Neonatal
Jaundice
(Hyperbilirubinemia)
Introduction
All babies develop elevated serum bilirubin (SBR)
levels,to a greater or lesser degree,in the first week
of life,This is due to:
? increased production (accelerated RBC breakdown);
? decreased removal (liver enzyme insufficiency)
? Increased reabsorption (enterohepatic circulation).
Introduction
? ~60% of infants become clinically jaundiced in 1st wk
? Bili levels peak at 3~5 days in full term infants
? ~1/6 of formula fed infants have bili levels over 12
? ~1/3 of breast fed infants have bili levels over 12
? Over 80% of all infants with bili levels>12.9 mg/dl in
the first four days of life are breast fed
Bilirubin Metabolism
? derived from the catabolism of proteins that contain heme
? the most important source is the breakdown of Hb from RBC
? native bilirubin is relatively insoluble in water at physiologic
pH,but it is very lipid soluble
? bilirubin circulates bound to albumin in equilibrium with its
unbound or "free" fraction
? the unbound fraction that readily crosses the blood-brain
barrier and results in neurotoxicity
Bilirubin Metabolism
? Bilirubin is made more water-soluble in the liver by
conjugation with glucuronic acid to form "conjugated" or
"direct-reacting" bilirubin,then cleared through the bile into
the intestines and out through the feces.
? Phototherapy works by producing photoisomers of bilirubin
that are more water soluble,and that can be cleared directly
in bile or urine without conjugation in the liver.
?,enterohepatic circulation”,b-glucuronidase in the gut
hydrolysis the conjugated bilirubin into unconjugated
bilirubin,and reabsorbed into liver
Characteristics of Neonatal
Bilirubin Metabolism
? Increased bilirubin production
8.8mg/kg daily vs 3.8mg/kg in adults
? Insufficiency of bilirubin transportation
acidosis,hypoalbuminemia
? Immature of liver function
lower ingestion (y,z protein); lower UDPGT activity
? Increased,enterohepatic circulation”
lower in gut bacteria; higher b-glucuronidase activity
“Physiological” Jaundice
? Seen in 60% of term infants and over 80% of preterm
? Serum values reaches maximum at 6mg/dl on 4~5d in
term and 10~12mg/dl on 5~7d in premature infants
? Jaundice declines gradually,reaching normal values
within 2 wks in term,and 3~4w (1~2m) in preterm
? Causes no damage in term infants
Up limit for abnormal? Undefined
(Term <12mg/dl,or term<13,preterm<15mg/dl)
Factors likely to make
“physiological jaundice” worse
? prematurity
? bruising
? cephalohematoma
? polycythaemia
? delayed passage of meconium
? breast feeding
? certain ethnic groups,esp Chinese
Characteristics of Pathological Jaundice
? Jaundice appears within 24 hrs of life
? Severe jaundice,SBR>12~15mg/dl,or >5mg/dl/day
? Sustained jaundice (term>2w,preterm>4w )
? Recurrence of jaundice
? Increased serum conjugated bilirubin (>1.5~2mg/dl)
Pathological Jaundice
? Infectious diseases
? Neonatal hepatitis (Torch infection)
? Neonatal septicemia
? Non-infectious diseases
? Hemolytic diseases
? Biliary atresia
? Breast milk jaundice
? Genetic metabolic diseases,G6PD,a1-antitrypsin,CF
? Drugs induced,Vitamin K3,K4
Breast Milk Jaundice
? Occurs infrequently (1%),peaks in 2~3wk,may persist at
moderately high levels for 3-4 weeks before declining slowly
? It is a diagnosis of exclusion
? In an otherwise well infant,it is considered a benign condition.
? If breast feeding stopped,the serum bilirubin usually falls
? The potential harms of stopping breast feeding would outweigh
any risks of a mild or moderate hyperbilirubinaemia
? Aetiology is unknown,some hormonal in the milk may acting
on the infant's hepatic metabolism,or enzyme (lipase)
facilitating intestinal absorption of bilirubin.
