approach to neonatal jaundice ,

1. NEONATAL JAUNDICE
Professor Dr. Sayed
Ismail
Alazhar school of
medicine

2. Objectives
• Definition of jaundice
• Metabolism of bilirubin
• Types of jaundice
• Causes of neonatal jaundices
• Management of neonatal jaundice

3. Neonatal hyperbilirubinemia
Definition :
Jaundice is the yellow color of the skin and sclerae caused
by deposits of bilirubin
When is visible ?
Adult sclera > 2mg / dl
Newborn skin > 5 mg / dl

4. Incidence of neonatal jaundice
Term : Occurs in 60%
Preterm : 80% of preterm neonates
Jaundice is the most common condition that requires
medical attention in newborns.

5. Bilirubin
Metabolism

7. Types of bilirubin
Unconjugated bilirubin
(Indirect )
Conjugated bilirubin
(Direct )
• Bind to albumen
• Fat soluble
• Can cross blood brain barrier
• Toxic in high level to brain
• Conjugated with glucoronic
acid
• Water soluble
• Excreted in urine and stool
• Not toxic

8. 1. Increased Bilirubin Load due to a high hemoglobin concentration.
• The normal newborn infant
• Hemolysis
• Cephalhematoma or bruising , Polycythemia
2. Decreased Bilirubin Conjugation in the liver
• Decreased uridine glucuronyl transferase Activity
• Glucuronyl Transferase Deficiency Type 1 (Crigler Najar Syndrome)
3. Defective Bilirubin Excretion
Mechanisms of Neonatal Jaundice

9. Etiology Of Jaundice

10. CAUSES

11. • Appears after 24 hours
• Total bilirubin rises by less than 5 mg/dl per
day
• Maximum intensity by 4th-5th day in term &
7th day in preterm
• Serum level less than 15 mg / dl
• Clinically not detectable after 14 days
Physiological
Jaundice
• Appears age Appears within 24 hours of age
• Increase of bilirubin > 5 mg / dl / day
• Serum bilirubin > 15 mg / dl
• Jaundice days Jaundice persisting after 14 days
• Stool clay / white colored and urine staining
yellow staining clothes
• Direct bilirubin > 2 mg / dl
Pathological
jaundice

12. Physiological Jaundice
Characteristics
• Appears after 24 hours
• Total bilirubin rises by less than 5 mg/dl per day
• Maximum intensity by 4th-5th day in term & 7th day in
preterm
• Serum level less than 15 mg / dl
• Clinically not detectable after 14 days

13. Why does physiological jaundice develop?
• Increased bilirubin load
• Defective conjugation
• Increased entero-hepatic circulation
• Incidence
– Term in 60%
– Preterm 80%

15. Breast milk jaundice
– It is caused by prolonged
increased enterohepatic
circulation of bilirubin. (β-GD↑)
– Bilirubin peaks at 10-15 days of
age.
– The level of unconjugated bil. is
at 10-30 mg/dL
– If nursing is interrupted for 24
hours, the bilirubin level falls
quickly
β glucuronidase present in the breast milk of some mothers)
Breast-milk jaundice; is
the commonest cause of
Prolonged jaundice in
term infants

18. Pathological
Jaundice

19. Pathological jaundice
1. Appears age Appears within 24 hours of age
2. Increase of bilirubin > 5 mg / dl / day
3. Serum bilirubin > 15 mg / dl
4. Jaundice days Jaundice persisting after 14 days
5. Stool clay / white colored and urine staining yellow staining
clothes
6. Direct bilirubin > 2 mg / dl

20. Conjugated
Bilirubin
Pathological
Unconjugated
Bilirubin (indirect)
Hepatic
Post-
hepatic
Non-hemolyticHemolytic
Pathological Jaundice

21. 1-Unconjugated (Indirect) hyperbilirubinemia
1. Hemolysis
• Rh , ABO and other blood group incompatibilities
• spherocytosis , elliptocytosis, Alpha thalassemia
• Sepsis ,DIC
• Hematomas
• Polycythemia
2. Non hemolytic
• Breast milk jaundice
• Crigler-Najjar syndrome, types I and II
• Gilbert syndrome
Pathological jaundice

22. – It is an isoimmunity
hemolysis associated
with
– Rh incompatibility or
– ABO
Hemolytic disease of
the newborn

23. Erythroblastosis
Fetalis

24. Hemolytic disease of the newborn due to ABO
incompatibility
•Mothers with type O blood may have circulating
antibodies of Ig G class to other red cell antigens that can
cross the placenta and cause hemolytic disease in a baby
with a different blood type, such as blood type A or B.
(ABO incompatibility )
•The baby develop jaundice in the 1st day of life

