12. Neonatal Jaundice B48 Sem 5.pdf

9/8/2023 Learning Outcomes • Metabolism of bilirubin Neonatal Jaundice • Physiological and pathological jaundice. • Diagnosis and complication of hyperbilirubinemia • Management of neonatal jaundice 1 2 Jaundice Jaundice (French jaune) yellow) Bilirubin Production Icterus (Greek ikteros) ye...

9/8/2023 Learning Outcomes • Metabolism of bilirubin Neonatal Jaundice • Physiological and pathological jaundice. • Diagnosis and complication of hyperbilirubinemia • Management of neonatal jaundice 1 2 Jaundice Jaundice (French jaune) yellow) Bilirubin Production Icterus (Greek ikteros) yellow bird Hepatic Bilirubin Uptake Glucuronyl transferase Hepatic excretion Enterohepatic circulation Bilirubin Elimination Golden oriole 3 4 Bilirubin Production O2 + NADPH CO + Fe Heme Heme oxygenase Biliverdin Bilirubin Excretion Heme breakdown glutathione Stransferase (Ligandin) Unconjugated Bilirubin Water soluble Intestine Liver Unconjugated Bilirubin Conjugated Bilirubin UDP-glucuronyl transferase Tissue/Bacteria Breastmilk  -Glucuronidase Biliverdin reductase Free Bilirubin increased in Acidosis Hypoalbuminemia Prematurity Drugs (sulfas, cephalosporins) Conjugated Bilirubin (Liver, spleen, bone marrow) Enterohepathic Circulation GIT Flora Urobilinogen Unconjugated Bilirubin Urobilin Albumin + Bilirubin Fat soluble Stercobilin 5 7 1 9/8/2023 Neonatal Jaundice Classification of Neonatal Jaundice • Physiological jaundice • Most common condition in newborns – Unconjugated hyperbilirubinemia – Typically appears at 2-4 days of life – Resolves by 7-10 days – Due to normal immaturity of the liver • 50-70% of term babies & 80% of preterm babies develop jaundice in the first week of life • Visible jaundice when • Pathological jaundice – Due to a variety of underlying medical conditions total serum bilirubin (TSB) 5 mg/dL (>85 mol/L) • 9 10 Physiological Jaundice Term Neonate 8 Physiologic Jaundice Peak 5-6 mg/dL (10-14 mg/dL Asian) 7 TSB (mg/dL 6 ↓ Liver Uptake ↓ Conjugation ↓ Ligandin ↓ Glucuronly transferase 5 ↑ Bilirubin Load 4 3 Rapid decline 5th day (7-10th day in Asians) 2 1 1 2 3 4 5 6 7 8 9 10 11 ↑ bld vol ↑ Hb level ↓ RBC life span (~ 85 days) ↑ turnover of nonhemoglobin heme proteins (cytochromes, myoglobin) ↑ Enterohepatic Circulation ↑ -glucuronidase ↑ Gut permeability Absence of gut flora Age (Days) 13 15 Causes of Pathological Jaundice When to Consider Pathological Jaundice Increased Bilirubin Load • • • • Haemolytic anaemias • Rhesus or ABO incompatibility • Glucose-6-phosphate dehydrogenase deficiency • Hereditary spherocytosis • -Thalassaemia • Drug-induced • Sepsis Early onset (<24 hours of life) Persistent (>10 days of age) TSB >12 mg/dL (205 μmol/L) at any time Rapid rate of rise of TSB (>8.5 μmol/L/hr or 0.5 mg/dL/hr) • Elevation of direct bilirubin (DB) DB >1 mg/dL (if TSB <5 mg/dL) DB >20% of TSB (if TSB >5 mg/dL) 20 Others • Polycythemia • Extravasation of blood (Cephalohematoma) 21 2 9/8/2023 Immune-Mediated Hemolytic Disease Features of Hemolytic Jaundice • Rhesus incompatibility • Early onset jaundice (24-36 hrs of life) – Mother Rh-D negative • Rapidly rising bilirubin (8.5 μmol/l or 0.5 mg/dl per hr) – Infant Rh-D positive • ABO incompatibility • Low Hb – Mother: Blood group O • Increased reticulocytes – Infants of Blood group A or B 22 25 Jaundice due to Cephalhematoma Increased enterohepatic circulation • Breast feeding jaundice • Breast milk jaundice • Pyloric stenosis • Duodenal or jejunal atresia 29 31 Breast Milk Jaundice Breast Feeding “Failure” Jaundice • • • • • • • Onset 1st wk of life • Due to decreased breastfeeding or poor latch • Dehydration, starvation,  enterohepatic circulation • Decrease stool output • Caloric deprivation • Excessive weight loss 32 Incidence 36% Onset 1-2 wk of life Duration 1-3 months Mild jaundice in a well suckling infant Normal weight gain, stool and urine Cause multifactorial 33 3 9/8/2023 Decreased Hepatic Bilirubin Clearance History • • • • • • • • • Prematurity including late-preterm gestation • Hormonal deficiency – Hypothyroidism – Hypopituitarism • Disorders of bilirubin conjugation—UGT1A1 gene variants – Crigler–Najjar syndrome – Gilbert disease 35 Pregnancy: (Diabetes, PE, IUGR) Maternal blood group (immune hemolysis) Prolonged rupture of membranes, fever (infection) Method of delivery (Trauma) Delayed cord clamping (Polycythemia) Feeding difficulties (dehydration) Stool & urine color (cholestasis) Family history of