Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

10

Fetal abdominal wall defects

Federico Prefumo, MD, PhD *, Claudia Izzi, MD
Prenatal Diagnosis Unit, Department of Obstetrics and Gynaecology, University of Brescia, Brescia, Italy

Keywords:
The most common fetal abdominal wall defects are gastroschisis
gastroschisis and omphalocele, both with a prevalence of about three in 10,000
omphalocele births. Prenatal ultrasound has a high sensitivity for these abnor-
pentalogy of Cantrell malities already at the time of the rst-trimester nuchal scan.
OEIS complex Major unrelated defects are associated with gastroschisis in about
prune-belly syndrome 10% of cases, whereas omphalocele is associated with chromo-
body stalk anomaly somal or genetic abnormalities in a much higher proportion of
exstrophy
cases. Challenges in management of gastroschisis are related to the
cloaca
prevention of late intrauterine death, and the prediction and
prenatal ultrasound
rst trimester treatment of complex forms. With omphalocele, the main dif-
mode of delivery culty is the exclusion of associated conditions, not all diagnosed
neonatal surgery prenatally. An outline of the postnatal treatment of abdominal wall
defects is given. Other rarer forms of abdominal wall defects are
pentalogy of Cantrell, omphalocele, bladder exstrophy, imperforate
anus, spina bida complex, prunebelly syndrome, body stalk
anomaly, and bladder and cloacal exstrophy; they deserve multi-
disciplinary counselling and management.
2013 Published by Elsevier Ltd.

Introduction

The most common abdominal wall defects include ectopia cordis, bladder exstrophy gastroschisis,
and omphalocele. The rst three are classied in the group of ventral body wall defects, share a similar
origin, and are likely to be caused by an abnormal closure of the later body wall folds that approach
each other in the midline and close by the end of the sixth postmenstrual week. Alternative hypotheses
for the cause of gastroschisis, such as amniotic membrane rupture at the insertion of the cord,
abnormal apoptotic patterns during regression of the right umbilical vein, or vascular damage to the

* Corresponding author. Tel.: 39 030 399 5340; Fax: 39 030 399 5034.
E-mail address: [email protected] (F. Prefumo).

1521-6934/$ see front matter 2013 Published by Elsevier Ltd.

http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
2 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112

base of the umbilicus caused by disruption of the omphalomesenteric artery, provide less convincing
explanations [1]. Omphalocele is a separate entity, whose origin is attributed to a failure of physio-
logically herniated bowel loops to return from the umbilical cord to the abdominal cavity by the 12th
postmenstrual week [1].

Epidemiology

In this chapter, we mainly concentrate on gastroschisis and omphalocele: they are the two most
common anomalies. In 2011, based on the European registries included in the EUROCAT network [2],
the total prevalence of gastroschisis was 3.09 per 10,000 births, with a live birth prevalence of 2.63 per
10,000 [2]. The corresponding gures for omphalocele were 3.29 and 1.13 per 10,000. The prevalence of
gastroschisis has increased from 1980 to 2011, whereas that of omphalocele has remained stable
(Fig. 1). A similar trend for an increasing prevalence of gastroschisis has been reported in North
American populations, involving particularly pregnancies from younger women of non-Hispanic white
maternal race and ethnicity [3]. It is speculated that these different trends are related to the cause of
the two conditions. Although omphalocele seems to be mainly genetically determined, some evidence
suggests that poor socioeconomic status and prenatal care, as well as teratogens (e.g. recreational
drugs, salicylates, paracetamol, and pseudoephedrine) may be important contributors to the devel-
opment of gastroschisis [4,5].
Another important historical trend has been the anticipation of the prenatal diagnosis of abdominal
wall defects. This is because omphalocele and gastroschisis are easily diagnosed at the 1114 weeks
nuchal scan: a recent study based on over 45,000 pregnancies reported a sensitivity of 100% for both
abnormalities [6], whereas a systematic review of the literature found a sensitivity near to 90% [7]. The
increasing diffusion of rst-trimester screening for chromosomal abnormalities has, therefore,
increased the proportion of cases of these two abnormalities diagnosed at the nuchal scan. In the
EUROCAT network, during the period 20072011, 22% of the chromosomally normal cases of gastro-
schisis were diagnosed before 14 weeks, and 50% between 14 and 23 weeks. The corresponding gures
for euploid omphalocele were 35% and 30%. The overall prenatal detection rate was 91.6% for gastro-
schisis and 83.3% for omphalocele [2].

