NEONATAL JAUNDICE GBMC PRESENTATION.pptx

NNJ

1. NEONATAL JAUNDICE BY DR MUHAMMAD HASSAN 25/04/24 GBMC

2. OUTLINE: INTRODUCTION EPIDEMIOLOGY BILIRUBIN METABOLISM CLASSIFICATION CAUSES CLINICAL MANIFESTATION INVESTIGATIONS TREATMENT COMPLICATION PREVENTION

3. DEFINATION: Jaundice is a clinical conditions that is characterized by yellowish discoloration of : sclera, mucous membrane, skin It occur due increased level of bilirubin, a pigment derived mainly from HB INTRODUCTION

4. The prevalence of jaundice in clinical practice is between 50-80%, common in preterm >80%, and in about 50% in term neonate. Jaundice appear in neonate when serum bilirubin is >7.1mg/dl 6.1% of well term neonate have serum bilirubin level >12.9mg/dl Also serum bilirubin >15mg/dl has been recorded in 3% of normal term neonate Normal baby produce 6-10mg of bilirubin /kg/day Epidemiology

5. About 80% of bilirubin is derived from catabolism of red blood cells in the reticulo -endothelial system (RES) – bone marrow, spleen, liver; Haemoglobin 75-80% The remaining 20% from other sources which include: Myoglobin } Haem -containing enzymes } Cytochromes } Catalase /Peroxidases } 20-25% Tryptophan pyrrolase } In-effective erythropoiesis Bilirubin metabolism

6. Physiological jaundice/Pathological Conjugated(direct)/unconjugated(indirect) jaundice Mild/moderate/severe jaundice CLASSIFICATION OF NEONATAL JAUNDICE

7. UNCONJUGATED HYPERBILIRUBINEMIA (HEAMOLYSIS) Blood group incompatibilities( ABO, Rhesus) Deficiency of red cell enzymes (G6PD, Hexokinase, pyruvate kinase) Congenital red cell membrane defects ( eliptocytosis , spherocytosis) Infections – Neonatal septicaemia Haemolytic agents (Naphthalene, Menepthone ) Extravasated blood ( cephalhaematoma , IVH)

8. UNCONJUGATED HYPERBILIRUBINEMIA (DEFECTIVE CONJUGATION) Crigler Najjar syndrome Breast milk jaundice Familial neonatal hyperbilirubinemia Hypothyroidism Down’s syndrome Infants of diabetic mothers prematurity

9. CAUSES OF CONJUGATED HYPERBILIRUBINEMIA INFECTION Toxoplasmosis, CMV, Hepatitis B, Rubella Giant cell hepatitis BIOCHEMICAL/METABOLIC Galactosemia, alfa-1-antitripsin deficiency, Roto’s & Dubin Johnson syndrome Hypothyroidism, tyrosinosis CONGENITAL OBLITERATION Congenital biliary atresia, Choledochal cyst, Bile duct stenosis Inspissated bile duct syndrome

10. It is a diagnosis of exclusion. Only diagnosed by excluding infection, haemolysis, and metabolic diseases, etc. Causes are multifactorial: RBC mass, RBC life span, decreased UDP- glucuronyl transferase and ligandin , increased enterohepatic circulation Begins at >36 hrs (usually not earlier than 24 hours) Peaks to 5-6mg/dl on 4 th day Bilirubin levels not more than 12mg/dl Returns to below 2mg/dl on the 7- 10 th day Direct bilirubin < 1.5-2mg/dl or 15% of total SBR PHYSIOLOGIC HYPERBILIRUBINAEMIA

11. Onset before 24 hours of life; Rate of rise of SBR > 5mg/dl./24 hours or >0.5 mg/dL/hour; usually signifying active haemolysis Term infant with SBR is above 12.9mg/dl. Preterm infant with SBR is above 15mg/dl. Direct bilirubin is above 1.5-2mg/dl. or 15% Jaundice persisting after 7 or 14 days in term and preterm babies. There may be associated hepatosplenomegaly or anaemia Due to Increased bilirubin load or Impaired bilirubin excretion or Mixed Pathological jaundice

