Vol. 45, No. 3
Printed in U.S.A.
T H E AMKHICAN JOURNAL OF CLINICAL PATHOLOGY
Copyright © 1906 by The Williams & Wilkins Co.
ABSENCE OF ONE UMBILICAL ARTERY
ANALYSIS OF 20 CASES IN A 5-YEAR STUDY
JOSEPH R. CIPPARONE, M.D.
St. Lawrence Hospital, Lansing, Michigan
The purpose of this paper is to add further
emphasis to the fact that an infant born
with an absence of 1 umbilical artery is
likely to have associated congenital anomalies which may or may not be manifest at
birth. There is also a high incidence of abnormalities of the placentas associated with
this anomaly.6
There has been a paucity of papers written
on this subject for several reasons: lack of
careful inspection of the severed end of the
cord at the time of delivery; infrequent submission of the placenta and cord to the
pathologist for thorough examination; disinterest in placental pathology on the part
of some pathologists; and finally, infrequent
participation of hospitals in perinatal mortality programs which stimulate interest in
congenital defects.
Although the older literature mentioned
this anomaly, 7 ' 10 it was not until the work
of Benirschke and Brown in 19555 that emphasis was placed on associated developmental aberrations. During the past 10
years, the prognostic significance of this
anomaly has been more clearly delineated in
series here and abroad.1"9' 12_17
This report pertains to observations made
in 20 cases of an absence of 1 umbilical
artery. Nineteen placentas were available
for detailed study.
MATERIALS AND METHODS
During the period from September 1,
1959, to August 31, 1964, there were 766
placentas examined grossly and microscopically in the department of pathology. The
placentas were not from consecutive deliveries. The routine practice in this hospital is
to save the placentas of all stillborn and
premature infants, and newborn infants with
a doubtful life expectancy. Occasional placentas are also sent for examination when
their gross morphology is deemed abnormal
Received, July 2, 1905.
247
by the clinician. During this 5-year period,
19 placentas were examined in which there
was absence of 1 umbilical artery. The incidence in this series is abnormally high (2.6
per cent) because of the selective nature of
the series. The exact incidence is not known,
but in most consecutive series it is approximately 1 per cent.
A minimum of 5 sections was made of
each placenta, exclusive of the multiple
sections of the cord. The sections of the placenta were taken from the peripheral and
middle areas, including segments of rolled
membranes. Sections were also taken from
any obvious gross abnormalities. All of the
sections were stained with hematoxylin and
eosin, and in a number of instances the Masson trichrome and PAS stains were used, in
addition. In the microscopic examination of
each placenta, the following were noted:
correlation of the morphology of the villi
with the gestational age; nature of the intervillous maternal blood; amount: of fibrin
deposited; character of the fetal membranes;
state of the vessels in the decidua basalis;
appearance of the decidual cells; and the
amount of calcification. In the cord, the
structure of the 2 remaining vessels was recorded, as well as the presence or absence of
leukocytic infiltrates.
Using the Michigan Perinatal Mortality
Stud}' sheets as a guide, detailed information
was obtained on the previous history of the
mother; the aspects of the current pregnancy, labor, and delivery; data regarding
the infant; and the pathology of the placenta
and cord.
MATERNAL
AND
PREGNANCY
DATA
The average age of the mothers was 2S;
the youngest mother was 16 and the oldest
43. The youngest father was 21 and the
oldest 53. The average age of the mother who
bore an infant with a proven congenital
anomaly was 27. Six of the mothers were
248
Vol. 45
CIPPARONE
primiparas. None of the multiparous mothers
had previously given birth to an infant with
a known absence of 1 umbilical artery. Six
multiparous mothers had had previous spontaneous abortions. The number of live-born
children of the multiparous mothers ranged
from 1 to 9.
Of the mothers, IS were Caucasian, 1 was
Negro and another Oriental. None had had
previous serious obstetrical complications.
Four had had previous systemic diseases.
All of these were multiparas. One had rheumatic fever and another rheumatoid arthritis; the other 2 had diabetes mellitus. The
complications or diseases the mothers had
during this pregnancy are listed in Table 1.
The maternal outcome was good in all cases.
The longest gestation period was 40 weeks.
TABLE 1
D E T A I L S OF 20 I N F A N T S BORN W I T H AN ABSENCE OF 1 UMBILICAL A R T E R Y
Case
No.
Sex
Weight
of
Infant
1
2
M
F
2125
1600
None
None
None
Left talipes
3
F
35
None
None
2600
1150
700
1530
050
1925
1000
P l a c e n t a previa
Preeclampsia
Diabetes mellitus
Hydramnios
None
Bronchial a s t h m a
Hydramnios
Living and well
Stillborn
Stillborn
Stillborn
Stillborn
Stillborn
Born live; died at 1
hr.
Born live; died at 30
days
Complications or Diseases
during Pregnancy
Fetal Anomalies
Follow-up
Causes of Death
Gm.
