Neonatal Jaundice

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

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 Glucuronyl Transferase Unconjugated (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: α 1 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 Jaundice Exaggerated 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

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

20. 2. General exam 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

21. 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

22. 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

23. 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

24. 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.

25. 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

26. 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

27. 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

28. Flow chart 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 Negative Positive

29. Direct bilirubin < 2mg/dl Htc → high → polycythemia RBC Morpho, Retics ↓ Abnormal Normal Hemolytic A Breast milk J, Sepsis, IEM H.sperocytosis Hypothyroidism, asphyxia , ∝ -thalassemia physiologic J, DIC,Drugs ,ABO incom H.Pyloric stenosis low

30. MANAGEMENT Phototherapy Drugs Exchange transfusion

31. 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

32. PHOTOTHERAPY

33. Phototherapy -MTH

34. Phototherapy -MTH

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

36. 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.

37. 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

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

39. 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

40. 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

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

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

43. Biliblanket or glow-worm ? Home phototherapy

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

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

46. Exchange blood transfusion -- changing the babies blood with the other blood. Usually in hemolytic disease of newborn. It removes partially hemolysed and antibody coated RBCs and also billirubin

47. Methods of exchange Single volume exchange- 80ml/kg Double volume exchange- 160ml/kg (87% of infant blood volume exchanged with new blood) Triple volume exchange.

48. Partial exchange transfusion Polycythemia Chronic anemia with heart failure Hydrops fetalis. Observed pcv - desired pcv X 100 / observed pcv.

49. Exchange Transfusion Indications: Rh and ABO incompatibility Unconjugated billirubin > 20 -25mg/dl in term, >15 -18mg/dl preterm babies. Sick neonates exchange at lower level Septicemia /DIC/ sclerema Neonatal ITP Severe anemia due to any cause with HF

50. Exchange Transfusion ( Indications) Early Kernicterus Cong H Sperocytosis G-6- PD deficiency Hepatic coma

51. In Hemolytic disease of the newborn (ABO / Rh) H/O previous severely affected infant Cord Hb <10gm% & bilirubin > 5mg/dl Rate of rise of bilirubun > 0.5mg/100ml/hr Jaundice in first 24 hrs of life Signs of hemolysis-clinical or lab Maternal ab titer > 1in 64 Positive DCT Preterm LBW with hyperbilirubinemia Reticulocyte >10

52. Rh incompatibility Due to Rh D-Ag < 1 mL of Rh-positive fetal blood is sufficient to sensitize the mother 90% sensitization during delivery/abortion So , most first born infants are not affected due to the short period of exposure which is insufficient to produce a significant maternal Ig G antibody response.

53. Rh incompatibility Sensitized mother produces Ab –IgG types—crosses placenta Once sensitized –small doses of Ag stimulate high Ab titer . So, risk and severity of sensitization response increases with each subsequent pregnancy with Rh-positive blood fetus

54. ABO incompatibility Mother is type O and the baby is either type A or B. O +ve Mothers makes antibodies which are IgM & (IgG) types - IgG types crosses the placenta No effects if the mother & baby have same blood group or baby is grp O, as there is nothing to make antibodies against.

55. ABO incompatibility If mother - type A or B Makes antibodies (IgM) type so does not cross the placenta So, even if baby has a different blood type no effect

56. Selection of blood Blood group O – no antigen Ab –anti -A, anti-B Blood group A – antigen A Ab - Anti-B Blood group B –antigen B Ab – anti -A

57. Blood for exchange transfusion Fresh CPD blood Rh HDN- ABO incompatibility -

58. Selection of blood In Rh incompatibility: (O,A,B,AB-Negative) choice - Rh negative – - Preferably baby’s ABO - O group cross matched against maternal serum In ABO incompatibility – “O” blood group same as baby’s Rh ( +/-) with low titre of Anti A and Anti B antibodies OR ABO type specific blood cross matched against infant serum - Septicemia – Same as baby’s ABO and Rh

59. Investigations Pre exchange : Hb%, PCV, billirubin, glucose K+, Ca+. Post exchange: Hb%, PCV, billirubin, glucose, Calcium, K+, culture.

