Epidemiology of Biliary Atresia: A Population-based Study

Paula W. Yoon, Joseph S. Bresee, Richard S. Olney, Levy M. James and Muin J.
Khoury
Pediatrics 1997;99;376
DOI: 10.1542/peds.99.3.376

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/99/3/376.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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Epidemiology of Biliary Atresia: A Population-based Study

Paula W. Yoon, ScD, MPH*; Joseph S. Bresee, MD;
Richard S. Olney, MD, MPH*; Levy M. James, MS*; and Muin J. Khoury, MD, PhD*
ABSTRACT. Objective. Biliary atresia is the leading
cause of extrahepatic obstructive jaundice in the newborn and is the single most frequent indication for liver
transplantation in children. The cause of biliary atresia is
unknown, although several mechanisms have been
postulated to explain the inflammatory process that
obliterates the bile ducts. Most interest has been directed
toward viral infections. Information about the epidemiologic characteristics of biliary atresia in well-defined
populations is lacking but is essential for developing and
addressing hypotheses of causation for the disease.
Methods. Infants with biliary atresia were identified
in metropolitan Atlanta from 1968 through 1993 by a
population-based birth defects surveillance system that
ascertains infants with serious birth defects in the first
year of life using active case ascertainment. Birth prevalence rates were analyzed for spatial and temporal clustering and effects attributable to county of residence, sex,
race, maternal age, parity, and birth weight. Logistic regression was used to study the independent effects of the
risk factors and to look for interactions.
Results. Fifty-seven infants with biliary atresia were
identified, for a rate of 0.73 per 10 000 live births. There
was significant seasonal clustering of the disease, with
rates three times higher from December through March
compared with rates from April through July. Rates were
significantly higher among nonwhite infants compared
with white infants (0.96 vs 0.44 per 10 000 live births) and
infants born at term with low birth weights (<2500 g)
compared with infants born at term with normal birth
weights ( 2500 g) (2.62 vs 0.75 per 10 000 live births).
Conclusions. Our study is the first in the United
States to describe the epidemiologic characteristics of
biliary atresia using a population-based approach. The
demonstration of significant seasonal clustering provides support for theories that biliary atresia may be
caused by environmental exposure (consistent with a
viral cause) during the perinatal period. Pediatrics 1997;
99:376 382; biliary atresia, bile ducts, space-time clustering, race.
ABBREVIATIONS. HLA, human leukocyte antigen; MACDP,
Metropolitan Atlanta Congenital Defects Program; NBW, normal
birth weight; LBW, low birth weight; RR, relative risk; CI, confidence interval.

From the Divisions of *Birth Defects and Developmental Disabilities and

Viral and Rickettsial Disease, National Center for Environmental Health,
Centers for Disease Control and Prevention, Atlanta, Georgia.
Received for publication Feb 2, 1996; accepted May 20, 1996.
Reprint requests to (P.W.Y.) Centers for Disease Control and Prevention,
National Center for Environmental Health/Birth Defects and Developmental Disabilities, MS F-45, 4770 Buford Hwy, NE, Atlanta, GA 303413724.
PEDIATRICS (ISSN 0031 4005). Copyright 1997 by the American Academy of Pediatrics.

