HYPERBILIRUBINEMIA

Presenter: Maddirala Sai krishna

OBJECTIVES
1. Define hyperbilirubinemia.
2. Differentiate physiologic and pathologic jaundice.
3. Discuss pathophysiology of hyperbilirubinemia in the newborn
4. Enumerate and discuss the signs and symptoms associated with
hyperbilirubinemia.
5. Discuss management and treatment
 HYPERBILIRUBINEMIA
• Total serum bilirubin (TSB) level greater than 1.5mg/dl.
• Common clinical sign-
JAUNDICE (1st week after birth).
• Jaundice: TSB: 5-7mg/dl.
• Progression: Cephalocaudal
• Hemolytic disease- common cause of
neonatal jaundice.
CAUSES OF HYPERBILIRUBINEMIA
• Increased Bilirubin Production
• - Increased rate of degradation
• A shortened circulating erythrocyte life span (70-90days).
• hematopoietic tissue heme degradation
2. Decreased Binding and Transport Capacity
• Unconjugated bilirubin is quickly bound to albumin in the serum
• Newborns: reduced albumin conc and binding capacity for
bilirubin
• Resulting in:- neurological damage in newborns
3. Limited Conjugation and Excretion Capacity
• Fetal life: removal of bilirubin  placenta
• Newborn: removal of bilirubin  conversion of
unconjugated bilirubin into conjugated bilirubin.

4. Increased Enterohepatic Circulation of Bilirubin

UDPGT
• UDPGT in the newborn liver must be induced
• UDPGT activity is extremely low in infants born at less than 30
weeks, 0.1% of adult levels while this activity increases to only
1% at term.
• The activity reaches adult levels by 6-12 weeks of age
HYPERBILIRUBINEMIA
Hyperbilirubinemia is classified as:-
1. unconjugated or indirect hyperbilirubinemia.
2. conjugated or direct hyperbilirubinemia.
 UNCONJUGATED BILIRUBIN CONJUGATED BILIRUBIN
1. Lipid soluble 1. Does not bound to lipids

2. Indirect reaction on Van den Bergh 2. Direct reaction on Van der Bergh
Reaction) Reaction

3. End-product of heme-protein 3. End-product from indirect,

catabolism unconjugated bilirubin

4. Can cross Blood Brain Barrier 4. Impermeable to conjugated water-

soluble bilirubin.
5. Neurotoxic when elevated
5. Serious hepatic disorder or a systemic
illness when elevated
UNCONJUGATED HYPERBILIRUBENEMIA
PRESENCE OF HEMOLYSIS

• Blood Group Incompatibility

o Abo Incompatibility
o Rh Incompatibility
• ABO INCOMPATIBILITY

oThis is a hemolytic disease

oJaundice appears at 24-72 hours.
oManifestations- significant anemia and
hyperbilirubinemia.
oLess severe than hemolysis in Rh-sensitized pregnancy
• Rh INCOMPATIBILITY

oManifestation- hemolytic anemia in the fetus and

newborn
oThe Rh antibody is produced by a Rh negative
mother after being exposed to an Rh antigen from
fetal blood
oInfants may develop hyperbilirubinemia rapidly after
birth.
HEMOLYSIS ABSENT

 Indirect Unconjugated Hyperbilirubinemia

1. Physiologic jaundice
2. Crigler-Najjar syndrome
3. Gilbert disease
4. Breast milk jaundice
 PHYSIOLOGIC JAUNDICE PATHOLOGIC JAUNDICE

1. Visible Jaundice > 24 HOL 1. Visible jaundice <24 HOL

2. Bilirubin peaks to 12-15mg/dl by 3rd 2. Serum bilirubin increases >5mg/dl in

DOL and then falls 24 HOL

3. TsB rise: <5mg/dl/day 3. TsB rise: > 5mg/dl/day

TsB level: TsB level:
- Preterm <15mg/dL - Preterm >15mg/dL
- Term < 12mg/dL - Term >12mg/dL