Living and well
Living, no other
anomalies
Abortus
11
F
2000
None
None
None
None
Anencephaly
None
None
Multiple anomalies*
Microcephaly
12
M
4500
Diabetes mellitus
None
Stillborn
13
F
2350
None
Stillborn
14
M
1900
First trimester
bleeding
None
Anencephaly
15
M
2000
Preeclampsia
None
16
F
2300
Kh sensitization
None
17
M
2000
Rubella and bleeding, first trimester
18
M
1575
None
19
M
1950
20
MJ 2450
Abruptio placentae;
afibrinogenemia
None
Idiopathic cardiac hypertrophy
Abnormal pulmonary a r t e r y
None
Born live; died a t 20
min.
Born live; died at 1
hr.
Born live; died at 1
hr.
Born live; died at 24
hr.
4 M
5 F
G M
7 M
8 F
9 F
10 F
None
'
Born live; died at 11
hr.
Stillborn
Spontaneous
tion
abor-
Prematurity
Immaturity
Anencephaly
Immaturity
Prematurity
Lethal anomalies
Microcephaly;
bronchopneumonia
Anoxia, infant of
diabetic mother
Prematurity
Anencephaly
Prematurity!
Erythroblastosis
fetalis
Cardiac failure
Hyaline membrane
disease
Prematurity
Living and well
* Spina bifida; short neck; bilateral clubbing of hands and feet; hypoplastic right clavicle; right
diaphragmatic hernia with herniated liver into thorax.
t There was diffuse calcification of the liver and adrenal glands (possible toxoplasmosis or cytomegalic inclusion disease—no organisms identified).
t Only twin in the series.
March J 966
249
ABSENCE OF 1 UMBILICAL AHTERY
TABLE 2
THIS PLACENTAS
Case No.
1
2
3
'1
5
(i
7
S
9
10
11
12
13
14
15
10
17
IS
19
20
Gross Changes
Weight of Placenta Gestational Age
Gm.
weeks
294
320
55
420
295
312
GOO
140
200
500
700
925
412
300
550
900
500
No specimen
390
980*
38
32
20
3S
30
30
33
30
30
30
37
40
37
27
32
37
40
32
32
40
Microscopic Changes
Cii'ciimmargination, infarcts
Circumvallation
Circumvallation
Infarcts
Infarcts
Immature villi
Chorioaninionil is
Immature villi
Cliorioamnionitis
Infarcts
Circumvallation
Circumvallation, infarcts
I m m a t u r e villi
I m m a t u r e villi
I m m a t u r e villi
I m m a t u r e villi
Circumvallation, infarcts
I m m a t u r e villi
Vclamentous insertion of cord
I m m a t u r e villi
* Diamnionic dichorionic placenta.
All of the mothers had a negative serologic
test for syphilis. Only 2 were Rh-negative.
One of these mothers delivered an infant
with erythroblastosis fetalis and an absence
of 1 umbilical artery. There were no additional anomalies. Other aspects of the current pregnancy, labor, and delivery yielded
no pertinent data.
THE INFANTS
There were 11 boys and 9 girls. Only 1 of
the infants was a twin. This infant, as well
as the other twin, is alive and well with no
obvious congenital defects. The placenta
was of the diamnionic dichorionic type. Of
the 16 who did not survive, S had a complete
autopsy; 4 of these had congenital defects.
If autopsies had been performed on all of
the infants, additional defects undoubtedly
would have been discovered.
There were 16 deaths among the 20 infants (SO per cent) (Table .1). Only 4 infants
survived and are still living. One of these was
born with a left talipes, therefore, of the
original 20 infants, only 3 survived with no
obvious congenital defects (15 per cent).
As the number of infants with congenital
defects in this series was small, no conclusion
could be drawn as to the predominant system involved. As noted in Table 1, anomalies
were seen in various systems, as follows: central nervous system, 3; musculoskeletal, 2;
cardiovascular, 2. In larger series reported
previously in the literature, anomalies have
been noted in every system.3'17
When the infants were grouped according
to 500-Gm. weight classifications, it was
noted that the greatest number fell in the
1751- to 2000-Gm. group. Correlation with
the weeks of gestation revealed that these
infants were smaller in weight than one
would normally expect for the gestational
age. This has been a consistent finding in
most series.
THE PLACENTAS
The placenta was examined grossly and
microscopically in 19 of the 20 cases. Gross
abnormalities were observed in 10 placentas
(53 per cent) (Table 2). As noted in other
series, the gross abnormalities included circumvallation, circummargination, velamentous insertion of the cord, and true infarcts.
The most common placental weight group
250
C1PPARONE
was 200 to 399 Gm. (7 cases). The site of insertion of the cord was velamentous, 1;
marginal, 6; central or slightly eccentric, 12.
Meconium staining of the membranes was
visible grossly in only 3 instances.
Microscopic examination of the umbilical
cords revealed that the artery was absent in
its entire length in each cord examined.
There was no appreciable degree of muscular
hypertrophy in the 1 remaining umbilical
artery. Leukocytic infiltrates were seen in 5
umbilical cords. In each placenta, a careful
search was made for viral inclusion bodies
but none were found.