25. 2-Conjugated hyperbilirubinemia
1. Hepatic
• Idiopathic neonatal hepatitis
• Infections - TORCH, sepsis
• Inborn errors of metabolism
• Galactosemia
• Tyrosinemia
2. Post hepatic
– Biliary atresia, choledochal cyst

26. Common causes of jaundice
• Physiological
• Blood group incompatibility
• G6PD deficiency
• Breast milk jaundice
• Cephalhaematoma
• Infections

27. Jaundice accompanying G6PD deficiency:
• Patients having G6PD deficiency also have
genetic defects in bilirubin conjugation as seen
in gilbert's disease.
• It is uncommon to have jaundice in G6PD def
infant due to severe hemolytic attack.
• Those G6PD deficient neonates who develop
higher maximal serum total bilirubin values had
significantly lower serum conjugated bilirubin
fractions.

29. • Crigler-Najjar syndrome type I - rare
• Complete absence of UDPGT and is characterized by severe
hyperbilirubinemia with the ongoing risk of kernicterus at any
point during an individual's lifespan.
• Currently, liver transplantation is the only definitive therapy
• Patients with Crigler-Najjar syndrome type II
partial absence of UDPGT similar to type I but dramatically
respond to therapy with phenobarbital, which is how the
diagnosis is made
Glucuronyl transferase

31. Risk factors for jaundice
• J - jaundice within first 24 hrs of life or premature
• A - a sibling who was jaundiced as neonate
• U - unrecognized hemolysis (ABO)
• N nursing – non-optimal sucking/nursing
• D - deficiency of G6PD , DRUGS , Ceftriaxone,
• I - infection
• C – Cephalhematoma /bruising
• E - East Asian/North Indian

32. Differential Diagnosis of jaundice
↑production ↓conjugation Impaired
excretion
Biliary
obstruction
↑ Unconjugate ↑ Unconjugate ↑ Conjugated ↑ Conjugated
Physiological
Hemolysis
Hematoma
Polycythemia
Sepsis
Gilbert’s
Crigler-Najarr
Hypothyroidism
Prematurity
Rotor’s
Dubin Johnson
Hepatitis
Metabolic
Biliary Atresia
Hepatitis

33. Approach to jaundiced baby
1. Determine birth weight, gestation and postnatal age
2. Assess clinical condition (well or ill) ,degree of jaundice
3. Decide whether jaundice is physiological or pathological
4. Look for evidence of kernicterus in deeply jaundiced NB

35. Clinical assessment of jaundice
Area of body Bilirubin levels/dlmg
• Face 6
• Upper trunk 9
• Lower trunk & thighs 12
• Arms and lower legs 15
• Palms & soles > 15

38. High bilirubin level kernicterus
(Bilirubin Encephalopathy)

39. Major Clinical Features of Acute Bilirubin Encephalopathy
• Lethargy
• poor sucking
• poor or absent Moro's,
• Retrocollis-opisthotonos
Convulsions
Retrocollis (backward arching of the neck)
Opisthotonus (backward arching of the back

40. This infant presented at age 30 days with a serum bilirubin level of 30 mg/dL (513 μmol/L)
secondary to the Crigler-Najjar syndrome type I. He demonstrates retrocollis and
opisthotonos, signs of the intermediate to advanced stage of acute bilirubin
encephalopathy.

41. Major clinical features of chronic bilirubin
encephalopathy
• Athetosis
• Upward gaze
• Sensorineural hearing loss
• Intellectual deficits, mild MR

42. Laboratory tests
• Total & direct bilirubin*
• Blood group and Rh for mother and baby*
• Hematocrit, retic count and peripheral smear*
• G6PD assay
• Coomb’s test
• Sepsis screen
• Liver and thyroid function
• TORCH titers
• Liver scan when conjugated hyperbilirubinemia
• Ultrasonography of the liver and bile ducts in cholestatsis
(must in all)*

43. Measurement of
bilirubin by
jaundice meter

44. Laboratory Diagnosis
Laboratory Features Of Hemolytic Disease
Laboratory Features Rh ABO
blood type of Mother Rh negative O
blood type of Infant Rh positive A or B
Anemia Marked Minimal
Direct Commb’s test Positive Negative
Indirect Commb’s test Positive Usually positive

45. Reticulocyte count (>7 mg/dL) can indicate the presence of an
ongoing hemolytic process in neonates
Direct hyperbilirubinemia in the neonate is defined as a direct fraction
more than 2 mg/dL
• or more than 20%of the total bilirubin concentration
is always pathologic.