Breast-feeding Jaundice
?increased bilirubin levels seen during the first week of life
in infants who are breast fed
?due to both caloric deprivation (mostly) and some fluid
deprivation (a small part) during the first few days of life
?The more frequently breast feeding occurs during the first
few days,the lower are subsequent bili levels
?can be prevented by teaching effective breast-feeding
practices and support policies
Clinical Investigation,Kramer's Rule
Zone 1 2 3 4 5
SBR (mmol/L) 100 150 200 250 >250
Cephalocaudal Progression of Jaundice
Clinical Investigation
?Total SBR
?conjugated SBR
?full blood count - may reveal spherocytes or septic
?Group & Direct Coombs test –hemolytic jaundice
?high TSH & low T4 - suspect thyroid disease
?G6PD screen - male and appropriate ethnic group
?sepsis screen if indicated
?galactosaemia
Rhesus isoimmunisation
?Rh antigen,C,D,E,c,d,e
?most common type is RhD [Rh (-) refers to D-]
?Rare in un-transfused 1st pregnancy
?In severe cases fetal anaemia develops,causing
congestive cardiac failure ("hydrops fetalis")
?The fetus is protected with placental removal of
bilirubin,following rapidly rising SBR after birth
ABO Incompatibility
?Most often seen in the setting of mother being group
O and the baby being groups A or B
?Milder that Rhesus disease,rarely affects the fetus
?Jaundice that becomes apparent on day 1 or 2
?Diagnosis with blood groups and direct Coombs Test
?Responds well to phototherapy
?Rarely requires exchange transfusion
1/5 for ABO,1/20 for Rh incompatibility will becoming hemolytic
Clinical Manifestation
? Jaundice,within 24h in >77% of Rh,28% in ABO
? Anemia
? Hepatosplenomegaly
? Bilirubin encephalopathy (Kernicterus)
? Early (2~7d),more in preterm,includes hypertonia,lethargy,feeding
difficulty,seizures,?~1/3 death,bilirubin staining of the basal gangia
? Late,Survivors may go on to develop sensorineural hearing loss and
cerebral palsy,often with ataxia and choreoathetosis; disorders in eye
movement; enamel hypoplasia
Diagnosis
? Family history,still birth,abortion,jaundice
? Parents ABO/Rh typing,antibody
? Ultrasound for hydrops fetalis
? Postnatal,jaundice,anemia,neurological symptom
? Blood type and antibody
Direct Coombs,Antibody release,& Free antibody Test
Management
? Prenatal,
? Rh (-),monitoring antibody,bilirubin,etc
? Terminate pregnancy when lungs are matured
? Plasma transfusion to remove antibody
? Intrauterine blood transfusion
? Maternal use of phenobarbitone to induce enzyme
Phototherapy
? Isomerisation of unconjugated bilirubin
? Wave length,427~475nm (blue),510~530nm (green)
? Blue light,green light/day light
? Protection of eyes/gonad
? Invisible water loss
? Side effects,skin rash,fever,diarrhea
? Beware of conjugated hyperbilirubinemia (bronze baby)
Phototherapy
Exchange Transfusion
? Prenatal diagnosed,Hb<120g/L at birth,with
edema,hepatosplenomegaly,heart failure
? Increasing SBR >12 mmol/L/hr (0.75mg/dl)
? SBR >342 mmol/L (20mg/dl)
? Preterm/Rh history/Hypoxia/Acidosis/Sepsis
? For Rh,Rh same as mother,ABO same as infant
? For ABO,AB/plasma and O/RBS; or type O
? Volume,150~180ml/kg via umbilical vein catheter
Other Intervention
? Albumin (1g/kg),plasma (25ml)
? Correct acidosis
? Phenobarbitone (5mg/kg) to induce enzymes
? Intravenous immunoglubulin (1g/kg)
? Prevent hypoxia/hypothermia/hypoglycemia
? Anti RhD IgG (300mg,im) for Rh (-) mother after
delivered a Rh (+) baby (within 72h)
Good perinatal care
Sleep well,
Baby!
