Conjugated Hyperbilirubinaemia

Reviewed by Carl Kuschel, Simon Chin, and Stephen Mouat (Paediatric Gastroenterology, Starship Hospital)

August
2007

Background	Stool Colour Chart	1st Line Investigations	2nd Line Investigations
Other Investigations	Treatment		Related Documents

Background

Conjugated hyperbilirubinaemia is relatively common occurrence in neonates. Generally, the direct (conjugated) fraction of bilirubin should not be greater than 20mcmol/L, or more than 10% of the total bilirubin if the bilirubin is greater than 200mcmol/L. Most commonly, it is seen in extremely immature infants who are recovering from their immediate neonatal illnesses, and who have had prolonged intravenous nutrition.

The list of possible causes is extensive and a decision to investigate will depend on the clinical circumstances. Investigations should be targeted towards either

confirming a clinically suspected diagnosis, or
excluding a condition for which there is an available treatment.

Therefore, the form below is a template for investigation - this is not an exhaustive list and other investigations may be warranted. In general, first line investigations should be performed prior to discussing the case with the Paediatric Gastroenterology Service. Other investigations should be performed as indicated.

Referral to the Paediatric Gastroenterology service should be considered early if:

there is progression of liver disease or liver failure
no clear cause is identified

This page can be printed out by clicking on the "Print" button on the toolbar at the top of the browser window. The page can be filed in the baby's notes and completed according to which investigations are ordered.

Remember: Identifying one possible cause does not exclude co-existent pathology. For example, it is entirely possible to have both CMV and biliary atresia as dual pathologies.

Stool Colour Chart

Stool colour is a useful screen for detecting biliary obstruction (primarily, biliary atresia). It is imperative that stools are examined, rather than a history obtained from parents or other caregivers. Stools in biliary obstruction are persistently pale. Urine colour may be dark or orange.

Healthy
stools

Suspicious
stools

Stools that are pale or acholic require urgent investigation.

Adapted from Children’s Liver Disease Foundation. Protocol for community healthcare professionals. Early identification of liver disease in infants. 2002.

First Line Investigations

These should be done prior to consulting the Gastroenterology Service.

Test	Date taken	Result
Full Blood Count and film
Total and conjugated bilirubin
Liver function tests - specify: AST ALT GGT ALP
Blood gas
Albumin Often low in preterm infants. If assessing synthetic function, consider a coagulation screen
INR and/or full coagulation screen
Blood group and Coombs
Liver ultrasound scan
Ferritin
Thyroid function tests
α1 Antitrypsin phenotype
Urine CMV
Maternal/congenital infection (can be obtained from the obstetric record as necessary)	Maternal toxoplasma serology
	Maternal Syphilis status
	Maternal Rubella status
	Maternal Hepatitis B status
Urine sample	bacterial culture
Urine sample	reducing substances

Second Line Investigations

Second line investigations that are relatively easy to obtain and may be considered early are:

Test	Date taken	Result
Urine organic acids
Urine amino acids
Serum amino acids
Plasma ammonia
Plasma Lactate and Pyruvate
Herpes simplex PCR (if clinically suspected)

Other Investigations

These should only be ordered after discussion with a specialist from the Paediatric Gastroenterology service and include:

Test	Date Taken	Result
Other acquired and congenital infections	Hepatitis A Virus IgM
	Adenovirus serology
	Epstein Barr Virus serology
	Stool Enterovirus (ECHO, coxsackie)
	Parvovirus PCR
	HHV6 PCR
	HCV (very uncommon cause in the initial perinatal period)
	HIV
Triglycerides and Cholesterol
Carnitine
Urine bile acids (bile acid synthetic defects)
Very long chain fatty acids (peroxisomal disorders)
White Blood Cell enzymes or Bone Marrow aspirate (storage disorders)
Karyotype
HIDA scan
Transferrin isoelectric focusing (congenital disorders of glycosylation)

Treatment

Nutritional support
- If no surgically-correctable lesion is identified, the primary focus is to provide adequate nutrition and vitamin supplementation.
- Malabsorption of long-chain fatty acids and fat-soluble vitamins is common, which may impact on growth, coagulation, and bone mineralisation.
- Consider early referral to a dietitian if they are not already involved.
- Establishing enteral feeds is a priority so that IVN can be discontinued.
Vitamins
Fat-soluble vitamins should be administered until some weeks after resolution of the jaundice. Usual doses are:
- Vitamin K: 2.5mg/day (orally)
- Vitadol C: 1ml daily (contains vitamin A 7500iU/ml)
- Vitamin D: 30-50 nanograms/kg once daily
- Micelle E: 0.5ml/day
Ursodeoxycholic acid
- The gastroenterology service may advise commencing ursodeoxycholic acid (URSO) at a dose of 20-30mg/kg/day in 2 divided doses.
  - URSO is a naturally-occurring bile acid that stimulates bile flow.
Other treatments
- Specific therapies may be directed at any identifiable underlying cause.

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