Ineffective erythropoyesisIneffective erythropoyesis Turnover of non Hb heme proteinsTurnover of non Hb heme proteins

Page 4: Neonatal Jaundice

MechanismMechanism

Enterohepatic recirculation: Enterohepatic recirculation: Glucuronidase Glucuronidase Bilirubin monoglucuronide Bilirubin monoglucuronide Intestinal bacteriaIntestinal bacteria Intestinal motility and stoolingIntestinal motility and stooling

Page 5: Neonatal Jaundice

MechanismMechanism

Bilirubin Uptake : ligandinBilirubin Uptake : ligandin

Conjugation : UDPG-T activityConjugation : UDPG-T activity

Hepatic excretion of bilirubinHepatic excretion of bilirubin

Page 6: Neonatal Jaundice

Neonatal Neonatal HyperbilirubinemiaHyperbilirubinemia

Visible jaundice: Visible jaundice: Adults: >2mg%Adults: >2mg%Newborns: >6mgNewborns: >6mg

Up to 50% of all newborns may Up to 50% of all newborns may develop jaundicedevelop jaundice

Page 7: Neonatal Jaundice

Source of BilirubinSource of BilirubinMetabolism of heme. 6-10 mg/kg/day. Metabolism of heme. 6-10 mg/kg/day. (adults 3-4mg/kg/day)(adults 3-4mg/kg/day)1gr Hemoglobine produces 34mg of 1gr Hemoglobine produces 34mg of bilirubinbilirubin75%: from old RBCs released from RES75%: from old RBCs released from RES25%: from ineffective erythropoyesis, 25%: from ineffective erythropoyesis, myoglobine, cytochromes, catalase, myoglobine, cytochromes, catalase, peroxidase.peroxidase.

Page 8: Neonatal Jaundice

MetabolismMetabolism

Heme Biliverdin + CO + FeHeme Biliverdin + CO + Fe

Heme Oxygenase + O2 Heme Oxygenase + O2

Biliverdin reductaseBiliverdin reductase

Indirect Indirect (unconjugated)(unconjugated) bilirubin bilirubinBinds to albumin in plasmaBinds to albumin in plasma

Page 9: Neonatal Jaundice

ConjugationConjugation

Liver Uptake (binds to ligandin) Endoplasmic reticullumLiver Uptake (binds to ligandin) Endoplasmic reticullum

Bilirubin Bilirubin Mono and diconjugated bilirubinMono and diconjugated bilirubinUDPG-TUDPG-T

StoolStoolBeta glucuronidaseBeta glucuronidaseBacteriaBacteria

Excretion

Excretion

GutGutEliminationEliminationEnterohepatic recirculationEnterohepatic recirculation

UrobilinoidsUrobilinoids

Indirect bilirubinIndirect bilirubin

LiverLiver

Page 10: Neonatal Jaundice

Jaundice: Physical Jaundice: Physical examinationexamination

Blanch skin with a finger Blanch skin with a finger JaundiceJaundice Significant when appears at palms or below knees.Significant when appears at palms or below knees.

Transcutaneous bilirubinometerTranscutaneous bilirubinometer

Bruising, cephalohematoma, others.Bruising, cephalohematoma, others.

OrganomegalyOrganomegaly

Page 11: Neonatal Jaundice

Dermal Zones of JaundiceDermal Zones of Jaundice

Dermal Zone Bilirubin range (mg% )1 4.5-82 5.5-123 8-16.54 11-185 > 15

After leaving RES bilirubin binds to After leaving RES bilirubin binds to albumin, initially with low affinity, thus albumin, initially with low affinity, thus bilirubin precipitates in the proximal bilirubin precipitates in the proximal parts of the body before it does it parts of the body before it does it distally. So jaundice appears first distally. So jaundice appears first proximally, and later distally. proximally, and later distally.

Page 12: Neonatal Jaundice

Jaundice: LaboratoryJaundice: Laboratory

Total serum bilirubinTotal serum bilirubin

Blood type, Rh, Coombs infant and Blood type, Rh, Coombs infant and mothermother

Smear (morphology and reticulocytes)Smear (morphology and reticulocytes)

HematocritHematocrit

Page 13: Neonatal Jaundice

Jaundice: LaboratoryJaundice: Laboratory

Antibody identificationAntibody identificationDirect bilirubin:Direct bilirubin:

When more than 2 weeks old or signs of cholestasisWhen more than 2 weeks old or signs of cholestasis

If prolonged: If prolonged: LFT, TORCH, sepsis work-up, metabolic, thyroid LFT, TORCH, sepsis work-up, metabolic, thyroid

G6PDG6PD

Page 14: Neonatal Jaundice

Non Physiologic JaundiceNon Physiologic Jaundice Onset at < 24 hsOnset at < 24 hs

