Clinical Aspect of Hyperbilirubinemia

CLINICAL JAUNDICE
80% of premature baby
Visible jaundice: serum bilirubin > 5 mg/dL

Neonatal Jaundice:
WHY WE WORRY ?

Acute Bilirubin Encephalopathy

Early phase
lethargic, hypotonia, suck poorly
Intermediate phase
stupor, irritability, hypertonia
(retrocollis and opistotonus)
Fever, high-pitched cry

Kernicterus
Chronic form of bilirubin encephalopathy
Athetoid CP, auditory dysfunction, paralysis upward
gaze

Kernicterus - Neuropathology
Yellow staining and neuronal necrosis

Basal ganglia:
globus pallidus
subthalamic nucleus

Cranial nerve nuclei:

vestibulocochlear
oculomotor
facial

Cerebellar nuclei

1990 - ..
125 CASES OF KERNICTERUS
in the United States

Cases of Kernicterus
in Indonesia ?

A preventable
tragedy

BILIRUBIN SYNTHESIS, TRANSPORT, AND

METABOLISM

BASIS FOR INCREASED BILIRUBIN LEVELS

IN THE NEWBORN

Serum Bilirubin levels

in term and preterm infants

Jaundice in preterm neonates

Onset earlier
Peaks later
Higher peak
Takes longer to resolve up to 3
weeks

What

level is physiologic?

Physiologic vs Non-physiologic
hyperbilirubinemia

Criteria that Rule Out the Diagnosis

of Physiologic Jaundice

Clinical jaundice in the first 24 hours of live

Jaundice lasting longer than 21 days in preterm infants

STB concentration increasing by more 0.2 mg/dL

per hour or 5 mg/dL per day

Direct serum bilirubin concentration exceeding

1.5-2 mg/dL

Jaundice who need phototherapy

Sign of underlying disease

CAUSES OF NEONATAL
INDIRECT HYPERBILIRUBINEMIA
BASIS

CAUSES

Indirect HYPERBILIRUBINEMIA
OVERPRODUCTION ( HEMOLYSIS)

Extravascular blood- hematomas, bruises

Feto-maternal blood group incompatibility
Rh - mom / baby Rh +
O group mom / baby A or B
Intrinsic red cell defects
G-6-PD deficiency
hereditary spherocytosis
Polycythemia

Indirect HYPERBILIRUBINEMIA
G6PD DEFICIENCY

X- Linked disorder (2-6% carrier rate in Indonesia)

enzyme protects red cell from oxidative damage
>150 mutations
Onset of jaundice usually day 2 - 3, peaks day 4 - 5
Hyperbilirubinemia may be out of proportion to
anemia
Diagnosis- enzyme assay baby and mother
DNA analysis

Indirect HYPERBILIRUBINEMIA
UNDERSECRETION

Prematurity
Hypothyroidism
Inherited deficiency of conjugating enzyme
uridine diphosphate glucuronyl transferase
Other metabolic disorders

Indirect HYPERBILIRUBINEMIA
SECRETED but REABSORBED from gut

ENTEROHEPATIC CIRCULATION
Decreased enteral intake
Pyloric stenosis
Intestinal atresia/ stenosis
Meconium ileus
Meconium plug
Hirschsprungs disease

Direct HYPERBILIRUBINEMIA
OBSTRUCTIVE DISORDERS

Cholestasis
Biliary atresia
Choledochal cyst

Direct bilirubin > 2 mg/dL

# Time of appearance
# Color of stools
# Color of urine
#

HYPERBILIRUBINEMIA
MIXED

Bacterial sepsis
Intrauterine infections: TORCH

HYPERBILIRUBINEMIA
DIAGNOSIS

History
Physical exam:
gestational age
activity/ feeding
level of icterus
pallor
hepatosplenomegaly
bruising,
cephalhematoma

HYPERBILIRUBINEMIA
DIAGNOSIS

Laboratory tests

Bilirubin levels: total and direct

Mothers blood group and Rh type
Babys blood group and Rh type
Direct Coombs test on baby
Hemoglobin
Blood smear
Reticulocyte count

Rapidly developing jaundice

on Day 1

Likely
Rhesus, ABO, or other hemolytic
disease
Spherocytosis
Less likely
Congenital infection
G-6-P-D deficiency

Rapidly onset jaundice

after 48 hours of age

Likely
Infection
G-6-P-D deficiency
Less likely
Congenital Rh, ABO, spherocytosis

HYPERBILIRUBINEMIA
MANAGEMENT

HYDRATION - FEEDING
PHOTOTHERAPY
EXCHANGE TRANSFUSION

Phenobarbital
Tin protoporphyrin

Management of Hyperbilirubinemia
in the Newborn Infant
35 or more weeks of gestation

Promote and support successful breast-feeding

Perform a systematic assessment before discharge
for the risk of severe hyperbilirubinemia
Provide early and focussed follow-up based on risk
assessment
When indicated, treat newborns with phototherapy
or exchange transfusion to prevent the development
of severe jaundice and possibly, kernicterus.

Feeding to Prevent and Treat

Neonatal Jaundice

Mothers should breast feed their

babies
caloric intake / dehydration
Jaundice
Supplementation with water or
dextrose water will not prevent or
treat hyperbilirubinemia

Systematic Assessment for Neonatal

Jaundice

Pregnant women:
Blood group and Rh type

If mom is Rh negative or O group:

Babys cord blood group/ Rh type/ DAT

Monitor infant for jaundice at least every 8-12 hours

If level of jaundice appears excessive for age,

perform transcutaneous bilirubin or total serum
bilirubin measurement

Clinical
assessment
of severity of
jaundice

Cephalocaudal progression
face 5 mg/dL (approximately)
upper chest 10 mg/dL (approximately)
abdomen and upper thighs 15 mg/dL
(approximately)
soles of feet 20 mg/dL (approximately)

Visual inspection may be misleading

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

Complications of phototherapy

Significant complications very rare

separation of mother and baby
increased insensible water loss and
dehydration in premature baby
PDA
ROP

What decline in serum bilirubin can

you expect with phototherapy?

Rate of decline depends on effectiveness of

phototherapy and underlying cause of jaundice

Intensive phototherapy should produce a decline in

STB of 1-2 mg/dL within 4-6 hours, and the STB level
should continue to decline and remain below the
threshold level for exchange transfusion

With standard phototherapy, expect decrease of 6%

to 20% of the initial bilirubin level in the first 24
hours

Exchange Transfusion

Exchange Transfusion
Double volume
Exchange Transfusion
2 X 85 mL/kg

Red Blood Cells

waste

EXCHANGE TRANSFUSION
COMPLICATIONS

cardiac failure

metabolic- hypoglycemia, hyperkalemia,

hypocalcemia

air embolism

bacterial sepsis

transfusion transmitted viral disease

necrotizing enterocolitis

portal vein thrombosis

Mortality / permanent sequelae 1-12%

Guidelines for the use of phototherapy and

exchange transfusion in low birth weight
infants
based on birth weight

Guidelines for use of phototherapy and

exchange transfusion in preterm infants based
on gestational age

Guidelines according to birth weight for

exchange transfusion in low birth weight infants
based on total serum bilirubin (mg/dL) and
bilirubin/albumin ratio (mg/g) (whichever comes
first)

Tatalaksana Ikterus

Pocket Book WHO, 2005