Definition

 An increase in the total serum bilirubin (TSB)

concentration caused by the rate of bilirubin production
exceeds the rate of bilirubin elimination

 HYPERBILIRUBINEMIA.
 The accumulation of bilirubin (the yellow-orange
pigment) in the skin, the sclera , and the mucosa

 JAUNDICE (ICTERUS)

(Visible jaundice: serum bilirubin > 5 mg/ dl)

 Incidence
☺Term infant : 60% -70 %
☺ Preterm : 80 %
☺ Higher in populations living at high altitudes
☺Varies with ethnicity: Higher in East Asians, Greeks living in
Greece, American Indian, African, People of Mediterranian.

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 Neonatal Jaundice:
WHY WE WORRY
 Unconjugated bilirubin in high concentration can cross the

blood brain barrier  penetrating the brain cells 

neurotoxic effects on cellular membranes & intracellular Ca

homeostasis  neuronal excitotoxicity & mitochondrial

energy failure  neurologic dysfunction & death.

 The Neurologic dysfunction  Bilirubin Encephalopathy,
 Bilirubin Encephalopathy:
 Acute bilirubin encephalopathy:
 Initial phase : lethargy, hypotonia, poor suck
 Intermediate phase : stupor, irritability, fever, hypertonia,
opisthotonus
 Advanced phase : shrill cry, pronounced opisthotonus
(or hypotonia after 1 week of age),
apnea, coma, and death.
(Commonly : †, if life  sequelae)
 Chronic bilirubin encephalopathy:
Also called Kernicterus ( it is a pathologic diagnosis  the yellow discoloration of the
deep nuclei of the brain), characterized by a clinical tetrad:
 Choreoathetoid cerebral palsy
 High-frequency sensoryneural hearing loss
 Palsy of vertical gaze
 Dental enamel hypoplasia

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 Patophysiology
 Hyperbilirubinemia 
unconjugated (Bilirubin I/ indirect bil) 

conjugated hyperbilirubinemia (Bilirubin II/ direct bil). 

Both of them 

 There are differences between unconjugated and conjugated

hyperbilirubinemia

 Bilirubin Metabolism
 Bilirubin Metabolism
Degradation Hb
Production
Bil. I (Bil. Indirek)
+
Transportation Albumine

Bil I Prot. Y & Z

Conjugation O2 gluc. Transt.
glukose
Bil II

Excretion B i l I
Bil II sfe r ase
n i l tr a n
or o
 gluk
Stercobilin

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Unconjugated Hyperbilirubinemia
Can be physiologic or pathologic
Physiologic Jaundice
 Note the natural history of physiologic jaundice in the full
term newborn-
onset after 24 hours
peaks at 3 to 5 days
decreases by 7 days.
 Average full term newborn has peak serum bilirubin level
of 5 to 6 mg/ dl.
 Exaggerated physiologic jaundice- when peak serum
bilirubin is 7 to 15 mg/ dl in full term neonates.
 Always consider age of the baby and bilirubin level
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PATHOLOGIC JAUNDICE

Jaundice appearing within the first 24 h of life

TSB level >95th percentile for age in hours based on a nomogram

for hour-specific serum bilirubin concentration (see nomogram)

 bilirubin > 5 mg% / day

Persistent after 2 weeks

Direct Bilirubin > 1.5 mg% or >10-20% of TSB

Associated with hemolysis, infection

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Nomogram for designation of risk based on
hour specific serum bilirubin levels at
discharge
Bhutani et al., Pediatrics 1999

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Conjugated Hyperbilirubinemia

 Conjugated bilirubin (direct bilirubin)

concentration > 1.5-2mg/dl or more than 10-
20% of TSB
 Always pathologic
 ETIOLOGY
ETIOLOGY

 Single / multiple factor

1. Over Production : hemolysis
  ABO/ Rh incompatibility
 def. G6PD
 Occult bleeding
 infection / septicemia
2. Transportation disorder :
 Concentration of serum albumin
 Organic Ion : sulfa, salicyl acid
 Concentration of hydrogen  : acidosis

