896 PEDIATRICS Vol. 68 No. 6 December 1981
then promised to discuss “ways in which the
Needleman et al study fails to satisfy these
con-cerns” (emphasis ours). The problems we listed are:
(1) insensitive markers of lead exposure, (2)
insen-sitive measures of performance, (3) biased
ascer-tainment of subjects, and (4) inadequate handling
of confounding variables. Close examination of their
paper discloses only two areas in which they find
the Boston study unsatisfactory: subject
ascertain-ment and control of confounding. They state that
high mobility, lack of parental interest, or
unwill-ingness to cooperate account for “almost half “ of
the exclusions of our provisionally eligible subjects.
They are incorrect. As table 1 in our paper indicates,
of 524 provisionally eligible families, 57 (10.8%) were
not interested, and 19 (3.6%) had moved. To be
precise, 14.4% of the families, not “almost half,”
were excluded for the reasons cited by Ernhart et
al.
Ernhart et al cite control of confounding as the
most serious problem in our study. They list two
types of problems under this heading: lack of
iden-tification of confounders and inadequate statistics
to control for those confounders identified; but we
cannot find where they fault us on identification of
confounders, and their second point appears to be
an indictment of the state of the art of biostatistics
in general. They cite parental IQ, parental
educa-tion, and parenting behavior as particularly
impor-ta.nt confounders. They argue that studies other
than their own “. . .have incorporated less stringent
attempts to control the difficulties.” It is difficult to
reconcile this criticism with our effort. We
con-trolled for parental IQ, six dimensions of parental
concern, and 37 additional variables, including both
maternal and paternal education. Interested
read-ers are referred to the original paper3 and two
comprehensive reviews4’5 of the human studies
lit-erature so that they may make their own appraisal.
SUMMARY
Ernhart et al, on the basis of their own follow-up
data and an incorrect critique of a single study, find
reason to question the entire literature
document-ing the adverse effects of low levels of lead. They
assert that, if effects exist, they are minimal. To
reach this sweeping conclusion, they contradict or
ignore the findings of the earlier study by Perino
and Ernhart, misread a table from the one study
they single out for criticism, and draw debatable
conclusions from their own data.
We conclude by calling the readers’ attention to
this sentence: “While the effects of subclinical lead
intoxication may not be noted in the individual
cases seen in a pediatric clinic, analysis of group
data indicate quite clearly (emphasis added) that
performance on an intelligence test is impaired.”
This statement was applied to 80 youngsters studied
by Perino and Ernhart in 1974, and still seems
applicable to 63 of the same group now five years
older.
HERBERT L. NEEDLEMAN, MD
Departments of Psychiatry and Pediatrics
University of Pittsburgh School of Medicine
Pittsburgh
DAVID BELLINGER, PhD
ALAN LEVITON, MD
Children’s Hospital Medical Center
Boston
REFERENCES
1. Perino J, Ernhart CB: The relation of subclinical lead level
to cognitive and sensorimotor impairment in black pre-schoolers. J Learn Disabil 7:26, 1974
2. Ernhart CB, Landa B, Schell N: Subclinical levels of lead
and developmental deficit: A multivariate follow-up reas-sessment. Pediatrics 67:911, 1981
3. Needleman HL, Gunnoe C, Leviton A, et al: Deficits in
psychologic and classroom performance of children with
elevated dentine lead levels. N Engi J Med 300:689, 1979 4. Rutter M: Raised lead levels and impaired
cognitive/behav-ioral functioning: A review of the evidence. Dev Med Child Neurol 22(suppl):1, 1980
5. Needleman H, Landrigan P: The health effects of low level exposure to lead. Annu Rev Public Health 2:277, 1981
Biliary
Atresia
Since Kasai et al’ demonstrated convincingly that
biliary atresia was a treatable, and in some
in-stances curable condition, the approach to the
jaun-diced infant has changed dramatically. Efforts to
identify infants with this disease were greatly
ac-celerated as the “hands off” philosophy, predicated
on the assumption that attempts to correct biiary
atresia would be futile, gave way to a more
aggres-sive approach. Inevitably, this led to a proliferation
of diagnostic studies, each attempting to
discrimi-nate between intrahepatic cholestasis and
extrahe-patic atresia of the bile ducts. Many of these studies
purported to be helpful are, in fact, of little value.
Undoubtedly, this is because biliary atresia is not
exclusively a condition afflicting the bile ducts,
ul-timately resulting in obstruction. Rather, the
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American Academy of Pediatrics.
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COMMENTARIES 897
ophysiology of biiary atresia is better understood
if the condition is regarded as a liver disease with
synchronous extrahepatic ductal involvement.
Thus, hepatic parenchymal dysfunction is implicit
in patients with biliary atresia.