jaundice/anemia (inherited disorders) 41 Signs of dehydration Sunken fontanel Reduced skin turgor Delayed capillary refill Reduced urine output General appearance Lethargic Activity Nappy: Urine and stool color Physical Examination Face Skin & eyes jaundice Pallor? Pink / cyanosis ‘Red flags’ • • • • • Mouth Tongue-tie/cleft palate Dry mucous membrane Abdomen Distension Hepatosplenomegaly Fever, poor handling or looks unwell (think infection) Pale stools (think obstructive jaundice) Pallor (think haemolysis) Refractory jaundice (think enzyme deficiency) Jaundice above the exchange transfusion line Weight Calculate percentage weight loss Ano-rectal malformation (causing delayed meconium passage) 46 47 Zones of Dermal Jaundice Kramer’s Rule Visual Assessment of Jaundice 1 Blanch skin for visual assessment of Jaundice TSB 5 mg/dL (>85 mol/L) 2 4 4 5 Before Phototherapy 48 After Phototherapy 5 Limitations: Skin pigmentation Plethora Decreased ambient light Prior exposure to sun or phototherapy 3 4 5 49 4 9/8/2023 Visual Recognition of Jaundice Transcutaneous bilirubinometer (TcB) • Measures bilirubin in subcutaneous tissue • Linear correlation between TSB and TcB • Not a sensitive measure, may miss many infants vulnerable to kernicterus • Constant underdetection of hyperbilirubinemia if visual recognition is the only method • Inaccurate in babies with darker skin tones Philips BiliChek 50 Dräger JM-105 Jaundice Meter 51 Coronal section through posterolateral lobes Investigations • Transcutaneous bilirubinometer (screening test) • Total serum bilirubin • Direct serum bilirubin (>20% ot TSB work-up for conjugated jaundice) • Hb / Hct (polycythemia) • WBC & platelets (sepsis) • Reticulocytes (hemolysis) • Peripheral blood smear (spherocytes) • Blood group of mother & baby • Direct Coombs test (Rh/ABO iso-immunization) • G6PD levels (hemolysis) • TSH (hypothyroidism) 52 1. Hippocampus 2. Basal ganglia 3. Substantia Nigra 4. Thalamus 54 Acute Bilirubin Encephalopathy Acute Bilirubin Encephalopathy Late Signs Early signs nonspecific • Lethargy • Bicycling movements • Poor sucking • Respiratory failure • Irritability, jitteriness • Progressive coma • High-pitched cry • Intractable seizures • Hypertonia • Retrocollis • Opisthotonos • Hypotonia • Recurrent apnea 55 56 5 9/8/2023 Paresis of upward gaze Chronic Bilirubin Encephalopathy (Kernicterus) • Choreoathetoid cerebral palsy chorea, ballismus, tremor, dystonia • Sensorineural hearing loss • Gaze abnormalities (paresis of upward gaze) • Dental enamel dysplasia • Cognitive function usually relatively spared 58 59 Enamel Dysplasia Management of Hyperbilirubinemia • Phototherapy • Exchange transfusion • Adequate feeding 60 64 Factors in Efficacy of Phototherapy Phototherapy: Light Source Fluorescent tube Spectrum of Light Blue most effective (460-490 nm) Irradiance Distance Minimize patientlight-source distance (10 to 15 cm) Light-emitting diode (LED) Fibreoptic (BiliBlanket) 69 Standard 10 W/cm2/nm Intensive ≥30 W/cm 2/nm Skin Area Exposed Additional light below infant 74 6 9/8/2023 Mechanism of Phototherapy Adverse Effects of Phototherapy Configurational Isomers Structural Isomers • • • • • Dehydration Hyperthermia Erythematous rash Loose stools Bronze baby syndrome (cholestasis) • Retinal degeneration (animal studies) Light Bilirubin Bile Bile, Urine Urine Colorless oxidation products 75 77 Exchange Transfusion Exchange Transfusion • Remove bilirubin rapidly • Also remove Antibodies & sensitized RBC • Indications – Signs of acute bilirubin encephalopathy – TSB levels >threshold values Port for Injections To Waste Container 79 Complications of Exchange Transfusion Catheter Related Complications of Exchange Transfusion Haemodynamic problems • Infection 83 A B D 78 To Infant C From Blood Bag • Hemorrhage • Cardiac failure • NEC • Hypovolaemic shock • Air embolism • Arrhythmia (catheter near SA node) • Portal and splenic vein thrombosis • Bradycardia with calcium bolus 84 7 9/8/2023 Neonatal Jaundice: Summary Complications of Exchange Transfusion Electrolyte Imbalance • Clinically apparent when TSB >85.5 mol/L (5 mg/dL) • Hyperkalemia • Mostly physiologic jaundice • Hypocalcemia • Investigate jaundice under 24 hrs of life for pathology • Hyper- and Hypo-glycaemia • Jaundice can potentially cause irreversible, life- long brain damage (kernicterus) • Metabolic acidosis, alkalosis (late breakdown of • Treatment includes phototherapy and/or exchange citrate) 85 transfusion 90 8