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
16
14
12
10
Normal term
8
Preterm
6
4
2
0
day 1 day 2 day 3 day 4 day 5 day 6 day 7
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

20
18
16
14
12
physiologic
10
non- physiologic
8
6
4
2
0
day 1 day 2 day 3 day 4 day 5 day 6 day 7
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
Total Bilirubin Level (mg/dL)*
Birth Weight (g)
Phototherapy Exchange Transfusion
< 1.500 5-8 13-16
1.500-1.999 8-12 16-18
2.000-2.499 11-14 18-20
 Guidelines for use of phototherapy and exchange
transfusion in preterm infants based on gestational age

Total bilirubin level (mg/dL)

Gestational age
Exchange transfusion
(weeks) Phototherapy
Sick* Well
36 14.6 17.5 20.5
32 8.8 14.6 17.5
28 5.8 11.7 14.6
24 4.7 8.8 11.7
 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)
< 1.250 g 1.250-1.499 g 1.500-1.999 g 2.000-2.499 g
Standard risk
Total bilirubin 13 15 17 18
B/A ratio 5.2 6.0 6.8 7.2
High risk*
Total bilirubin 10 13 15 17
B/A ratio 4.0 5.2 6.0 6.8
Guidelines for the Management of Hyperbilirubinemia Based on
Birth Weight and Relative Health of the Newborn

Serum Total Bilirubin Level (mg/dL)

Healthy Sick
Birth Weight
Phototherapy Exchange Phototherapy Exchange
Transfusion Transfusion
Premature
< 1000 g 5 7 Variable 4 6 Variable
1001 1500 g 7 10 Variable 6 8 Variable
1501 2000 g 10 12 Variable 8 10 Variable
2001 2500 g 12 15 Variable 10 12 Variable

Term
> 2500 g 15 18 20 25 12 15 18 20

Averys Diseases of the Newborn. 2005
Tatalaksana Ikterus
Bilirubin Serum Total (mg/dL)
Terapi sinar Transfusi tukar
USIA
Tanpa Prematur atau Tanpa Prematur atau
Faktor Risiko Dengan Faktor Risiko Faktor Risiko Dengan Faktor Risiko

Hari 1 Setiap ikterus yang terlihat 15 13

Hari 2 15 13 25 15
Hari 3 18 16 30 20
Hari 4 dst 20 17 30 20

Pocket Book WHO, 2005