Download Abdominal Wall Defect Associated with Persistent Cloaca

ANATOMIC PATHOLOGY
Original Article
Abdominal Wall Defect Associated
with Persistent Cloaca
The Embryologic Clues in Autopsy
NICO G. HARTWIG, M.D.,1 JAN-WILLEM STEFFELAAR,1'2 D.MED.SC., 2
CHRISTINE VAN DE KAA, M.D.,3 JOANNE A. SCHUELER, M.D.,4
AND CHRISTL VERMEIJ-KEERS, M.D., D.MED.SC. 1
Three stillborn fetuses are reported in which an abdominal wall
defect was associated with defects in the urogenital and anal
region. Autopsy of these fetuses provided clues indicative of how
and where the embryonic development went wrong. The malformation involved a disturbance of the cell deposition process, occurring in the caudal part of the embryo. During the cell deposition process, which takes place in the neural crest and the body
wall placode, ectodermal cells are added to the mesodermal com-
partment of the embryo, thus contributing to the anlagen of several structures, including the ventral body wall. In addition, a
change in the shape of the embryo is generated. The sequence
of events resulting from a disturbance of the cell deposition process is explained. (Key words: Abdominal wall defect; Omphalocele; Primary abdominoschisis; Cloaca; Embryology) Am J Clin
Pathol 1991;96:640-647
Congenital abdominal wall defects (AWDs) are found in
many forms. They are associated frequently with other
anomalies, which has resulted in a variety of nomenclatures and classifications.'"3 Recently, Hartwig and
associates4,5 proposed a new classification of AWD based
on early development of the umbilical cord and abdominal wall. This classification advantageously divides the
complete spectrum of AWDs into four types: primary abdominoschisis, secondary abdominoschisis, body wall
dysplasia, and omphalocele. Each type is characterized
by the relationship between the placenta, membranes,
umbilical cord, and fetus. Furthermore, in this classification, confusing and improper terms {e.g., exomphalos
[outside the umbilicus] or gastroschisis [split stomach])
are avoided.
It seems difficult to fit some complex manifestations of
AWD into this new classification. However, when these
manifestations are considered as a combination of interrelated malformations, and when the AWD is examined
according to the above principle, the type of AWD can
be recognized. In this article, three cases of AWD in combination with an adjacent cloacal structure are presented.
The probable derailments of embryogenesis are discussed,
thereby elucidating the interrelation of the malformations
observed.
PATHOLOGIC FINDINGS
The data on pregnancies and autopsies are summarized
in Table 1.
Fetus 1 was delivered together with the placenta (Fig.
\A). A cylindriform membrane, which proved to be amnion, attached the fetus to the placenta. The umbilical
ring, defined as the site of transition from the amnion to
the fetal skin, had a diameter of 6 cm. At the placenta, a
ring-like insertion of amnion also was seen (Fig. \A). The
From the 'Department of Anatomy
and Embryology. Universityplacental
of
1
Leiden: the Departments of Pathology and ^Obstetrics
and Gynecology. part within this ring was not covered by amnion.
3
Through the membrane, the abdominal contents was visLeyenburg Hospital. The Hague; and the Department of Pathology.
University of Nijmegen. Nijmegen. The Netherlands.
ible. Furthermore, a gelatinous cord, running between the
placenta and fetus and containing two umbilical vessels,
Received October 11,1990; received revised manuscript and accepted
was seen in a membranous fold (Fig. \B). According to
for publication December 12, 1990.
Supported by the Dutch "Praeventiefonds," The Hague.
Hartwig and associates,4,5 this situation is classified as priAddress reprint requests to Dr. Hartwig: Department of Anatomy and mary abdominoschisis. In addition, the caudal border of
Embryology, University of Leiden, P.O. Box 9602, NL 2300 RC Leiden,
the umbilical ring was related directly to a membranous
The Netherlands.
640
HARTWIG ET AL.
Defects of Abdominal Wall and Cloaca
641
TABLE 1. PREGNANCY AND AUTOPSY DATA
Fetus 1
Pregnancy
Maternal age
Gravidity
28
Gravida 1,
clomid
induction
None
reported
20
Gravida 1
Disorders in pregnancy
Increased fundal height
Malformations diagnosed
Course of action
ECHO at 25 weeks gest.
