NEONATAL

HYPERBILIRUBINEMIA
By: UMALI, JOZA A.

BILIRUBIN PRODUCTION

1g Hgb = 35mg Bilirubin Newborn

2-3 fold greater rate compared to adults y 6-10mg/kg/24hrs vs 3mg/kg/24hrs
y

UNCONJUGATED BILIRUBIN
Indirect Toxic to the CNS Insoluble to water; lipid soluble Binds to albumin (1g : 8.5mg Bilirubin) Transferred across the placenta conjugated by maternal hepatic enzyme

CONJUGATED BILIRUBIN
Direct Water soluble Mostly excreted through the bile small intestine stool When hydrolysed unconjugated by glucuronidase With bacteria: converted to: (limits bilirubin reabsorption)

Urobilinogen y Stercobilinogen
y

ETIOLOGY OF INDIRECT UNCONJUGATED BILIRUBIN

Physiologic Jaundice Criggler Najjar Syndrome

y

Gilbert Disease

Breastmilk Jaundice Jaundice on 1st day of life

PHYSIOLOGIC JAUNDICE
Common cause of increased bilirubin in NB Diagnosis of exclusion Results from Bilirubin production

RBC mass y Shortened RBC life span y Hepatic immaturity of ligandin & gluconyltransferase
y

Term: not >12mg/dL on D3 Preterm: 15mg/dL on D5 Breastfed infant: 15-17mg/dL vs 12mg/dL

CRIGLER-NAJJAR SYNDROME
Serious, rare, permanent deficiency of gluconyltransferase Severe indirect hyperbilirubinemia

Autosomal Dominant
y

Responds to enzyme induction by phenobarbital enzyme activity and bilirubin level

Autosomal Recessive
Does not respond to phenobarbital y Persistent indirect hyperbilirubinemia
y

kernicterus

GILBERT DISEASE
Caused by a mutation of the promoter region of gluconyltransferase Results in mild indirect hyperbilirubinemia If with icterogenic factor more severe jaundice

BREAST MILK JAUNDICE

Associated with unconjugated hyperbilirubinemia No hemolysis at 1st & 2nd wk of life Bilirubin >20mg/dL

TX: interruption of breastfeeding for 1-2days Breastmilk

May contain an inhibitor of bilirubin conjugation y May enterohepatic recirculation
y

JAUNDICE ON 1ST DAY OF LIFE

Pathologic Early onset results from:

Hemolysis y Internal Hemorrhage y Infection

y

Bilirubin
0.5mg/dL/hr y Peak: >13mg/dL (term) y Direct: >1.5mg/dL
y

ETIOLOGY OF DIRECT CONJUGATED HYPERBILIRUBINEMIA

Cholestasis (i.e. Biliary Atresia) Hepatocellular injury

Direct Bilirubin >2mg/dL or >20% of Total Bilirubin Do not respond to phototherapy/exchange transfusion

KERNICTERUS

Indirect Bilirubin crossing BBB

y

Disrupts neuronal metabolism and function esp. in basal ganglia

Caused by increase indirect bilirubin exceeding the binding capacity of albumin May be noted if Bilirubin

>25mg/dL y <20mg/dL
y

i.e. sepsis, meningitis, hemolysis, asphyxia, hypoxia, hypothermia, hypoglycemia, sulfa-drugs, prematurity

TX: Exchange transfusion

KERNICTERUS MANIFESTATION

Early (Within 4DOL)

y y y y y y y

Late
y y y y y y y

Lethargy Hypotonia Irritability Poor Moro response Poor feeding High pitched cry emesis

Bulging fontanelle Opisthotonic posturing Pulmonary hemorrhage Fever Hypertonicity Paralysis of upward gaze seizure

KERNICTERUS COMPLICATIONS
Nerve deafness Choreoathetoid cerebral palsy Mental retardation Enamel displasia Discoloration of teeth

THERAPHY FOR INDIRECT HYPERBILIRUBINEMIA

Phototherapy Exchange Transfusion

PHOTOTHERAPY
Effective Safe Started if IBL between 16 & 18mg/dL Max: 425-275nm wavelength Indirect Bilirubin isomers; lumirubin

Complications
y y y y y y y y y

insensible water loss Diarrhea Dehydration Macular-papular red skin rash Lethargy Masking of cyanosis Nasal obstruction Retinal damage Skin-bronzing

EXCHANGE TRANSFUSION
For infants with dangerously IBL and at risk of kernicterus Rule of Thumb:

y

IBL 20mg/dL (exchange #) with hemolysis for infants with hemolysis weighing >2000g

Breastfed: no need unless IBL>25mg/dL exchangeable level of indirect bilirubin for other infants may be estimated by:

y

10% of the birth weight in grams: the level in an infant weighing 1500 g would be 15 mg/dL

Infants <1000g if IBL >10mg/dL

EXCHANGE TRANSFUSION
Small infusions of whole blood crossmatched with that of the mother and infant are alternated with withdrawals of an equivalent quantity of the infant's blood Aliquots of 5-20ml/cycle

y

Depends on infants size

Duration: 45-90mins Amt of Bld Exchange = Wt(kg) x 85ml/kg x 2

EXCHANGE TRANSFUSION COMPLICATION

Blood
Transfusion reaction y Metabolic instability y infection
y

Unusual
Thrombocytopenia y Graft vs Host disease
y

Catheter
Vessel perforation y Hemorrhage
y

Procedure
Hypotension y Necrotizing enterocolitis
y

THANK YOU!