1. Neonatal Jaundice Dr. Kalpana Malla MD Pediatrics
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Neonatal Jaundice
Dr. Kalpana Malla
MD Pediatrics
Manipal Teaching Hospital
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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
4/20/2017
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 days
No Treatment necessary
Rajitha Fernando. 8 8

9. PATHOLOGICAL JAUNDICE
4/20/2017
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 ++
Rajitha Fernando. 9 9

10. Pathological Jaundice - Hemolytic causes (unconjugated)
4/20/2017
Pathological Jaundice - Hemolytic causes (unconjugated)
Coombs' test negative
Red blood cell membrane defects
Red blood cell enzyme defects
Drugs
Hemoglobinopathies
Sepsis
Coombs' test positive
Rh incompatibility
ABO incompatibility
Rajitha Fernando. 10 10

11. Pathological Jaundice - Non-hemolytic (unconjugated)
4/20/2017
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
Rajitha Fernando. 11 11

12. Pathological Jaundice – Defective Conjugation(unconjugated)
4/20/2017
Pathological Jaundice – Defective Conjugation(unconjugated)
Crigler-Najjar syndrome types 1 and 2
Gilbert syndrome
Hypothyroidism
Breast milk jaundice
Rajitha Fernando. 12 12

13. Pathological Jaundice – Defective Conjugation
4/20/2017
Metabolic disorder:
α1 AT deficiency
Cystic fibrosis
Galactosemia
Gaucher's disease
Niemann-Pick disease
Hypothyroidism
Chromosomal disorders
Turner's syndrome,
trisomy 18 and 21
Rajitha Fernando. 13 13

14. Pathological Jaundice – Defective excretion
4/20/2017
Biliary obstruction:
biliary atresia
choledochal cyst
Sclerosing cholangitis
Dubin-Johnson syndrome
Rotor's syndrome
Infection:
Sepsis
UTI
STORCH infections
Rajitha Fernando. 14 14

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

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

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. 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

31. 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

32. MANAGEMENT Phototherapy Drugs Exchange transfusion 4/20/2017
Rajitha Fernando. 32 32

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 nm 39

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
4/20/2017
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
Rajitha Fernando. 41 41

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

43. 43

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

45. Change position once in every 2-4 hrs Skin bleached by PT
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 hrs
Frequent temperature monitoring & daily weight check 45

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

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

48. Biliblanket or glow-worm ?
Home phototherapy
Biliblanket or glow-worm ? 48

49. DRUGS Phenobarbitone – increase y and z ligands
4/20/2017
DRUGS
Phenobarbitone – increase y and z ligands
-induces liver ezymes - ↑↑ conjugation phenobarbitone
Metalloporphyrins (tin and zinc porphyrins and meso prophyrins)
-inhibits heme oxygenase
Rajitha Fernando. 49 49

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

51. Usually in hemolytic disease of newborn.
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 51

52. 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. 52

53. Partial exchange transfusion
Polycythemia
Chronic anemia with heart failure
Hydrops fetalis.
Observed pcv - desired pcv X 100 / observed pcv. 53

54. Exchange Transfusion Indications: Rh and ABO incompatibility
Unconjugated billirubin > mg/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

55. Exchange Transfusion (Indications)
Early Kernicterus
Cong H Sperocytosis
G-6- PD deficiency
Hepatic coma 55

56. 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

57. 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.

58. 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

59. 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.

60. 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

61. 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

62. Blood for exchange transfusion
Fresh CPD blood
Rh HDN-
ABO incompatibility - 62

63. 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

64. Investigations Pre exchange: Hb%, PCV, billirubin, glucose K+, Ca+.
Post exchange: Hb%, PCV, billirubin, glucose, Calcium, K+, culture. 64

65. 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 65

66. Small aliquots of blood removed 5 to10ml -PUSH PULL method.
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. 66

67. Complications Hypocalcemia and Hypomagnesemia - Citrate in CPD blood.
Hypoglycemia
Metabolic alkalosis or acidosis.
Hyperkelemia.
CVS: overload and arrythmias
Infections: HBV HIV
Hemolysis
Hypothermia, NEC. 67

68. Other roots for exchange
Umbilical vein cut down- incision above umbilicus in midline.
Femoral vein canulation with radial artery canulation. 68

69. 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
7-10
13-15
6-8
15-18
8-10
12-15
18-20
Term:
2500
20-25

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

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

72. 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

73. 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 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

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

75. 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

76. 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. (2nd week)
Those who survive develop chronic bilirubin encephalopathy
STAGE 3: Hypotonia replaces hypertonia after 3rd week age

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

78. 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

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

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

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