Obstructive cholestasis |
Structural |
• Biliary atresia | Ultrasound (presence, size, and appearance of gallbladder; evidence of cirrhosis and portal hypertension, polysplenia, or asplenia) Hepatobiliary s cintigraphy (delayed or absent excretion) Liver biopsy Intraoperative cholangiogram |
• Choledochal cyst, or other congenital bile duct anomaly | Ultrasound Cholangiogram (percutaneous and scintigraphic, to show communication with biliary tree and to rule out associated atresia) |
• Caroli disease and congenital hepatic fibrosis | Ultrasound (liver and kidneys) Liver biopsy (rarely required) |
• Gallstones or biliary sludge | Ultrasound |
• Neonatal sclerosing cholangitis | Cholangiogram (endoscopic retrograde, percutaneous or intraoperative) |
Duct paucity syndrome |
• Alagille syndrome | Physical examination for typical facial features, which might not be obvious during newborn period (broad forehead, pointed chin, elongated nose with bulbous tip) Chest x-ray scan (butterfly vertebrae) Ophthalmologic examination (posterior embryotoxon) Echocardiogram (peripheral pulmonic stenosis) Liver biopsy (paucity of small ducts) Genetic analysis (mutations in JAG1 gene) |
Hepatocellular cholestasis |
• Idiopathic neonatal hepatitis | Diagnosed by exclusion of other causes of neonatal liver disease Liver biopsy (often not required) |
Genetic and metabolic disorders |
• α 1-Antitrypsin deficiency | ∝1-Antitrypsin levels (reduced) Protein or genetic analysis (homozygous Pi type ZZ, SZ, or other rare deficiency variant) |
• Galactosemia | Results of newborn screening Non–glucose reducing substances (positive) Galactose-1-phosphate uridyl transferase in red blood cells (low activity) Blood cultures (association with Escherichia coli sepsis) |
• Tyrosinemia | Results of newborn screening Serum tyrosine and methionine levels (high) Serum α-fetoprotein levels (high) Succinylacetone detection in urine |
• Hereditary fructosemia | Fructose-1-phosphate aldolase B activity low or absent in liver tissue Liver biopsy with EM Genetic analysis |
• Neonatal hemochromatosis | Ferritin (high, usually > 1000 μg/L) Total iron binding capacity (low) Liver biopsy with iron stain, or buccal mucosal biopsy MRI (abdomen, for typical pattern of iron deposition) |
• Cystic fibrosis | Results of newborn screening Sweat chloride test Genetic analysis |
• Inborn errors of bile acid synthesis | Urinary bile acid analysis |
• Progressive familial intrahepatic cholestasis | GGT (low to normal in types 1 and 2, high in type 3) Liver biopsy Genetic analysis |
Endocrine disorders |
• Hypothyroidism | Results of newborn screening TSH (high), free T4 (usually low) |
• Panhypopituitarism | Glucose (hypoglycemia common) Cortisol (low) TSH (low), T4 (low) |
Toxic or secondary disorders |
• Parenteral nutrition–associated cholestasis | Correlation with clinical history Exclusion of other causes of cholestasis |
• Drugs (acetaminophen, anticonvulsants, etc) | Correlation with clinical history Urine and serum toxicology screen |
Infectious disorders |
• Toxoplasmosis | IgM-specific antibodies (detectable 2 weeks after infection, peak approximately 4 weeks after infection) Isolation of organism from blood, CSF, or liver Ophthalmologic examination (chorioretinitis) CT (head, intracranial calcifications) |
• Rubella | IgM-specific antibodies (detectable 2 weeks after infection) Viral isolation (CSF, liver, urine, pharyngeal secretions) Ophthalmologic examination (cataracts) |
• Cytomegalovirus | IgM-specific antibodies Viral isolation from blood, urine, CSF Ophthalmologic examination (for chorioretinitis) CT (head, intracranial calcifications) |
• Herpes simplex virus | EM or viral culture of vesicle scrapings PCR of blood and CSF |
• Human immunodeficiency virus | HIV DNA PCR Immunoglobulin levels CD4 count |
• Syphilis | VDRL test Syphilis indirect hemagglutination test (TPHA) Fluorescent treponemal antibody levels Long-bone x-ray scans (osteochondritis, periostitis) |
• Urinary tract infection | Urine culture, full septic workup where indicated |
• Sepsis | Blood culture, full septic workup where indicated |