Neonatal Jaundice

1. Neonatal Jaundice Dr. KalpanaMalla MD Pediatrics Manipal Teaching Hospital Download more documents and slide shows on The Medical Post [ www.themedicalpost.net ]

2. Incidence Term—60% Preterm—80% • Bilirubin Source – Hb – 75% Non Hb – 25% (Myoglobin)

3. Normal Physiology • Bilirubin -breakdown of hemoglobin • Unconjugated bilirubin (insoluble in water) transported to liver- Bound to albumin • Transported into hepatocyte (Ligandin / y- protein ) & conjugated - With glucuronic acid → now water soluble • Secreted into bile

4. Normal Physiology • Secreted into bile • In ileum & colon, converted to stercobilin • 10-20% (Deconjugated by β glucuronidase)reabsorbed into portal circulation (Enterohepatic circulation )and re-excreted into bile or into urine by kidneys - urobilinogen

5. Bilirubin Metabolism Unconjugated Glucuronyl Transferase (Bilirubin Diglucuronide)

6. NEWBORN JAUNDICE(PHYSIOLOGICAL) Etiology 1. Decreased RBC survival 90 days, increased RBC vol /Kg, polycythemia of NB 2. Poor hepatic uptake due to immature liver-decreased ligandin or Y- protein 3. Poor conjugation due to enzyme deficiency-UDPG-T activity

7. NEWBORN JAUNDICE(PHYSIOLOGICAL) 4. Increased enterohepatic circulation due to - High level of intst beta-glucoronidase - delayed colonization by bacteria - Decreased gut motility 5.Decreased hepatic excretion of bilirubin

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

9. PATHOLOGICAL JAUNDICE Suspect if... Jaundice in first 24 hours Rise of >5mg/24 hours or 0.5 mg/dl/hr Jaundice beyond physiological limits Conjugated bilirubin- >2mg or 20% of total Beyond 2 weeks Signs of underlying illness ++

10. Pathological Jaundice - Hemolytic causes (unconjugated) Coombs' test positive • Rh incompatibility • ABO incompatibility Coombs' test negative • Red blood cell membrane defects • Red blood cell enzyme defects • Drugs • Hemoglobinopathies • Sepsis

11. Pathological Jaundice - Non-hemolytic (unconjugated) Extravascular sources - cephalohematoma - Polycythemia: • fetal-maternal transfusion, • delayed cord clamping • twin-twin transfusion Increased Enterohepatic circulation • Cystic fibrosis • Ileal atresia • Hirschsprung's disease • Breast milk jaundice

12. Pathological Jaundice – Defective Conjugation(unconjugated) Crigler-Najjar syndrome types 1 and 2 Gilbert syndrome Hypothyroidism Breast milk jaundice

13. Pathological Jaundice – Defective Conjugation Metabolic disorder: • α1 AT deficiency • Cystic fibrosis • Galactosemia • Gaucher's disease • Niemann-Pick disease • Hypothyroidism Chromosomal disorders • Turner's syndrome, • trisomy 18 and 21

14. Pathological Jaundice – Defective excretion Biliary obstruction: • biliary atresia • choledochal cyst • Sclerosing cholangitis • Dubin-Johnson syndrome • Rotor's syndrome Infection: • Sepsis • UTI • STORCH infections

15. Causes of Jaundice –as per time of onset Within 24 hrs • HDN—Rh, ABO Incompatibility • IU infections-CMV, HSV, Toxo, Syphilis • RBC Enzyme deficiencies-G-6PD defi, pyruvate kinase deficiency • Drugs—large dose of vit k , syntocin drip, Salicylates, sulphas etc • Hereditary Spherocytosis • Criggler-Najjar syndrome • Alpha thalassemia

16. 24-72 hrs—Physiological JaundiceExaggerated Physiological Jaundice (MATERNAL FACTORS) • -Blood type ABO or Rh incompatibility • -Breastfeeding • -Drugs: Diazepam, Oxytocin • -Maternal illness: gestational diabetes

17. Exaggerated Physiological Jaundice (neonatal factors) • Birth trauma: cephalohematoma, cutaneous bruising, instrumented delivery • Drugs: Erythromycin, Chloramphenicol • Immaturity ▪ Birth asphyxia • Acidosis ▪ Cretinism • Hypothermia • Hypoglycemia • Hypothyroidism • Polycythemia

18. After 72 hrs (within 2 weeks) • Septicemia • Neonatal Hepatitis, other IU infections • Extra hepatic Biliary atresia • Breast milk jaundice • Metabolic diseases—galactosaemia, CF, alpha-1 antitrypsin deficiency, hypothyroidism • Hypertrophic Pyloric stenosis

21. Diagnosis 1)History—Antenatal Drugs Trauma Family H/O of jaundice Liver disease H/O delayed feeding Sepsis Sibling jaundice Splenectomy in family

22. Cramer’s Index 1.Face-4-6 mg/dl 2.Chest &Upper trunk – 8-10 mg/dl 3.Lower abdomen,thigh-12 -14mg/dl 4.Forearms &lower legs -15 -18 mg/dl Palms & sloes->15-20 mg/dl 2. General exam

23. Examine • Gestation age-preterm, IUGR • Cephalhematoma, bruising • Pallor-hemolytic anemia • Patechiea -sepsis, erythroblastosis, cong infections • HSM-hemolytic anemia, cong infections • Evidence of hypothyroidism, cong infections