376

Biliary atresia is the most common cause of extrahepatic obstructive jaundice in the newborn and is
the most frequent indication for liver transplantation
in children.1,2 The disease is characterized by an inflammatory process that results in progressive obliteration of extrahepatic and intrahepatic bile ducts
and scarring of surrounding tissues. Clinically, biliary atresia occurs as an isolated abnormality or in
combination with other congenital anomalies. Although the latter situation suggests prenatal pathogenesis, the presence of progressive inflammatory
lesions of the bile ducts in children with isolated
biliary atresia suggests perinatal exposure to a noxious agent.3,4 Efforts to associate hepatitis viruses
with extrahepatic biliary atresia have been unsuccessful,5,6 and there have been only a few anecdotal
reports of biliary atresia associated with cytomegalovirus,7 respiratory syncytial virus,8 and EpsteinBarr virus.9 After it was found that reovirus type 3
was able to cause pathologic abnormalities similar to
biliary atresia in animal models,10 investigators reported the presence of antibodies and antigen to
reovirus type 3 in higher proportions of children
with biliary atresia than in control children.1113 However, these results have not been supported in other
studies,14 16 possibly reflecting differences in testing
methods, the timing of specimen collection, or other
unknown factors. More recently, group C rotavirus
RNA was detected in two children with biliary atresia,17 and group A rotavirus infections have been
found to produce extrahepatic biliary obstruction in
mice.18
A few studies suggest that biliary atresia may be
the result of a two-hit phenomenon dependent on
genetic vulnerability to environmental precipitating
factors. Silveira et al,19 in a case-control study of
human leukocyte antigen (HLA) typing, reported a
significant increase in the frequency of HLA B12
antigens among patients with biliary atresia compared with control subjects. They also found an increased frequency of haplotypes A9-B5 and A28-B35.
These findings raise the possibility that biliary atresia, like other diseases associated with specific HLA
subtypes, may be immune mediated. Schreiber et
al,20 using an allograft model of murine extrahepatic
bile ducts, have demonstrated that alloreactive lymphocytes can target and mediate a fibrosclerosing
injury to the extrahepatic biliary epithelium. Their
model emphasizes the importance of cell surface immune determinants in the mediation of the bile duct
epithelial injury.
Although space-time clustering of biliary atresia

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has been reported in a few studies, little else is

known about the epidemiologic characteristics of biliary atresia. A study in northern Texas by Strickland
and Shannon21 found that there was a preponderance
of affected infants from rural counties and infants
born in August through October. Danks et al22 also
noted a suspicion of space-time clusters in Australia,
but more recent studies by Houwen et al23 in both the
Netherlands and Germany did not find any evidence
for clustering in specific years or periods during the
year or in rural versus urban geographic areas.
In this study we used data from a populationbased birth defect surveillance system in metropolitan Atlanta and analyzed the temporal and geographic distribution of biliary atresia during a 26year-period. We also describe new findings related
to sex, race, maternal age, birth weight for gestational age, and parity. To our knowledge, these data
are the first population-based findings on biliary
atresia in the United States.
METHODS
Metropolitan Atlanta Congenital Defects Program
Infants with biliary atresia were identified from 1968 through
1993 by the Metropolitan Atlanta Congenital Defects Program
(MACDP). The MACDP is a population-based birth defect registry
with active case ascertainment from multiple sources, including
medical records from local childrens hospitals. Data are collected
on all live and stillborn infants of at least 20 weeks gestation who
have major congenital anomalies. The MACDP includes children
with anomalies diagnosed up to the first year of life. This is
important for detecting biliary atresia, which is usually not diagnosed until the infant is at least 2 weeks of age. The diagnosis of
biliary atresia, as found in the infants medical records, was usually based on laboratory reports and liver biopsy. Further details
on case finding and the criteria for inclusion in the MACDP have
been described elsewhere.24
The population at risk in this study included 773 360 infants
born alive from 1968 through 1993 to residents of metropolitan
Atlanta. The data file, which was compiled from birth certificates,
included information on the mothers county of residence, age,
and parity at time of birth and the infants sex, race, birth weight,
and gestational age.

Case Classification
It has been suggested that biliary atresia in association with
other unrelated congenital anomalies may represent a different
etiologic group than does isolated biliary atresia.25 For this reason,
we grouped our case infants into three categories: (1) isolated and
sequence, those with biliary atresia alone and those with biliary
atresia plus hernias or other defects on the MACDP exclusion list
or related hepatobiliary anomalies; (2) multiples, those with biliary atresia and major unrelated anomalies; and (3) syndromes,
those with biliary atresia in combination with a recognized syndrome of known etiology.

