(Neonatal hyperbilirubinemia)

bilirubin
2 3
(physiologic jaundice)
(pathologic jaundice) unconjugated bilirubin

Bilirubin metabolism
bilirubin reticuloendothelial system (RE system)
unconjugated indirect bilirubin
Indirect bilirubin ( 1)
1. Indirect bilirubin albumin
2. conjugate bilirubin enzyme uridine diphosphate glucuronyl transferase
( UDPG-T) conjugated direct bilirubin
3. Direct bilirubin
4. Direct bilirubin enzyme beta glucuronidase
deconjugate direct bilirubin indirect bilirubin
(enterohepatic circulation)
1 Bilirubin metabolism

( Maisels MJ. Jaundice. In: MacDonald MG,

Seshia MM, Mullett MD, eds. Neonatology
pathophysiology and management of the newborn
6th ed. Philadelphia: Lippincott William & Willkins,
2005: 768-846)

Neonatal hyperbilirubinemia 2014

Physiologic jaundice
indirect bilirubin cord blood 1.4-1.9 mg/dl
5 mg/dl 24 4-5
12-15 mg/dl
10-14 bilirubin 7-10

physiologic jaundice
1. bilirubin
1.1 Hct
1.2 90 120
1.3 (ineffective erythropoiesis)
1.4 (turn over) heme protein
2. uptake bilirubin conjugate bilirubin
3. enterohepatic circulation beta glucuronidase activity bacteria

Pathologic jaundice
physiologic jaundice

pathologic jaundice
1. 24
2. bilirubin 5 mg/dL 0.2 mg/dL
3. serum bilirubin 12-15 mg/dL
4. 14
5. conjugated bilirubin 2 mg/dL
Pathologic jaundice 2
1. Conjugated hyperbilirubinemia (extrahepatic) biliary atresia, choledochal cyst
(intrahepatic) neonatal hepatitis, congenital infection (TORCH)
2. Unconjugated hyperbilirubinemia
2.1 bilirubin
2.1.1 hemolysis ABO, Rh , minor blood group incompatibility , G6PD deficiency
2.1.2 cephalhematoma hematoma
2.1.3 (polycythemia)
2.2 enterohepatic circulation
2.2.1
2.2.2 ( bowel ileus/ obstruction)
2.3 bilirubin
2

Neonatal hyperbilirubinemia 2014

2.3.1
2.3.2 G6PD deficiency
2.3.3 Inborn error of metabolism Crigler-Najjar, Gilberts syndrome, Galactosemia
2.3.4 Hypothyroidism
2.3.5 Sepsis
pathologic jaundice hemolysis , G6PD
Hemolytic disease of the newborn ( HDN )
( hemolysis )
IgG antibody hemolysis
ABO, Rh minor blood group incompatibility
1. ABO hemolytic disease HDN A B O
anti A anti B IgG antibody

ABO incompatibility anti A anti B titer
24
indirect bilirubin hemolysis hematocrit
reticulocyte count ( 7-10%) peripheral blood smear microspherocyte polychromasia
direct Coombs test indirect Coombs test

hemolysis
2. Rh hemolytic disease Rh Rh
anti D
anti D titer
hemolysis hydrops fetalis
bilirubin toxicity

2
Rh Rh Coombs test (strongly positive) hematocrit reticulocyte count
periphral blood smear severe hemolysis anisocytosis, polychromasia nucleated red blood
cell microspherocyte
3. Minor blood group hemolytic disease Rh hemolytic disease antibody
minor blood group Kell , E , c hemolysis antigen
G6PD deficiency

hemolysis
3

Neonatal hyperbilirubinemia 2014

 hemolysis hemolysis

G6PD deficiency hemolysis Hct , reticulocyte count
peripheral blood smear basket cell , blister cell bite cell hemolysis Hct, reticulocyte
count blood smear

1. Breast feeding jaundice bilirubin 3-4

enterohepatic circulation

8-10 5-6 3-4
3-4
1-2 8-12

2. Breast milk jaundice 10 5
physiologic
jaundice 3-12

3 breast milk jaundice

hypothyroidism, biliary atresia
G6PD deficiency
bilirubin

phototherapy
24-48
Indirect hyperbilirubinemia
indirect bilirubin
brainstem, cerebellum, basal ganglia hippocampus bilirubin toxicity 2
1. Acute bilirubin encephalopathy (hypotonia)
(sepsis) (CNS infection)
biliurbin encephalopathy
(irritable) (high-pitched cry)
(hypertonia) (retrocollis) (opisthotonos)