Termination by
prostaglandin infusion
26
Gestational weeks at delivery
Fetus 3
Fetus 2
ECHO
Expectative
34
Autopsy
Body weight
Chromosomal constitution
Umbilicus
Umbilical ring diameter
Umbilical cord
Umbilical vessels
995 g
46, XX
2020 g
46, XY
1280 g
46, XY
6 cm
primary abdomionschisis
1 artery (left)
1 vein
5 cm
Omphalocele
1 artery (left)
1 vein
5.5 cm
Omphalocele
1 artery (right)
1 vein
Ileum
Yes, blind ending and
atretric at cloaca
2 normal endings
Ileum and coecum
Yes, blind ending with
double appendix
Right: normal ending
Left: absent
Cecum
Yes, blind ending
Agenesis left
2 testes in abdomen
External genitalia
Normal
2 ovaries and 2 fallopian
tubes, blind ending;
uterus and vagina
absent
None formed
Pubic bones
Neural tube and spine
Absent symphysis
Sacral meningocele
Rudimentary penis and
2 scrotal swellings,
not fused
Absent symphysis
Normal
Cardiovascular
Normal
Normal
Lung
Miscellaneous
Bilobated right lung
Agenesis of gall-bladder
Normal
None
Cloacal region
Gut-part that ends
Presence of rectal/colonic
remnant
Ureters
Kidneys
Internal genitalia
structure in the pubic area (Fig. IB). This structure, determined to be cloaca, showed proliferations of urothelium, squamous epithelium, and colon-type mucosa, as
well as ostia of two ureters and the gut. Internally in this
region, malformations of the colon and urogenital system
were found. No external genitalia were present. Internally,
two ovaries and two blind-ending fallopian tubes were
found. Furthermore, a sacral meningocele was observed
in the caudal region.
Fetuses 2 (Fig. 2A) and 3 (Fig. 3) were monochorionic,
monoamniotic twins. The mother was treated with an
ovulation-stimulating drug because of a fertility disorder.
Right: normal ending
Left: distally atretic
megaureter
Hydronephrosis left
2 testes in abdomen
Rudimentary penis and
2 scrotal swellings,
not fused
Absent symphysis
Sacral meningocele
hydromyelia
Right aortic arch
Arterial transposition
Ventricular septal defect
Mitral valve atresia
Abnormal venous
return
Bilateral hypoplasia
Retrognathia
Both fetuses showed a similar malformation pattern. They
had omphaloceles with umbilical ring diameters of 5 and
5.5 cm, respectively. Their umbilical cords contained only
two vessels each. In both, the umbilical ring immediately
bordered a cloacal structure in the pubic region, and malformations of the rectum, colon, and urogenital system
were observed. Of the external genitalia, a rudimentary
penis, emerging from the cloacal surface, and two nonfused scrotal swellings were recognized. These scrotal
swellings were situated at the borders of the cloaca (Figs.
2B and 3). In addition, fetus 3 showed a sacral meningocele.
Vol. 96 • No. 5
642
ANATOMIC PATHOLOGY
E-f
E1
FIGS. 1A and B. (A) External appearance of fetus 1, connected to the placenta (PI) by a cylindriform amniotic membrane. The arrow indicates the
transition of the skin into the amnion, i.e., the site of the umbilical ring. The arrowheads show the insertion of the amniotic membrane to the
placenta. (B) Exposed is the membranous structure of the pubic region, which exhibits orifices into the gut (G) and the ureters (the arrowhead
indicates one ureter orifice). In addition, proliferations of different kinds of epithelia are present, represented by the different shades of gray. A
gelatinous cord (C) with two umbilical vessels is running between fetus and placenta, laying within a fold of the amniotic membrane.
DISCUSSION
Duhamel3 presented an embryologic explanation of
AWD, in which the curving of the embryo, because of
growth and differentiation of the neural tube and the paraxial mesoderm, was held responsible for the formation
of four folds of the embryonic body wall: two lateral, one
cephalic, and one caudal fold. Disturbances in the formation of these folds were believed to lead to hernias of
the abdominal wall, which were called celosomias. However, in the description of the celosomias, no attention
was paid to the initial disturbance of development (i.e.,
the insufficient growth and lack of differentiation of the
neural tube and paraxial mesoderm). According to the
above principle, one would expect that an AWD must be
associated with malformations of the neural tube or dorsal
spine. Furthermore, in Duhamel's description,3 the relationships between the different embryonic folds, membranes, and placenta were not defined clearly.
