Approach to a case of Neonatal Cholestasis

Ira Shah (Co-Incharge, Consultant Pediatrician, Pediatric Liver Clinic)

Gunjan Narkhede (Resident in Pediatric Liver Clinic)
Pediatric Hepatobiliary Clinic, B.J.Wadia Hospital For Children, Mumbai.
Email: irashah@pediatriconcall.com
Introduction:
Neonatal cholestasis accounts for almost 30% of pediatric hepatobiliary diseases. It requires prompt
evaluation and management as some of the causes are fatal in early life if untreated whereas others
cause substantial morbidity by causing chronic liver disease. It is defined as prolonged elevation of
conjugated bilirubin beyond 14 days of life (i.e. the conjugated fraction >20% of total bilirubin.).
Conjugated Jaundice that appears within 3 months of life is called as neonatal cholestasis. History of
jaundice with high coloured urine (often noted as yellow staining of diapers), clay coloured /light stools
with or without hepatomegaly is suggestive of cholestasis. Thus any jaundice that persists beyond 2
weeks of life, progresses after this time or does not regress by this time get a serum bilirubin done
with a conjugated fraction.

Etiology:
The cause of neonatal cholestasis can be genetic, metabolic, infectious or undefined causing mechanical obstruction of bile flow e.g. Biliary atresia or bile acid secretion or functional impairment of
hepatic excretory e.g. Congenital infections.
The common causes of Neonatal cholestasis include:
1.
2.
3.
4.

Obstructive causes: Biliary Atresia, Choledochal cysts

Infections TORCH infections, Reo virus and Group C rotavirus infections
Metabolic Tyrosinemia, Fructosemia, galactosemia, Hypothyroidism, Panhypopituitarism
Genetic Alagille syndrome, Progressive familial intrahepatic cholestasis (PFIC), bile acid
defects, Cystic fibrosis
5. Storage Niemann Pick Disease C.
6. Idiopathic

Why is neonatal cholestasis an emergency?

Neonatal cholestasis is an emergency as timely intervention can prevent liver cirrhosis and death. Biliary
atresia is an emergency as prognosis depends on age of presentation, age of operation, expertise of the
surgeon and the bile duct size at the time of porta. At our center, incidence of Biliary Atresia amongst
neonatal cholestasis syndrome is 36.4%. We see about 45-50 new patients of neonatal cholestasis
syndrome per year in our Pediatric Liver Clinic. The mean age of presentation of patients with biliary
atresia is 89 days + 55.8days. (almost 3 months). Those with bile duct sizes >200microns had better
prognosis than those with sizes 100-200 microns (Odds ratio=1.8) and <100microns (Odds ratio=3).
Operation before 3 months had a better prognosis as compared to operation after 3 months of age.
(Odds ratio = 2). (1)
Other conditions such as Galactosemia and metabolic disorders are also urgent as timely intervention
can prevent irreversible liver damage. At our center, common causes of neonatal cholestasis have
included Biliary atresia, CMV infection, galactosemia, alagille syndrome, PFIC and idiopathic causes. Thus
urgent diagnosis becomes essential in these conditions.

Investigations
Lets take a short overview of the investigations helpful in diagnosis. Investigations of preference depend
on the clinical presentation of the patient. Usual investigations done are :
Test

Implication

Serum bilirubin fractionation

Confirms cholestasis

Liver function tests including GGTP High GGTP with high alkaline phosphatase suggests
obstruction
and alkaline phosphatase
Low GGTP with high alkaline phosphatase suggests PFIC
Normal GGTP and normal alkaline phosphatase may suggest
non-obstructive causes
Indicates bile flow into intestine. Clay coloured stools
Assessment of stool colour
suggests obstruction
Urine/serum bile acid measurement

Confirms cholestasis

USG

Suggests/excludes choledochal cyst, may show triangular

cord sign suggestive of biliary atresia.