coma

Neonatal hyperbilirubinemia 2014

2. Chronic bilirubin encephalopathy kernicterus

extrapyramidal tract athetosis, (facial grimacing)
sensorineural hearing loss
bilirubin encephalopathy
bilirubin 20-25 mg/dl
bilirubin
1. indirect bilirubin hemolysis
2. serum albumin 3.0 mg/dL indirect bilirubin free bilirubin
3. albumin ceftriaxone, sulfonamides, salicylates
4. sepsis, acidosis
5. perinatal asphyxia
6.
bilirubin encephalopathy hemolysis, perinatal asphyxia, sepsis

hemolysis
bilirubin encephalopathy
( 35-37 )
( 48 ) 10

1.
1.1
1.1.1 38
GA 38
1.1.2

1.1.3
1.1.4 bilirubin encephalopathy sepsis

1.1.5
8 40

breastfeeding jaundice breast milk
jaundice
1.1.6
4-6
3-4 3-4
5

Neonatal hyperbilirubinemia 2014

 obstructive
jaundice
1.1
1.1.1 Rh HDN
1.1.2 ,TORCH infection
1.1.3 sulfa, oxytocin
1.2
1.2.6 HDN, G6PD deficiency
1.2.7
1.2.8
2
2.1
bilirubin (cephalocaudal progression)
bilirubin ( 2)

bilirubin
(transcutaneous bilirubinometer)

2.2
2.2.1 , , (hypotonia) (poor sucking) , Moro reflex
sepsis, metabolic disturbance bilirubin encephalopathy
2.2.2 6- 8%

2.2.3 (anemia) (severe HDN)
(polycythemia) (ecchymosis, hematoma)
(petechiae, purpura) (TORCH infection)
2.2.4 (cephalhematoma, subgaleal hematoma)
(OFC) microcephaly hydrocephalus
fontanelle anterior fontanelle intracranial hemorrhage CNS infection posterior
fontanelle hypothyroidism
2.2.5 sepsis severe hemolytic disease of
the newborn (congenital infection)
3 pathologic jaundice
3.1 Hct, Total biliurbin, direct biliurbin, blood group, Rh, Coombs test, G6PD,
peripheral blood smear
3.2 blood group, Rh Coombs test

Neonatal hyperbilirubinemia 2014

 2 Dermal zone : cephalocaudal distribution of bilirubin

Zone
1
2
3
4
5

Jaundice
Limited to head and neck
Over upper trunk
Over lower trunk, thighs
Over arms, legs, below knee
Hands, feet

Serum indirect bilirubin (mg/dL)

Average
Maximum
6
8
9
12
12
16
15
18
>15

( Kramer LI. Advancement of dermal icterus in the jaundice newborn. Am J Dis Child 1969;118:454-9)

3 neonatal jaundice

( Piazza AJ, Stoll BJ. Jaundice and hyperbilirubinemia in newborn. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson
Textbook of Pediatrics. 18th ed. Philadelphia: Saunders Elsevier; 2007: p756-66)

Neonatal hyperbilirubinemia 2014


1. (phototherapy)
2. (exchange transfusion)
3. (pharmacological agents)
neonatal jaundice
1. unconjugated bilirubin bilirubin encephalopathy
2.
Phototherapy
(wavelength) 420-475 nm. indirect bilirubin
isomer (isomerization)

phototherapy
1) 35 4
2) 35 1
phototherapy
1) direct hyperbilirubinemia
2) light sensitive porphyria
4 phototherapy 35

Risk factors isoimmune hemolytic disease (ABO, Rh, minor blood group incompatibility), G6PD deficiency,
asphyxia (Apgar score 5 < 7 hypoxic ischemic encephalopathy, renal impairment), significant
lethargy. temperature instability, sepsis, acidosis, albumin < 3.0 g/dL
** bilirubin TSB direct bilirubin **
35 phototherapy TSB 36 6/7
TSB
( American Academy of pediatrics, Subcommittee on Hyperbiliurbinemia. Management of hyperbiliurbinemia in the
newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114:297-316)

Neonatal hyperbilirubinemia 2014

 1 serum bilirubin
Serum bilirubin level (mg/dl)