If operative intervention and biiary
reconstruc-tion by the portoenterostomy procedure will,
in-deed, help a significant number of these infants,
then the necessity for an expeditious diagnostic
work-up is apparent. The initial observation of
Ka-58_i and associates that the operation is successful
only when performed before the 12th week of life
has been confirmed in many centers. Data from a
cooperative study coordinated through the auspices
of the Surgical Section of the American Academy
of Pediatrics suggest that operative success is
greater when surgery is performed by the tenth
week of life (J. R. Lilly, unpublished data, 1981).
Thus, extended periods of observation for these
infants with elevated fractions of direct bilirubin
and the performance of multiple laboratory tests of
limited usefulness are inappropriate.
Serial percutaneous needle biopsies2 and
duo-denal aspiration for the presence of bile3 have been
established as reliable diagnostic modalities.
An-other significant refinement in diagnosis has been
the application of nuclear scanning techniques
em-ploying isotopes of technetium 99m. This
radio-pharmaceutical has largely replaced 1-131 rose
ben-gal for biiary imaging. In our experience it has
proven to be a highly reliable study for defining
biiary tract patency in those jaundiced infants
hay-ing syndromes of intrahepatic cholestasis
(“neo-natal hepatitis”).4 The appearance of isotope in the
gastrointestinal tract unequivocally establishes
pat-ency of the bile ducts. Diagnostic accuracy is
en-hanced by pretreatment with phenobarbital.5
Fail-ure of isotope to appear in the gastrointestinal tract
has been regarded as an indication for surgical
exploration with the presumption that the diagnosis
of biiary atresia will be confirmed at laparotomy.
Thus, we can now distinguish with a high degree
of reliability those infants who are candidates for
surgery, ie, biliary atresia, from those with
choles-tatic syndromes. What can be accomplished for the
former group and why does the portoenterostomy
succeed when many surgical procedures previously
applied for correction of biliary atresia have been
discarded?
The process which results in obliteration of the
bile ducts is a dynamic one rather than the result of
a single static intrauterine insult.6 Scarred fibrotic
bile ducts will not conduct bile nor is there any
evidence to suggest that these can recanalize. The
crucial difference between this operation and those
that preceded it is based upon the observation of
Kasai et al that within the fibrous tissue investing
the bile ducts at the porta hepatis are found
micro-scopically patent biliary channels which
commu-nicate with the intrahepatic ductal system.79 In
some instances, an unfavorable surgical outcome
undoubtedly results from failure to identify this
fibrous tissue accurately, or its improper transection
too distal in the biliary tree.’#{176}” Even if the
extra-hepatic biliary tract is not anatomically intact, this
fibrous tissue at the porta is almost invariably
pres-ent. Thus, an inflexible operative approach
predi-cated upon identification of the gallbladder,
corn-mon bile duct, and common hepatic duct with a
plan to follow these structures cephalad to the porta
may not be feasible. The most reliable anatomic
landmark for identification of the fibrous tissue at
the ports is the bifurcating portal vein. Transection
of this tissue outside the liver substance above this
vein provides the only opportunity to establish a
functional biiary intestinal anastomosis. It is
spec-ulated that these patent biliary structures at the
ports themselves become obliterated at some time
around the 12th week of life, precluding success if
the operation is delayed beyond this time. Why
these ductules remain patent if surgery is carried
out earlier than 3 months of age has not been
established.
Bile drainage is anticipated in most infants
op-erated upon by the tenth to 12th week of life. We
have learned, however, that provision of bile
drain-age is not equivalent to “cure.” In a personal
expe-rience of 82 cases of biliary atresia, unequivocal bile
drainage was accomplished in 63 infants.
Notwith-standing bile drainage, 30 of these patients never
lost their jaundice. For the remaining 33 the
provi-sion of bile drainage has provided an opportunity
for the hepatic component of this disease to run its
course and in most to resolve completely allowing
normal growth and development. Some among this
group of anicteric patients continue to have
mini-mal to moderate functional hepatic impairment.
Cirrhosis and portal hypertension have emerged as
new problems in a few children relieved of jaundice
by functioning biliary intestinal conduits. In three
infants gastrointestinal hemorrhage from
esopha-geal varices has required intervention by
endo-scopic sclerotherapy or portosystemic shunting.’2
These measures are appropriate if the primary liver
insult has, in fact, resolved.
Based upon the experience reported from centers
throughout the world, there seems little doubt that
the infant with conjugated hyperbilirubinemia
de-serves an expeditious diagnostic evaluation. When
the cause of jaundice is unknown, or if there is a
high suspicion that the underlying condition is
bil-iary atresia, prompt surgical intervention is
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898 PEDIATRICS Vol. 68 No. 6 December 1981
ranted.’3’6 The surgeon undertaking biliary
explo-ration in the jaundiced neonate should be
commit-ted to the belief that successful biliary
reconstruc-tion can be accomplished for most patients. The
solution to the potentially devastating
postopera-tive problem of cholangitis has been elusive.
