Article Figures & Data
Figures
- Figure 1
Algorithm for investigation of the neonate with cholestatic jaundice
Tables
DISEASE DIAGNOSTIC APPROACH 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 analysisEndocrine 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 screenInfectious 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 -
Adapted from Walsh et al.5
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CSF—cerebrospinal fluid, CT—computed tomography, DNA—deoxyribonucleic acid, EM—electron microscopy, GGT—γ-glutamyltransferase, HIV—human immunodeficiency virus, IgM—immunoglobulin M, MRI—magnetic resonance imaging, PCR—polymerase chain reaction, T4—thyroxine, TPHA—treponema pallidum hemagglutination, TSH—thyroid stimulating hormone, VDRL—venereal disease research laboratory.
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- Table 2
Summary of recommendations and evidence base for strategies to improve outcome of patients with neonatal cholestasis
RECOMMENDATION STRATEGY EVIDENCE Test at 2 weeks (fractionated bilirubin levels at 2–3 weeks of age) Early identification of neonatal cholestasis Level III: Guidelines from professional organizations (NASPGHAN, CPS, AAP) Application of diagnostic algorithm and early referral to pediatric gastroenterologist Accurate diagnosis of cause of cholestasis enables early initiation of treatment Level III: Case series, guidelines from professional organizations (NASPGHAN, CPS, AAP) Immediate intervention to address the underlying condition if cholestasis is identified Early intervention improves outcomes of biliary atresia, congenital hypothyroidism, galactosemia, tyrosinemia, congenital CMV infection Level II and III: Retrospective cohort studies, guidelines from professional organizations (NASPGHAN) Further investigation of efficacy and feasibility of screening for neonatal cholestasis Early identification of neonatal cholestasis results in early intervention Level II: Prospective cohort studies -
AAP—American Academy of Pediatrics, CMV—cytomegalovirus, CPS—Canadian Paediatric Society, NASPGHAN—North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
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Early diagnosis of neonatal cholestatic jaundice