Bilirubin binding capacity 12

3. Defective uptake and conjugation
 Decreased concentration / activity of glucoronyl
transferase
 Immaturity of liver function
 Liver dysfunction : acidosis, hypoxia, infection
4. Impaired excretion into bile
 Obstruction intra / extra hepatic

infection, etc Congenital

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5.  enterohepatic circulation
 Decreased enteral intake
 Pyloric stenosis
 Intestinal atresia/ stenosis
 Meconium ileus
 Meconium plug
 Hirschsprung’s disease

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Systematic Assessment for Neonatal Jaundice

 Pregnant women - Blood group and Rh type

 If mom is Rh negative or O group: Baby’s cord
blood group/ Rh type/ DAT
 Monitor infant for jaundice at least every 8 to 12
hours
 If level of jaundice appears excessive for age,
perform transcutaneous bilirubin or total serum
bilirubin measurement

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Clinical assessment
of severity of
jaundice

 Cephalocaudal progression
face 5 mg/ dl (approximately)
upper chest 10 mg/ dl (approx)
abdomen and upper thighs 15 mg/ dl ( approx)
soles of feet 20 mg/ dl ( approx)
 Visual inspection may be misleading

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 
1
KRAMER
KRAMER 2
4
3
5
4

5
Area of jaundice Range of bilirubin concentration

TERM : 1. 4,3 – 7,8 mg%

2. 5,4 – 12,2
3. 8,1 – 16,5
4. 11,1 – 18,3
5. > 15 - ….
PRETERM : 1. 4,1 – 7,5 mg%
2. 5,6 – 12,1
3. 7,1 – 14,8
4. 9,3 – 18,4
5. > 10,5
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Clinical estimation
of severity of jaundice
Age Jaundice visible on Classify as
Day 1 Any visible jaundice *
Day 2 Arms and legs* Serious jaundice
Day 3 and thereafter Hands and feet

* Visible jaundice seen anywhere on the body on day 1 or on

the hands and feet in addition to the arms and legs on day 2 is
very serious and needs to be treated with phototherapy
immediately.
Do not wait to begin phototherapy until the serum bilirubin
level is known
Assess risk factors for significant jaundice

 Blood group incompatibility with positive DAT

 Gestational age 35- 36 weeks
 Exclusive breast feeding - first time mom
 Cephalhematoma or significant bruising
 Asian race
 Previous sibling had significant jaundice
 Jaundice in the first 24 hours of life
 Predischarge bilirubin in the high risk zone

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NEONATAL HYPERBILIRUBINEMIA
MANAGEMENT
I. Determine the ETIOLOGY
 When the first time the jaundice occurred
(HARPER + YOON)

1. In the first 24 hours of life :

Blood Incompatibility
Intrauterine infection
Def. G6PD

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2. 24 – 72 hours of life :

Physiologic

Blood incompatibility (probable)

Def. G6PD

Polycythemia

Hemolytic of occult bleeding

Hypoxia

Dehydration, acidosis
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3. > 72 hours – Last of the first week :
• Infection / sepsis
• Dehydration + acidosis
• Def. G6PD
• Drugs, etc
4. Last of the first week :
Obstructive jaundice
Hypothyroidism
Breast Milk Jaundice
Infection
Neonatal hepatitis, etc 22
NEONATAL HYPERBILIRUBINEMIA
MANAGEMENT

 HYDRATION - FEEDING
 PHOTOTHERAPY
 EXCHANGE TRANSFUSION

 Phenobarbital
 Tin protoporphyrin

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Feeding to Prevent and Treat
Neonatal Jaundice

Mothers should breast feed their babies

at least 8 to 12 times per day
for the first several days

  caloric intake / dehydration   Jaundice

 Supplementation with water or dextrose water will

not prevent or treat hyperbilirubinemia

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Hour Specific Serum Bilirubin
Bhutani et al, Pediatrics 1999

Predictive Ability of a Predischarge Hour Specific Serum Bilirubin for

Subsequent Significant Hyperbilirubinemia in Healthy Term and Near -
term Newborns.
Serum Bilirubin levels pre- discharge in 13,003 babies
Serum Bilirubin levels post- discharge in 2840 babies
Racially diverse - 5% Asian
Nomogram- 95th percentile for serum bilirubin level
24 hours:  8 mg/ dl (137 M/ L)
48 hours:  14 mg/ dl (239 M/ L)
72 hours:  16 mg/ dl ( M/ L)
84 hours:  17 mg/ dl (290 M/ L)

