Yellowing of a newborn

1. 1
DICM 213:NEONATOLOGY AND
CHILD HEALTH (3 CHRS)
Assessing Reflexes

2. NEONATAL JAUNDICE
NEONATAL JAUNDICE
Haemolytic Disease of Newborn

3. Introduction
• Neonatal jaundice is yellowing of the skin
and other tissues of the infant due to
accumulation of bilirubin in circulation
• In neonates bilirubin level of >5mg/dl is
required for jaundice to manifest
• In neonates dermal icterus is first noted in
the face, progresses to the trunk and then
extremities

4. Normal bilirubin metabolism
Can be conveniently divided into:-
Pre hepatic
Hepatic
Post hepatic

5. Normal bilirubin metabolism
Pre Hepatic
• 80% of bilirubin is derived from senescent
red blood cells
• Remaining 20% comes from hepatic
haemoproteins myoglobins and
cytochrome
• 1g of haemoglobin gives 34mg of bilirubin
• Nonhaemoglobin sources give 1mg/kg

6. Normal bilirubin metabolism
Pre Hepatic
• RBCs are taken up by macrophages in the
RES releasing haemoglobin
• Haemoglobin is broken down into globin
chains and haem portion
• Globin chains broken further into amino
acids for recycling

7. Normal bilirubin metabolism
Pre Hepatic
• Haem portion is cleaved by haem oxygenase
liberatinng iron cations, carbon monoxide and
biliverdin
• Biliverdin is converted into bilirubin by biliverdin
reductase
• This uncojugated bilirubin-(ucb) is bound to
albumin before uptake by the liver
• If not taken by the liver or if produced in excess,
ucb is deposited in extra hepatic tissues-pre
hepatic jaundice

8. Normal bilirubin metabolism-
Hepatic
• UCB is taken up and bound by special proteins
Y-ligadin and Z
• Glucuronic acid reacts with bilirubin under
influence of glucuronide transferase to form
bilirubin diglucuronide- Conjugated bilirubin-(cb)
which is water soluble
• Disorders of uptake and conjugation lead to
hepatic jaundice

9. Normal bilirubin metabolism
Post Hepatic
• CB is actively secreted into bile canaliculi,
descends the biliary tract to the duodenum
• It is acted upon by bacterial enzymes in the gut
to form stercobilinogen
• 90% of stercobilinogen is oxidised to stercobilin
which gives feaces it’s colour
• 10% may be reabsorbed into plasma for
recycling or excretion by the kidney
• Failure of bilirubin to reach the gut as in
obstructive jaundice results in pale stool

10. Physiologic jaundice
• 60% of full term infants develop visible
jaundice due to elevation of unconjugated
bilirubin concentration during first week of
life
• Normally appears on 2nd or 3rd day of life
• Reaches maximum intensity by 3rd-4th day
• Clinically not detectable after 14 days

11. Characteristics of physiological
jaundice
• Bilirubin levels may reach 12mg/dl
• Usually disappears without any treatment
• This is referred to as physiologic jaundice

12. Hyperbilirubinaemia of prematures
• 80% of prems. develop jaundice due to
unconjugated hyperbilirubnaemia
• Appears on 2nd-3rd postnatal day
• Reaches a peak around the 5th day
• Levels may rise up to 15mg/dl or higher
• Clinically undetectable by the 14th day
• These babies should be monitored for
worsening jaundice and action taken

13. Physiologic jaundice
Causes
 Increased bilirubin load on the liver
- increased red blood cell volume
- decreased red blood cell survival
 Defective hepatic uptake of bilirubin
- decreased protein Y (ligadin) and Z
- increased binding of Y and Z by other ions
 Defective bilirubin conjugation
- decreased glucuronyl transferase activity
 Decreased hepatic excretion
 Increased entero-hepatic circulation
-high concent. of bilirubin in meconium
-decreased bowel motility

14. Pathologic Neonatal Jaundice
Neonatal jaundice is considered
pathologic if time of appearance, duration,
or rate of increase of ucb varies
significantly from that of physiologic
jaundice

15. Pathologic jaundice
characteristics
• Jaundice appearing in the first 24 hrs.
• Increases of total bilirubin >5mg/dl in
24hrs
• Total bilirubin level >19.5mg/dl
• Direct bilirubin more than 2mg/dl

16. Pathologic Jaundice
causes
• Increased production
-Foeto-maternal blood group incompatibility
-Hereditary sherocytosis
-Glucose 6 phosphate dehydrogenase
deficiency
-Sepsis
-Increased entero-hepatic circulation

17. Pathological jaundice
Causes
• Decreased clearance
- Inborn errors of metabolism: Cigler-
Najjar syndrome
- Drug and hormones: hypothyroidism,
breast milk jaundice

18. Pathologic Jaundice
Other causes
• Biliary atresia
• Hepatitis
• TORCH infections
• Galactosemia
• Cystic fibrosis
• Cephalohaematoma
• Breast feeding
• Breast milk

19. Haemolytic Disease of Newborn
• Excessive haemolysis in Newborn results
from incompatibility of maternal and foetal
blood groups
• Rhesus factor is the most important, but
other systems such as ABO, Kell, Lewis,
Duffy and Kidd may also result in
haemolysis

20. Haemolytic Disease of Newborn
Rhesus Incompatibility
• Incidence : 6 per 1000 births
• Large proportion of the population carry
the Rhesus antigen in their red cells and
are said to be Rhesus positive
• The rest do not posses this antigen and
are Rhesus negative
• Haemolytic disease of newborn occurs
when mother and foetus are of different
groups