Another developmental model was presented indirectly
by Smits-van Prooije and associates.6 From their data, it
can be concluded that the formation of the ventral body
wall and the closure of the abdominal cavity from the
extraembryonic coelom are phenomena intrinsic to a cell
deposition process occurring at the site of the umbilical
ring. Here, the ectoderm is regarded as a surface ectodermal placode (body wall placode) that has the capacity to
deposit ectodermal cells into the mesodermal compartment, which will contribute to the formation of the ventral
body wall. In this concept, an AWD can be considered a
disturbance of a local developmental process. Depending
on the time of onset or the severity of the disturbance,
the AWD may be found alone or in combination with
other related malformations.
To comprehend the genesis of an AWD in association
with malformations of the urogenital and anal regions, as
observed in the three presented cases, it is necessary to
understand normal development in those regions. Because
AJ.C.P. • November 1991
HARTWIG ET AL.
Defects of Abdominal Wall and Cloaca
FIGS. 2A and B. (A) External appearance of fetus 2. The omphalocele is
opened, revealing the abdominal contents. The arrowhead points at the
normal piece of the umbilical cord. (B) Pubic area of fetus 2. Between
the two scrotal swellings (*) lays a rudimentary penis (white arrow). To
the left, the orifice into the gut (G) is found.
Vol. 96 • No. 5
643
644
ANATOMIC PATHOLOGY
Original Article
called the umbilical ring.4 When the cloacal membrane
is removed, the site of the anal and urogenital opening is
exposed, represented by an orifice into the yolk sac, a
structure from which the gut will develop, and an orifice
into the allantois, the precursor of the primitive urogenital
sinus/urinary bladder. Between these two entrances there
is an area covered with endoderm, representing the future
perineal area (Fig. 4).
During the embryonic folding process (Fig. 5), the spatial relations between the above-mentioned structures
change. Because of the expansive longitudinal growth of
the developing neural tube,7 the embryo starts to curve
and grows beyond the umbilical ring. As a result, the cloacal membrane and surrounding areas revolve under the
ventral surface of the embryonic disk. The primitive urogenital sinus and the hindgut (rectum and colon) also are
formed by this process. Parts of the allantois and yolk sac
are incorporated within the embryo, taking the positions
of the primitive urogenital sinus/urinary bladder and the
rectum, respectively (Fig. 5). Fusion of the mesoderm
surrounding these incorporated parts givesriseto the formation of the urorectal septum, which is interposed between the urogenital sinus and rectum. As is shown in
Figure 5, the top of this urorectal septum corresponds to
the perineal area. Its endodermal epithelium eventually
FIG. 3. External appearance of fetus 3. The omphalocele is opened. Here,
also two scrotal swellings are present (arrows).
two cases showed a sacral meningocele, the development
of that region also is considered.
Normal Development
In human development, the formation of the lower abdominal wall, anal opening, rectum and colon, primitive
urogenital sinus, and caudal end of the neural tube are
closely related. When a trilaminar embryo (embryonic
stage 8 of Carnegie7) is viewed from above, the anlagen
of some of these structures already can be recognized (Fig.
4). Rostral to the cloacal membrane, in the midline, is
the site of the developing neural tube. The area caudal to
the cloacal membrane represents the initial anlage of the
lower abdominal wall. Slightly further caudal, it ends in
the edge of the embryonic disk that represents the transition from the surface ectoderm to the amnion. This
transition is found around the embryonic disk and corresponds to the site of umbilical insertion in later developmental stages. Therefore, this transition zone also is
FIG. 4. Schematic representation of an embryo of late Carnegie stage 8.
For simplification, only the ectoderm (ec) and endoderm (ed) are drawn.
The sites b and cm represent the buccopharyngeal and the cloacal membrane, respectively. At these sites the endoderm and ectoderm are not
separated by mesoderm. In the midline between these membranes, the
neural tube (nt) will develop. Caudal to the cloacal membrane the initial
anlage of the lower abdominal wall is found (asterix). The cut-edge of
the embryo is the transition from surface ectoderm into amnion, i.e..
the umbilical ring. The allantois (a) and yolk sac (y) are continuous with
each other right below the cloacal membrane. The space that is created
between the cloacal membrane and the orifices into the allantois and
the yolk sac is called the cloaca. The bottom of the cloaca represents the
future perineum (p).
A.J.C.P. • November 1991
HARTWIG ET AL.