Bilirubin Bilirubin over levels for phototherapy over levels for phototherapy

Bilirubin rise > 0.5 mg%/hrBilirubin rise > 0.5 mg%/hr

Signs of underlying illnessSigns of underlying illness

Vomiting, lethargy, poor feeding, Vomiting, lethargy, poor feeding, weight weight

Age > 8 days in term or 15 days in Age > 8 days in term or 15 days in prematurepremature

Page 15: Neonatal Jaundice

Non Physiologic Jaundice: Non Physiologic Jaundice: AnamnesisAnamnesis

Familial: Familial: G6PD, spherocytosis, metabolic, G6PD, spherocytosis, metabolic,

enzymes.enzymes.Siblings:Siblings:

Immune, breast milk.Immune, breast milk.Pregnancy: Pregnancy:

Infections, drugs, diabetes.Infections, drugs, diabetes.Delivery: Delivery:

Trauma, cord clumping, asphyxia.Trauma, cord clumping, asphyxia.

Page 16: Neonatal Jaundice

Bilirubin toxicity:Bilirubin toxicity:

Disrupted BB barrierDisrupted BB barrierHyperosmolarityHyperosmolarityAnoxiaAnoxiaHypercarbiaHypercarbiaPrematurityPrematurity

Cerebral Penetration: Cerebral Penetration: As free indirect bilirubin or bound when As free indirect bilirubin or bound when disrupted BBBdisrupted BBB

Page 17: Neonatal Jaundice

Bilirubin toxicity: FactorsBilirubin toxicity: Factors Unbound indirect bilirubinUnbound indirect bilirubin

Albumin concentration Albumin concentration 1gr albumin binds 8.5mg bilirubin1gr albumin binds 8.5mg bilirubin

Displacement from albumin siteDisplacement from albumin siteFFAFFADrugs: SulfonamidesDrugs: SulfonamidesCorrection of acidosisCorrection of acidosis

Page 18: Neonatal Jaundice

Bilirubin toxicity: Bilirubin toxicity: KernicterusKernicterus

Basal gangliaBasal gangliaCranial nerve and cerebral nucleiCranial nerve and cerebral nucleiHippocampusHippocampusAnterior horn of spinal cordAnterior horn of spinal cord

Neuronal injury + yellow staining of brainNeuronal injury + yellow staining of brain incidence in hemolytic disease (especially RH)incidence in hemolytic disease (especially RH)

LocalizationLocalization

Page 19: Neonatal Jaundice

Bilirubin toxicity: Bilirubin toxicity: Chronic Chronic complicationscomplications

AthetosisAthetosisSensorial deafnessSensorial deafnessLimited upward gazeLimited upward gazeIntellectual deficitsIntellectual deficitsDental dysplasiaDental dysplasia

Page 20: Neonatal Jaundice

Bilirubin toxicityBilirubin toxicityHealthy full-term infants: Healthy full-term infants:

Abnormality in ABRAbnormality in ABRHypotony: Hypotony: reverses with reverses with bilirubin bilirubin levelslevelsVery rarely kernicterusVery rarely kernicterus

Low birth weight infants:Low birth weight infants: Damage most probably due to Damage most probably due to accompanying factors than to high accompanying factors than to high bilirubin.bilirubin.

Page 21: Neonatal Jaundice

Breast Feeding JaundiceBreast Feeding JaundiceBilirubin Bilirubin after 4 days of age. Healthy infants after 4 days of age. Healthy infants

Resolves after holding breast milk for 1-2 Resolves after holding breast milk for 1-2 daysdays

PresentationPresentationEarly: 2-4 days of ageEarly: 2-4 days of ageLate: after 4 days of age Late: after 4 days of age

Page 22: Neonatal Jaundice

Breast Feeding Jaundice: Breast Feeding Jaundice: MechanismMechanism

Interference with hepatic conjugationInterference with hepatic conjugation

Beta glucuronidase in milkBeta glucuronidase in milk

Reduced bacterial colonization of gutReduced bacterial colonization of gut

Caloric intake Caloric intake intestinal motility intestinal motility recirculationrecirculation

FFA suggested to reduce bilirubin metabolismFFA suggested to reduce bilirubin metabolism

Page 23: Neonatal Jaundice

Treatment Options for Treatment Options for Jaundiced Breast-fed InfantsJaundiced Breast-fed Infants

OObbsseerrvvee

CCoonnttiinnuuee bbrreeaasstt--ffeeeeddiinngg;; pphhoottootthheerraappyy

SSuupppplleemmeenntt wwiitthh ffoorrmmuullaa wwiitthh oorr wwiitthhoouutt pphhoottootthheerraappyy