21. Rhesus incompatibility
• The mother is usually Rh negative and
foetus is Rh positive
• When foetal red cells enter maternal
circulation, the mother may become
sensitized to the Rh antigen and form Rh
antibodies – Isoimmunisation
• Later in pregnancy these maternal Rh
antibodies cross the placenta to act upon
foetal red cells

22. Rhesus incompatibility
• It is exceedingly rare for the first infant to
be affected, but can occur in two ways:-
1. Mother wrongly transfused with Rh
incompatible blood
2. Mother had miscarriage of Rh positive
infant

23. Haemolytic Disease of Newborn
Clinical Features
A. Affected Foetus
1) Stillbirth – intrauterine death with birth of a
macerated baby
2) Birth of a live infant with hydrops foetalis
-rarely compatible with life beyond a few hours
- Infant is grossly oedematous with
hepatoslenomegally
- Placenta is large pale and oedematous
Liqour amnii has a golden yellow colour

24. Haemolytic Disease of Newborn
Clinical features
B Affected Infant
1) Icterus Gravis – Born apparently normal but
subsequently develops signs
- Jaundice appears minutes or hours after birth
- Purpura and other haemorrhages
- Spleen and liver greatly enlarged
- Peripheral blood shows anaemia, many
erythoblasts and normoblasts, reticulocytosis,
immature whitecells, ‘indirect’ bilirubin is high
with some increase in ‘direct’ bilirubin

25. Haemolytic Disease of Newborn
Clinical Features
C Haemolytic anaemia – Less frequently the
disease takes the form of haemolytic
anaemia
- anaemia develops shortly after birth
- jaundice is absent or quite minimal with
splenomegally, erythroblastaemia and
reticulocytosis

26. Diagnosis
• In most instances it is possible to predict
occurrence of HDN during pregnancy
• History of previous pregnancy
• Rh and ABO blood group of every
pregnant should be determined early in
pregnancy

27. Diagnosis
• In Rh negative women Rh antibodies be
tested periodically throughout pregnancy
• Amniocentesis for spectophotometry
• Coombs’ test in infant’s blood is positive
• Delivery in hospital

28. Prevention of Isoimmunisation
• ‘Bleed’ from Rh positive foetus occurs at
the end of pregnancy or during birth
• Rh antibodies take some weeks to
develop
• Therefore intramuscular administration of
anti D immunoglobulin to RhD negative
mothers soon after birth of her Rh positive
baby provides a high degree of prevention
of isoimmunisation

29. Haemolytic Disease of Newborn
ABO Incompatibility
• Not uncommon but tends to be mild and
may be mistaken as ‘physiological’
jaundice
• Jaundice which develops within 24 hrs. is
never to be neglected as benign
• Unusually severe degree of jaundice may
develop
• Blood group of mother and infant should
be determined

30. ABO Incompatibility
• If potentially incompatible ( e.g. mother O
and infant A or B)
• Coombs’ test in infant is usually negative
• ABO disease rarely predictable antenatelly
• Usually no emergency in this situation

31. Differential Diagnosis
• Time of first appearance of jaundice is a
major guide to the type of neonatal
jaundice
• Jaundice present at birth or appears within
the first 24 hrs of life may be due to:-
Rhesus factor, ABO incompatibility
Concealed haemorrhage
CMV inclusion disease, Rubella
Congenital toxoplasmosis

32. Differential Diagnosis
• Jaundice that first appears on the 2nd or 3rd
day is usually ‘physiological’
• Familial non-haemolytic icterus (Crigler-
Najjar syndrome) is seen initially on the 2nd
or 3rd day
• Jaundice appearing after the 3rd day and
within the first week should suggest
septicaemia (note TORCH infections )

33. Differential Diagnosis
• Jaundice noted initially after 1st week of life
suggests:- atresia of bile duct, breast milk
jaundice, septicaemia, rubella,
galactosemia, hypothyroidism,
spherocytosis, G6PD deficiency
• Persistent jaundice during 1st mo. of life
suggests insipissated bile syndrome,
atresia of bile duct, TORCH, galactosemia

34. Investigations
Regardless of the gestational age or time
of appearance of jaundice, all patients
require complete diagnostic evaluation

35. Invasive measurements
• Determination of direct and indirect
bilirubin
• Haemoglobin estimation
• Reticulocyte count
• Blood type
• Coombs test
• Peripheral blood smear

36. Kernicterus
• The direct complication of ‘indirect’
hyperbilirubinaemia
• Unconjugated bilirubin is deposited in the brain
cells interfering with oxidative phosphorylation -
lesions in basal ganglia
• Precise blood levels above which indirect
bilirubin will be toxic for an individual infant is
unpredictable – 20mg/dl
• Risk factors are prematurity and heamolytic
disease of the newborn

37. Clinical features
• High pitched cry, opisthotonus, bulging
anterior fontanel and seizures
• As the condition progresses – hearing loss
mental retardation, muscle rigidity, speech
difficulty, seizures, movement disorders
• Kernicterus is irreversible, best option is to
prevent by treating the hyperbilirubinaemia

38. Neonatal Hyperbilirubinaemia
Treatment
• Phototherapy
• Drugs
• Exchange Transfusion

39. Phototherapy
• Mainstay in treatment of hyperbilirubinemia
• Safe and widely available.
• In one large study, only 4% of those treated
with phototherapy required exchange
transfusion, compared with 24.4% of those who
did not receive phototherapy.
• Light emitted at a wavelength of 425 to 475 nm
converts bilirubin (deposited in subcutaneous
tissue) to a water-soluble form that can be
excreted in the bile or urine without
glucuronidation.

40. Exchange transfusion
• Full-term infants rarely require exchange
transfusion if intense phototherapy is timely.
• Should be considered if the total serum bilirubin
level is higher than 25 mg/dL and continues to
rise despite intense in-hospital phototherapy.