4. Resolves within 1st two weeks after 4. Persistent jaundice beyond 2 weeks
birth after birth
Physiologic jaundice
• Common cause of hyperbilirubinemia among newborns.
• Result of many factors that are normal physiologic characteristics of
newborns.
• Term infants: peak indirect-reacting bilirubin level of no more than 12
mg/dL on day 3 of life.
• Preterm infants: the peak is higher (15 mg/dL) and occurs on fifth day
of life.
PATHOLOGIC UNCONJUGATED HYPERBILIRUBINEMIA
• Occurs on the 1st day of life.
• Defined as prolonged or exaggerated hyperbilirubinemia.
• Early onset often is a result of:-
o Hemolysis
o Internal hemorrhage
o Infection
• Occurs because of disorders of:
a. Production
b. Hepatic Uptake
c. Conjugation
d. Enterohepatic Circulation
Crigler-Najjar syndrome
• A serious, rare, autosomal recessive, permanent deficiency of
glucuronosyltransferase that results in severe indirect
hyperbilirubinemia.
• Type I does not respond to phenobarbital
• Manifestations-persistent indirect hyperbilirubinemia, often leading
to kernicterus.
Gilbert disease
• Caused by a mutation of the promoter region of
glucuronosyltransferase
• Manifestation- mild indirect hyperbilirubinemia.
• In the presence of another icterogenic factor (hemolysis), more
severe jaundice may develop.
Breast milk jaundice
• Occurs during the 1st to 2nd week of life.
• Peak level of indirect bilirubin- 15 to 17 mg/dL
• This higher level may be partly a result of the decreased fluid intake of
infants fed breast milk.
• In a breastfed newborn with early-onset hyperbilirubinemia
• Frequency of feedings needs to be increased to more than 10 per day.
• Causes- may contain an inhibitor of bilirubin conjugation or may
increase enterohepatic recirculation of bilirubin because of breast milk
glucuronidase.
CONJUGATED HYPERBILIRUBINEMIA
• Direct bilirubin level >2 mg/dL or >20% of the total bilirubin (Direct-
reacting hyperbilirubinemia).
• Its not neurotoxic to the infant but signifies a serious underlying disorder.
• Diagnostic evaluation of patients with direct-reacting hyperbilirubinemia
involves:-
o Determination of the levels of liver enzymes
o Bacterial and viral cultures
o Metabolic screening tests
Bilirubin Toxicity
Kernicterus (Bilirubin Encephalopathy)
• Indirect bilirubin is deposited in brain cells and disrupts neuronal
metabolism and function.
• Bilirubin levels <20 mg/dL + [sepsis, meningitis, hemolysis, asphyxia,
hypoxia, hypothermia, hypoglycemia, bilirubin-displacing drugs (sulfa
drugs), and prematurity].
• The earliest clinical manifestations-
• Lethargy, hypotonia
• irritability,
• poor Moro response
• poor feeding. Early signs- day 4 of life.
General symptoms of neonatal jaundice
• The most pervasive sign of infant jaundice is
yellow skin and sclerae.(Cephalocaudal Progression)

• Dark urine - a newborn's urine should be colorless

• Pale stools - breast-fed babies should have greenish-yellow stools, while those of
bottle fed babies should be a greenish-mustard color.
• Drowsiness
MANAGEMENT
• 2 KEY ELEMENTS:
• Prevention of hyperbilirubinemia by identifying at-risk infants and
initiation of preventive therapeutic interventions as needed
• Reduction of TB in infants with hyperbilirubinemia:
• Enhanced enteral nutrition
• Interventions used to reduce TB levels for infants at-risk for severe
hyperbilirubinemia:
1. Phototherapy
2. Exchange Transfusion
PHOTOTHERAPY
• An effective and safe method for reducing indirect bilirubin levels.
• In term infants, phototherapy is begun when indirect bilirubin levels
are between 16 and 18 mg/dL.
• Initiated in premature infants when bilirubin is at lower levels, to
prevent bilirubin from reaching the high concentrations necessitating
exchange transfusion.
• Blue lights and white lights are effective in reducing
bilirubin levels.
 Exchange transfusion
• Exchange transfusion usually is reserved for infants
with dangerously high indirect bilirubin levels who are
at risk for kernicterus.
• As a rule of thumb, a level of 20 mg/dL for
indirect-reacting bilirubin is the exchange number
for infants with hemolysis who weigh more than 2000 g.
Pharmacologic
• Phenobarbital – increase rate of conjugation
• Albumin–binds with unconjugated bilirubin to be brought to the
liver for conjugation
• Intravenous gamma-globulin
• Shown to reduce the need for exchange transfusions in isoimmune
hemolytic disease
JOURNAL APPRAISAL

Efficacy of Intensive Phototherapy in Management of Neonatal

Hyperbilirubinemia in Neonatal Unit of Assiut University Children Hospital

P- hyperbilirubinemia patients
I- intensive phototherapy
C- conventional phototherapy
O- it is effective in lowering total serum Bilirubin
M- prospective cohort study
JOURNAL APPRAISAL
Among patients with hyperbilirubinemia, how
effective is intensive phototherapy in lowering total
serum Bilirubin when compared to conventional
phototherapy in the Management of Neonatal
Hyperbilirubinemia
According to the journal, the Total Serum Bilirubin
decline rate 6 h after admission was significantly
more in intensive phototherapy group than the
controls (p<0.01). Thus use of intensive phototherapy
in the treatment of indirect pathological
hyperbilirubinaemia is very effective in lowering total
serum Bilirubin when its level is within 2-3 mg/dl (34-
50 umol/l) of the exchange transfusion level a
JOURNAL APPRAISAL
Summary
• The study was based on assessing the effectiveness of intensive
phototherapy in comparison with conventional phototherapy in
reducing the need for exchange transfusion and the duration of
phototherapy for management of neonatal hyperbilirubinemia. It is a
prospective study comprising of neonates with indirect
hyperbilirubinemia and treated with intensive phototherapy (group
1). These neonates were compared with a historical retrospective
group who had been treated with conventional therapy (group 2).
The study has shown that The use of intensive phototherapy in the
treatment of indirect pathological hyperbilirubinaemia is very
effective in lowering total serum Bilirubin.
REFERENCE:
BOOK:
• Nelson Textbook of Pediatrics 2oth Edition “Chapter 62 Anemia and
Hyperbilirubinemia”.
JOURNAL:
• Abdelazeem,K.S., Soliman A.A., & Askar E.A.A. (2017). Efficacy of
Intensive Phototherapy in Management of Neonatal
Hyperbilirubinemia in Neonatal Unit of Assiut University Children,
Hospital, Journal of Neonatal Biology, 6(3). DOI: 10.4172/2167-
0897.1000266