Neonatal JaundiceNeonatal Jaundice

Sahisnuta BasnetSahisnuta Basnet

PHYSIOLOGYPHYSIOLOGY

• Destruction of circulating Destruction of circulating senescent RBC accounts for 75% senescent RBC accounts for 75% of daily bilirubin productionof daily bilirubin production

• Rest 25%- turnover of nonHb heme Rest 25%- turnover of nonHb heme proteins and destruction of proteins and destruction of immature &ineffective RBCimmature &ineffective RBC

• 1gm of Hb-35 mg bilirubin 1gm of Hb-35 mg bilirubin amounting to 6-10 mg/kg/day of amounting to 6-10 mg/kg/day of bilirubinbilirubin

PhysiologyPhysiology• Bilirubin is from breakdown of hemoglobinBilirubin is from breakdown of hemoglobin• Unconjugated bilirubin transported to liver Unconjugated bilirubin transported to liver

– Bound to albumin because Bound to albumin because insolubleinsoluble in water in water

• Transported into hepatocyte & conjugated Transported into hepatocyte & conjugated • Primarily bound to ligandin within the cell & Primarily bound to ligandin within the cell &

this prevents the backflow into circulationthis prevents the backflow into circulation– With glucuronic acid → now water solubleWith glucuronic acid → now water soluble

(by action of uridine diphosphate gluconoryl (by action of uridine diphosphate gluconoryl transferase)transferase)

• Secreted into bileSecreted into bile• In ileum & colon, converted to In ileum & colon, converted to

urobilinogenurobilinogen• Excreted from urine as urobilinExcreted from urine as urobilin• Excreted from feces as stercobilinExcreted from feces as stercobilin

Bilirubin MetabolismBilirubin Metabolism

Glucuronyl TransferaseUnconjugated

(Bilirubin Diglucuronide)

Why do newborns Why do newborns develop jaundice?develop jaundice?

Increased production (↑RBC mass, so ↑ed Increased production (↑RBC mass, so ↑ed hemolysishemolysisFetus is in a hypoxic environment – high HbFetus is in a hypoxic environment – high HbPostnatal rise in PO2Postnatal rise in PO2Decrease in erythropoietin prodn.Decrease in erythropoietin prodn.Destruction of excess Hb.Destruction of excess Hb.

Decreased conjugation(immature liver enzyme Decreased conjugation(immature liver enzyme system)system)

Neonatal RBC lesser life span (60-90days)Neonatal RBC lesser life span (60-90days) Increased entero-hepatic circulation – sterile gut Increased entero-hepatic circulation – sterile gut

• Enterohepatic Circulation:Enterohepatic Circulation:– Sterile intestines of neonate is rich in Sterile intestines of neonate is rich in

glucoronidase glucoronidase – This enzyme splits bilirubin glucoronide This enzyme splits bilirubin glucoronide

to bilirubin and glucoronic acidto bilirubin and glucoronic acid– Unconjugated bilirubin again Unconjugated bilirubin again

reabsorbed through the portal reabsorbed through the portal circulation circulation

PHYSIOLOGICAL PHYSIOLOGICAL JAUNDICEJAUNDICE

• Seen both in term and pretermsSeen both in term and preterms

• Self limitingSelf limiting

• Develops after 24 hours Develops after 24 hours

• Peaks by day 4- 5 in terms and day 7-8 Peaks by day 4- 5 in terms and day 7-8 in pretermsin preterms

• Peak levels -12mg/dl in term & 15mg/dl Peak levels -12mg/dl in term & 15mg/dl in pretermin preterm

• Gradually subsides by 10-14 days Gradually subsides by 10-14 days

• No Treatment necessaryNo Treatment necessary

PATHOLOGICAL PATHOLOGICAL JAUNDICEJAUNDICE

Suspect if...Suspect if...• Jaundice in first 24 hoursJaundice in first 24 hours• rise of >5mg/24 hours or rise of >5mg/24 hours or

0.5mg/dl/hour0.5mg/dl/hour• Jaundice beyond physiological limitsJaundice beyond physiological limits• Conjugated bilirubin >2mg/dlConjugated bilirubin >2mg/dl• Persists beyond 2 weeksPersists beyond 2 weeks• Signs of underlying illnessSigns of underlying illness

EtiologyEtiology

• Early Jaundice (jaundice within Early Jaundice (jaundice within 10days of life)10days of life)– A. Within first 2 days of life:A. Within first 2 days of life:– Hemolytic disease of NBHemolytic disease of NB

Rh incompatibilityRh incompatibility

ABO incompatibilityABO incompatibility– G-6PD deficiencyG-6PD deficiency– Congenital spherocytosisCongenital spherocytosis– SepsisSepsis