Gastroschisis

Gastroschisis is observed on ultrasound as a full-thickness defect in the abdominal wall, in most

cases to the right of the insertion of the umbilical cord. It is only rarely located to the left of cord

Fig. 1. Total prevalence of gastroschisis and omphalocele (cases per 10,000 births) in the EUROCAT network, 1980 to 2011.

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112 3

insertion. Bowel loops and occasionally parts of other abdominal organs herniate outside the
abdominal wall with no covering membrane or sac (Fig. 2).
A diagnosis of gastroschisis should prompt a careful search for other abnormalities. No close as-
sociation exists with aneuploidies; therefore, most centres do not actively offer fetal karyotyping in
these fetuses. Mastroiacovo et al. [8] analysed 3322 cases of gastroschisis from 24 birth-defect regis-
tries worldwide, and found that 469 (14.1%) cases were registered as non isolated, including 41
chromosomal syndromes, 24 other syndromes, and 404 multiple congenital anomalies. Among cases of
multiple congenital anomalies, two patterns emerged, with 26 cases resembling limbbody wall
complex and 26 others resembling the omphalocele, bladder exstrophy, imperforate anus, spina bida
(OEIS) complex (see below in the omphalocele paragraph). In both situations, omphalocele rather than
gastroschisis is more commonly reported, and the investigators argued that these cases might
represent misdiagnoses of the abdominal wall defect. Therefore, combining their review with other
published reports, the investigators stated that the best estimate of the proportion of gastroschisis
associated with major unrelated defects is about 10%. Similar gures were reported in another registry-
based study [9], and in a recent prenatal series [10]. Arthrogryposis may also be present in a minority of
these fetuses [11].
In recent studies, survival of gastroschisis approaches 95% [12,13]. Morbidity related to intestinal
complications, however, can be relevant. It has, therefore, been proposed that gastroschisis should be
classied as simple (if isolated) or as complex (if associated with intestinal atresia, perforation, ste-
nosis, or volvulus) [14].

Prediction of outcome

Ideally, it would be useful to have reliable prenatal predictors of gastroschisis complications, to

provide parents with a more accurate prognostic assessment, and identify candidates for investiga-
tional preventive treatments. One main outcome of interest is that gastroschisis is known to be
associated with a risk of intrauterine death of about 5% [15]. This increased risk is supposed to be
associated with compression of the umbilical vessels by herniated viscera, as well with the increased
incidence of fetal growth restriction or small-for-gestational age weight in fetuses with this condition
[16]. The prenatal detection of fetal growth restriction has actually been shown to predict a higher risk
of adverse outcomes [17]. Diagnosis of fetal growth restriction, unless extreme, is not an easy task in
gastroschisis, as abdominal circumference measurements are affected by the condition. It has been

Fig. 2. Transverse view of the fetal abdomen at 12 weeks of gestation, showing gastroschisis: herniated bowel loops (*) can be seen
lateral to umbilical cord insertion (arrow).

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
4 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112

debated whether using fetal weight estimation formulas that do not include abdominal circumference
is helpful [18,19]. A recent report also suggested that fetuses with gastroschisis associated with bladder
herniation (a nding present in about 6% of cases during gestation) might present a higher risk of fetal
distress and perinatal death [20].
Another main outcome of interest is that complex gastroschisis, which is present in slightly more
than 10% of cases, involves a higher risk of postnatal complications [12,21]. Unfortunately, it is not even
clear what causes the increased incidence of bowel complications in gastroschisis: a considerable
amount of data suggest that components of the amniotic uid, particularly in the third trimester, are
able to cause inammation of the exposed bowel, possibly leading to perivisceritis [22]; the bowel may
become constricted at the level of the abdominal defect, suffering ischaemic injury; bowel atresia is
associated with gastroschisis in 515% of cases [1113,23]. A number of prenatal ultrasound ndings
have been reported in association with complex gastroschisis: intra- and extra-abdominal bowel
dilatation; stomach dilatation or herniation; and thickening of the bowel wall. The presence of intra-
abdominal bowel dilatation (variably dened as a luminal diameter more than 6, 10 or 14 mm) seems
to be the only nding consistently associated with complex gastroschisis [13,23,24].