645
I Wall and Cloaca
Defects OJ
FIG. 5. Schematic representations of three embryos of Carnegie stages
9, 11, and 13, proportionally enlarged. These stages concur with the
period of the embryonic folding process. The diameter of the umbilical
ring (whiteringindicated by arrowhead) is the same in all three embryos.
In this way, the umbilical ring relatively decreases in relation to the
embryo. Due to the folding at the caudal end of the embryo (curved
arrow), parts of the allantois (a) and the yolk sac (y) are incorporated,
resulting in the formation of the primitive urogenital sinus and hindgut,
respectively. These latter structures are separated by the urorectal septum
(us), which is formed through fusion of the mesoderm surrounding the
allantois and yolk sac (split arrow in stage 9). The diverticular process
of the hindgut near the cloaca present in stages 11 and 13 represents the
postanal gut (pg). In stage 13, the cloacal membranes has disappeared,
thereby the perineum (p) is exposed, situated between the orifices of the
primitive urogenital sinus and hindgut. In the cranial part of the embryos
of stages 9 and 11, the buccopharyngel membrane (b) and the open
neural tube (nt) can be discerned.
transforms into multilayered keratinized squamous epithelium after disruption of the cloacal membrane.
Furthermore, during the folding process, the hindgut
Vol.
forms a diverticular process known as the postanal gut.7
This structure will take part in the development of the
rectum and colon2 (Fig. 5).
In the meanwhile, the neural tube is forming at the
rostral side of the cloacal membrane. During its formation,
a process of cell deposition takes place.8,9 At the site of
the transition from neuroectoderm into surface ectoderm,
also known as the neural crest, cell death is observed. The
cell death is responsible for disruption of the basement
membrane, thereby allowing other ectodermal cells to
leave their epithelial arrangement 9 and enter the mesodermal compartment, where they will contribute to the
formation of the local structures around the neural tube,
such as ganglia, neural arches, and dorsal muscles.
A similar process of cell deposition is found at the site
of the umbilical ring (in rat embryos, from a 8-somite
stage onward6). Here, the surface ectoderm bordering the
amniotic epithelium deposits ectodermal cells into the
mesodermal compartment, which will contribute to the
formation of the ventral body wall.
At the neural crest and umbilical ring, the actual cell
deposition is a focal process that changes in time with
alternating active spots along the neural crest and around
the umbilical ring.
In addition to affecting the body wall formation, cell
death and cell deposition inhibit growth of the umbilical
ring, in absolute terms. Thus, in comparison with the embryo, the ring gets smaller (see Fig. 5).
During further development, the umbilical cord also
takes a definite form. As the embryo curves and the amniotic cavity enlarges, the part of the amniotic membrane
connected with the cranial part of the umbilical ring comes
in close contact with the yolk sac and the connecting stalk.
Eventually, at approximately Carnegie stage 14,10 that
amniotic part applies itself to these structures, thereby
closing the abdominal cavity off from the extraembryonic
coelom (i.e., the space between the amniotic membrane,
connecting stalk, and chorionic membrane). 4 Additional
enlargement of the amniotic cavity causes the amniotic
membrane to join to the chorionic membrane, thereby
completely obliterating the extraembryonic coelom. This
occurs at approximately the ninth week of development.
Maldevelopmen t
Because congenital malformations reflect disturbed developmental processes, autopsy presents clues indicating
which processes malfunctioned. The first clue, indicating
a developmental disturbance of the abdominal wall, is
expressed by the localization and size of the umbilical
ring. As is described above, the umbilical ring represents
the transition from skin (surface ectoderm) to the amnion.
•No. 5
646
ANATOMIC PATHOLOGY
Original Article
It determines the border between the fetal tissue on one
side and the placental tissue with membranes on the other.
In the three fetuses presented, the umbilical ring had a
large diameter, thereby indicating disturbances in the cell
deposition process during the formation of the abdominal
wall. Insufficient cell death and cell deposition have led
to persistent growth and an increase in size of the umbilical
ring in absolute terms, whereas the abdominal wall itself
has not been well formed.4
As a direct result of the enlarged umbilical ring, disturbances in the formation of the umbilical cord also are
expected. Because of the enlargement, the distance between the amnion attached to the cranial part of the umbilical ring on one side and the yolk sac and connecting
stalk on the other may become so large, that this part of
the amnion cannot apply itself to the yolk sac and connecting stalk at all. In less severe cases, it may apply itself
to a more distal part of the connecting stalk than it normally would. By the abnormal appliance of the amnion,
the connecting stalk remains partly deprived of an amniotic covering, and the abdominal cavity remains in open
connection with the extraembryonic coelom. Furthermore, through the enlarged umbilical ring, the abdominal
contents will protrude easily into the extraembryonic
coelom.
