Neonatal Jaundice 3g3w4f

Neonatal Jaundice Sahisnuta Basnet

PHYSIOLOGY • Destruction of circulating senescent RBC s for 75% of daily bilirubin production • Rest 25%- turnover of nonHb heme proteins and destruction of immature &ineffective RBC • 1gm of Hb-35 mg bilirubin amounting to 6-10 mg/kg/day of bilirubin

Physiology • Bilirubin is from breakdown of hemoglobin • Unconjugated bilirubin transported to liver – Bound to albumin because insoluble in water

• Transported into hepatocyte & conjugated • Primarily bound to ligandin within the cell & this prevents the backflow into circulation – With glucuronic acid → now water soluble

(by action of uridine diphosphate gluconoryl transferase)

• Secreted into bile • In ileum & colon, converted to urobilinogen • Excreted from urine as urobilin • Excreted from feces as stercobilin

Bilirubin Metabolism

Unconjugated

Glucuronyl Transferase

(Bilirubin Diglucuronide)

Why do newborns develop jaundice?  Increased production (↑RBC mass, so ↑ed hemolysis  Fetus is in a hypoxic environment – high Hb  Postnatal rise in PO2  Decrease in erythropoietin prodn.  Destruction of excess Hb.

 Decreased conjugation(immature liver enzyme system)  Neonatal RBC lesser life span (60-90days)  Increased entero-hepatic circulation – sterile gut

• Enterohepatic Circulation: – Sterile intestines of neonate is rich in glucoronidase – This enzyme splits bilirubin glucoronide to bilirubin and glucoronic acid – Unconjugated bilirubin again reabsorbed through the portal circulation

PHYSIOLOGICAL JAUNDICE • Seen both in term and pre • Self limiting • Develops after 24 hours • Peaks by day 4- 5 in and day 7-8 in pre • Peak levels -12mg/dl in term & 15mg/dl in preterm • Gradually subsides by 10-14 days • No Treatment necessary

PATHOLOGICAL JAUNDICE Suspect if...

• Jaundice in first 24 hours • rise of >5mg/24 hours or 0.5mg/dl/hour • Jaundice beyond physiological limits • Conjugated bilirubin >2mg/dl • Persists beyond 2 weeks • Signs of underlying illness

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

Rh incompatibility ABO incompatibility – – –

G-6PD deficiency Congenital spherocytosis Sepsis

• B. Within 3-10 days of life – – – – – – – – – – –

Physiological jaundice Prematurity Hypoglycemia Acidosis Sepsis Congenital hemolytic anemia Crigler Najjar & Gilberts syndrome Galactosemia Cephalhematoma Subcutaneous bruising Drugs:

• Prolonged Jaundice (jaundice at more than 10 days of life) • A. Prolonged Unconjugated hyperbilirubinemia breast milk jaundice breast feeding jaundice sepsis hypothyroidism galactosemia infantile pyloric stenosis persisting hemolysis hemoglobinopathies drugs: erythromycin , chloramphenicol

• Pronged conjugated hyperbilirubinemia – 1. intrahepatic cholestasis • A. Infections: – Septicemia – UTI – Hepatitis – STORCH infections

• B. Metabolic – Galactosemia – Alpha 1 antitrypsin deficiency – MPS – Gauchers disease – Cystic Fibrosis

• 3. Endrocrine – – –

Hypothyroidism Hypoparathyroidism Hypopituiterism

4. 5. 6. 7.

Total parental nutrition Drugs: sulphonamides Intrahepatic bile duct disease Idiopathic neonatal hepatitis

• B. Extra hepatic cholestasis – – –

Biliary atresia Choledochal cyst Bile duct stenosis

Breast Feeding Jaundice Breast Feeding Jaundice • Misnomer • Higher levels on day 4 compared to formula fed babies due decreased intake of milk • This leads to increased enterohepatic circulation

Breast milk jaundice Breast Milk Jaundice • By day 7, instead of usual fall in bilirubin level, bilirubin level continues to rise • May sometimes reach 20-30mg/dl by 2nd -3rd wk of life • gradually returns to normal by 4-12 weeks

• Exact mech unknown, but thought to be due to factors in breast milk ( a glucoronidase in breast milk) interfering with bilirubin conjugation or metabolism • If breast feeding is stopped for 48hours , bilirubin level will fall rapidly • Rebound increase after resumption of feeding of 2-3mg/dl • Chance of reoccurance in future pregnancies: 70%

CLINICAL EVALUATION • • • • • •

History to rule out other causes Careful physical examination Dermal progression of jaundice Icterometer Transcutaneous bilirubinometer Laboratory investigations

Cramer’s Index • Face ~ 4-6 mg % • Chest and Upper abdomen ~ 8-10 mg % • Lower abdomen and thighs ~ 12-14 mg% • Fore arms and legs ~ 15-18 mg % • Palms and soles ~ 15-20 mg %

Lab Investigations

• • • • • • •

Hemoglobin, PCV Peripheral smear examination Coombs’ test Reticulocyte count Blood group and Rh typing Bilirubin level – Total / Direct & Indirect Special tests – – – –

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

Approach • Age at appearance <24 hrs 24hrs – 2 weeks Incompatibilities Direct Indirect Sepsis

Sepsis Hypothyroid Obstructive Syndromic

>2 weeks sepsis IEM Thyroid

Hemolytic Non hemolytic Rh / ABO Cephalhematoma Enzyme defects Polycythemia Membrane defects

Laboratory Evaluation of Term Newborn with Jaundice

MANAGEMENT

• Phototherapy • Drugs • Exchange transfusion

Indications for Phototherapy • • • • • •

TSB > 15 mg % in term TSB > 12 mg% in preterm TSB > 5 mg% within 24 hours Adjuvant to exchange transfusion VLBW with Perinatal risk factors Precautions – – –

Cover the eyes and Genitals Supplemental hydration Watch for side effects

PHOTOTHERAPY • • • •

Blue light (425-475 nm) Fibreoptic blankets or overhead banks As close as possible ( 25cm) Continuos therapy-interruptions for feeding allowed

Mechanism Of Phototherapy Conversion of insoluble Bilirubin into soluble bilirubin – Photo-isomerization: natural isomer ofunconjugated bilirubin is converted to less toxic polar isomer which diffuses into blood & excreted into bile without need of conjugation

– Structural isomerization: of bilirubin into lumirubin & is excreted into bile and urine without conjugation – Photo-oxidation: bilirubin converted to small polar products which are excreted in urine

Phototherapy Complications • Dehydration: insensible water loss is increased • Hypothermia: particularly in winters • Increased frequency of greenish stools: ↑ed bile salts and unconjugated bilirubin in bowel

• Retinal damage • Bronze baby: when PT given with direct hyperbilirubinemia • Testicular damage: mutations, sister chromatid exchange, DNA strand breaks • Hampering of materno-fetal bonding

DRUGS • Phenobarbitone -induces liver ezymes: useful for Crigler Najjar Syndrome Type II • Metalloporphyrins -inhibits heme oxygenase and therefore conversion of biliverdin to bilirubin • IVIG: may be used in hemolytic anemia • Oral agar • Albumin infusions

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