The significance of accurate bilirubin estimation in the clinical management of jaundiced neonates'

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The significance of accurate bilirubin estimation
in the clinical management of jaundiced neonates.

• Dr Jessie N. Githangá,
• Pathologist/Haematologist

HuQAS Workshop 18th November, 2006, Nairobi.
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Outline of talk

• Introduction
• Reference ranges in neonates
• Bilirubin metabolism
• Major causes for jaundice
• Neonatal jaundice
• Performance guidelines for bilirubin testing
• Importance of accurate measurements

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• Jaundice remains the red flag for identification
  of liver pathology and measuring the total and
  direct bilirubin in serum is used to classify
  liver disease into
• Prehepatic
• Hepatic
• Post hepatic disorders

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Introduction

• Bilirubin
• A bile pigment produced by heme breakdown and
  reduction of biliverdin.
• It circulates in plasma and is taken up by liver
  cells and conjugated to bilirubin glucuronide
  (water soluable)

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• Unconjugated form (lipid soluable) circulates in
  a loose association with plasma proteins.
• Increase causes jaundice yellowing of the skin
  and sclera (gt 50umol/L)

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Reference Ranges in Neonates

• Age Levels (umol/L)
• Cord blood lt34.2
• 0 -1 day 34 103
• 1 -2 day 103 171
• 3 -5 day 68 137
• Adult 3.4 17.1

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Bilirubin metabolism

• Hb

Spleen RE cells
Globin
Heme
Iron
Blirubin
Liver
Li
Conjugation to bilirubin diglucuronide
Kid
Kidney
Intestines
Excretion as urobilinogen
Urobilinogen Stercobilinogen
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Major causes for jaundice
POST-HEPATIC Gall stones Biliary
stricture Carcinoma of pancreas Cholangitis
PRE-HEPATIC Haemolysis

HEPATIC Prematurity Cirrhosis Hepatitis Tumour
infiltrates Biliary atresia Inherited disorders
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Neonatal Jaundice

• Physiologic jaundice
• Up to 50 newborns present with
• Mainly due to immaturity of liver enzymes
• Rarely is greater than 100umol/L
• Can be made worse by other factors e.g.
  prematurity, dehydration, hypoxia etc.

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Neonatal jaundice causes cont.

• Increased haemolysis
• Haemolytic disease of the newborn. (Conjugated
  bilirubin also increased to a much lesser extent)
• Associated with a rise in unconjugated bilirubin
• Rhesus incompatibility
• ABO blood group incompatibility
• Red cell enzyme defects (G6PD deficiency)

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Neonatal jaundice causes cont.

• Decreased conjugation
• Associated with a rise in unconjugated bilirubin
• Crigler- Najjar syndrome (absence/defective
  glucuronyl transferase)
• Hypothyroidism, breast milk jaundice
• Some inherited abnormalities of bilirubin
  metabolism (Gilberts)

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Neonatal jaundice causes cont.

• Hepatic dysfunction
• Hepatitis, sepsis, metabolic disorders
  (galactosaemia etc.)
• Both conjugated and unconjugated bilirubin rise

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Neonatal jaundice causes cont

• Congenital abnormalities
• Biliary atresia
• Some inherited abnormalities of bilirubin
  metabolism (Dubin-Johnson, Rotor)
• Associated with increased conj. bilirubin

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Factors affecting test reliability

• Laboratory tests are used by clinicians for
  diagnosis, monitoring and prognosis in patients
  with liver disease
• A number of factors, primarily pre-analytical and
  analytical affect accuracy of tests
• Bias and imprecision affect the reliability of
  laboratory tests
• Bias is an analytical characteristic

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• Imprecision (lack of reproducibility) is due to
  physiological and analytical factors
• Intra-individual variation and inter-individual
  variation exist e.g.
• Day to day variation
• Fasting (increases 2-fold with fasting)
• Race (lower in Africans)
• Exercise (30 in men)
• Haemolysis
• Oral contraceptives
• Light exposure
• Haemolysis

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Importance of accurate measurements

• Consequences of excessive unconjugated bilirubin
  in neonate is kernicterus
• Condition associated with severe neurological
  symptoms associated with increased levels of
  bilirubin (gt340 umol/L)
• Management of neonates very much hinges on the
  bilirubin levels esp. the unconjugated form

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Thank you for listening!
Thanks for listening! Questions??
Questions??