The spectrum of pathologic conditions related to an
enlarged umbilical ring and an abnormal appliance of the
amnion may range from primary abdominoschisis to mild
forms of omphalocele. In primary abdominoschisis, the
amnion has not applied to the connecting stalk at all, so
that the protrusion of abdominal organs reaches the placenta,4 as in case 1. In omphalocele, the amnion has applied itself to a more distal part of the connecting stalk.
Then, a normal piece of umbilical cord is found in the
vicinity of the placenta, as illustrated in cases 2 and 3.
Another clue of abnormal development is expressed by
the immediate connection between the caudal border of
the umbilical ring and a cloacal structure in the pubic
region, as was observed in all three cases. This finding
suggests that no lower abdominal wall has been formed
at all and that the immediate connection between the
cloacal membrane and the umbilical ring has existed since
early embryonic stage 8 of Carnegie. Furthermore, such
an immediate connection suggests that, at the caudal border of the umbilical ring, no process of cell death and cell
deposition has taken place at all. Consequently, the folding
process at the caudal end of the embryo will be hindered.
As a result, the incorporation of parts of the yolk sac and
the allantois will be prohibited as well; thereby, the urorectal septum does not form, and a division into a primitive urogenital sinus or hindgut cannot be discerned. After
the normal disappearance of the cloacal membrane, a
membranous structure will be exposed, revealing an en-
dodermal epithelium that can differentiate into the epithelia of the urogenital sinus, the hindgut, and/or the perineum. Of the two orifices, the one into the allantois obliterates (as normally) and the other will communicate with
the midgut region. Sometimes, however, a blind-ending
rectal/colonic remnant may be found. This may be formed
from the postanal gut (Fig. 5) (i.e., the diverticular process
of the embryonic gut near the cloacal membrane). 2
When the cloacal membrane immediately borders the
umbilical ring, a compartment (i.e., anlage of the lower
abdominal wall) from which the external genitalia and
the pubic bones will develop is not present. These defects
were observed in all three fetuses as well.
As stated previously, the formation of the abdominal
wall and neural tube share a cell deposition process. During neural tube formation, the neural crest deposits cells
into the mesodermal compartment around the neural
tube. From this mesodermal compartment, the meninges,
spinal ganglia, neural arches, and subcutis of that region
are derived.6 Insufficient deposition will lead to a lack of
mesodermal tissue, so that the meninges will differentiate
in close relation to the surface ectoderm (skin), whereas
no neural arches will be formed in between. The malformation that results may range from meningocele to spina
bifida occulta, as illustrated by cases 1 and 3.
The combination of malformations in the fetuses presented here is best summarized as resulting from disturbances in the cell deposition process, localized at the umbilical ring or the neural crest in the caudal part of the
embryo. The disturbance started early in development,
from Carnegie stage 8 onward, at approximately 32 days
of gestation. The large umbilical ring in all three fetuses,
resulting in primary abdominoschisis or omphalocele, and
the meningoceles in fetuses 1 and 3 are related directly
to disturbances of this process. The persistence of cloacal
structures is regarded as an indirect defect, resulting from
a hindrance of the normal folding process at the caudal
end of the embryo.
Abdominal wall defects often are associated with other
anomalies, 1 '"' 3 especially omphalocele.12 Although the
term "primary abdominoschisis" was introduced recently,4'5 reports in the literature that meet this description
frequently are associated with other anomalies as
well. 1 ' 414 "' 6 This is in agreement with our suggestion that,
in principle, omphalocele and primary abdominoschises
are similar defects, but of a different grade. Of these two,
primary abdominoschisis is the most severe form in which
no normal piece of umbilical cord has been formed.
Several combinations of AWDs with other anomalies
have been regarded as specific entities, such as limb body
wall complex, OEIS complex (omphalocele, exstrophy of
the bladder, imperforate anus, and sacral meningocele),
pentalogy of Cantrell, amniotic band syndrome, and ce-
A.J.C.P. • November 1991
HARTWIG ET AL.
Defects of Abdominal Wall and Cloaca
losomias. However, as is stressed in this article, an AWD
in combination with another defect should not be designated as a specific entity, for there are grades of abnormal
development, depending on the location, severity, and
time of onset of a specific developmental process.
