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Jaundice - investigation of prolonged

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Prolonged jaundice = Jaundice persisting for more than 14 days.

Children with clinically apparent jaundice present after 14 days of life require:

  1. Clinical review including examination of stool colour
  2. Conjugated and total bilirubin measured

Any delay in follow-up for children with neonatal jaundice can lead to poor long term outcomes.

Primary investigation of prolonged jaundice will include: feeding history, examination of the baby, examination of stool colour (acholic stools are highly characteristic of cholestasis in infancy). Initial laboratory tests should include:

  • Bilirubin (total & direct (conjugated)). Bilirubin fractionation is the most important test in any infant who has more than two weeks of jaundice. 
  • Urine (for infection and reducing substances) 
  • FBC 
  • and possibly a G6PD screen. 

Unconjugated Hyperbilirubinaemia

  • Total conjugated bilirubin < 20 umol/L and 
  • Conjugated bilirubin <20% total bilirubin 

Children with unconjugated hyperbilirubinaemia require assessment for underlying diagnosis and therapy.

Important issues

  1. Clinical assessment - sepsis
  2. Does the child require phototherapy?
  3. Urine for Dipstick +- culture?
  4. Consider FBC and film/ G6PD/ Coombs for haemolysis
  5. Review maternal blood group for ABO/ rhesus incompatibility

Conjugated Hyperbilirubinaemia

  • Total conjugated bilirubin > 20 umol/L or
  • Conjugated bilirubin >20% total bilirubin

Any patient with conjugated hyperbilirubinaemia will be urgently reviewed by the Paediatric Gastroenterology/Hepatology service.

Important clinic issues

  1. Most children with conjugated hyperbilirubinaemia look well but may have important disease.
  2. Stool colour - pale stool and dark urine suggests Biliary Atresia
  3. All children with conjugated hyperbilirubinamia require additional Vitamin A,D,E,K

Causes of neonatal cholestasis

Disorders in bold are more common or have specific therapy available

Bile duct abnormalities Endocrine disorders  Inherited and metabolic disorders 
Biliary atresia
Choledochal cyst
Inspissated bile 

Caroli disease
Spontaneous perforation of bile ducts
Neonatal sclerosing cholangitis 
 α1-Antitrypsin deficiency
Alagille's syndrome
Cystic fibrosis
Neonatal haemochromatosis
Bile acid synthesis disorders
Progressive familial intrahepatic cholestasis
Gauchers disease

Neimann-Pick type C
Wolmans disease
Peroxisomal disorders
Congenital disorders of glycosylation 
Dubin-Johnson syndrome
Rotor syndrome
Aagenaes syndrome
Citrin deficiency
Fatty acid oxidation disorders
Mitochondrial disorders
Mevalonic acidemia
Hereditary Fructose Intolerance 
 Infections  Toxic
Urinary tract infection
TORCH infections
(toxoplasmosis, rubella, CMV, herpes viruses)
Human Herpes virus-6, Varicella-zoster
HIV, Hepatitis B
Echo, Adeno, Coxsackie-virus
Parvovirus, EBV 
Parenteral nutrition

Chloral hydrate
Foetal alcohol syndrome
Vascular Disorders  Chromosomal Disorders  Miscellaneous
Perinatal asphyxia
Budd-Chiari syndrome
Multiple haemangiomata

Congestive heart failure 
Trisomy 21, 13, 18
Turner syndrome 
Haemophagocytic lymphohisticytosis

ARC syndrome (Arthrogryposis, renal tubular dysfunction and cholestasis) 

Adapted from McKiernan 2002

Flow Chart for Investigation of Neonatal Cholestasis

flow chart


  • Acholic stools are highly characteristic of cholestasis in infancy. 
  • Bilirubin fractionation is the most important test in any infant who has more than two weeks of jaundice. 
  • Liver enzymes are of limited help to differentiate between hepatocellular and cholestatic liver injury. 
  • Synthetic liver function is best assessed by albumin level and clotting function. Untreated hypothrombinaemia may lead to spontaneous bleeding and intracranial haemorrhage. 

First line investigations conjugated Hyperbilirubinaemia

  Date Result
FBC and blood film    
Total and conjugated bilirubin     
Blood group and coombs     
T4 and TSH     
α1 Antitrypsin phenotype (not level)     
Cholesterol / triglycerides     
INR/ APTT/ Fibrinogen     
Blood sugar q4 hours first 24hours     
Urine CMV     
Liver Ultrasound     
Guthrie card result review     
Maternal toxoplasma serology     
Maternal Syphilis status     
Maternal Rubella status     
Maternal Hepatitis B status     

Download printable pdf of First Line Investigations

Second line investigations conjugated Hyperbilirubinaemia

  Date Result
Urine organic acids    
Urine amino acids     
Serum amino acids     
Plasma ammonia     
Plasma Lactate     
Herpes simplex PCR
(if clinically suspected) 
Hepatitis A Virus IgM     
Adenovirus serology     
Epstein Barr Virus serology     
Stool Enterovirus     
Parvovirus PCR    
HHV6 PCR     
Spine x-rays     
Ophthalmology review      
Urine calcium/Phosphate creatinine ratio     
Sweat test     

Download printable pdf of Second Line Investigations

Third line investigations conjugated Hyperbilirubinaemia

  Date Result
Metabolic review-    
Acyl-Carnitine profile 
(repeat if normal & suspect diagnosis) 
Urine bile acids     
Very long chain fatty acids     
White Blood Cell enzymes if indicated    
Muscle/ skin biopsy     
Short synacthen     
Transferrin Isoelectric Focusing     
CSF Lactate     
Bone Marrow aspirate     

Download printable pdf of Third Line Investigations


  • All infants with conjugated hyperbilirubinaemia are started on Vit A, D, E, K 
  • Early consideration for starting MCT based formula (peptijunior) 

Fat Soluble Vitamin Supplementation

All infants undergoing investigation of conjugated hyperbilirubinaemia should commence fat-soluble vitamin supplementation as soon as possible. 

Vitamin A
Available preparation: Vitadol C® = 2000 micrograms vitamin A per gram = 1 ml =7500 IU
Starting dose is 1ml once daily  
NB: Vitadol C® is only partially subsidised in the community; families should be informed they will be required to pay a part charge for this medicine.  
 Vitamin D
Starting dose = 30-50 nanograms/kg once a day rounded to nearest 100 nanograms  
Available preparation = Alfacalcidol (One-Alpha drops®) = 100 nanograms of 1-alpha-OH vitamin D3 per drop. 
NB: This preparation should be prescribed in drops. 
Vitamin E
Starting dose = 50 mg (68 IU) once a day.  
Available preparation = d-alpha-tocopheryl acetate (Micelle E®) = 156 IU/ml 
Suggested dose is therefore 0.5 ml once daily. 
NB: SPECIAL AUTHORITY is required for vitamin E administration and will be completed by the child's paediatrician prior to the child leaving hospital.  
 Vitamin K
Suggested dose = 2.5 mg once a day 
This is ¼ of an adult 10 mg Konakion tablet which can be crushed and mixed with water  


Mckiernan P. Neonatal cholestasis. Seminars in Neonatology. 2002 7 (2): 153 - 165 

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Document Control

  • Date last published: 01 April 2010
  • Document type: Clinical Guideline
  • Services responsible: Paediatric Gastroenterology/Hepatology
  • Author(s): Simon Chin, Stephen Mouat
  • Editor: Greg Williams
  • Review frequency: 2 years

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