HYPERBILIRUBINEMIA

PADA NEONATUS
Aristida Cahyono Putro
Rasvinder singh
Caesar Bimoseno

Jaundice
Yellowish

discoloration of skin +/- sclera

of newborns due to bilirubin

Affects
Peak:

nearly all newborns

48-120 hours, typically 5-6 mg/dL,

usually does not exceed 17-18 mg/dL

60%

of newborn
Visible jaundice: serum bilirubin > 5 mg/
dl

CLINICAL JAUNDICE
3

 bilirubin bilirubin encephalopathy

Kernicterus
Stage 1:
lethargy, hypotonia, poor suck
Stage 2:
fever, hypertonia, opisthotonus
Stage 3:
apparent improvement
Sequelae: Sensorineural hearing loss
Choreoathetoid cerebral palsy
Gaze abnormalities

Bilirubin metabolism
HEME + Globin

(He
me

LIVER

Ox

y ge

CO

nas BILIVERDIN
e)

UCB
BILIRUBIN

Alb

Conjugated bilirubin

Free unconjugated
bilirubin

UNCONJUGATED
Indirect bilirubin
Water- insoluble
Bound to albumin
for transport
Free component
fat - soluble
Free component
TOXIC to brain

CONJUGATED
Direct bilirubin
Water soluble

Not

fat soluble

Not

toxic to brain

BILIRUBIN

Why do babies have jaundice in the

first week of life?
Increased

bilirubin production
Higher turnover of red blood cells
Decreased life span of red blood cells
Decreased excretion of bilirubin
Decreased uptake in the liver
Decreased conjugation by the liver
Increased enterohepatic circulation of bilirubin

Bilirubin excretion improves after 1 week

7

PHYSIOLOGICAL JAUNDICE

Physiological 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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 Bilirubin

level of 10 mg/ dl at 72 hours of age in

a term newborn is probably physiological.
Bilirubin level of 10 mg/ dl at 10 hours of age is
NOT physiological, and needs immediate
attention.
(see natural history of physiological jaundice)

Hour- specific bilirubin level

10

Serum Bilirubin levels

in term and preterm infants

11

Jaundice in preterm neonates

Onset

earlier
Peaks later
Higher peak
Takes longer to resolve- up to 2 weeks

12

Physiologic vs Non- physiologic

hyperbilirubinemia

13

NON- PHYSIOLOGIC JAUNDICE

Onset

before 24 hours of age

Rate of rise > 0.5 mg/ dl/ hour
Cutoff levels
> 15 mg/ dl in term infant?
> 17 mg/ dl in preterm infant?
Jaundice

persisting

> 8 days in term infant

> 14 days in preterm infant
Other

signs of illness
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Tipe dari jaundice

15

HYPERBILIRUBINEMIA - CAUSES
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

16

 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
microspherocytes/ bite cells/ normal blood picture
Diagnosis- enzyme assay baby and mother
False negative test with reticulocytosis
DNA analysis

G6PD DEFICIENCY
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HYPERBILIRUBINEMIA YANG
DISEBABKAN PENURUNAN SEKRESI
Prematurity
Hypothyroidism
Infants

of diabetic mothers
Inherited deficiency of conjugating
enzyme uridine diphosphate glucuronyl
transferase
Other metabolic disorders

18

HYPERBILIRUBINEMIA CAUSES
Disekresikan tapi diserap kembali
ENTEROHEPATIC CIRCULATION
Decreased enteral intake
Pyloric stenosis
Intestinal atresia/ stenosis
Meconium ileus
Meconium plug
Hirschsprungs disease
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Cholestasis
Biliary

atresia
Choledochal cyst
# Direct

bilirubin > 2 mg/ dL

# Time of appearance
# Color of stools
# Color of urine
OBSTRUCTIVE DISORDERS direct hyperbilirubinemia
20

Bacterial

sepsis
Intrauterine infections: TORCH
Asphyxia

HYPERBILIRUBINEMIA CAUSES
MIXED
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History
Physical

exam:

gestational age
activity/ feeding
level of icterus
pallor
hepatosplenomegaly
bruising, cephalhematoma

Hyperbilirubinemia- diagnosis
22

Likely
Rhesus, ABO, or other hemolytic disease
Spherocytosis

Less likely
Congenital infection
G-6-P-D deficiency

Peningkatan kadar bilirubin yang cepat

di hari 1 oleh karena?
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 Likely

Infection
G-6-P-D deficiency
Unlikely

Rh, ABO, spherocytosis

Peningkatan kadar bilirubin yang cepat

hari ke 2 oleh karena?
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 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 to 12
hours
If level of jaundice appears excessive for age,
perform transcutaneous bilirubin or total serum
bilirubin measurement

Asesment sistemik untuk neonatal

jaundice
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Kramer

Scoring

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Cephalocaudal

progression

Face
Abdomen (umbilical)
Knee
soles of feet

Visual

inspection may be misleading

Tingkat kronisitas
27

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

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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)

Hour Specific Serum Bilirubin

Bhutani et al, Pediatrics 1999

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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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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

Hyperbilirubinemia- diagnosis
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Management

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PHOTOTHERAPY
EXCHANGE

TRANSFUSION

Not effective
Phenobarbital
Tin protoporphyrin

MANAGEMENT NEONATAL
HYPERBILIRUBINEMIA
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Panduan umum terapi pada bayi cukup

bulan
Fototerapi (mg%)

Transfusi tukar (mg%)

Hari

1
2
3
4

Sehat

+Faktor risiko

Sehat

+Faktor risiko

15
18
20

13
16
17

19
30
30

15
20
20

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Fototerapi dan Transfusi Tukar pada

BBLSR
Berat (g)
Memulai
Pertimbangkan
(Cashore WJ, Clin Pediatr
2000)
fototerapi

500 - 750

(mg/ dl)
5- 8

transfusi tukar
(mg/ dl)
12- 15

750 - 1000

6 - 10

> 15

1000 - 1250

8 - 10

15 - 18

1250 1500

10 - 12

17 - 20

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Guidelines for phototherapy in infants 35 or more weeks gestation

American Academy of Pediatrics, July 2004

36

 Light

wavelength 450 to 460 nm

Blue lamps: 425 to 475 nm
Cool white lamps: 380 to 700 nm
Spectral

irradiance: 30 W / cm2 / nm

PHOTOTHERAPY
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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.

Penurunan bilirubin yang

diharapkan dari fototerapi
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Double volume
Exchange Transfusion
2 X 85 mL/ kg

Partially packed
Red Blood Cells

waste

Exchange Transfusion
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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%

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