()
(uncomplicated)
(complicated*)
<1000
12-13
10-12
1001-1250
12-14
10-12
1251-1499
14-16
12-14
1500-1999
16-20
15-17
2000-2500
20-22
18-20
* perinatal asphyxia, acidosis, hypoxia, hypothermia, hypoalbuminemia, meningitis,
intraventricular hemorrhage, intraventricular hemorrhage, hemolysis, hypoglycemia, bilrubin encephalopathy
Phototherapy serum bilirubin 50-70%
Exchange transfusion serum bilirubin phototherapy
serum bilirubin bilirubin encephalopathy
( Piazza AJ, Stoll BJ. Jaundice and hyperbilirubinemia in newborn. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF,
editors. Nelson Textbook of Pediatrics. 18th ed. Philadelphia: Saunders Elsevier; 2007: p756-66)

phototherapy
1. (retina)
2.
3. 4
4. 20-30
(dehydrate)
5.
6. TSB 12-24 4-6 TSB
exchange transfusion phototherapy TSB
transcutaneous bilirubinometer bilirubin
7. daylight fluorescent 4-8
30 . bilirubin special blue (F20 T12BB General
Electrics , TL52/20 W Phillips , FL18W / T8 / DB deep blue lamp Toshiba )
special blue light
day light halogen
daylight
light-emitting diodes (LED) fiber optic light

8. Intensive phototherapy 430-490nm

30-35w/cm2/nm serum total bilirubin 0.5-1 mg/dL/ 4-8
9

Neonatal hyperbilirubinemia 2014

 special blue LED 15-20 .

2-3
9. 15-20 w/cm2/nm (standard phototherapy)
30 w/cm2/nm (intensive phototherapy)
2,000 3 bilirubin

10. ultraviolet
phototherapy
phototherapy
1. (retinal damage)
2.
3.
4.
5. (nonspecific erythematous rash)
6.
7. (burn)
8. Bronze baby direct hyperbilirubinemia
phototherapy
bilirubin 13-14 mg/dL phototherapy
3-4 hemolysis bilirubin 12-24
(exchange transfusion)
bilirubin antibody hemolysis
2
75-85 bilirubin 50 30-45 bilirubin
60-75
exchange transfusion
serum total bilirubin bilirubin toxicity
1. 35 1
2. 35 5
2.1 acute biliurbin encephalopathy serum total biliurbin 5
5 mg/dL exchange transfusion intensive
phototherapy
2.2 bilirubin encephalopathy serum total bilirubin 5 mg/dL
intensive phototherapy bilirubin 2-3 acute
bilirubin encephalopathy serum total bilirubin intensive
phototherapy bilirubin encephalopathy exchange transfusion
10

Neonatal hyperbilirubinemia 2014

 5 exchange transfusion 35

Risk factors isoimmune hemolytic disease (ABO, Rh, minor blood group incompatibility), G6PD deficiency,
asphyxia, significant lethargy, temperature instability, sepsis, acidosis
** bilirubin TSB direct bilirubin **
( American Academy of pediatrics, Subcommittee on Hyperbiliurbinemia. Management of hyperbiliurbinemia in the
newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114:297-316)

1. exchange transfusion 5
2. 2x80x
3.
3.1 group O group A B packed red cell (PRC) group O fresh frozen plasma
(FFP) group AB PRC group O FFP group
3.2 Rh negative Rh positive Rh negative
3.3 HDN cross match
4. 10
60-90
5. Hct,TB 4-6
hemoculture, liver function test, electrolyte
6. phototherapy bilirubin

1. , hypovolvemia ,volume overload ,

2. (thrombosis embolism) (vasospasm)
3. (coagulopathy) , , (hemolysis)
graft versus host reaction
4. (hemoperitoneum), portal hypertension, (NEC)
5. , , , (acidosis)
6. sepsis, CMV, HIV, hepatitis
7.
11

Neonatal hyperbilirubinemia 2014


1.
Intravenous immunoglobulin 0.5-1 /./ 12 HDN serum
bilirubin exchange transfusion
2. Metalloporphyrins ( Sn mesoporphyrin) enzyme heme oxygenase heme protein
biliverdin bilirubin
3. Phenobarbital

48-72
serum bilirubin

bilirubin encephalopathy

1. TSB TcB high risk zone 95 percentile ( 6)
2. 24
3. hemolytic disease ABO, Rh incompatibility, Coombs test G6PD deficiency
4. 8-10

5. 35-36
6. cephalhematoma bruising

1. Jaundice work up
2. phototherapy exchange transfusion
3. TSB TcB 12-24

1. TSB TcB intermediate risk zone ( 6)
2. 37-38
3.

1. Jaundice work up phototherapy exchange transfusion

2. TSB TcB 24-48
3.
72-120

12

Neonatal hyperbilirubinemia 2014


1. TSB TCB low risk zone ( 6)
2. >41
3.

5-7
6 bilirubin (nomogram)

( Bhutani VK, Johnson LH, Sivieri EM. Predictive ability of a prediacharge hour-specific serum biliurbin for subsequent
significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999;103: 6-14.)

1. 48 48

2. 48
48

3. HDN 1-2

4. (Auditory brainstem evoke response)
6 bilirubin

bilirubin encephalopathy
(urgency)
TSB/TcB
120
13

Neonatal hyperbilirubinemia 2014