Data Analysis
All cases of biliary atresia ascertained in metropolitan Atlanta
from 1968 through 1993 were mapped by street address to examine the geographic distribution of the cases. Maps were also created for five periods (1968 through 1974, 1975 through 1979, 1980
through 1984, 1985 through 1989, and 1990 through 1993) to
examine changes in the geographic distribution over time.
We limited our epidemiologic analysis to the isolated and
sequence cases, because the cases classified as multiples and syndromes most likely represent different clinical entities (and were
too few for accurate analysis). The rates of isolated and sequence
biliary atresia were calculated for each of the 26 years and for each
month for the combined period of 1968 through 1993. The test of
Walter and Elwood26 for seasonality of events was used to determine whether there was significant seasonal variation in the oc-

currence of biliary atresia. This test compares the 12 monthly

observed frequencies with the 12 expected frequencies (assuming
lack of seasonal variation) using a x2 statistic. The birth prevalence
rates of biliary atresia by season, county, sex, race, maternal age,
parity, and birth weight for gestational age were also calculated
using the population data. The birth weight for gestational age
classification of the Centers for Disease Control and Prevention27
was used to group the infants into four categories: (1) term ($37
weeks) with normal birth weight (NBW) ($2500 g), (2) preterm
(,37 weeks) with NBW, (3) preterm with low birth weight (LBW)
(,2500 g), and (4) Term with LBW. We compared the prevalence
rates between groups of infants using relative risks (RRs) calculated from 2 3 2 x2 tables with Yates correction. Confidence limits
for the RRs were those of Greenland and Robins.28
We used logistic regression analysis29 to assess whether the
variables studied (season, county, sex, race, maternal age, parity,
and birth weight for gestational age) were independent risk factors for isolated and sequence biliary atresia and to look for
confounding and interaction among the variables. The BreslowDay test for interaction30 was used to determine the significance of
the interaction terms considered for inclusion in the regression
models.

RESULTS

For the period from 1968 through 1993, we identified 57 infants with biliary atresia in metropolitan
Atlanta, a rate of 0.74 per 10 000 live births. Fortynine infants were in the isolated and sequence category, 6 were in the multiples category, and 2 were in
the syndromes category. Table 1 shows the frequency of biliary atresia and associated anomalies.
The isolated and sequence category included 38 infants with biliary atresia alone; 6 infants with biliary
atresia and umbilical or inguinal hernias; and 5 infants with biliary atresia with other hepatobiliary
defects. The 6 infants who were in the multiples
category had biliary atresia plus central nervous system anomalies, heart defects, urogenital anomalies,
and musculoskeletal and limb defects. Two infants
were stillborn and had biliary atresia and chromosomal syndromes trisomy 18 and trisomy 13.
When we mapped the location of cases, there
seemed to be no unusual geographic clustering of
biliary atresia in metropolitan Atlanta after we accounted for population density (maps not shown).
The maps for the five periods showed that, in the
earlier years, cases were concentrated in the center of
the metropolitan area, as was the population. By the
late 1980s and early 1990s, cases were more widely
distributed, reflecting the rapid population growth
in the outlying counties.
The overall birth prevalence rate of isolated and
sequence biliary atresia for the 26-year period was
0.63 per 10 000 live births (approximately 1 per
16 000 live births). The number of cases per year
varied between 0 and 5, with rates ranging from 0 to
1.83 per 10 000 live births. Of the infants with isolated and sequence biliary atresia, 21 were white, 26
were black, 1 was Asian, and 1 was Hispanic. Because the numbers were small, we divided the infants into two racial groups (white and nonwhite) to
make comparisons. (In the birth population from
1968 through 1993, 96% of nonwhite infants were
black). Figure 1 shows the moving 3-year average
rates of isolated and sequence biliary atresia by year
for white and nonwhite infants. Nonwhite infants
had an average rate of 0.96 per 10 000 live births, and
white infants had an average rate of 0.44 per 10 000

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TABLE 1.