IInntteerrrruupptt bbrreeaasstt--ffeeeeddiinngg;; ssuubbssttiittuuttee ffoorrmmuullaa

IInntteerrrruupptt bbrreeaasstt--ffeeeeddiinngg;; ssuubbssttiittuuttee ffoorrmmuullaa;; pphhoottootthheerraappyy

Page 24: Neonatal Jaundice

Isoimmune hemolytic disease of the Isoimmune hemolytic disease of the newbornnewborn

Rh , or minor types (Kell, Duffy, E, C,c)Rh , or minor types (Kell, Duffy, E, C,c)

15% of people are Rh-15% of people are Rh-

Coombs +Coombs +

Maternal sensitization d/t previous Maternal sensitization d/t previous pregnancy, transfusion, amniocentesis, pregnancy, transfusion, amniocentesis, abortionabortion

Page 25: Neonatal Jaundice

IHDN: Pregnancy IHDN: Pregnancy ManagementManagement

Coombs titers >1/16 or previous history of Coombs titers >1/16 or previous history of severe disease severe disease AmniocentesisAmniocentesis for optical for optical densitydensity

High levels, and clinical signs of hydrops High levels, and clinical signs of hydrops Intrauterine transfusionIntrauterine transfusion

IntraperitonealIntraperitoneal, , intravascularintravascular or or intracardiacintracardiac Repeated transfusions Repeated transfusions switched fetal blood type switched fetal blood type

Page 26: Neonatal Jaundice

IHDN: Newborn IHDN: Newborn ManagementManagement

Check immediately after birthCheck immediately after birthHematocritHematocritBilirubinBilirubinBlood typeBlood type

50% will only need 50% will only need phototherapyphototherapy24% will be anemic and cord bilirubin 24% will be anemic and cord bilirubin >4mg%>4mg% exchange transfusionexchange transfusion

Page 27: Neonatal Jaundice

IHDN: PreventionIHDN: PreventionAnti D (Rh) immune globulin indicationsAnti D (Rh) immune globulin indications

At 28 weeksAt 28 weeks within 72 hours since birth.within 72 hours since birth.Procedures or suspected Procedures or suspected transplacental hemorrhage.transplacental hemorrhage.

Page 28: Neonatal Jaundice

ABO hemolytic disease of the ABO hemolytic disease of the newbornnewborn15% of pregnancies mother O infant A or B15% of pregnancies mother O infant A or B20% will develop significant jaundice20% will develop significant jaundice10% will need phototherapy. 10% will need phototherapy. Presentation:Presentation:

Early jaundice (<24hs of life)Early jaundice (<24hs of life)Many times Combs -, but there are Many times Combs -, but there are antibodiesantibodiesBlood smear: spherocytesBlood smear: spherocytes

Page 29: Neonatal Jaundice

Treatment: PhototherapyTreatment: Phototherapy

Bilirubin best absorbs light at 450 Bilirubin best absorbs light at 450 m. m. The best is to provide it with blue light. The best is to provide it with blue light. White range: 380-700 White range: 380-700 m also adequate.m also adequate.Irradiation generates photochemical reaction in Irradiation generates photochemical reaction in the extravascular space of the skinthe extravascular space of the skinA higher illuminated area increases effectivenessA higher illuminated area increases effectiveness

Page 30: Neonatal Jaundice

Treatment: Treatment: Phototherapy Phototherapy MechanismMechanism

Photoisomerization: Photoisomerization: Natural Isomer 4Z,15Z Natural Isomer 4Z,15Z 4Z,15E hydrosoluble 4Z,15E hydrosoluble blood blood biliar secretion (unconjugated) biliar secretion (unconjugated) Slow excretion and fast reisomerization Slow excretion and fast reisomerization reabsorbed. reabsorbed.

Photooxydation: Small polar products. SlowPhotooxydation: Small polar products. Slow

Page 31: Neonatal Jaundice

Treatment: Treatment: Phototherapy Phototherapy mechanismmechanism

Structural isomerization: Structural isomerization: Ciclization to lumirubin (irreversible) Ciclization to lumirubin (irreversible) bile and urinebile and urine

Fast excretion not reabsorption. Fast excretion not reabsorption. Related to dose of phototherapy Related to dose of phototherapy (intensity of light)(intensity of light)

Page 32: Neonatal Jaundice

Treatment:Treatment: Phototherapy mechanism Phototherapy mechanism

Bilirubin Lumirubin

Main PathwayMain Pathway

Page 33: Neonatal Jaundice

Phototherapy: TechniquePhototherapy: Technique

Fluorescents ,spots or biliblanketsFluorescents ,spots or biliblanketsMore than 5More than 5w/cm2 at 425-475w/cm2 at 425-475mmNaked , covering eyesNaked , covering eyesIncrease fluids 10-20%Increase fluids 10-20%Check bilirubin every 12-24hsCheck bilirubin every 12-24hsStop: 13Stop: 13±±1mg% in term, 101mg% in term, 10±±1mg% in preterm1mg% in pretermCheck 12-24hs later for reboundCheck 12-24hs later for rebound