24. 3) Lab investigations 1. Hemoglobin, PCV with peripheral smear 2. Total Bilirubin (Total / Direct & Indirect) - >12 mg /<24hr - <12 mg/ >24 hr 3. Bilirubin level –Special tests – • TORCH titres - Thyroid function tests • Metabolic work up - Sepsis screen • USG / X ray abdomen • Blood group and Rh typing • Reticulocyte count

25. Investigations in RH incompatibility • Antenatal - (mother Rh-ve, previous baby Rh + ve, father Rh +ve. • H/o of abortion, H/o having taken Anti D gammaglobulin • USG for baby maturation ,HSM, ascites, hydrominos, gen. anasraca

26. Investigations in RH incompatibility • Antenatal - - Blood grp (ABO & Rh) of father ,earlier baby - Indirect Coomb’s test – to detect antibodies in mother’s serum IgG Anti body Titre to D TO be estimated at 12-16,28-32 and 36 weeks. If anti D antibody Titre 1:16 it should be tested serially - Ab titre in mother’s blood ->1:64 dignostic of HDN- TO CONSIDER TERMINATION OF PREGNANCY.

27. Investigations in RH incompatibility • Anmiocentesis: • Look for lecithin sphingomyelin ratio to suggest maturity. • Shake test for 15 sec. with equal vol etanol 95%-allowed to stand-ring of buble at the disc • Optical density-by spectrophotometer OD.>0.15 denotes maturity of lungs • Alpha feto protein level increased –rh issoimun • Fetal bloob grp prenatally – amniocentesis

28. POSTNATAL INVESTIGATION BABY Cord blood—all babies of Rh-ve mothers, all Unknown blood groups, all with prior h/o jaundice in earlier babies Blood group-both mother and baby • For evidence of hemolysis – Direct Coombs test Reticulocyte count - >10 suggest hemolysis. Hemoglobin cord Peripheral smear -RBC morphology Bilirubin

29. Others RBC membrane defects • RBC enzymes –G-6-PD screen Neonatal hepatitis – LFT Metabolic studies – including hypothyroidism Biliary obstruction – USG,HIDA scan • PCV inc  polycythaemia

30. Jaundice >12mg/dl,age <24 hrs<12mg/dl,age>24 hrs ↓ DCT............................. Negative ↓ ↓ Positive Direct bilirubin ↓ >2mg/dl Rh, ABO ,Others Hepatitis, TORCH, Sepsis, Biliary obstruction Flow chart Negative Positive

31. Direct bilirubin < 2mg/dl Htc→high → polycythemia RBC Morpho, Retics ↓ Abnormal Normal Hemolytic ABreast milk J, Sepsis, IEM H.sperocytosisHypothyroidism, asphyxia, ∝-thalassemiaphysiologic J, DIC,Drugs ,ABO incom H.Pyloric stenosis low

32. MANAGEMENT Phototherapy Drugs Exchange transfusion

33. MANAGEMENT OF JAUNDICE • To Decrease Bilirubin: -↑↑excretion Phototherapy, ET - ↑↑conjugation phenobarbitone - ↓ enterohepatic circ- Agar, Cholestyramine - Inhibit Bili production—metalloporphyrins - Inhibit haemolysis high dose IVIG - Inc albumin binding—Albumin

34. PHOTOTHERAPY

35. Phototherapy -MTH

36. Phototherapy -MTH

39. Phototherapy • Safe and effective method for treatment of neonatal jaundice • Bilirubin absorbs light maximum at 420-460 nm

40. Mechanism of Action Conversion of insoluble Bilirubin into soluble bilirubin 1.Photo-isomerization-conversion into soluble form – takes place in extravascular space of skin –conversion to less toxic polar isomer-diffuses into the blood –excreted easily into bile 2.Structural isomerization - conv to lumirubin -rapidly excreted in bile and urine 3. Photo-oxidation- of Bilirubin to water soluble polymers colourless by product.

41. Indications for Phototherapy TSB > 15 mg % in term TSB > 12 mg% in preterm TSB > 5 mg% within 24 hours Adjuvant to exchange transfusion Prophylactic PT – ELBW, bruised babies, hemolytic disease of NB,VLBW with Perinatal risk factors

42. Indications • Precautions • Cover the eyes and Genitals • Supplemental hydration • Watch for side effects

44. Procedure • Best is narrow spectral blue lights (425-475nm) • White lamps (380-700nm) • Distance from skin – 45cm • Intensive PT – 15-20 cm • Shield eyes & genitalia • Space of 5-8cm between phototherapy unit & incubator

45. Double surface PT – can be given by fiber-optic blankets (biliblankets) Change position once in every 2-4 hrs Skin bleached by PT Level to be checked every 10-20 hrs Frequent temperature monitoring & daily weight check

46. Side Effects • Immediate – • Loose stools • Dehydration, • Hyperthermia, • ‘Bronze baby’ syndrome, • Rashes, • Upsets maternal infant interactions (bond)

47. Late – • Risk of skin malignancies • Damage to intracellular DNA • Retinal damage • Disturbance in circadian rhythm Testicular damage

48. Biliblanket or glow-worm ? Home phototherapy

49. DRUGS • Phenobarbitone – increase y and z ligands -induces liver ezymes - ↑↑conjugation phenobarbitone • Metalloporphyrins (tin and zinc porphyrins and meso prophyrins) -inhibits heme oxygenase

50. IVIG - Inhibit haemolysis • Oral agar, Cholestyramine-↓ enterohepatic circ • Albumin infusionsInc albumin binding