NEONATAL JAUNDICE

DR. AJERO JEREMIAH

MBBS
 OUTLINE
• INTRODUCTION
• EPIDEMIOLOGY
• CAUSES
• PATHOPHYSIOLOGY
• TYPES
• CLINICAL FEATURES
• MANAGEMENT
• COMPLICATIONS
• PREVENTION
• PROGNOSIS
• CONCLUSION
• REFERENCES
 Introduction
• Definition– Neonatal Jaundice (NNJ) is a clinical
description of the yellowish discoloration of the
newborn’s skin, sclera and mucous membranes resulting
from excessive accumulation of bilirubin in blood
( hyperbilirubinemia).
• NNJ is the most common medical problem in neonates,
affecting both term and preterm newborns during the 1st
week of life.
• It could be physiologic or pathologic.
• Hyperbilirubinaemia may be unconjugated, conjugated or
mixed.
• jaundice in the newborn is unique,
because, it is only in the neonatal period
that serum bilirubin poses a threat to the
wellbeing of the infant.
• Poor management of jaundice in a
neonate can have dire consequences.
• Where death does not result, varying
forms of central nervous system damage
may result.
Bilirubin production

• Bilirubin is the end-product of the catabolism of

haem, derived principally from circulating
haemoglobin (1g of haemoglobin, when catabolised
yields 35mg of bilirubin).
• 75% of bilirubin is from red blood cell haemoglobin
• 25% is derived from tissue (non-haemoglobin)
haemproteins myoglobin and haem containing
enzymes (cytchromes, catalases, peroxidases etc) in
the liver.
• Haem Heme oxygenase
→ Biliverdin
• Biliverdin biliverdin reductase
→ Bilirubin.
 Bilirubin metabolism
• Bilirubin is water insoluble and is transported to liver bound to albumin

• Albumin bound unconjugated bilirubin does not cross blood brain barrier
(BBB). However a small fraction is free.

• once within the liver, unconjugated bilirubin which is largely water

insoluble is convert to water soluble conjugated bilirubin. The process is
mediated by a membrane-bound enzyme, uridine-diphosphate-
glucuronyl-transferase (UDPG-T)

• Conjugated bilirubin is rapidly excreted into bile from where it gets into
gastro-intestinal tract (GIT).

• within the GIT, some bilirubin is acted upon by intestinal bacteria and
converted to urobilinogen.

• some proportion of urobilinogen is reabsorbed into the circulation and

excreted in the urine while some are excreted with faeces as stercobilin
which gives clour to faeces.
 Epidemiology
• The prevalence in hospital practice is estimated
between 60-80%, being more common in
preterm (about 80%) than in term infants (about
60%) on a global scale.
• The incidence of NNJ is reported to be highest in
African region, with 667.8 per 10,000 live births,
followed by 251.3 per 10,000 in southeast Asia
• Community-based on severe NNJ in Nigeria
suggest an incidence of 55 per 1000 infants
requiring phototherapy and 19 per 1000 infants
requiring exchange bood transfusion.
 CAUSES OF NNJ
Important causes of jaundice in neonates include:
 High red cell mass
• Polycythemia

 Increased Haemolysis
• Rhesus incompatibility, ABO incompatability,
•Red cell enzyme deficiencies like :- G6PD deficiency,
pyruvate kinase deficiency.
•Defect of red cell membrane: congenital spherocytosis,
elliptocytosis, poikilocytosis and stomatocytosis
• Infection: Neonatal septicemia
•haemoglobinopathies: e.g Thalassaemia
•Extravasated blood: Cephalohaematoma, intraventricular
hemorrhage
 Causes of NNJ
 Defective uptake of bilirubin by liver cells :
Prematurity
 Deficiency of liver enzymes: Crigler-Najjar
syndrome and Gilbert syndrome
 Depressed function of liver enzymes eg
hypothyroidism, hypoglycaemia, hypothermia,
infections
 Defective excretion of conjugated bilirubin in
bile: eg Rotor and Dubin Johnson syndrome
 Obstruction of biliary flow (intra or extra hepatic).
The most important causes of pathologic jaundice
in Nigeria are :
•Prematurity
•ABO and Rhesus incompatibility,
•G6PD deficiency
•Sepsis
 PATHOPHYSIOLOGY