12. Immune mediated: ABO incompatibility; Rhesus alloimmunization ; and Other blood group incompatibilities Heritable disorders: Red cell membrane defects: – congenital spherocytosis Red cell enzyme deficiencies: - G6PD deficiency Haemoglobinopathies : -  - thalassaemia  -  - thalassaemia Causes of increase bilirubin load in pathological neonatal jaundice

13. Sepsis Disseminated intravascular coagulation Extravasation of blood: Haematoma Pulmonary or intracranial haemorrhage Swallowed maternal blood Polycythaemia Macrosomic infants of diabetic mothers 0thers

14. Breast milk jaundice Pyloric stenosis Intestinal obstruction Prematurity Causes of Increased Enterohepatic Circulation and Decreased Clearance of Bilirubin

15. Crigler -Najjar Syndrome types I and II Gilbert’s disease Hypothyroidism Hypopituitarism Causes Of increased Clearance of Bilirubin: Metabolic

16. Extrahepatic biliary atresia Trisomy 18 Intrahepatic biliary atresia ( nonsyndromatic paucity of bile ducts) Extrahepatic biliary atresia and choledochal cyst Bile plug syndrome Cystic disease Causes of ductal disturbances in pathological jaundice

17. Major Aetiological Factors of Pathological Neonatal Hyperbilirubinaemia in Nigeria i . ABO Incompatibility, ii. Bacterial Infections(sepsis) iii G-6-PD Deficiency iv. Low Birthweight In a variable proportion of cases the cause is unknown – partly due incomplete evaluation. Major causes of pathological jaundice in Nigeria

18. COMMONLY USED ICTEROGENIC AGENTS

19. Jaundice may appear any time during neonatal period Jaundice begins on the face and as the level increases, progress to the abdomen and feet Unconjugated bilirubin appears bright yellow or orange Conjugated bilirubin appears greenish or muddy yellow Infants usually lethargic and feed poorly Signs of primary disease.(sepsis, etc) CLINICAL PRESENTATION

20. Discoloration of the sclera Mucous membrane Skin Urine Other body fluids Irritability High pitched cry Acute encephalopathy Clinical features of NNJ

21. KREMER RULE FOR ESTIMATION OF NNJ Zone SBR mmol/L 1 = 100 mmol/L 2 = 150 mmol/L 3 = 200 mmol/L 4 = 250 mmol/L 5 > 250 mmol/L

22. BIND SCORE

23. BIND SCORE – CLINICAL IMPLICATION STAGE SCORE SIGNS 1A 0 - 3 Minimal signs, totally reversible with therapy 1B 4 - 6 Progressive signs but reversible with therapy II 7 - 10 Irreversible signs but severity decreases with prompt and aggressive therapy

24. Good History: Thorough Physical Examination and Essential Laboratory Investigations The questions to answer are: Any cause of the hyperbilirubinaemia that needs to treated e.g. sepsis What is risk of acute bilirubin encephalopathy? This will depend on a number of factors – SBR level, gestational age of the baby and co-morbidities. MANAGEMENT OF NEONATAL JAUNDICE

25. Good History: Family History Parent or sibling with history of jaundice/anaemia Previous sibling with NN hyperbilirubinaemia History of liver disease in sibling or disorders such as cystic fibrosis, galactosaemia, tyrosinaemia , hypermethionaemia , Crigler-Najjar syndrome or alpha1-antitrypsin deficiency. Management of neonatal jaundice

26. Maternal History Unexplained illness during pregnancy Diabetes mellitus in mother Drug intake during pregnancy Management of neonatal jaundice

27. Perinatal History History of labour: Vacuum extraction Oxytocin -induced labour APGAR score Delayed passage of meconium/few stools Infant’s: Caloric intake Management of neonatal jaundice

28. Infant’s Physical Examination Size for gestational age Head size Cephalhaematoma Pallor Petechiae Appearance of umbilical stump/hernia Hepatosplenomegaly Congenital anomalies Management of neonatal jaundice