Jaundice
(Hyperbilirubinemia)
Introduction
All babies develop elevated serum bilirubin (SBR)
levels,to a greater or lesser degree,in the first week
of life,This is due to:
? increased production (accelerated RBC breakdown);
? decreased removal (liver enzyme insufficiency)
? Increased reabsorption (enterohepatic circulation).
Introduction
? ~60% of infants become clinically jaundiced in 1st wk
? Bili levels peak at 3~5 days in full term infants
? ~1/6 of formula fed infants have bili levels over 12
? ~1/3 of breast fed infants have bili levels over 12
? Over 80% of all infants with bili levels>12.9 mg/dl in
the first four days of life are breast fed
Bilirubin Metabolism
? derived from the catabolism of proteins that contain heme
? the most important source is the breakdown of Hb from RBC
? native bilirubin is relatively insoluble in water at physiologic
pH,but it is very lipid soluble
? bilirubin circulates bound to albumin in equilibrium with its
unbound or "free" fraction
? the unbound fraction that readily crosses the blood-brain
barrier and results in neurotoxicity
Bilirubin Metabolism
? Bilirubin is made more water-soluble in the liver by
conjugation with glucuronic acid to form "conjugated" or
"direct-reacting" bilirubin,then cleared through the bile into
the intestines and out through the feces.
? Phototherapy works by producing photoisomers of bilirubin
that are more water soluble,and that can be cleared directly
in bile or urine without conjugation in the liver.
?,enterohepatic circulation”,b-glucuronidase in the gut
hydrolysis the conjugated bilirubin into unconjugated
bilirubin,and reabsorbed into liver
Characteristics of Neonatal
Bilirubin Metabolism
? Increased bilirubin production
8.8mg/kg daily vs 3.8mg/kg in adults
? Insufficiency of bilirubin transportation
acidosis,hypoalbuminemia
? Immature of liver function
lower ingestion (y,z protein); lower UDPGT activity
? Increased,enterohepatic circulation”
lower in gut bacteria; higher b-glucuronidase activity
“Physiological” Jaundice
? Seen in 60% of term infants and over 80% of preterm
? Serum values reaches maximum at 6mg/dl on 4~5d in
term and 10~12mg/dl on 5~7d in premature infants
? Jaundice declines gradually,reaching normal values
within 2 wks in term,and 3~4w (1~2m) in preterm
? Causes no damage in term infants
Up limit for abnormal? Undefined
(Term <12mg/dl,or term<13,preterm<15mg/dl)
Factors likely to make
“physiological jaundice” worse
? prematurity
? bruising
? cephalohematoma
? polycythaemia
? delayed passage of meconium
? breast feeding
? certain ethnic groups,esp Chinese
Characteristics of Pathological Jaundice
? Jaundice appears within 24 hrs of life
? Severe jaundice,SBR>12~15mg/dl,or >5mg/dl/day
? Sustained jaundice (term>2w,preterm>4w )
? Recurrence of jaundice
? Increased serum conjugated bilirubin (>1.5~2mg/dl)
Pathological Jaundice
? Infectious diseases
? Neonatal hepatitis (Torch infection)
? Neonatal septicemia
? Non-infectious diseases
? Hemolytic diseases
? Biliary atresia
? Breast milk jaundice
? Genetic metabolic diseases,G6PD,a1-antitrypsin,CF
? Drugs induced,Vitamin K3,K4
Breast Milk Jaundice
? Occurs infrequently (1%),peaks in 2~3wk,may persist at
moderately high levels for 3-4 weeks before declining slowly
? It is a diagnosis of exclusion
? In an otherwise well infant,it is considered a benign condition.
? If breast feeding stopped,the serum bilirubin usually falls
? The potential harms of stopping breast feeding would outweigh
any risks of a mild or moderate hyperbilirubinaemia
? Aetiology is unknown,some hormonal in the milk may acting
on the infant's hepatic metabolism,or enzyme (lipase)
facilitating intestinal absorption of bilirubin.