Frequency of Biliary Atresia and Associated Anomalies, Metropolitan Atlanta, 1968 Through 1993
Category

Frequency

Congential Anomalies

Isolated/sequence

38
6
2
1
1
1

Biliary atresia (BA) alone

BA with inguinal or umbilical hernias
BA with choledochal cyst
BA with inguinal hernia, umbilical hernia, no gallbladder
BA with small contracted gallbladder, transverse liver
BA with umbilical hernia, small atretic gallbladder,
fibrosed common bile duct
BA with hypoplastic vertebrae, multiple minor craniofacial
defects, short extremities, webbed fingers
BA with cleft lip and palate, omphalocele, anophthalmia
renal agenesis, absent diaphragm, complex congenital
heart defects, anorectal atresia, thyroid agenesis, bladder
exstrophy, costovertebral defects
BA with splenonephric agenesis, intestinal malrotation,
imperforate anus, hypoplastic femur, atrial septal defect,
mandibular hypoplasia
Ba with jeujunal atresia, hip dislocation
BA with patent ductus arteriosus/patent foramen ovale,
small bowel volvulus
BA with pulmonary stenosis, annular pancreas
BA with trisomy 18, obstructive uropathy, complex
congenital heart defects, hydrocephalus
BA with trisomy 13, holoprosencephaly sequence,
polydactyly, truncus arteriosus, uterine duplication

Multiples

1
1

1
1
1
Syndromes

1
1
1

Fig 1. Moving 3-year average rates

(per 10 000 live births) of isolated and
sequence biliary atresia by year and
race, metropolitan Atlanta, 1968
through 1993.

live births. Before 1987, nonwhite infants had consistently higher rates of biliary atresia than white infants; after 1987, the rates seem to converge. Overall,
there was no statistically significant change in biliary
atresia rates over time.
Figure 2 shows the observed and expected rates of
isolated and sequence biliary atresia by month for
the combined 26-year period. The highest rate of

Fig 2. Observed and expected rates (per 10 000) live births) of

isolated and sequence biliary atresia by month of birth, metropolitan Atlanta, 1968 through 1993.

378

biliary atresia was for infants born in March (1.09 per

10 000 live births), and the lowest rate was for infants
born in June (0.16 per 10 000 live births). According
to the test of Walter and Elwood26 for seasonal variation, the rate of biliary atresia peaked December 22,
and the x2 test for center of gravity had a P value of
.059, providing evidence against the null hypothesis
of no seasonal variation. The x2 goodness of fit test
had a P value of .95, suggesting that the observed
and expected values were consistent with the model.
When the months were grouped into three seasons,
the rate from December through March was nearly
three times greater than the rate from April through
July (Table 2).
The rate of biliary atresia varied by county from
0.29 per 10 000 live births in Clayton to 0.95 per
10 000 live births in Fulton (Table 2). The differences
in the RR estimates among counties were not statistically significant, although the rate in Fulton County
was three times greater than the rate in Clayton
County. There were slightly more girls (53%) with
biliary atresia than boys (47%). The birth prevalence
rate was higher for girls than for boys, but the difference was not statistically significant (RR, 1.19; 95%

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TABLE 2.
Frequencies, Birth Prevalence Rates, and Relative Risks by Season, County, Sex, Race, Maternal Age, Parity, and Birth
Weight for Gestational Age for Isolated and Sequence Biliary Atresia, Metropolitan Atlanta, 1968 Through 1993
Variable

Frequency

Rate per 10 000 Live Births

Relative Risk (95% Confidence Interval)

Isolated/sequence cases
Season
AprilJuly
AugustNovember
DecemberMarch
County
Fulton
DeKalb
Cobb
Gwinnett
Clayton
Sex
M
F
Race
White
Nonwhite*
Maternal age y
,25
2534
$35
Parity
1st born
2nd born
3rd born
$4th born
Weight for gestational age
Term NBW
Preterm NBW
Preterm LBW
Term LBW

49

0.63

...