29. Maternal: Blood group/indirect Coombs’ test Serology Haematocrit/ Haemoglobin Laboratory investigations

30. Baby: Bilirubin (indirect and direct) Blood group/direct & indirect Coombs’ tests Urinalysis (including test for reducing substances) Reticulocyte count RBC morphology G-6-PD status Platelets count; clotting test White blood cell count Serology (specific IgM antibodies - TORCHES) Carboxyhaemoglobin level Albumin binding capacity for bilirubin Free bilirubin Laboratory investigations

31. Laboratory Evaluation of Neonatal Conjugated Hyperbilirubinemia LFT: transaminases, etc. Serum protein /protein electrophoresis Erythrocyte sedimentation rate Hepatitis-associated antigens Alpha 1 -anti-trypsin concentration Liver biopsy Laboratory investigation

32. Urine Tests: Routine urinalysis, Urine culture Bilirubin and urobilinogen Amino acid screening Laboratory investigation

33. PRINCIPLES Observation/monitoring Resucitation Reduce bilirubin load Phototherapy(unconjugated) Exchange blood transfusion Phenobarbital therapy Treat underlying cause Prevent/control complications Supportive therapy Treatment of NNJ

34. Treatment of NNJ

35. Phototherapy Effectiveness depends on: Amount of light energy emitted in effective wavelengths Distance from light source to the baby Amount of skin exposed Rate of underlying process generating excess bilirubin In vivo metabolism and excretion of bilirubin Indication: unconjugated bilirubin 16-18 mg/dl; lower in preterm infants Contra indicated in obstructive jaundice Has significantly reduced the need for exchange blood transfusion Must simultaneously treat identifiable causes of hyperbilirubinemia Prophylactically used in VLBW infants Treatment of NNJ

36. Tanning Bronze baby syndrome Lactose intolerance Haemolysis Skin burns Dehydration Diarrhoea Macular-papular Skin rashes Complication of phototherapy

37. Exchange Blood Transfusion (EBT) - Reserved for infants at risk for kernicterus (>20 mg/dL) - Asymptomatic infants with physiologic or breast milk jaundice do not need transfusion until >= 25 mg/dL - Otherwise, if BR > 10% of weight for those less than 2000 grams Indications for Exchange Blood Transfusion: Infant with uncomplicated haemlytic disease Anaemia (PCV < 45%), + ve Coombs’ test, and a rise of S. bilirubin > 0.5mg/dl./hour In ABO haemolytic disease, rate of rise of serum bilirubin >1.0mg/dl./hour Serum bilirubin > 20 mg/dl. at any time Serum bilirubin > 20 mg/dl. for more than 36 hours and binding capacity not available Reduced biding capacity if available. Treatment of NNJ

38. Results when indirect BR exceeds ability of albumin to bind Deposited in brain due to lipid solubility Disrupts neuronal metabolism and function Concentration required to cause kernicterus is dependent on gestational age and health status - Term: 20-25 mg/dL - Preterm: 20 mg/dL - Very immature (< 1000g): 10 mg/dL Kernicterus

39. Kernicterus Choreoathetoid Cerebral Palsy SN Deafness Enamel Dysplasia Mental Retardation Death Complications from phototherapy Complications from EBT COMPLICATIONS

40. Hyperbilirubinemia in neonates is a common condition caused by multiple and variety of factors which if identified can be treated Poor management of jaundice can lead to severe neurological damage and death CONCLUSION

41. B.C Ibe . Neonatal jaundice. In: Paediatrics and Child Health in the Tropical Region .Eds. Azubuike and Nkanginieme 2 nd Edition African Pub.2007, 204-211 Martins C.M and Cloherty J.P . Neonatal hyperbilirubinaemia. In : MANUAL OF NEONATAL CARE 6 th ED , 2008;181-212 Kaplan M, Merlob P, Regev R. guidelines for the management of neonatal hyperbilirubinaemia. J Perinatol 2008;1-9 REFERENCES