If the relationships between the placenta, membranes,
cord, and fetus are differentiated, it will be easy for each
clinician who encounters AWDs to classify the defect on
a macroscopic basis. Additionally, this approach eliminates nomenclature that obscures basic developmental
disturbances.
Acknowledgments. The authors thank the following for their support
and contributions: Dr. J. P. Holm, gynecologist, and Dr. W. Vandenbroucke, gynecologist/echographist (Leyenburg Hospital, The Hague);
D. Oepkes, echographist (Leiden University Hospital, Leiden); Dr. J.
Nijhuis, gynecologist, and Dr. M. Pruszczynski, pathologist (St. Radboud
University Hospital, Nijmegen); L. Pronk and H. E. de Vries, laboratory
assistants, J. Lens, photographer, and S. B. Blankevoort and J. WetselaarWhittaker, medical illustrators (Department of Anatomy and Embryology, University of Leiden, Leiden).
REFERENCES
1. Van Allen MI, Curry C, Gallagher L. Limb body wall complex: I.
Pathogenesis. Am J Med Genet 1987;28:529-548.
2. Carey JC, Greenbaum B, Hall BD. The OElS-complex (omphalocele,
exstrophy, imperforate anus, spinal defects). Birth Defects OAS
XIV 1978;6B:253-263.
3. Duhamel B. Embryology of exomphalos and allied malformations.
Arch Dis Child 1963;38:142-147.
4. Hartwig NG, Vermeij-Keers C, De Vries HE, Kagie M, Kragt H.
Limb body wall malformation complex: an embryological etiology? Hum Pathol 1989;20:1071-1077.
647
5. Hartwig NG, Vermeij-Keers C. A new classification of malformations
of the ventral body wall. In: Versteegh FG, Ens-Dokkum M, Ooms
ECM, Kuypers JC, Peters PWJ, Van Velzen D, eds. Abstracts of
the First International Congress in Paediatric Pathology, Pynacher,
The Netherlands: Dutch Efficiency Bureau, 1989, p. B13.
6. Smits-van Prooije AE, Vermeij-Keers C, Poelmann RE, Mentink
MMT, Dubbeldam JA. The formation of mesoderm and mesectoderm in 5- to 41-somite rat embryos cultured in vitro, using
WGA-AU as a marker. Anat Embryol (Berl) 1988;177:245-256.
7. O'Rahilly R, Miiller F. Developmental stages in human embryos.
Washington, D.C.: Carnegie Institution, publication 637, 1989.
8. Smits-van Prooije AE, Vermeij-Keers C, Poelmann RE, Mentink
MMT, Dubbeldam JA. The neural crest in presomite to 40-somite
murine embryos. Acta Morphol Neerl Scand 1985;23:99-114.
9. Vermeij-Keers C, Poelmann RE. The neural crest: a study on cell
degeneration and the improbability of cell migration in mouse
embryos. Netherlands Journal of Zoology 1980;30:74-81.
10. Miintener M. Zur Genese der Omphalozele und "Gastroschisis"
(paraumbilikaler Bauchwanddefect). Z Kinderchir 1970;8:380390.
11. Gilbert WM, Nicolaides KH. Fetal omphalocele: associated malformations and chromosomal defects. Obstet Gynecol 1987;70:
633-635.
12. Czeizel A, Vitez M. Etiological study of omphalocele. Hum Genet
1981;58:390-395.
13. Mann L, Ferguson-Smith MA, Desai M, Gibson AAM, Raine PAM.
Prenatal assessment of anterior abdominal wall defects and their
prognosis. Prenat Diagn 1984;4:427-435.
14. Lockwood CJ, Scioscia AL, Hobbins JC. Congenital absence of the
umbilical cord resulting from maldevelopment of embryonic body
folding. Am J Obstet Gynecol 1986;155:1049-1051.
15. Molz G, Bulla L, Tondury G, Manestar M. Eventration und fetoplazentare Verwachsungen: Verbildungskombination mit haufigerem Vorkommen beim weiblichen Geschlecht. Z Kinderchir
1981;31:70-81.
16. Sermer M, Benzie RJ, Pitson L, Carr M, Skidmore M. Prenatal
diagnosis and management of congenital defects of the anterior
abdominal wall. Am J Obstet Gynecol 1987;156:308-312.
Vol. 96 • No. 5