8
19
22

0.31
0.71
0.87

Referent
2.27 (0.995.17)
2.77 (1.236.22)

26
9
7
5
2

0.95
0.45
0.51
0.53
0.29

3.30 (0.7813.92)
1.56 (0.347.23)
1.79 (0.378.60)
1.83 (0.359.41)
Referent

23
26

0.58
0.70

Referent
1.19 (0.682.08)

21
28

0.44
0.96

Referent
2.21 (1.253.89)

24
22
3

0.70
0.59
0.57

1.22 (0.374.04)
1.03 (0.313.44)
Referent

21
14
9
5

0.61
0.58
0.85
0.75

Referent
0.96 (0.491.88)
1.40 (0.643.05)
1.23 (0.463.27)

29
4
4
4

0.75
1.05
1.74
2.62

Referent
1.41 (0.504.02)
2.34 (0.826.65)
3.52 (1.2410.02)

* From 1968 through 1993, 96% of nonwhite infants born were black.
Term, $37 weeks; preterm, ,37 weeks; normal birth weight (NBW), $2500 g; low birth weight (LBW), ,2500 g; seven records of infants
were missing gestational age.

confidence interval [CI], 0.68 to 2.08). The birth prevalence rate of biliary atresia in the nonwhite group
was twice as high as the rate in the white group and
was statistically significant (RR, 2.21; 95% CI, 1.25 to
3.89). When the rates between white and black infants were compared (Asian, Hispanic, and other
groups were excluded), the difference was still twofold and significant (RR, 2.14; 95% CI, 1.20 to 3.80).
Forty-nine percent of the infants with biliary atresia were born to mothers younger than 25 years of
age, compared with 45% of overall births in the same
age group. The rate of biliary atresia was highest
among offspring of mothers younger than 25 years of
age and lowest among offspring of mothers 35 years
of age and older (Table 2). The difference in the rates
by maternal age were not statistically significant.
Forty-three percent of the infants with biliary atresia
were firstborn, compared with 46% of the infants in
the birth population. The rates of biliary atresia were
higher among children who were third-born or
greater, compared with rates for children who were
firstborn or second-born, but the difference was not
statistically significant. Only one of the infants with
biliary atresia in this data set was a twin, and the
cotwin was reported to have no congenital anomalies.
The mean birth weight for the infants with isolated
and sequence biliary atresia was 2979 g, and the
mean gestational age was 38.3 weeks. Twenty-one
percent of the case infants had LBW, compared with

8% of the infants in the birth population. Infants who

were preterm with NBW, preterm with LBW, and
term with LBW were compared with the term NBW
infants. The term LBW infants, who are considered
intrauterine growth retarded, had the highest rate of
biliary atresia and were at 3.5 times the risk for this
defect compared with the infants born at term with
NBW (RR, 3.52; 95% CI, 1.24 to 10.02). Preterm LBW
infants were also at increased risk, although the difference was not statistically significant (RR, 2.34; 95%
CI, 0.82 to 6.65).
Table 3 shows the best fit logistic regression model
after accounting for all reasonable combinations of
interactions among the variables and potential confounders. We began with a core model, which included all the variables that were significant risk
factors according to the crude analysis: season, race,
and birth weight for gestational age. Adding sex,
age, and parity to the model, one at a time, had no
effect on the risk estimates or their significance. Adding the county of the mothers residence at the time
of birth to the model reduced the risk estimate for
race from 2.07 (95% CI, 1.16 to 3.70) to 1.80 (95% CI,
0.93 to 3.48). Because county may be a confounder for
race, it was kept in the model. There was no interaction between sex and race (Breslow-Day test for interaction, P 5 .54). An interaction between race and
birth weight for gestational age was found to be
borderline significant (Breslow-Day test for interaction, P 5 .06). In the nonwhite birth population, the

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TABLE 3.
Results of the Multivariate Logistic Regression
Analysis: Best-fit Model With Season, County, Race, and Birth
Weight for Gestational Age as Independent Risk Factors, Metroplitan Atlanta, 1968 Through 1993
Covariates