• B. Within 3-10 days of lifeB. Within 3-10 days of life– Physiological jaundicePhysiological jaundice– PrematurityPrematurity– HypoglycemiaHypoglycemia– AcidosisAcidosis– SepsisSepsis– Congenital hemolytic anemiaCongenital hemolytic anemia– Crigler Najjar & Gilberts syndromeCrigler Najjar & Gilberts syndrome– GalactosemiaGalactosemia– CephalhematomaCephalhematoma– Subcutaneous bruisingSubcutaneous bruising– Drugs: Drugs:

• Prolonged Jaundice (jaundice at more than 10 days Prolonged Jaundice (jaundice at more than 10 days of life)of life)

• A. Prolonged Unconjugated hyperbilirubinemiaA. Prolonged Unconjugated hyperbilirubinemiabreast milk jaundicebreast milk jaundicebreast feeding jaundicebreast feeding jaundicesepsissepsishypothyroidismhypothyroidismgalactosemiagalactosemiainfantile pyloric stenosisinfantile pyloric stenosispersisting hemolysispersisting hemolysishemoglobinopathieshemoglobinopathiesdrugs: erythromycin , chloramphenicoldrugs: erythromycin , chloramphenicol

• Pronged conjugated hyperbilirubinemiaPronged conjugated hyperbilirubinemia– 1. intrahepatic cholestasis1. intrahepatic cholestasis

•A. Infections: A. Infections: – Septicemia Septicemia – UTIUTI– HepatitisHepatitis– STORCH infectionsSTORCH infections

•B. MetabolicB. Metabolic– GalactosemiaGalactosemia– Alpha 1 antitrypsin deficiencyAlpha 1 antitrypsin deficiency– MPSMPS– Gauchers disease Gauchers disease – Cystic FibrosisCystic Fibrosis

• 3. Endrocrine 3. Endrocrine – HypothyroidismHypothyroidism– HypoparathyroidismHypoparathyroidism– HypopituiterismHypopituiterism

4.4. Total parental nutritionTotal parental nutrition5.5. Drugs: sulphonamidesDrugs: sulphonamides6.6. Intrahepatic bile duct diseaseIntrahepatic bile duct disease7.7. Idiopathic neonatal hepatitisIdiopathic neonatal hepatitis

• B. Extra hepatic cholestasisB. Extra hepatic cholestasis– Biliary atresiaBiliary atresia– Choledochal cystCholedochal cyst– Bile duct stenosisBile duct stenosis

Breast Feeding JaundiceBreast Feeding Jaundice

Breast Feeding JaundiceBreast Feeding Jaundice• MisnomerMisnomer• Higher levels on day 4 compared Higher levels on day 4 compared

to formula fed babies due to formula fed babies due decreased intake of milkdecreased intake of milk

• This leads to increased This leads to increased enterohepatic circulationenterohepatic circulation

Breast milk jaundiceBreast milk jaundice

Breast Milk JaundiceBreast Milk Jaundice• By day 7, instead of usual fall in By day 7, instead of usual fall in

bilirubin level, bilirubin level bilirubin level, bilirubin level continues to risecontinues to rise

• May sometimes reach May sometimes reach 20-30mg/dl by 220-30mg/dl by 2ndnd-3-3rdrd wk of life wk of life

• gradually returns to normal by gradually returns to normal by 4-12 weeks4-12 weeks

• Exact mech unknown, but thought to Exact mech unknown, but thought to be due to factors in breast milk ( a be due to factors in breast milk ( a glucoronidase in breast milk) glucoronidase in breast milk) interfering with bilirubin conjugation interfering with bilirubin conjugation or metabolismor metabolism

• If breast feeding is stopped for If breast feeding is stopped for 48hours , bilirubin level will fall rapidly48hours , bilirubin level will fall rapidly

• Rebound increase after resumption of Rebound increase after resumption of feeding of 2-3mg/dlfeeding of 2-3mg/dl

• Chance of reoccurance in future Chance of reoccurance in future pregnancies: 70%pregnancies: 70%

CLINICAL EVALUATIONCLINICAL EVALUATION

• History to rule out other causesHistory to rule out other causes• Careful physical examinationCareful physical examination• Dermal progression of jaundiceDermal progression of jaundice• IcterometerIcterometer• Transcutaneous bilirubinometerTranscutaneous bilirubinometer• Laboratory investigationsLaboratory investigations

Cramer’s IndexCramer’s Index

• Face Face ~ ~ 4-6 mg 4-6 mg %%

• Chest and Upper abdomen ~Chest and Upper abdomen ~ 8-10 8-10 mg %mg %

• Lower abdomen and thighs ~Lower abdomen and thighs ~ 12-14 12-14 mg%mg%

• Fore arms and legsFore arms and legs ~ ~ 15-18 15-18 mg %mg %

• Palms and solesPalms and soles ~ ~ 15-20 mg 15-20 mg %%

Lab InvestigationsLab Investigations• Hemoglobin, PCVHemoglobin, PCV• Peripheral smear examinationPeripheral smear examination• Coombs’ testCoombs’ test• Reticulocyte countReticulocyte count• Blood group and Rh typingBlood group and Rh typing• Bilirubin level – Total / Direct & IndirectBilirubin level – Total / Direct & Indirect• Special tests – Special tests –