Breast-feeding Jaundice
?increased bilirubin levels seen during the first week of life
in infants who are breast fed
?due to both caloric deprivation (mostly) and some fluid
deprivation (a small part) during the first few days of life
?The more frequently breast feeding occurs during the first
few days,the lower are subsequent bili levels
?can be prevented by teaching effective breast-feeding
practices and support policies
Clinical Investigation,Kramer's Rule
Zone 1 2 3 4 5
SBR (mmol/L) 100 150 200 250 >250
Cephalocaudal Progression of Jaundice
Clinical Investigation
?Total SBR
?conjugated SBR
?full blood count - may reveal spherocytes or septic
?Group & Direct Coombs test –hemolytic jaundice
?high TSH & low T4 - suspect thyroid disease
?G6PD screen - male and appropriate ethnic group
?sepsis screen if indicated
?galactosaemia
Rhesus isoimmunisation
?Rh antigen,C,D,E,c,d,e
?most common type is RhD [Rh (-) refers to D-]
?Rare in un-transfused 1st pregnancy
?In severe cases fetal anaemia develops,causing
congestive cardiac failure ("hydrops fetalis")
?The fetus is protected with placental removal of
bilirubin,following rapidly rising SBR after birth
ABO Incompatibility
?Most often seen in the setting of mother being group
O and the baby being groups A or B
?Milder that Rhesus disease,rarely affects the fetus
?Jaundice that becomes apparent on day 1 or 2
?Diagnosis with blood groups and direct Coombs Test
?Responds well to phototherapy
?Rarely requires exchange transfusion
1/5 for ABO,1/20 for Rh incompatibility will becoming hemolytic
Clinical Manifestation
? Jaundice,within 24h in >77% of Rh,28% in ABO
? Anemia
? Hepatosplenomegaly
? Bilirubin encephalopathy (Kernicterus)
? Early (2~7d),more in preterm,includes hypertonia,lethargy,feeding
difficulty,seizures,?~1/3 death,bilirubin staining of the basal gangia
? Late,Survivors may go on to develop sensorineural hearing loss and
cerebral palsy,often with ataxia and choreoathetosis; disorders in eye
movement; enamel hypoplasia
Diagnosis
? Family history,still birth,abortion,jaundice
? Parents ABO/Rh typing,antibody
? Ultrasound for hydrops fetalis
? Postnatal,jaundice,anemia,neurological symptom
? Blood type and antibody
Direct Coombs,Antibody release,& Free antibody Test
Management
? Prenatal,
? Rh (-),monitoring antibody,bilirubin,etc
? Terminate pregnancy when lungs are matured
? Plasma transfusion to remove antibody
? Intrauterine blood transfusion
? Maternal use of phenobarbitone to induce enzyme
Phototherapy
? Isomerisation of unconjugated bilirubin
? Wave length,427~475nm (blue),510~530nm (green)
? Blue light,green light/day light
? Protection of eyes/gonad
? Invisible water loss
? Side effects,skin rash,fever,diarrhea
? Beware of conjugated hyperbilirubinemia (bronze baby)
Phototherapy
Exchange Transfusion
? Prenatal diagnosed,Hb<120g/L at birth,with
edema,hepatosplenomegaly,heart failure
? Increasing SBR >12 mmol/L/hr (0.75mg/dl)
? SBR >342 mmol/L (20mg/dl)
? Preterm/Rh history/Hypoxia/Acidosis/Sepsis
? For Rh,Rh same as mother,ABO same as infant
? For ABO,AB/plasma and O/RBS; or type O
? Volume,150~180ml/kg via umbilical vein catheter
Other Intervention
? Albumin (1g/kg),plasma (25ml)
? Correct acidosis
? Phenobarbitone (5mg/kg) to induce enzymes
? Intravenous immunoglubulin (1g/kg)
? Prevent hypoxia/hypothermia/hypoglycemia
? Anti RhD IgG (300mg,im) for Rh (-) mother after
delivered a Rh (+) baby (within 72h)
Good perinatal care
Sleep well,
Baby!