Prevention of adverse outcomes

The limited knowledge of the mechanisms causing adverse outcomes in gastroschisis does not help
in their prevention. Experimental studies on animal models and preliminary data from humans studies
suggest that regularly exchanging the amniotic uid by aspiration and replacement with saline
(amnioexchange) may improve the neonatal outcomes [22]. A randomised-controlled trial comparing
saline amnioexchange (performed every two weeks from 30 weeks) to standard management, is
currently near to completion [25].
Given the increased risk of intrauterine fetal death, it is also generally recommended that pregnant
women with gastroschisis should be considered high risk, deserving some form of increased fetal
monitoring. The modalities of such monitoring lack consensus: the most common options are car-
diotocography, suggested even daily in the third trimester [26], and umbilical and middle cerebral
artery Doppler [16]. Daily fetal heart rate home monitoring has also been successfully used, by training
pregnant women to record fetal heart rate for a 30-min period and transmit the trace by fax or email to
the supervising centre [27].

Timing and mode of delivery

Some evidence of limited quality on when and how to deliver pregnancies complicated by fetal
gastroschisis has been published. Many centres advocate planned preterm birth at 3638 weeks, but
studies on this subject have reported variable and conicting results. Moreover, most studies report a
mean gestational age at spontaneous delivery around 3637 weeks. A recent systematic review could
include only one small randomised trial [28], and drew no rm conclusions about preterm birth for
infants with gastroschisis [29]. Studies on caesarean section are not conclusive and do not show any
consistent advantage over vaginal delivery; it must be remembered that trauma to the abdominal
viscera can occur with either modality, and delivery must therefore be careful [30]. Most investigators
recommend delivery in a tertiary centre with neonatal intensive care and paediatric surgery facilities.
Although this is likely to reduce morbidity, no good evidence is available on the subject.

Postnatal management

The exposed bowel loops can cause signicant water loss by evaporation. Immediately after de-
livery, intravenous uid resuscitation should be started. The herniated loops should be wrapped in
warm saline-soaked gauze, and covered with plastic wrap to reduce water and heat losses. The
newborn should be positioned on the right side, with the packed bowel placed centrally on the
abdomen to prevent kinking of the mesentery [31].
The ideal treatment of gastroschisis is immediate repositioning of the herniated bowel into the
abdominal cavity, with closure of the abdominal wall (primary reduction and repair). If the patient is

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112 5

unstable, however, or if reduction is likely to cause an abdominal compartment syndrome, staged

repair is preferred: it consists of applying a plastic silo around the bowel, which allows to progressively
push the bowel into the abdominal cavity over days, until denitive closure is possible. Prefabricated
silos are available, with a circular retention spring that can be placed into the abdominal defect without
sutures or general anesthesia [31]. Immediate closure may be associated with a higher risk of respi-
ratory complications, whereas delayed closure usually involves a longer time to reach full enteral feeds.
Most evidence, however, comes from retrospective studies, which may be biased by the policies of
individual centres, as well as by association with complex gastroschisis: when bowel atresia is present,
primary anastomosis is often impossible owing to bowel thickness and extent of the peel of the serosa.
These children are therefore more likely to remain on parenteral nutrition for some weeks until repair
is possible, with the inherent risk of increased infectious and cholestatic complications [31,32].