Relative Risk (95%

Confidence Interval)

Season
AprilJuly
AugustNovember
DecemberMarch
County
Clayton
DeKalb
Cobb
Gwinnett
Fulton
Race
White
Nonwhite*
Weight for gestational age
Term NBW
Preterm NBW
Preterm LBW
Term LBW

Referent
2.23 (0.985.10)
2.63 (1.165.93)
Referent
1.31 (0.286.13)
1.69 (0.348.42)
1.88 (0.369.71)
2.48 (0.5710.71)
Referent
1.80 (0.933.48)
Referent
1.26 (0.443.61)
2.00 (0.705.74)
2.95 (1.038.44)

* From 1968 through 1993, 96% of nonwhite infants born were

black.
Term, $37 weeks; preterm, ,37 weeks; normal birth weight
(NBW), $2500 g; low birth weight (LBW), ,2500 g.

rate of biliary atresia among term LBW infants was

1.5 times greater than among term NBW infants, but
the difference was not statistically significant (RR,
1.53; 95% CI, 0.25 to 6.72). Among the white birth
population, the rate of biliary atresia among term
LBW infants was 9 times greater than among term
NBW infants, and the difference was statistically significant (RR, 9.40; 95% CI, 1.38 to 47.46). The small
sample size (some cells had as few as two case infants), limitations of birth certificate data, and differential reporting of white and nonwhite birth data
may have had an effect on the apparent interaction
between race and birth weight for age. Because of
these limitations and the finding of borderline significance, the interaction for race and birth weight for
gestational age was not included in the model. The
final model included season, which was significantly
associated with biliary atresia; birth weight for gestational age, which was also significantly associated
with biliary atresia; race, which was borderline significant; and county, which was not significant but
may have confounded the association between race
and biliary atresia.
DISCUSSION

This epidemiologic analysis of biliary atresia during a 26-year period in a well-defined population
estimates the magnitude of biliary atresia and provides evidence of seasonal variation and associations
with race and birth weight for gestational age. We
have shown that the rates of biliary atresia in metropolitan Atlanta vary by season, with the peak occurring for infants born between December and March,
when the rates are nearly three times higher than
from April through July. We have also shown an
association between biliary atresia and race. The rate
was twice as high among nonwhite infants (96% of
whom were black) compared with white infants.
380

Birth weight for gestational age was also an independent risk factor for biliary atresia. Infants born at
term with LBW were at 3.5 times the risk for biliary
atresia compared with infants born at term with
NBW. Preterm infants also seemed to be at increased
risk.
We found no significant association between biliary atresia and sex or maternal age. There was some
suggestion that biliary atresia was associated with
parity and population density. Rates were higher
among infants who had two or more siblings compared with firstborn infants or infants with only one
sibling, but the differences were not statistically significant. Rates in Fulton County, which has the largest and densest population, were more than three
times higher than rates in the other counties, but
again, the differences were not statistically significant.
The seasonality of biliary atresia and the association with population density and parity, noted in the
results of this study as well as in others,21,22,31 are
consistent with environmental causes such as viral
agents. Although the epidemiologic characteristics of
the viral agents that have attracted the most interest
(reovirus type 3 and group C rotavirus) are largely
undefined, the winter peak in the month of birth
noted in our study coincides with the peak of group
A rotavirus infections in the United States. This ecologic observation warrants further investigation into
the timing of possible viral infections around the
perinatal period and the subsequent identification of
biliary atresia.
The association between biliary atresia and race
may also provide clues to the etiology of the disease.
One other study,32 reported in 1974, found an association with race, but since then, no other researchers
have reported a clear racial predominance. In a Hawaiian study, Shim et al32 found wide variation in the
incidence of biliary atresia among Chinese (3 in
10 000), Filipino (2 in 10 000), and white (0 in 10 000)
infants. Differences in biliary atresia rates by racial
group were interpreted as supporting a hypothesis
for a genetic susceptibility for developing biliary
atresia. We think that in our population the racial
differences in biliary atresia rates may reflect genetic,
socioeconomic, and environmental factors as well.
Additional support for a genetic component to biliary atresia are reports of increased incidence among
family members3335 and the prevalence of the HLA
B12 antigen among patients with biliary atresia compared with control subjects.19 A simple Mendelian
inheritance pattern for the genetic hypothesis, however, is unlikely because of reports of discordance in
twins, including at least three sets of monozygotic
twins.36,37 To date, only two twin pairs have been
reported as concordant for biliary atresia.38,39 We had
one pair of discordant dizygotic twins in our study.
The lack of concordance in twins, on the other hand,
is evidence against a genetic hypothesis.
The association found between biliary atresia and
birth weight for gestational age is interesting, although the sequence of events is not clear. For example, it is not clear whether intrauterine growth
retardation makes a fetus or an infant more suscep-