– STORCH titresSTORCH titres - Thyroid function tests- Thyroid function tests– Metabolic work upMetabolic work up - Sepsis screen- Sepsis screen– USG / X ray abdomenUSG / X ray abdomen

ApproachApproach• Age at appearanceAge at appearance

<24 hrs<24 hrs 24hrs – 2 weeks24hrs – 2 weeks >2 >2 weeksweeks

IncompatibilitiesIncompatibilities Direct Direct Indirect Indirect sepsissepsis

SepsisSepsis IEMIEM

ThyroidThyroid

SepsisSepsis HemolyticHemolytic Non hemolyticNon hemolytic

HypothyroidHypothyroid Rh / ABO Rh / ABO CephalhematomaCephalhematoma

ObstructiveObstructive Enzyme defectsEnzyme defects Polycythemia Polycythemia

SyndromicSyndromic Membrane defectsMembrane defects

Laboratory Evaluation of Term Newborn with Laboratory Evaluation of Term Newborn with

JaundiceJaundice

MANAGEMENTMANAGEMENT

• PhototherapyPhototherapy• DrugsDrugs• Exchange Exchange

transfusiontransfusion

Indications for Indications for PhototherapyPhototherapy

• TSB > 15 mg % in termTSB > 15 mg % in term• TSB > 12 mg% in pretermTSB > 12 mg% in preterm• TSB > 5 mg% within 24 hoursTSB > 5 mg% within 24 hours• Adjuvant to exchange transfusionAdjuvant to exchange transfusion• VLBW with Perinatal risk factorsVLBW with Perinatal risk factors• PrecautionsPrecautions

– Cover the eyes and GenitalsCover the eyes and Genitals– Supplemental hydrationSupplemental hydration– Watch for side effectsWatch for side effects

PHOTOTHERAPYPHOTOTHERAPY

• Blue light (425-475 nm)Blue light (425-475 nm)• Fibreoptic blankets Fibreoptic blankets or or overhead overhead

banksbanks• As close as possible As close as possible ( 25cm)( 25cm)• Continuos therapy-interruptions for Continuos therapy-interruptions for

feeding allowedfeeding allowed

Mechanism Of PhototherapyMechanism Of Phototherapy

Conversion of insoluble Bilirubin Conversion of insoluble Bilirubin into soluble bilirubininto soluble bilirubin– Photo-isomerization: natural isomer Photo-isomerization: natural isomer

ofunconjugated bilirubin is ofunconjugated bilirubin is converted to less toxic polar isomer converted to less toxic polar isomer which diffuses into blood & excreted which diffuses into blood & excreted into bile without need of conjugationinto bile without need of conjugation

– Structural isomerization: of Structural isomerization: of bilirubin into lumirubin & is bilirubin into lumirubin & is excreted into bile and urine excreted into bile and urine without conjugationwithout conjugation

– Photo-oxidation: bilirubin Photo-oxidation: bilirubin converted to small polar converted to small polar products which are excreted in products which are excreted in urineurine

Phototherapy ComplicationsPhototherapy Complications

• Dehydration: insensible water loss Dehydration: insensible water loss is increasedis increased

• Hypothermia: particularly in Hypothermia: particularly in winterswinters

• Increased frequency of greenish Increased frequency of greenish stools: stools: ↑ed bile salts and ↑ed bile salts and unconjugated bilirubin in bowelunconjugated bilirubin in bowel

• Retinal damageRetinal damage• Bronze baby: when PT given with Bronze baby: when PT given with

direct hyperbilirubinemiadirect hyperbilirubinemia• Testicular damage: mutations, Testicular damage: mutations,

sister chromatid exchange, DNA sister chromatid exchange, DNA strand breaksstrand breaks

• Hampering of materno-fetal Hampering of materno-fetal bondingbonding

DRUGSDRUGS

• PhenobarbitonePhenobarbitone

-induces liver ezymes: useful for Crigler -induces liver ezymes: useful for Crigler Najjar Syndrome Type IINajjar Syndrome Type II

• MetalloporphyrinsMetalloporphyrins

-inhibits heme oxygenase and therefore -inhibits heme oxygenase and therefore conversion of biliverdin to bilirubinconversion of biliverdin to bilirubin

• IVIG: may be used in hemolytic anemiaIVIG: may be used in hemolytic anemia• Oral agarOral agar• Albumin infusionsAlbumin infusions

THANK YOUTHANK YOU