Omphalocele

In omphalocele (also called exomphalos), a midline defect with intra-abdominal contents is present,
which herniate within a peritoneal sac into the amniotic cavity through the base of the umbilical cord.
The membrane covering the sac consists of peritoneum on the inner side, amnion on the outer side,
and Whartons jelly between the layers. The size of the wall defect is variable, and the umbilical vessels
insert onto the sacs membrane rather than on the intact abdominal wall. The sac usually contains
bowel loops, but also the liver and other organs may herniate (Fig. 3).
Spontaneous rupture of the omphalocele sac in utero has been sparsely reported, with bowel loops
oating freely in the amniotic uid and mimicking gastroschisis. This condition is rare, and can be
differentiated from gastroschisis because, in the latter, the umbilical cord always inserts on a normal
segment of abdominal wall. Another condition that can be confused with omphalocele is umbilical cord
hernia. Cord hernia is characterised by a normal insertion of the cord into the umbilical ring with intact
skin covering, whereas, in omphalocele, there is a large defect of the umbilical ring area without
muscles and skin [33]. In one of the largest studies of prenatally diagnosed omphalocele, the preva-
lence of omphalocele at the time of the nuchal scan (1114 weeks) was 1:381 (0.08%) [34]. The
prevalence was, however, related to crown-rump length (CRL) and sac content: when only bowel loops
were herniated, the prevalence ranged from 1 out of 98 for a CRL of 4555 mm to 1 out of 2073 for a CRL
of 65.084.0 mm. For cases of omphalocele where also the liver was herniated, the prevalence was 1
out of 3360. The same study observed that, in 53 euploid fetuses with omphalocele containing only
bowel at the nuchal scan, 49 (92.5%) had spontaneous resolution of the omphalocele by 20 weeks, and
four fetuses had persistence until delivery. These ndings have been interpreted as a delay in the

Fig. 3. Transverse view of the fetal abdomen at 12 weeks of gestation, showing a large omphalocele (*).

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
6 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112

recovery of physiological herniation of the bowel, which is usually complete by 11 weeks; this delay is
more frequent in aneuploid than euploid fetuses [34]. Spontaneous resolution of rst-trimester
omphalocele was reported, but with lower frequency also in other studies; spontaneous resolution
has not been observed in cases with herniated liver [35,36].

Associated abnormalities

The nding of an omphalocele on prenatal ultrasound should prompt a careful search for associated
anomalies and discussion of prenatal invasive testing. As introduced above, the presence of ompha-
locele indicates an increased risk of aneuploidy: in a recent rst trimester study, fetuses with
omphalocele were found to carry a chromosomal abnormality in 5457% of cases [3436]. The most
common aneuploidy is trisomy 18, which is present in 80% of fetuses with omphalocele and associated
malformations, and in 54% of fetuses with isolated omphalocele but increased nuchal translucency
[36]. The risk of aneuploidy does not change if the omphalocele contains only bowel or also the liver
[34,35], but correlates with nuchal translucency thickness. A normal nuchal translucency is therefore a
reassuring sign, but the residual risk of aneuploidy may still be as high as 28% [35]. The role of
comparative genomic hybridization (CGH)-based microarrays is still uncertain, given the small number
of cases of omphalocele included in prenatal series [37].
Given the increased risk of intrauterine death with many chromosomal abnormalities, the associ-
ation with aneuploidy will be less strong when the diagnosis of omphalocele is made in the second or
third trimester of pregnancy, or at birth. In the EUROCAT registry, which reects screening policies who
differ among countries and who have changed in the past 30 years, the overall prevalence of aneu-
ploidy is 23% [2].
Omphalocele can be associated with a number of abnormalities. Therefore, even if apparently iso-
lated at the nuchal scan, further ultrasound follow up in the second trimester is recommended. The list of
the possible associations is long. Pentalogy of Cantrell, which is usually diagnosed already in the rst
trimester, is a complex anomaly involving omphalocele and a spectrum comprising an anterior dia-
phragmatic hernia, sternal clefting, ectopia cordis, and an intracardiac defect [38]. Not all ve elements
are always present, but survival is on average less than 40%, falling to 510% in the case of severe ectopia
cordis [39]. The cause of these midline supraumbilical defects has yet to be identied: although sporadic
in most of the described infants, X-linked recessive inheritance was suggested for some families and
genes located on the X-chromosome (Xq25-q26.1) may be involved in some of the reported cases [40].
Postnatally, BeckwithWiedemann syndrome is a growth disorder characterised by macroglossia,
macrosomia, omphalocele, hypoglycaemia leading to seizures, visceromegaly, hemihyperplasia, renal
abnormalities, ear creases and pits, nevus ammeus, and embryonic tumours (e.g. Wilms tumour,
hepatoblastoma, neuroblastoma, and rhabdomyosarcoma) [41]. Although omphalocele is not invari-
ably present, when observed prenatally it should guide a targeted ultrasound examination searching
for all possible prenatal features of the syndrome, which include additionally polyhydramnios, pla-
centomegaly, and placental mesenchymal dysplasia (observed on ultrasound as multiple cystic
changes in the placenta). In 2005, a diagnostic model was proposed, combining ultrasound, patho-
logical, cytogenetic and molecular ndings. The presence of two major criteria (abdominal wall defect,
macroglossia, macrosomia) or one major plus two minor criteria (nephromegaly or dysgenesis, adrenal
cytomegaly, aneuploidy or abnormal loci, and polyhydramnios) should enable diagnosis of Beckwith
Wiedemann syndrome [42]. This model, however, has neither been validated prospectively, nor takes
into account newer molecular tools for diagnosis from fetal samples. BeckwithWiedemann syndrome
involves dysregulation of imprinted growth regulatory genes on chromosome 11p15.5 (also known as
the BeckwithWiedemann syndrome critical region) [43]. Regulation may be disrupted by any one of
numerous mechanisms. Comprehensive laboratory evaluation includes karyotype analysis, DNA
methylation tests, and genomic analysis of chromosome 11p15.5. About 85% of individuals have no
family history of BeckwithWiedemann syndrome, whereas about 15% have a family history consistent
with autosomal dominant transmission. Children of subfertile parents conceived by assisted repro-
ductive technology may have an increased risk for imprinting disorders, including BeckwithWiede-
mann syndrome. Cytogenetically detectable abnormalities involving chromosome 11p15 are found in
1% or fewer of affected individuals. Molecular genetic testing can identify epigenetic and genomic

