Starship Childrens Health Clinical Guideline

Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.

JAUNDICE -
INVESTIGATION OF PROLONGED NEONATAL JAUNDICE

Definition First Line Investigations

Unconjugated hyperbilirubinaemia Second Line Investigations
Conjugated Hyperbilirubinaemia Third Line Investigations
Causes of Neonatal Cholestatsis Interventions
Flow Chart for Investigation of Neonatal Fat soluble vitamins supplementation
Cholestasis References

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

Unconjugated
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
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.

Author: Simon Chin, Stephen Mouat Service: Paed Gastroenterology

Editor: Dr Raewyn Gavin Date Reviewed April 2010
Jaundice Investigation of prolonged neonatal jaundice Page: 1 of 7
 Starship Childrens Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.

JAUNDICE -
INVESTIGATION OF PROLONGED NEONATAL JAUNDICE
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

cholestasis
Disorders in bold are more common or have specific therapy available

Bile duct abnormalities Endocrine disorders Inherited and metabolic

disorders
1-Antitrypsin deficiency
Biliary atresia Hypopituitarism Alagilles syndrome
Choledochal cyst Hypothyroidism Galactosaemia
Inspissated bile Hypoadrenalism Cystic fibrosis
Neonatal
Caroli disease haemochromatosis
Gall-stones Bile acid synthesis
Spontaneous perforation of disorders
bile ducts Tyrosinaemia
Neonatal sclerosing Progressive familial
cholangitis intrahepatic cholestasis
Gauchers disease

NeimannPick type C
Wolmans disease
Peroxisomal disorders
Congenital disorders of
glycosylation
Infections Toxic DubinJohnson syndrome
Septicaemia Rotor syndrome
Urinary tract infection Parenteral nutrition Aagenaes syndrome
TORCH infections Citrin deficiency
(toxoplasmosis, rubella, Chloral hydrate Fatty acid oxidation disorders
CMV, herpes viruses) Foetal alcohol syndrome Mitochondrial disorders
Human Herpes virus-6, Transaldolase
Varicella-zoster GSD IV
HIV, Hepatitis B Mevalonic acidemia
Echo, Adeno, Coxsackie- Hereditary Fructose
virus Intolerance
Parvovirus, EBV

Vascular disorders Chromosomal disorders Miscellaneous

Perinatal asphyxia Trisomy 21, 13, 18 Haemophagocytic

BuddChiari syndrome Turner syndrome lymphohisticytosis
Multiple haemangiomata
ARC syndrome
Congestive heart failure (Arthrogryposis, renal tubular
dysfunction and cholestasis)

Adapted from McKiernan 2002

Author: Simon Chin, Stephen Mouat Service: Paed Gastroenterology

Editor: Dr Raewyn Gavin Date Reviewed April 2010
Jaundice Investigation of prolonged neonatal jaundice Page: 2 of 7
 Starship Childrens Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.

JAUNDICE -
INVESTIGATION OF PROLONGED NEONATAL JAUNDICE

Flow Chart for Investigation of Neonatal Cholestasis

Clinical & stool colour review

First line investigations

Liver Biopsy

2nd and 3rd line No Yes

Diagnosis? Specific therapy?
investigations

Yes

Biliary Atresia

Kasai

Note:

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.

Author: Simon Chin, Stephen Mouat Service: Paed Gastroenterology

Editor: Dr Raewyn Gavin Date Reviewed April 2010
Jaundice Investigation of prolonged neonatal jaundice Page: 3 of 7
 Starship Childrens Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.

JAUNDICE -
INVESTIGATION OF PROLONGED NEONATAL JAUNDICE

First line investigations conjugated Hyperbilirubinaemia

Date Result
FBC and blood film

Total and conjugated bilirubin

AST, ALT, GGT, ALP

Blood group and coombs

T4 and TSH

1 Antitrypsin phenotype (not

level)

Ferritin

Cholesterol / triglycerides

INR/ APTT/ Fibrinogen

Blood sugar q4 hours first

24hours

Cortisol

Urine CMV

Liver Ultrasound

Guthrie card result review

Maternal toxoplasma serology

Maternal Syphilis status

Maternal Rubella status

Maternal Hepatitis B status

Author: Simon Chin, Stephen Mouat Service: Paed Gastroenterology

Editor: Dr Raewyn Gavin Date Reviewed April 2010
Jaundice Investigation of prolonged neonatal jaundice Page: 4 of 7
 Starship Childrens Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.

JAUNDICE -
INVESTIGATION OF PROLONGED NEONATAL JAUNDICE

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

HIV

Spine x-rays

Ophthalmology review

Urine calcium/Phosphate
creatinine ratio

Sweat test

Author: Simon Chin, Stephen Mouat Service: Paed Gastroenterology

Editor: Dr Raewyn Gavin Date Reviewed April 2010
Jaundice Investigation of prolonged neonatal jaundice Page: 5 of 7
 Starship Childrens Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.

JAUNDICE -
INVESTIGATION OF PROLONGED NEONATAL JAUNDICE

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

Karyotype

Muscle/ skin biopsy

Short synacthen

Transferrin Isoelectric Focusing

CSF Lactate

Bone Marrow aspirate

Author: Simon Chin, Stephen Mouat Service: Paed Gastroenterology

Editor: Dr Raewyn Gavin Date Reviewed April 2010
Jaundice Investigation of prolonged neonatal jaundice Page: 6 of 7
 Starship Childrens Health Clinical Guideline
Note: The electronic version of this guideline is the version currently in use. Any printed version can
not be assumed to be current. Please remember to read our disclaimer.

JAUNDICE -
INVESTIGATION OF PROLONGED NEONATAL JAUNDICE

Interventions
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 = 3050 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 childs paediatrician prior to the child leaving hospital.

Vitamin K
Suggested dose = 2.5 mg once a day
This is of an adult 10 mg Konakion tablet which can be crushed and mixed with water

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

Author: Simon Chin, Stephen Mouat Service: Paed Gastroenterology

Editor: Dr Raewyn Gavin Date Reviewed April 2010
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