46. Liver function tests:
• Aspartate aminotransferase (ASAT or SGOT) and alanine
aminotransferase (ALAT or SGPT) levels are elevated in hepatocellular
disease.
• Alkaline phosphatase and γ -glutamyltransferase (GGT) levels are
often elevated in cholestatic disease.
• A γ -GT/ALAT ratio of more than 1 is strongly suggestive of biliary
obstruction. However, it does not distinguish between intrahepatic and
extrahepatic cholestasis (do ultrasoud)
Reducing substance in urine: is a useful screening test for galactosemia,
provided the infant has received sufficient quantities of milk.

47. Other Tests
• Hearing tests (Brainstem auditory-evoked potentials)
should be obtained in aftermath of severe neonatal
jaundice to exclude sensorineural hearing loss.
• MRI in kernicterus

48. bilateral basal ganglia hyperintensity

49. Management
1. Phototherapy
2. intravenous immune globulin (IVIG)
3. Exchange transfusion
4. Drugs

50. Baby under triple unit intense
phototherapy
Baby under conventional phototherapy Baby under triple unit intense phototherapy

51. Principle of phototherapy
Native bilirubin ( water Insoluble)
450-460nm of light
`Photo isomers of bilirubin (water Soluble)
Urine

52. Copyright ©2004 American Academy of Pediatrics
Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316
Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation
μmol X0.055 = mg/dl

53. In the left panel, the solid line refers to the current recommendation of the American Academy of
Pediatrics (AAP) for low-risk infants, the line consisting of long dashes (- - - - -) for infants at intermediate
risk, and the line with short dashes (-----) for infants at high risk.
In the right panel, the dotted line (......) represents the AAP suggested intervention level for exchange
transfusion in infants considered at low risk, the line consisting of dash-dot-dash (-.-.-.-.) for intermediate
risk, and the line consisting of dash-dot-dot-dash (-..-..-..-) for infants at high risk. ( AAP,2004)

54. Phototherapy Technique
• Perform hand wash
• Place baby naked in cradle or incubator
• Fix eye shades
• Keep baby at least 45 cm from lights
• Start phototherapy
• Frequent extra breast feeding every 2 hourly
• Turn baby after each feed
• Temperature record 2 to 4 hourly
• Weight record- daily
• Monitor urine frequency
• Monitor bilirubin level

55. A common mistake while managing hyperbilirubinemia is the
false believes in the efficacy of the ordinary florescent lamps
(not Day-light), and D5% orally.

56. Side effects of phototherapy
• Increased insensible water loss
• Loose stools
• Skin rash
• Bronze baby syndrome
• Hyperthermia
• May result in hypocalcemia

57. Intravenous immune globulin
• IVIG in infants with Rh or ABO isoimmunization can
significantly reduce the need for exchange transfusions.
• Now IVIG has replaced exchange transfusion as the
second-line treatment in infants with isoimmune
jaundice.
• 1 gm/kg/dose IV

58. Exchange transfusion
• Exchange transfusion is indicated
for avoiding bilirubin neurotoxicity
when other therapeutic modalities
have failed or are not sufficient.
• the procedure may be indicated in
infants with erythroblastosis who
present with severe anemia,
hydrops, or both, even in the
absence of high serum bilirubin

60. Phenobarbital (Luminal)
• Hyperbilirubinemia: 3-8 mg/kg/d PO/IV
initially; may increase up to 12 mg/kg/d
Not to exceed IV administration rate of 1
mg/kg/min or 30 mg/min for infants

61. Prolonged indirect jaundice
Causes
• Breast milk jaundice
• Hypothyroidism
• Pyloric stenosis
• Ongoing hemolysis
• Crigler Najjar syndrome

62. Conjugated hyperbilirubinemia
Suspect
• High colored urine
• White or clay colored stool
Caution
• Always refer to hospital for investigations so
that biliary atresia or metabolic disorders can
be diagnosed and managed early

63. Remember that:
• Jaundice is the most frequent cause of admission after
early discharge from nursery.
• It is not physiological if: appear in first 24 hrs, increases
by > 0.5 mg/dL/hr , evidence of hemolysis, abnormal
examination, direct bilirubin is > 20% of total, or persists
> 3 weeks.
• Jaundice present in the first 24 hrs of life must be
investigated and treated as an emergency.