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112 7

alterations of chromosome 11p15 in individuals with BeckwithWiedemann syndrome: (1) loss of

methylation on the maternal chromosome at imprinting centre 2 (IC2) in 50% of affected individuals;
(2) paternal uniparental disomy for chromosome 11p15 in 20%; and (3) gain of methylation on the
maternal chromosome at imprinting center 1 (IC1) in 5%. Methylation alterations that are associated
with microdeletions or microduplications in this region are associated with high heritability. Experi-
ence with prenatal diagnosis of methylation abnormalities involved in BeckwithWiedemann syn-
drome, however, is quite limited [44]. Sequence analysis of CDKN1C identies mutations in about 40%
of familial cases and 510% of cases with no family history of the syndrome.
In the omphalocele, bladder exstrophy, imperforate anus, spina bida complex (OEIS) complex, the
prenatal ndings are omphalocele, a skin-covered lumbosacral neural tube defect, impossibility to
visualise the bladder, and limb defects. Anal atresia, bladder exstrophy, and abnormal genitalia are
more difcult to visualise. The OEIS complex is usually identied after 16 weeks, even if reports of
earlier diagnoses exist [45,46]. The underlying cause remains unknown, although genetic and envi-
ronmental factors are likely to play a role.
Omphalocele has been found to be associated with a number of other conditions: neural tube
defects, defects of the diaphragm, fetal valproate syndrome, and a number of single gene disorders and
syndromes. A comprehensive review of such associations is given in the article by Chen [47]. The
presence of associated anomalies on ultrasound, or a signicant family history, may raise the suspicion
for one of these conditions.

