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Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2001 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347.
Presentation
A 10-week-old female infant who presents to her primary
care physician for her 2-month health supervision visit
has jaundice (Fig 1). She is the product of a term preg-
nancy, delivered via elective repeat cesarean section. Her
birthweight was 3,300 g (50th percentile). The mother
denies having any infections or taking medications dur-
ing her pregnancy. The infant has appeared yellow since
birth. She was breastfed for the first 2 months, then
switched to formula feedings when her mother believed
she had an inadequate milk supply. The infant has had no
feeding difficulties; she is taking 4-oz feedings five to six
times per day.
For the past week, the infant has been colicky and
fussy, but she has had no fever, vomiting, or diarrhea.
Her appetite and urine output have been unchanged.
There is no history of change in stool color; the stools
always have been light yellow (Fig 2). Nothing remark-
able is noted on a review of systems.
The infant lifts her head well when placed on her
Figure 1. A 10-week-old female infant who has jaundice. abdomen, follows a moving object to midline, and re-
sponds to a friendly face with a social smile.
The patient lives with her mother and father and two
siblings. All are healthy. She always has consumed treated
city water, and she has not traveled recently.
There is a family history of ulcer disease, and the father
had a hiatal hernia. There is no family history of blood
transfusions, hepatitis, or emphysema.
Physical examination reveals an active, jaundiced fe-
male infant whose abdomen is distended. Her weight is
4.54 kg (10th percentile), length is 55 cm (5th percen-
tile), and head circumference is 37.5 cm (5th percentile).
Skin examination reveals an increased venous pattern
over the abdomen (Fig 3); there are no rashes. Her head
is normocephalic, with an open, soft anterior fontanelle.
Examination of her eyes reveals yellow sclerae (Fig 4).
Nose, throat, and neck findings are normal. Pulmonary
examination reveals clear breath sounds bilaterally. There
is an early II/VI systolic murmur along the left sternal
Figure 2. Light yellow-colored stool. border that does not radiate to the back. Abdominal
examination is remarkable for an 8 cm liver span and a
*Doernbecher Children’s Hospital, Oregon Health and Science University, palpable liver edge 6 cm below the costal margin. There
Portland, OR. is no abdominal fluid wave. There is no edema in the
Figure 3. Increased venous pattern over distended abdomen. Figure 4. Yellow sclera.
of hyperbilirubinemia. Developmental delay may indi- have similar, overlapping clinical features. Determining
cate an inborn error of metabolism. Pale skin and a the type of cholestasis present is important because early
cardiac flow murmur may indicate hemolytic anemia. An surgical correction of extrahepatic cholestasis may avoid
enlarged liver (liver span ⬎5 cm) may suggest liver irreversible liver damage.
disease due to inflammation, storage disease, infiltration, Extrahepatic biliary atresia describes obstruction of
intrahepatic or suprahepatic obstruction to hepatic vein the biliary tree due to congenitally absent openings of
outflow, or intrahepatic or extrahepatic obstruction to the major bile ducts. Biliary atresia results from an
biliary flow. Caput medusae, or dilated tortuous veins inflammatory process that leads to obliteration of ex-
radiating from the umbilicus, may indicate portal hyper- trahepatic ducts. Proliferation of small bile ducts is a
tension with obstruction of venous blood flow in the common finding. Uncorrected biliary atresia eventu-
liver. Acholic or light-colored stools indicate biliary tract ally leads to periportal fibrosis and cirrhosis of the liver.
obstruction. Polysplenia, trisomy 18, and absence of the gall blad-
High serum unconjugated bilirubin levels may sug- der also are associated with biliary atresia. On dis-
gest increased bilirubin production (ie, increased red covery of conjugated hyperbilirubinemia, it is impor-
blood cell hemolysis), decreased delivery of unconju- tant to diagnose the presence or absence of biliary
gated bilirubin to the liver, decreased bilirubin uptake atresia before the infant is 2 months of age because the
across hepatocyte membranes, increased enterohepatic prognosis significantly worsens for affected infants
recirculation, or decreased bilirubin conjugation. undergoing a corrective Kasai portoenterostomy after
Conjugated bilirubin levels greater than 1.5 mg/dL 2 months of age. The 5-year survival rate for surgery
(25.7 mcmol/L) or greater than 20% of the total biliru- performed before 60 days of age is 70%, between
bin level indicate decreased bilirubin excretion due to 71 and 90 days of age is 34%, and after 90 days of age
either liver disease or biliary obstruction. is 10%.