Exter-nal venting of the biiary conduit and long-term
antibiotic therapy have modified, but not
corn-pletely eliminated this hazard.’7’9 In spite of these
remaining difficulties, ongoing efforts on behalf of
these patients are justified when one considers the
tangible accomplishments that have been achieved
for a condition so recently regarded as hopeless.20’2’
REFERENCES
R. PETER ALTMAN, MD
Division of Pediatric Surgery
College of Physicians & Surgeons
Babies Hospital
Columbia-Presbyterian Medical Center
New York
1. Kasai M, et al: Surgical treatment of biliary atresia. J
Pe-diatr Surg 3:665, 1968
2. Brough AJ, Bernstein J: Liver biopsy in the diagnosis of infantile obstructive jaundice. Pediatrics 43:519, 1969 3. Greene HL, Helinek GL, Moran R, et a!: A diagnostic
ap-proach to prolonged obstructive jaundice by 24-hour
collec-tion of duodenal fluid. J Pediatr 95:412, 1979
4. Majd M, Reba RC, Altman RP: Hepatobiiary scintigraphy with “mTc-PIPIDA in the evaluation of neonatal jaundice.
Pediatrics 67:140, 1981
5. Majd M, Reba RC, Altman RP: Effect of phenobarbital on “Tc-IDA scintigraphy in the evaluation of neonatal jaun-dice. Semin Nuci Med 1 1:194, 1981
6. Landing BH: Considerations of the Pathogenesis of Neo-natal Hepatitis, Biliary Atresia, and Choledochal Cyst:
The Concept oflnfantile Obstructive Cholangiography.
Ba!-timore, University Park Press, 1972
7. Chiba T, Kasai M, Sasano N: Histopathological studies on
intrahepatic bile ducts in the vicinity of ports hepatis in
biliary atresia. Tohuku J Exp Med 118:199, 1976
8. Chandra RS, Altman RP: Ductal remnants in extrahepatic
biliary atresia: A histopathologic study with clinical corre-lation. J Pediatr 93:196, 1978
9. Suruga K, Nagashima K, Kohno 5, et a!: A clinical patho-logical study of congenital biliary atresia. J Pediatr Surg 7:
655, 1972
10. Kimura K, Tsugawa C, Kubo M, et a!: Technical aspects of
hepatic portal dissection in biliary atresia. J Pediatr Surg
14:27, 1979
11. Altman RP, Lilly JR: Technical details in the surgical
cor-rection of extrahepatic biliary atresia. Surg Gynecol Obstet
140:952, 1975
12. Altman RP: Portal decompression by interposition
mesoca-val shunt in patients with biliary atresia. JPediatr Surg 11:
809, 1976
13. Altman RP: The portoenterostomy procedure for biliary
atresia: A five year experience. Ann Surg 188:351, 1978
14. Carcassone M, Bensoussan A: Long-term results in treat-ment of biiary atresia, in Rickham PP, Hecker WCh, Prevot
J (eds): Progress in Pediatric Surgery. Baltimore, Urban &
Schwarzenberg, 1977
15. Miyata M, et a!: Long-term results of hepatic
portoenteros-tomy for biiary atresia: Special reference to postoperative portal hypertension. Surgery 76:234, 1974
16. Valayer J: Hepatic portoenterostomy: Surgical problems and
results, in Brenberg SR (ed): Liver Diseases in Infancy and
Childhood. The Hague, Martinus Nijhoff Medical Division,
1976
17. Kasai M, Asakura Y, Suzuki H, et a!: Modifications of
hepatic portoenterostomy to prevent postoperative ascend-ing cholangitis. Proc Pacific Assoc Pediatr Surg 5:83, 1972
18. Kobayashi A, Utsunomiya T, Yoshior 0, et a!: Ascending
cholangitis after successful surgical repair of biiary atresia.
Arch Dis Child 48:697, 1973
19. Hitch DC, Lffly JR, Reller LB, et al: Biliary flora and
antimicrobial concentrations after Kasai’s operation. J
Pe-diatr Surg 14:648, 1979
20. Sondheimer JM, Shandling B, Weber JL, et al: Hepatic
function following portoenterostomy for extrahepatic biliary atresia. Can Med Assoc J 118:255, 1978
21. Adelman 5: Prognosis of uncorrected biliary atresia: An
update. J Pediatr Surg 13:389, 1978.
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1981;68;896
Pediatrics
R. Peter Altman
Biliary Atresia
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Biliary Atresia
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