Prediction of outcome

Given the impressive list of conditions associated with omphalocele, only some of which are
amenable to prenatal diagnosis, it is clear that the prognosis is driven by the presence and nature of the
associated features. How accurate then is a prenatal diagnosis of isolated omphalocele? This is affected
by the gestational age at examination, as well by the availability and use of more or less sophisticated
molecular diagnosis tools. In a recent study from the Netherlands, which is a good example of
contemporary practice, 12 out of 31 apparently isolated cases at prenatal diagnosis (39%; 95% con-
dence interval 2258%) were found to have associated anomalies after delivery [48]. In a similar study
from the USA, ve out of 19 fetuses with omphalocele prenatally isolated or associated with minor
anomalies (e.g. renal pelvis dilation, single umbilical artery, and umbilical cord cyst) were found to
have additional abnormalities after birth (26%; 95% condence interval 951%) [49]. In both studies,
karyotype was offered in all cases, and fetuses with aneuploidies were excluded. It is of interest that, in
the study by Porter et al. [49], preterm birth complicated more than one-third of cases, and the only
neonatal deaths occurred because of complications of prematurity. In another Dutch study, 12 (14%) out
of 88 fetuses with a prenatal diagnosis of omphalocele were alive and well at paediatric follow up,
including two with multiple associated anomalies that could be corrected [50]. In the largest prenatal
study available, including cases from a single institution in the UK observed from 1991 to 2002, only 55
out of 445 fetuses with persistent omphalocele were liveborns, and 44 made it to surgery [51].
A peculiar group of fetuses with omphalocele is that of giant omphaloceles (i.e. those omphaloceles
with a large defect, signicant herniation of the liver, or both). Wide variation among denitions of giant
omphalocele exist: one of the most authoritative (and restrictive) ones denes it as a defect containing
most (>75%) of the liver [52]. Among the other denitions proposed, some are based on absolute size,
and some on the relative size to the fetus [50]. Intuitively, the larger the defect, the higher the risk of
postnatal complications, such as pulmonary hypoplasia leading to respiratory insufciency and pro-
longed ventilatory support, often with delayed closure of the abdominal wall defect. Among these in-
fants, an increased prevalence of decits in developmental achievements has to be expected [52].

Timing and mode of delivery

No randomised-controlled trials have been conducted on mode of delivery in fetuses with

omphalocele, and the decision for a caesarean section should be dictated by obstetric indications. Many
clinicians decide to deliver fetuses with large defects by caesarean section, as they fear sac rupture or
liver damage during delivery [31]. As the denition of a large omphalocele is not standardised,

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
8 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112

retrospective studies are difcult to compare. In the recent study by Kleinrouweler et al. [50] 17 out of
21 (81%) deliveries were vaginal, with four caesarean sections based exclusively on obstetric in-
dications and not on features such as size or liver herniation (present in 47% of vaginal deliveries). No
complications such as sac rupture or liver haemorrhage were observed. Preterm delivery in ompha-
locele is not indicated.

Postnatal management

The immediate postnatal management of newborn babies with omphalocele should aim to stabilize
vital functions and search for associated anomalies that might affect treatment or monitoring (e.g.
congenital heart disease, pulmonary hypoplasia). Although uid and heath losses are less than with
gastroschisis, the omphalocele should be covered with saline-soaked gauze to minimise them.
Neonatal hypoglycaemia should alert for BeckwithWiedemann syndrome. Treatment is driven by
gestational age, size of the defect, and associated anomalies if present [31]. If the abdominal wall defect
is small or medium-sized (up to about 4 cm in diameter), treatment usually is by primary closure and
does not usually involve technical problems. Larger defects, on the contrary, can pose major challenges:
most cases are not considered amenable to primary repair owing to the lack of abdominal domain.
Non-operative techniques use agents (e.g. povidoneiodine, sulfadiazine, neomycin, silver-
impregnated dressings, neomycin, polymyxin, and bacitracin ointments), helping the amnion sac to
form an eschar, which then epithelialises in 410 weeks. These methods are used when the defect is
too large for primary repair, and also when cardiac or respiratory comorbidities preclude surgery. Most
women who have given birth to babies with omphalocele will require a later repair of the ventral
hernia defect, which can be carried out during infancy. Finally, neonatal staged closure implies the
closure of the abdominal wall with multiple procedures. This can by achieved by either using the
amnion sac with serial reductions, or by replacing the sac with a mesh and closing it gradually over
time [32].