• Bilirubin is transported in plasma, bound

tightly to plasma albumin.
• The albumin-bilirubin binding is stable
when the molar concentration ratio of
bilirubin to albumin is 0.5-1:1.
• When the molar concentration ratio is
above 1:1, dissociation occurs, releasing
“free” unbound bilirubin into the circulation.
• Dissociation also occurs at pH of <7.4. These facts are
of clinical importance because in condition of
hypoalbuminaemia, hyperbilirubinaemia or acidosis,
concentration of ‘free’ bilirubin in plasma increases and it
is this “free” bilirubin which has the capacity to cross the
blood-brain barrier, and stain and damage the cells of
the brain.
• in other words, it is the “free” bilirubin that is toxic to the
neonatal brain.
 TYPES OF NEONATAL JAUNDICE
Bilirubin is conjugated in the liver before excretion
in stool and urine. Thus, there are two fractions of
serum bilirubin:
 Unconjugated Hyperbilirubinaemia:
• Physiological unconjugated hyperbiliribinaemia (physiologic
NNJ)
•Pathological unconjugated huperbilirubinaemia (pathologic
NNJ)

 Conjugated Hyperbilirubinaemia
 PHYSIOLOGIC NNJ :
•Appears on 2nd or 3rd day of life and clears within
7-10 days of life(term)/ 10-14 days (preterm).
• Peak serum bilirubin level on 3rd to 5th day of life
(term)/ 5th to 7th day of life (preterm).
• Baby is otherwise well
•Often does not require treatment
PATHOLOGIC NNJ:
•Appear within 24 hrs of life
•TSB ↑es by >0.5mg/dl/hr (8.55umol/L/hr) or
5mg/dl/day (85.5umol/L/day)
•TSB > 12mg/dl (>205.2umol/L) in term and
15mg/dl (256.5umol/L) in pre-term infants
•Persists beyond 2 weeks
•Conjugated hyperbilirubinaemia
•Baby often sick
Conjugated Hyperbilirubinaemia

• It is due to failure of excretion of

conjugated bilirubin from liver cells or
obstruction to biliary flow before it gets into
the duodenum, also known as cholestatic
jaundice
 CLINICAL FEATURES
• Time of presentation depends on aetiology
• Progresses in cephalocaudal direction. Part of skin
affected may depict serum concentration
(face=5mg/dl, mid-abdomen =15mg/dl, soles=
20mg/dl).
• Visual assessment may not be reliable. SB should
be determined
• Jaundice from deposition of unconjugated bilirubin
in skin may appear bright yellow while that from
conjugated hyperbilirubinaemia 20 to obstructive
jaundice has a greenish tinge.
• Baby may have signs of either the 10 aetiology or
kernicterus(poor feeding, irritability, a high-pitched
cry, no startle reflex, letharg, apnea, floppy muscles
 Management – Unconjugated
Hyperbilirubinaemia
Note
– Only the “free” unconjugated bilirubin is
toxic to the newborn brain.
– There’s no absolute safe level of bilirubin.
– Toxicity is increased by factors that
destabilize the bilirubin-albumin binding
and/or integrity of the BBB.
– Jaundice in 1st 24hrs is almost always
pathological.
– Bilirubin is a free radical scavenger and in
low levels play useful role in the overall
wellbeing of the infant esp. in LBW,
preterms
 Evaluation.
• History
– Pregnancy, labour, delivery, perinatal
events, drugs, Asphyxia,
cephalhaematoma
– Family hx of NNJ in older sibs, mother’s
blood group
– Feeding pattern, general activity
• Physical Examination: assess level of
jaundice, pallor, general activity, signs of
encephalopathy, transcutaneous bilirubin
estimation if available should be done as
visual assessment is not reliable
• Lab. Investigations:
– SB (Total and Conjugated bilirubin)
– Full blood count
– Blood culture
– Blood group (child & mother), Rhesus
Factor
– Coombs test
– G6PD assay
– Others depending on presentation of baby
 Treatment Options
 Pharmacotherapy
• Phenobarbital: enhances hepatic uptake of
bilirubin. can be given to both mother and child
and bilirubin level reduces with first week and
can be given prophylactically to patients at risk.
• phenobarbital is not used routinely, and it is of
no value in most cases of pathological jaundice
that occur because of rapidly acting
mecchanisms e.g sepsis and G6PD deficiency.
• It is used in cases of Crigler-Najjar
• Limited by slow action (takes 72hrs to become
effective). No use in acute jaundice
• In iso-immune haemolytic disease,
administration of intravenous gamma
globulin (0.5-1.0g/kg) over 2 hoursac is
recommended
 Phototherapy.
– Currently major mode of treatment.
– Phototherapy acts by several ways:
Configurational isomerization:
• Here the Z-isomers of bilirubin are converted into
E-isomers.
• The reaction is instantaneous upon exposure to
light but reversible as bilirubin reaches into the
bile duct.
• After exposure of 8-12 hr of phototherapy, this
constitutes about 25% of TSB, which is nontoxic.
• Since this is excreted slowly from body this is not
a major mechanism for decrease in TSB.
Structural isomerization:
•This is an irreversible reaction where the
bilirubin is converted into lumirubin.
•The reaction is directly proportional to dose
of phototherapy.
•This product forms 2-6% of TSB which is
rapidly excreted from body thus is mainly
responsible for phototherapy induced
decline in TSB.
Photo oxidation:
•This is a minor reaction, where photo-
products are excreted in urine.
Important basic principles of phototherapy
• Wavelength: 450-460nm. blue light is commonly
used in health institutes
• Distance between infant and light source.
– Should not be >50 cm. 10 – 20 cm distance
ideal.
• Surface area
– The larger the surface area the better.
Reflective materials maybe used to increase
area of irradiation.
• Nature & Character of light source
– May affect energy delivery. Narrow spectrum
light sources are more efficient though more
expensive
Phototherapy.
• Indications:
– Moderate to severe hyperbilirubinaema
– Prophylaxis in preterm babies
– Prevention of post-EBT rebound
hyperbilirubinaemia