60. Procedure IN NICU OR OT Radiant warmer, Monitor HR, BP and other vitals, infants arms and legs are restrained. Assistant to record volume in & out, to check vitals. Blood pre warmed to 37 c Dried umbilical cord soaked with wet gauze. Canulation of umbilical vein- 12 o’clock

61. Catheter inserted till free flow of blood or SHOULDER UMBILICAL LENGTH. Small aliquots of blood removed 5 to10ml -PUSH PULL method. Blood in the bag gently mixed. Procedure over 1 to 2 hr. Tie around the cord for 1 hr, or hold tightly at the end of procedure.

62. Complications Hypocalcemia and Hypomagnesemia - Citrate in CPD blood. Hypoglycemia Metabolic alkalosis or acidosis. Hyperkelemia. CVS: overload and arrythmias Infections: HBV HIV Hemolysis Hypothermia, NEC.

63. Other roots for exchange Umbilical vein cut down- incision above umbilicus in midline. Femoral vein canulation with radial artery canulation.

64. Guidelines for management of hyperbilirubenemia Gestation and birth wt. Phototherapy( healthy) Exchange(healthy) Phototherapy(sick) Exchange(sick) Preterm: <1000gm. 5-7 11-13 4-7 10-12 1001-1500 7-10 13-15 6-8 11-13 1501-2000 10-12 15-18 8-10 13-15 2001-2500 12-15 18-20 10-12 15-18 Term: 2500 15-18 20-25 12-15 18-20

65. Breast milk jaundice Late onset Due to factors in breast milk – Interfere with bilirubin conjugation: - P regnanediol - Free fatty acids - β -glucoronidase Instead of ↓ by 7 days it continues to rise may go upto 20-30mg/dl by 2 nd -3 rd wks of age & return to normal by 4-12 wks

66. Management Stop breast feeding -48 hrs Again resume it, bilirubin may rise again but not reach previous high level

67. Breast feeding jaundice Decreased intake of milk leads to increased enterohepatic circulation Higher levels on day 4 compared to formula fed babies due decreased intake of milk

68. Prevention 1. Anti D to be given to the mother after delivery of the baby-within 48hrs. Also can be given to all unsensitized mothers at 28-32 weeks of gestation 2. Amniocentesis and IU transfusion to severely affected babies 3. Preterm delivery of severely affected babies 4. Cord blood studies-followed by Phototherapy 5. Exchange transfusion

69. KERNICTERUS Entry of unbound bilirubin into brain as free or albumin bound bilirubin Acidosis affects bilirubin solubility Hyperosmolarity, anoxia and hypercarbia disrupt BBB

70. Yellow staining of brain assc with neuronal injury Affects basal ganglia, cranial nerve nuclei, brain stem nuclei, hippocampus and AHC of spinal cord (cortex usually spared) Necrosis, neuronal loss and gliosis …pathological findings

71. ACUTE BILIRUBIN ENCEPHALOPATHY STAGE 1 : hypotonia, lethargy, high pitched cry and poor suck (D1-3) STAGE 2: hypertonia, opisthotonus, rigidity, oculogyric crisis, retrocollis, fever, seizures. (2 nd week) Those who survive develop chronic bilirubin encephalopathy STAGE 3 : Hypotonia replaces hypertonia after 3rd week age

72. CHRONIC BILIRUBIN ENCEPHALOPATHY Choreo-Athetosis Partial or complete sensorineural hearing loss Limitation of upward gaze Dental dysplasia Intellectual deficits

73. LOW BILIRUBIN KERNICTERUS In LBW babies, preterms Overt changes not seen Other factors: IVH, drugs, benzyl alcohol More likely to suffer from anoxia, hypercarbia and sepsis

74. TREATMENT Phototherapy Exchange transfusion Albumin infusion Anticonvulsants: phenobarbitone BERA at follow up

75. Neonatal cholestasis Intrahepatic extrahepatic Hepatocyte injury bile injury EH –biliary atresia metabolic viral intrahepatic bile duct paucity idiopathic neonatal hepatitis

76. Thank you Download more documents and slide shows on The Medical Post [ www.themedicalpost.net ]