Page 34: Neonatal Jaundice

Phototherapy: Side effectsPhototherapy: Side effectsIncreased water lossIncreased water lossDiarrheaDiarrheaRetinal damageRetinal damageBronze baby, tanningBronze baby, tanningMutations in DNA? Mutations in DNA? shield scrotum shield scrotumDisturb of mother-infant interaction.Disturb of mother-infant interaction.

Page 35: Neonatal Jaundice

Exchange transfusion: Exchange transfusion: TechniqueTechniqueIrradiated PC < 7 days + FFP. WarmedIrradiated PC < 7 days + FFP. WarmedDouble of blood volume.Double of blood volume.Open incubator, monitorsOpen incubator, monitorsRoute Route

UV: push-pull, over > 1hrUV: push-pull, over > 1hrArtery-vein: IsovolumetricArtery-vein: Isovolumetric

Page 36: Neonatal Jaundice

Exchange transfusion: Exchange transfusion: ComplicationsComplications

Hypocalcemia-hypomagnesemia (CPD)Hypocalcemia-hypomagnesemia (CPD)Hypoglycemia (monitor Dx after exchange)Hypoglycemia (monitor Dx after exchange)Acid base disturbancesAcid base disturbancesHyperkalemiaHyperkalemiaCardiovascular:Cardiovascular:

Embolizations, arrhythmia, perforation, arrest.Embolizations, arrhythmia, perforation, arrest.

Page 37: Neonatal Jaundice

Exchange transfusion: Exchange transfusion: ComplicationsComplicationsBleedingBleeding

Thrombocytopenia, loss of factors.Thrombocytopenia, loss of factors.

InfectionsInfectionsHemolysisHemolysisGVHDGVHDOtherOther

Fever, hypothermia, NEC?Fever, hypothermia, NEC?

Page 38: Neonatal Jaundice

Neonatal Jaundice:Neonatal Jaundice:Other treatmentsOther treatments

Phenobarbital: Phenobarbital: conjugation conjugationOral agar: Oral agar: enterohepatic circulation enterohepatic circulationMetalloporphyrins: inhibit bilirubin Metalloporphyrins: inhibit bilirubin production.production.

Competitors of heme oxygenaseCompetitors of heme oxygenase

IVIGg: inhibits hemolysis.IVIGg: inhibits hemolysis.Binds to FC receptor of reticuloendothelial Binds to FC receptor of reticuloendothelial cellscells

Page 39: Neonatal Jaundice

Management of Hyperbilirubinemia Management of Hyperbilirubinemia in the Healthy Term Newborn*in the Healthy Term Newborn*

Age,hours TSB Level, mg/ dL (pmol/ L) Consider

PhototherapyPhototherapy Exchange

Transfusion ifIntensive Photo

therapy Fails

ExchangeTransfusion and

IntensivePhototherapy

<=24§ ... ... ... ...25-48 >12 (170) >15 (260) >20 (340) >25 (430)49-72 >15 (260) >18 (310) >25 (430) >30 (510)>72 >17 (290) >20 (340) >25 (430) >30 (510)* TSB mdicates total serum bilirubin.

§ Term infants who are clinically jaundiced at <=24 hours old are notconsidered healthy and require further evaluation.

Page 40: Neonatal Jaundice

Diagnostic approach to neonatal jaundiceDiagnostic approach to neonatal jaundiceJaundiceJaundice

Measure BilirubinMeasure BilirubinNon physiologic Non physiologic

Blood type, Rh, CoombsBlood type, Rh, CoombsHematocrit, Smear, ReticulocytesHematocrit, Smear, Reticulocytes

Increased direct biliIncreased direct bili Increased indirect biliIncreased indirect biliCoombs +Coombs +Coombs -Coombs -ABOABO

RhRhminor groupminor group

SepsisSepsisTORCHTORCHBiliary AtresiaBiliary AtresiaCholestasisCholestasisInspissated BiInspissated BiHepatitisHepatitisCFCFTyrosinosisTyrosinosisGalactosemiaGalactosemia

ororHematocriHematocritt

HematocritHematocritPolycytemiaPolycytemia

RC shapeRC shape NormalNormal

AbnormalAbnormal

BleedingsBleedingsEnterohepaticEnterohepaticMetabolicMetabolicDrugsDrugsOtherOtherSpecific and non specificSpecific and non specific

AbnormalitiesAbnormalities


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