Immature villi were seen in 8 placentas
(42 per cent). The change was focal in character. The affected villi exhibited hypertrophy, edema, persistent Hofbauer cells in
the stroma, and occasional persistence of
Langhans' layer. The presence of these immature villi cannot be interpreted as the result of the absent artery, as less than half of
the placentas showed these changes.
The abnormal villi were seen in all of the
placentas associated with infants that had
the congenital defects (6 cases). They were
seen in only 2 of those remaining cases which
had no known congenital defects. Seki and
Strauss,17 in studying 52 placental specimens
associated with this anomaly, also noted
these immature villi, out of phase with the
gestational age of the placenta. They stated
that "abnormally large or edematous chorionic villi were observed in some specimens.
Such changes may be encountered in association with a variety of congenital defects, regardless of the state of • the umbilical
arteries." Inasmuch as immature villi can
focally persist in some otherwise normal
placentas or can be associated with a variety
of congenital defects, no special significance
can be attached to this observation. The
change is but another poorly understood
mechanism which can occur in the placenta
with or without an absence of 1 umbilical
artery.
COMMENT
The pathogenesis of this anomaly is still
in doubt. There is evidence in favor of primary absence of 1 vessel, as well as evidence
Vol. 45
that 1 of the arteries becomes arrested in its
development.4' 12' 13 In none of the cases presented did the umbilical arteries join within
the body of the fetus or in the cord, although
this has been observed previously by other
investigators.13' "
A cause-and-effeet relation between an
absence of 1 umbilical artery and the multiplicity of congenital defects on a hypoxic
basis has also not been definitely established.
The anomaly has been described in several
infants with chromosomal
abnormalities.12' 16' " No chromosomal studies were
performed on the infants in this series.
A nongenetic cause of the anomaly has
been postulated principally on the basis that
only 1 of monozygotic twins may have the
anomaly and that there seems to be no
familial occurrence. The great majority of
the multiparous mothers in the various
series in the literature have only had 1 infant with this anomaly.
In this series, the mortality rate was high
(80 per cent). Only 3 infants survived with
no obvious congenital defects. Causes of
death of the 16 infants were varied (Table
1). The high mortality rate, therefore, cannot be ascribed to the anomaly of the umbilical cord per se. These findings are consistent
with those reported in other series. 5,7
The review of the charts of these cases revealed that an absence of 1 umbilical artery
was observed at the time of delivery in only
2 instances. Much more information about
this anomaly and its sequelae in infants
could be gained if every physician delivering
an infant would make it a routine procedure
to count the number of vessels in the cord
by means of gross inspection. If there is any
question regarding the absence of a vessel, a
segment of the cord should be submitted for
microscopic examination. This simple procedure would alert the physician subsequently following the progress of the
infant. In several cases cited in the literature, 3, 7 the congenital defects were surgically
correctable and the immediate action taken
was life-saving. Long-term follow-ups of infants with this anomaly are necessary if the
true prognostic significance is to be known.
March 1966
ABSENCE OF 1 UMBILICAL ARTERY
SUMMARY AND CONCLUSIONS
Twenty cases of an absence of 1 umbilical
artery have been presented. The incidence
of this anomaly in this selective series was
2.6 per cent. Only 1 of the infants was a
twin. Associated congenital defects were observed in 7 infants (35 per cent).
There were 16 deaths in this group, with
the high mortality rate (SO per cent) not
being due to the anomaly of the umbilical
cord per se; however, only 3 infants survived,
with no obvious congenital defects (15 per
cent). Five infants died because the congenital defects were of the lethal type.
Analysis of maternal factors and characteristics of each pregnancy yielded no significant data.
Gross abnormalities were noted in 10 of
the 19 placentas studied (53 per cent). Immature hydropic villi out of phase with the
rest of the placenta were noted in S placentas (42 per cent). The change was focal in
character. These villi exhibited hypertrophy,
edema, persistent Hofbauer cells in the
stroma, and occasional persistence of Langhans' layer. No special significance could be
attached to the presence of these immature
villi, as they may occasionally be seen in
otherwise normal placentas.
If the etiologic mechanisms of birth defects are to be better understood, there must
be a greater interest in the pathology of the
placenta by the pathologist in the general
hospital and greater participation of hospitals in perinatal mortality programs. The
combined efforts at the time of delivery of
the physician and the pathologist in the laboratory can help save the life of an infant who
has a surgically correctable lesion if both are
aware of the significance of this lesion. Absence of 1 umbilical artery is a simple clue
to the early detection of birth defects.
Acknowledgments.
Miss Viola Schuller typed t h e
251
manuscript, and Mr. Russell Bressler prepared the
microscopic sections.
REFERENCES
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N . : Absence of one umbilical a r t e r y and its
relationship to congenital malformations.
Harefuah, 65: 280-288, 1903.
2. Benirschke, K . : Single umbilical a r t e r y .
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1961.
3. Benirschke, K., and Bourne, G. L.: Absent
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A. M. A. Arch. Dis. Child., 35: 534-543, 1900.
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