Overview
Definition:
Neonatal cholestasis is a clinical syndrome characterized by impaired bile flow from the liver to the duodenum, leading to a buildup of bilirubin and other bile constituents in the blood and tissues
It is defined by conjugated hyperbilirubinemia (serum direct bilirubin > 1 mg/dL if total bilirubin > 5 mg/dL, or > 20% of total bilirubin).
Epidemiology:
The incidence of neonatal cholestasis is approximately 1 in 2,500 live births, with a higher prevalence in premature infants
Biliary atresia is the most common indication for liver transplantation in children and accounts for about one-third of neonatal cholestasis cases.
Clinical Significance:
Early recognition and prompt management of neonatal cholestasis are crucial to prevent irreversible liver damage, liver failure, and death
Delay in diagnosis, particularly in conditions like biliary atresia, significantly impacts the success of surgical interventions and long-term outcomes.
Clinical Presentation
Symptoms:
Jaundice appearing after 2 weeks of life
Dark urine leading to staining of diapers
Pale or acholic stools
Poor weight gain and failure to thrive
Irritability or lethargy
Vomiting
Abdominal distension.
Signs:
Prolonged conjugated jaundice
Pale or white stools (acholic)
Dark urine
Hepatomegaly
Splenomegaly may be present in later stages
Signs of malabsorption such as steatorrhea.
Diagnostic Criteria:
Diagnosis is confirmed by laboratory evidence of conjugated hyperbilirubinemia (serum direct bilirubin > 1 mg/dL or > 20% of total bilirubin)
Clinical suspicion is raised by prolonged jaundice and pale stools
A universally accepted stool color chart aids in objective assessment.
Diagnostic Approach
History Taking:
Detailed birth history: gestational age, mode of delivery, any perinatal insults
Feeding history: type of milk, volume, suckling
Maternal history: infections during pregnancy, medications
Family history of liver or metabolic diseases
Onset and progression of jaundice
Urine color and stool color observations.
Physical Examination:
Thorough physical examination focusing on the abdomen
Palpate for hepatomegaly and splenomegaly
Assess for ascites or abdominal masses
Examine for dysmorphic features suggestive of genetic syndromes
Assess hydration status and overall well-being.
Investigations:
Initial investigations include complete blood count, liver function tests (ALT, AST, GGT, ALP, Total and Direct Bilirubin), coagulation profile (PT, INR), and urine analysis
Ultrasound abdomen is crucial to assess liver and gallbladder morphology, biliary tree patency
TORCH screening, metabolic workup (e.g., galactosemia, tyrosinemia, alpha-1 antitrypsin deficiency), and sometimes a liver biopsy may be required
Consider stool color assessment using a standardized chart.
Differential Diagnosis:
Includes infective causes (sepsis, viral hepatitis), metabolic disorders (galactosemia, tyrosinemia), genetic syndromes (Down syndrome, Alagille syndrome), endocrine disorders (hypothyroidism), parenteral nutrition-associated cholestasis, and structural abnormalities of the biliary system (biliary atresia, choledochal cyst)
Congenital intrahepatic shunts also need consideration.
Stool Color Assessment
Importance:
Objective assessment of stool color is vital for early detection of cholestasis
Normal infant stools vary in color from yellow to green or brown
Pale or acholic stools (white, clay-colored, or chalky) are a hallmark of cholestasis.
Stool Color Chart:
A standardized stool color chart (e.g., the Japanese or Hong Kong stool color chart) should be used
Parents are educated to compare their infant's stool color to the chart
A color from 1-3 (on most charts) indicates pale stools and requires immediate medical attention.
Parental Education:
Educating parents about normal stool color and the significance of pale stools is a critical public health measure
This empowers them to seek timely medical help, thus facilitating early referral and intervention.
Early Referral And Management
Timing Is Key:
Prompt referral to a pediatrician or a pediatric gastroenterologist is paramount
For suspected biliary atresia, referral within the first 6-8 weeks of life offers the best chance for successful portoenterostomy (Kasai procedure).
Initial Management:
Once diagnosed, management focuses on addressing the underlying cause
For biliary atresia, surgical intervention (Kasai procedure) is time-sensitive
For other causes, specific medical or surgical treatments are initiated.
Nutritional Support:
Infants with cholestasis often have malabsorption of fat-soluble vitamins (A, D, E, K) and require specialized nutritional support
Medium-chain triglyceride (MCT) based formulas and supplementation of fat-soluble vitamins are essential
Adequate caloric intake is crucial for growth.
Follow Up:
Close monitoring of liver function tests, growth parameters, and nutritional status is essential
Long-term follow-up may be required, and some infants may eventually need liver transplantation.
Key Points
Exam Focus:
Understand the definition of conjugated hyperbilirubinemia
Recognize the importance of pale stools and the use of stool color charts
Differentiate common causes of neonatal cholestasis, with emphasis on biliary atresia.
Clinical Pearls:
Always ask parents about stool color if a newborn has prolonged jaundice
Educate parents about the stool color chart at well-baby visits
Biliary atresia is a surgical emergency
timely referral dramatically improves prognosis
GGT is a sensitive marker for cholestasis.
Common Mistakes:
Misinterpreting prolonged jaundice as physiological
Delaying referral for pale stools
Inadequate nutritional management
Failing to perform a timely ultrasound or consider a liver biopsy when indicated.