HIDA scan

Confirms flow of bile into the intestine though absence of

same does not confirm atresia- can occur in severe hepatitis.
Depends on the liver function and low uptake of the tracer by
liver due to poor function can lead to poor excretion and
false sense of obstructions

Specific investigations:
Thyroxine and TSH

Hypothyroidism, panhypopituitarism

Sweat chloride

Cystic fibrosis

Urine/plasma amino
reducing substance

acids,urine Metabolic liver disease

TORCH titres

For congenital infections

2 D Echo

For Alagille syndrome and congenital infections

Hearing
and
examination

Ophthalmology For hearing loss and chorioretinitis respectively for congenital

infections

Liver biopsy

Intra operative cholangiogram

Most valuableBiliary atresia- bile ductular proliferation,portal/perilobular

fibrosis, BUT BAISC ARCHITECTURE INTACT;
Neonatal hepatitis- severediffuse hepatocellular
disease,DISTORTION OF LOBULAR ARCHITECTURE,marked
infiltration with inflammatory cells,focal hepatocellular
necrosis.
A low threshold should be kept for IOC in patients with clay
stools without waiting for HIDA as HIDA is very often

inconclusive.

How to differentiate biliary atresia from non-obstructive causes?

This simple table will help to differentiate between obstructive and non-obstructive causes. However it
may not be the same all the time and thus an individual based approach will be essential.
Obstructive causes

Non-obstructive causes

Full term

Preterm/Full term

Normal birth weight

AGA/LBW

No ANC/PNC complications

ANC- fever, rash, lymphnodes

CLAY COLOURED STOOLS

Yellow stools

Growing well

Failure to thrive

Usually isolated hepatomegaly

Hepatosplenomegaly

Approach to Neonatal Cholestasis:

Consensus Report on Neonatal Cholestasis Syndrome by Pediatric Gastroenterology Subspecialty
Chapter of Indian Academy of Pediatrics (Indian Pediatrics 2000;37: 845-851) has suggested the
following algorithm for approach to Neonatal cholestasis. (2)

* Babies with NCS due to infections of Herpes, Toxoplasmosis and rarely CMV may be sick, look for their
extra hepatic manifestations. Stop milk feeds till galactosemia is ruled out. In febrile babies, look for
malarial parasite, sepsis and UTI.
** This is to look for galactose in urine while on milk feeds. If reducing substances are positive, check
urine samples with glucose stick. If negative, most likely reducing substances in urine are due to
galactose. Treat as galactosemia. GALI-PUT should be done to confirm the diagnosis.
However there may be instances where liver biopsy may be inconclusive due to improper reporting or
due to evolving disease and in such instances either serial liver biopsies or urgent cholangiogram may be
needed to find out the cause. (3). Thus based on our clinical experience of over 200 patients, where the
only clinical marker for biliary atresia was clay stools (4) we have modified our approach to neonatal
cholestasis as follows:

Approach to Neonatal Cholestasis (Wadia Protocol)

* Liver biopsy and Intraoperative cholangiogram are done depending on the reports of the tests in
patients with yellow stools.

Conclusion: Neonatal cholestasis syndrome is a hepatobiliary emergency and timely referral is essential
to avoid irreversible liver damage.
References:
1. Sanghai Saket, Shah Ira, Bhatnagar Sushmita. Incidence and Prognostic factors associated with
Biliary Atresia in Western India. Annals Hepatol. 2009; 8: 120-122.
2. Pediatric Gastroenterology Subspecialty Chapter of Indian Academy of Pediatrics. Consensus
Report on Neonatal Cholestasis Syndrome. Indian Pediatrics 2000;37: 845-851
3. Sweta Mohanty, Ira Shah, Sushmita Bhatnagar. Evolving Biliary Atresia With Cytomegalovirus.
Accepted For Publication In Indian Pediatrics. 2010
4. Ira Shah, Sushmita Bhatnagar. Clinical and Laboratory Markers predictive of Biliary Atresia.
Mahapedicon 2008, Mahabaleshwar, 14-15th November 2008.