• Undesirable &Toxic effects (minimal) include:

Increased fluid loss
Retinal damage –Eyes should be covered.
Damage to gonads in males.
Erythema of the skin (transient)
Bronze-baby syndrome- high conjugated bilirubin
levels
 Exchange Blood Transfusion
– Indications for EBT
• If serum bilirubin is 10mg/dl (170umol/L) by
24 hrs of age
• 15mg/dl (255umol/L) by 48hrs
• 20mg/dl (340umol/L) at any age
• High rate of rise of bilirubin>5mg/dl/24hrs
(>85umol/L/24hrs) or > 0.5mg/dl/hr
(8.5umol/L/hr)
• Hypoalbuminaemia
• Anaemia (Hb. <12g/dl) (pcv <36%)
• Whenever features of bilirubin
encephalopathy set in, no matter the
bilirubin level.
• Usually a double volume exchange is done over 60
to 90 minutes.
• For double exchange transfusion (Weight x 85 x2)
• a neonate is assumed to have blood volume of
about 85ml/kg, therefore, 170ml/kg of blood is
usually exchange.
• Blood is exchanged in aliquots of 5, 10, or 20, or
smaller volume for small infants.
• The EBT should be performed by pull and push
technique using umbilical venous route.
• Umbilical catheter should be inserted just enough to
get free flow of blood.
– All precautions regarding blood
transfusion should be observed.
– Fresh whole blood X-matched against
baby and mother’s blood (not more than
4 days for ACD or CPD blood)
 COMPLICATIONS

• Seizures
• Cerebral palsy
• Kernicterus (bilirubin encephalopathy): it is
a bilirubin-induced brain dysfunction.
 PREVENTIONS
 General health promotion:
• Parent education regarding danger signs should
include yellowish discoloration below knees and
elbows or persistent jaundice beyond 15 days as
reason for immediate checkup by health personnel.
 Specific Protection:
• Antenatal investigation should include maternal
blood grouping, Rh positive baby born to a Rh
negative mother is at higher risk for
hyperbilirubinemia and requires greater monitoring.
Anti D (RhoGam) injection after first obstetrical
event ensures decreased risk of sensitization in
future pregnancies.
• Ensuring adequate breastfeeding
 Early diagnosis and prompt treatment:
• High risk babies such as ones with large
cephalohematoma or family history of jaundice should be
followed up after 2-3 days of discharge.
• Routine medical sreening.
 PROGNOSIS

• Most cases are benign with an excellente

prognosis and resolve with or without
treatment
• However, bilirubin encepalopathy can
complicate clinical course in a few.
 CONCLUSION
• Neonatal jaundice still contributes
significantly to neonatal mortality and
long-term handicap in our sub-region
• Education is very important both to
health workers and the public (esp. at
ANC)
• No case of clinical jaundice should
dismissed without investigation
• Early discharges should be well advised
about jaundice
 REFERENCES

• Azubuike and Nkanginieme. Paediatrics and Child

Health in a Tropical Region
• Ghai Essential Paediatrics
• [Link]
228478123_neonatal_jaundice_prevalence
_and_associated_factors_as_seen_in_Federal_Medical_
Centre_Abakaliki_Southeast_Nigeria/citation
• [Link]
15/5/505/6872749