1. 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
• 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 Coombs' test
– Rh incompatibility negative
– ABO – Red blood cell
incompatibility membrane defects
– Red blood cell
enzyme defects
– Drugs
– Hemoglobinopathies
– Sepsis

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

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: Chromosomal
• α1 AT deficiency disorders
• Turner's syndrome,
• Cystic fibrosis
• trisomy 18 and 21
• Galactosemia
• Gaucher's disease
• Niemann-Pick
disease
• Hypothyroidism

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

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-12 -14mg/dl
4.Forearms &lower legs -15 -18 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.
1) H/o of abortion, H/o having taken Anti D
gammaglobulin
2) 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 chart
Flow
>12mg/dl,age <24 hrs <12mg/dl,age>24 hrs
↓
Negative
DCT............................. Negative
↓ ↓
Positive
Positive Direct bilirubin
↓ >2mg/dl
Rh, ABO ,Others Hepatitis, TORCH,
Sepsis, Biliary obstruction

31. Direct bilirubin < 2mg/dl
Htc →high → polycythemia
low
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

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. Home
phototherapy
Biliblanket or glow-worm ?

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

51. • 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

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.

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

54. 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

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

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 -

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.

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

66. • 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.

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.

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

69. Guidelines for management of
hyperbilirubenemia
Gestation Photother Exchange Photother Exchange
and birth apy( (healthy) apy(sick) (sick)
wt. healthy)
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

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 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

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
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