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tible to biliary atresia or whether an infectious cause

of biliary atresia results in intrauterine growth retardation. Shim et al32 also found that birth weight was
significantly associated with biliary atresia, with affected infants tending to be smaller than unaffected
infants.
The coexistence of biliary atresia with other congenital anomalies has been widely reported, with
incidence rates ranging from 10% to 50%.40 42 The
most commonly reported anomalies are common
cardiac defects (patent foramen ovale, patent ductus
arteriosus, and ventricular septal defect) and splenic
and gastrointestinal defects.43 In metropolitan Atlanta, biliary atresia occurred as an isolated defect in
67% of the case infants and was associated with other
anomalies in 33% of case infants. Nineteen percent of
the case infants had related anomalies of the gastrointestinal system, 11% had multiple unrelated congenital anomalies, and 4% had chromosomal disorders (trisomy 13 and trisomy 18). The occurrence of
associated anomalies in our population of infants
with biliary atresia supports the hypothesis that the
disease represents more than one clinical entity with
different causes. The cases of isolated biliary atresia
with or without associated gastrointestinal anomalies may be the result of a late intrauterine or early
neonatal insult associated with a presumed inflammatory process, whereas cases of biliary atresia with
major unrelated congenital anomalies could arise
through malformations, disruptions, or chromosomal abnormalities.
Our population-based study provides additional
information about the epidemiologic characteristics
of biliary atresia and supports the theory that one
cause of the disease may be the result of significant
environmental exposure (possibly viral) in the perinatal period. The occurrence of unrelated congenital
anomalies among a proportion of the infants with
biliary atresia in our study suggests, in addition, that
the disease may represent more than a single clinical
entity, each with a different cause. Studies are
needed to determine the role of newborn and maternal exposures to specific viral agents, such as rotaviruses, in the development of biliary atresia, and to
detect environmental and genetic factors that may
cause or precipitate the disease.
ACKNOWLEDGMENTS
We acknowledge the MACDP abstractors Charlie Peters,
Connie Thompson, Debbie Nurmi, Joan Garcia, Joann Donaldson,
and Jo Anne Croghan, whose constant data collection efforts provide the foundation on which the MACDP is built. We also thank
Elaine Rhodenhiser and Mike Atkinson for their invaluable data
management assistance.

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HOW DOES HE/SHE KNOW WHAT TO DO?

Oncologists said they feared that the patient would lose confidence in their
expertise if they recommended a [randomized] trial, which they felt suggests that
the oncologist doesnt know what else to do.

Harby K. Low autologous bone marrow Tx trial accruals in breast cancer sparks National Cancer
Institute studies. Oncology Times. 1996; 18:120.

Submitted by Student

382

EPIDEMIOLOGY OF BILIARY ATRESIA

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Epidemiology of Biliary Atresia: A Population-based Study

Paula W. Yoon, Joseph S. Bresee, Richard S. Olney, Levy M. James and Muin J.
Khoury
Pediatrics 1997;99;376
DOI: 10.1542/peds.99.3.376
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