Other abdominal wall abnormalities

We have already mentioned some rare and complex abnormalities involving the abdominal wall,
such as pentalogy of Cantrell and the OEIS complex.
Body stalk anomaly is characterised by herniation of the abdominal contents into the extraem-
bryonic coelom through a large wall defect, and by a short or absent umbilical cord. The ultrasound
features change with gestation: in early pregnancy, the upper part of the embryo is clearly situated in
the amniotic cavity, whereas the lower part is located in the extraembryonic coelom, with abdominal
contents protruding into it (Fig. 4); later in pregnancy, the umbilical cord becomes short or absent
[53,54]; kyphoscoliosis, cranial defects, and limb defects can be also be observed. In case of limb de-
fects, the term limbbody wall defect or complex has been used: however, body-stalk anomaly and
limbbody wall complex seem to be part of the same spectrum of primary ectodermal failure in the
early embryonic disc [55].
In prune-belly syndrome, a combination of decient abdominal wall muscles, urinary tract ab-
normalities, and cryptorchidism in males exists. Early in gestation, this condition should be suspected
in case of a large megacystis. It is still unclear whether the hypoplasia of abdominal wall muscles is
secondary to the stretching caused by megacystis, or if an unknown underlying cause may explain both
[56].
In bladder exstrophy, mesenchymal cells fail to migrate between the abdominal ectoderm and the
cloaca. Consequently, no muscular or connective tissue covers the anterior abdominal wall. Five ul-
trasound ndings are described for prenatal diagnosis: (1) non-visualisation of the bladder; (2) a lower
abdominal bulge formed by the exstrophied bladder; (3) small penis with anteriorly displaced
scrotum; (3) low umbilical insertion; and (5) widening of the iliac crests [57]. Not all signs, however, are
always present, and an urachal cyst may mimic the presence of the bladder; consequently, the accuracy
and sensitivity of ultrasound are relatively low, particularly if no associated ndings (such as in the
OEIS complex) are present [58]. Cloacal exstrophy is associated with rupture of the cloacal membrane
before fusion with the urorectal septum. As a consequence, these fetuses present with two exstrophied

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112 9

Fig. 4. Body stalk anomaly at 9 weeks. Arrows delineate the amniotic membrane. The upper part of the fetal body is on the left of the
amniotic membrane, within the amniotic cavity. The dysmorphic lower part of the body is on the right, in the extraembryonic
coelom.

Table 1
Ultrasound ndings in fetal abdominal wall defects.

Abnormality Covering Site of defect Umbilical cord Additional ndings

membrane insertion
Omphalocele Yes Umbilical insertion Omphalocele
membrane
Gastroschisis No Right of umbilical Normal insertion
insertion
Umbilical hernia Yes No umbilical Normal insertion
ring defect
Pentalogy of Yes Above umbilical Omphalocele Anterior diaphragmatic
Cantrell insertion membrane hernia, sternal clefting,
ectopia cordis, and
intracardiac defect.
OEIS complex Yes Umbilical insertion Omphalocele Bladder exstrophy,
membrane imperforate anus, and
spina bida.
Body-stalk Herniated Whole anterior Cord absent or Kyphoscoliosis, cranial defects,
anomaly organs in abdominal wall shortened and limb defects.
extraembryonic
coelom
Bladder Not applicable Below umbilical Low insertion Non-visualisation of bladder,
exstrophy insertion lower abdominal bulge
(exstrophied bladder), small
penis with anteriorly displaced
scrotum (if male), and widening
of the iliac crests.
Cloacal Not applicable Below umbilical Low insertion Renal anomalies, neural tube
exstrophy insertion defect, omphalocele, vertebral
anomalies, non-visualisation of
the bladder, distended bladder,
hydrocolpos, dilated or echogenic
bowel, umbilical cord cyst,
separated pubic bones, and
elephant trunk sign.

OEIS, omphalocele, bladder exstrophy, imperforate anus, spina bida complex.

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
10 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112

hemibladders separated by a foreshortened hindgut or cecum, sometimes with a constellation of

associated ndings. In a recent postnatal series of 11 cases, the following prenatal ultrasound ndings
were variably present: hydronephrosis, neural tube defects, omphalocele, vertebral anomalies
(particularly involving the sacrum), non-visualisation of the bladder, distended bladder, hydrocolpos,
dilated or echogenic bowel, umbilical cord cyst, separated pubic bones, and the elephant trunk sign
(protrusion of ileum through the defect, resembling the trunk of an elephant oating in amniotic uid)
[59]. The postnatal correction and prognosis of bladder and cloacal exstrophy depends on a number of
anatomical details, not all accurately investigated prenatally, and counselling and delivery in a centre
with experience in their treatment are of paramount importance [58,59].