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Transcutaneous Bilirubinometers
•Useful as screening device
•TcB measurement fairly accurate
in most infants with TSB< 15mg/ dL.
•Independent of age, race and weight of n
•Not accurate after phototherapy

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PHOTOTHERAPY
 If the baby weighs 2 kg / more  place the baby naked in
the cot/ bassinet.
 Preterm baby  in incubator
 Cover the baby’s eyes with patches, ensuring that the
patches do not block the baby’s nostrils.
 Turn the baby every three hours
 Measure the baby’s temperature
 Measure serum bilirubin level. If can not be measured 
discontinue phototherapy after 3 days.
 Ensure the baby is fed :
 Encourage the mother  to breastfed on demand, at least
every 3 hours
 During feeding  remove the baby from phototherapy unit
and remove the eye patches
 If the baby is receiving IV fluid or expressed breast milk, 
increase the volume of fluid/milk by 10% of the total daily
volume per day for as long as the baby is under the
phototherapy lights
 If the baby is receiving IV fluid or is being fed by gastric tube
 do not remove the baby from phototherapy lights.
PHOTOTHERAPY

Natural unconjugated bilirubin isomer: ZZ

ZZ ZE( toxic, no conjugation
need)
Photo
isomerization
ZZ lumibilirubin
Structural isomerization
ZZ photooxidation products

photooxidation

Module: Neonatal Hyperbilirubinemia - Session 1 29

Guidelines for phototherapy in infants 35 or more weeks gestation
American Academy of Pediatrics, July 2004

Module: Neonatal Hyperbilirubinemia - Session 1 30

Complication of phototherapy

 The retinal effects  retinal degeneration

 Increased insensible fluid loss  stool may be looser
and more frequent
 Bronze baby syndrome: Phototherapy causes
photodestruction of copper porphyrins  causing urine
and skin to become bronze
 Congenital erythropoietic porphyria
 severe bullous lesions on exposed skin and may
lead to death
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Complications of phototherapy
 Significant complications very rare
separation of mother and baby
increased insensible water loss and
dehydration in premature baby
Bronze- baby syndrome (in babies with
cholestatic jaundice)

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What decline in serum bilirubin can you
expect with phototherapy?
 Rate of decline depends on effectiveness
of phototherapy and underlying cause of
jaundice.
 With intensive phototherapy, the initial
decline can be 0.5 to 1.0 mg/ dl/ hour in the
first 4 to 8 hours, then slower.
 With standard phototherapy, expect
decrease of 6% to 20% of the initial
bilirubin level in the first 24 hours.

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When should phototherapy be stopped?

 Depends on the age of the baby

 Cause of the hyperbilirubinemia

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 Bilirubin in the skin rapidly disappears under
phototherapy.
 Skin colour cannot be used as guide to serum
bilirubin level while the baby is receiving
phototherapy and for 24 hours after discontuing
phototherapy.
Exchange Transfusion

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Guidelines for Exchange Transfusion in Infants
35 or more weeks gestation
American Academy of Pediatrics, July 2004

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Exchange Transfusion

Double volume
Exchange Transfusion
2 X 85 mL/ kg

Partially packed
Red Blood Cells waste

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EXCHANGE TRANSFUSION -
COMPLICATIONS
 cardiac failure
 metabolic- hypoglycemia, hyperkalemia,
hypocalcemia, citrate toxicity,
 air embolism
 thrombocytopenia
 bacterial sepsis
 transfusion transmitted viral disease
 necrotizing enterocolitis
 portal vein thrombosis
Mortality / permanent sequelae 1-12%
Phototherapy and Exchange Transfusion ???
in VLBW infants (Cashore WJ, Clin Pediatr 2000)

Weight (g) Start phototherapy Consider exchange

(mg/ dl) transfusion (mg/ dl)
500 - 750 5- 8 12- 15

750 - 1000 6 - 10 > 15

1000 - 1250 8 - 10 15 - 18

1250 – 1500 10 - 12 17 - 20

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PREVENTION
PREVENTION

1. Antenatal care
2. Avoid using drugs in pregnancy & intrapartum period :
• Sulfa furazole
• Novobiocin
• Oxytocin, etc
3. Prevent hypoxia in fetus & neonatus
4. R/ luminal for pregnant mother 1 – 2 day before labor
5. Good Ilumination
6. Early feeding
7. Prevent infection
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