Neonatal cholestasis represents prolonged elevation
of serum levels of conjugated bilirubin beyond the first Diagnosis of Biliary Atresia
14 days of life. Neonatal cholestasis may be due to The appropriate imaging of patients in whom biliary
infectious, toxic, metabolic, or genetic causes or to func- atresia is suspected is an area of continuing debate. The
tional impairment of bile secretion or mechanical ob- gold standard for diagnosing biliary atresia has been open
struction of bile excretion. Infectious causes include viral laparotomy with intraoperative cholangiography. Con-
hepatitis (CMV; hepatitis A, B, or C; rubella) toxoplas- cern for possible unnecessary surgery has suggested other
mosis, syphilis, tuberculosis, and listeriosis. Among toxic diagnostic methods.
causes are sepsis, drugs, and total parenteral nutrition. The traditional initial imaging study for infants who
Metabolic diseases include disorders of amino acid have persistent jaundice is abdominal ultrasonography
metabolism (tyrosinemia), disorders of lipid metabo- because of its easy accessibility and ability to detect a
lism (Niemann-Pick disease, Gaucher disease), disor- choledochal cyst and other intra-abdominal pathology.
ders of carbohydrate metabolism (galactosemia, fruc- However, abdominal ultrasonography cannot demon-
tosemia), and other metabolic defects, such as alpha-1 strate hepatitis, and the presence or absence of the gall
antitrypsin deficiency, hypothyroidism, cystic fibrosis, bladder does not prove the absence or presence of biliary
and Zellweger syndrome. Chromosomal defects in- atresia. Ultrasonography is useful for detecting polysple-
clude Down syndrome and trisomy E. Intrahepatic nia or asplenia, conditions that are associated with biliary
duct disease and extrahepatic duct failure lead to ob- atresia. Published studies suggest that the presence of a
struction of bile flow. Intrahepatic duct diseases in- triangular or tubular echodensity on hepatic ultrasonog-
clude “idiopathic” neonatal hepatitis, Alagille syn- raphy may herald biliary atresia.
drome, intrahepatic biliary hypoplasia or paucity of Hepatobiliary scintigraphy is used commonly to visu-
intrahepatic bile ducts, and Byler disease. The two alize the patency of extrahepatic bile ducts. Injected
most common causes of intrahepatic cholestasis are radioactive-labeled imidodiacetic acid analogs are selec-
“idiopathic” neonatal hepatitis and alpha-1 antitrypsin tively taken up by the liver and excreted into bile. Patients
deficiency. Among the causes of extrahepatic duct are pretreated with phenobarbital to increase biliary ex-
failure/obstruction are biliary atresia, sclerosing cretion. The absence of tracer excreted into the small
cholangitis, bile duct stenosis, choledochal cyst, and intestine within 24 hours indicates biliary atresia. The
bile/mucous plug (“inspissated bile”). sensitivity of hepatobiliary scintigraphy is 100%, but the
Neonatal intrahepatic and extrahepatic cholestasis specificity is only 46% to 88% because patients who have
a patent biliary system may not excrete detectable dye atresia because early surgical correction, preferably be-
into the bowel within the 24-hour test period. Some fore the infant is 2 months old, significantly reduces
studies suggest that the presence of a functioning gall- morbidity and mortality.
bladder on scintigraphic examination excludes the possi-
bility of biliary atresia, even if there is no tracer in the EDITOR’S NOTE. Because we do not routinely see in-
small intestine. fants for health supervision visits between 2 weeks and 2
A promising new option for imaging infants in whom months of age, we may not see the infant who has biliary
biliary atresia is suspected is magnetic resonance (MR) atresia until it is too late for a good prognosis. We should
cholangiography. MR cholangiography can provide clear stress to parents the importance of seeking medical at-
images of intrahepatic ducts and the common bile duct. tention if newborn jaundice persists beyond the first
The delineation of an incomplete extrahepatic bile duct 2 weeks of life.
and atrophic gall bladder on MR cholangiography sug-
gests biliary atresia. MR cholangiography also may dem-
onstrate periportal thickening. Unfortunately, MR im- Suggested Reading
Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbiliru-
ages take time to collect and may be difficult to obtain in
binemia. N Engl J Med. 2001;344:581–590
an infant. Gartner LM, Lee K. Jaundice in the breastfed infant. Clin Perinatol.
Liver biopsy may help in the diagnosis of biliary 1999;26:431– 445
atresia. The histologic findings of intrahepatic biliary Hay SA, Soliman HE, Sherif HM, Abdelrahman AH, Kabesh AA,
duct proliferation in the absence of extrahepatic biliary Hamza AF. Neonatal jaundice: the role of laparoscopy. J Pediatr
Surg. 2000;35:1706 –1709
ducts are highly indicative but not 100% specific for
Jaw TS, Kuo YT, Liu GC, Chen SH, Wang CK. MR cholangiogra-
extrahepatic biliary atresia. phy in the evaluation of neonatal cholestasis. Radiol. 1999;212:
249 –256
Summary Lee CH, Wang PW, Lee TT, et al. The significance of functioning
The infant’s persistent jaundice, light-colored stools, gallbladder visualization on hepatobiliary scintigraphy in infants
with persistent jaundice. J Nucl Med. 2000;41:1209 –1213
hepatomegaly, increased abdominal venous pattern, and
Tan Kendrick AP, Phua KB, Subramaniam R, Goh ASW, Ooi BC,
poor weight gain suggested obstructive liver disease. Tan CE. Making the diagnosis of biliary atresia using the trian-
Although potential causes were many, investigation fo- gular chord sign and gallbladder length. Pediatr Radiol. 2000;
cused on determining the presence or absence of biliary 30:69 –73