Conclusion

The most common abdominal wall defects are gastroschisis and omphalocele, both with a preva-
lence of about 3 in 10,000 births. The prevalence of gastroschisis has increased in the past 30 years,
whereas that of omphalocele has remained basically stable. Prenatal ultrasound has a high sensitivity
for these abnormalities already at the time of the rst trimester nuchal scan. A summary of ultrasound
ndings in fetal abdominal wall defects is given in Table 1.
Major unrelated defects are associated with gastroschisis in about 10% of cases, whereas ompha-
locele is associated with chromosomal or genetic abnormalities in a much higher proportion of cases.
Challenges in the management of gastroschisis are related to the prevention of late intrauterine death,
and the prediction and treatment of complex forms (those associated with intestinal atresia, perfo-
ration, stenosis, or volvulus). With omphalocele, the main difculty is counselling the woman about
the possible associated conditions, not all easily diagnosed prenatally. Other rarer forms of abdominal
wall defects (e.g. pentalogy of Cantrell, OEIS complex, prune-belly syndrome, body stalk anomaly, and
exstrophies) deserve multidisciplinary counselling and management.

Conict of interest

None declared.

Practice points

 Prenatal ultrasound has a high sensitivity for omphalocele and gastroschisis.

 In most western countries, the prevalence of gastroschisis has been increasing over the past
few decades.
 Gastroschisis is associated with a risk of intrauterine death of 5%.
 Gastroschisis has a high survival, but bowel-related morbidity is high in cases of complex
gastroschisis (associated with intestinal atresia, perforation, stenosis, or volvulus).
 Omphalocele is often associated with chromosomal or genetic abnormalities.
 Large (giant) omphaloceles can present with pulmonary hypoplasia.
 In the absence of randomised-controlled trials, mode of delivery of abdominal wall defects
should be dictated by obstetric indications.

Research agenda

 Trials on fetal well-being assessment in gastroschisis.

 Role of comparative genomic hybridisation array and other molecular techniques to exclude
associated syndromes in omphalocele.
 Randomised trials evaluating mode of delivery and postnatal surgical management in
omphalocele and gastroschisis.

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112 11

References

[1] Sadler TW. The embryologic origin of ventral body wall defects. Semin Pediatr Surg 2010;19:20914.
[2] EUROCAT. http://www.eurocat-network.eu [last accessed 08.10.13].
[3] Kirby RS, Marshall J, Tanner JP, et al. Prevalence and correlates of gastroschisis in 15 States, 1995 to 2005. Obstet Gynecol
2013;122:27581.
*[4] Frolov P, Alali J, Klein MD. Clinical risk factors for gastroschisis and omphalocele in humans: a review of the literature.
Pediatr Surg Int 2010;26:113548.
[5] Van Dorp DR, Malleis JM, Sullivan BP, et al. Teratogens inducing congenital abdominal wall defects in animal models.
Pediatr Surg Int 2010;26:12739.
[6] Syngelaki A, Chelemen T, Dagklis T, et al. Challenges in the diagnosis of fetal non-chromosomal abnormalities at 1113
weeks. Prenat Diagn 2011;31:90102.
[7] Rossi AC, Prefumo F. Accuracy of ultrasonography at 1114 weeks of gestation for detection of fetal structural anomalies: a
systematic review. Obstet Gynecol 2013;122:11607.
[8] Mastroiacovo P, Lisi A, Castilla EE, et al. Gastroschisis and associated defects: an international study. Am J Med Genet A
2007;143:66071.
[9] Stoll C, Alembik Y, Dott B, et al. Omphalocele and gastroschisis and associated malformations. Am J Med Genet A 2008;
146A:12805.
[10] Durfee SM, Benson CB, Adams SR, et al. Postnatal outcome of fetuses with the prenatal diagnosis of gastroschisis.
J Ultrasound Med 2013;32:40712.
[11] Ruano R, Picone O, Bernardes L, et al. The association of gastroschisis with other congenital anomalies: how important is
it? Prenat Diagn 2011;31:34750.
[12] Bradnock TJ, Marven S, Owen A, et al. Gastroschisis: one year outcomes from national cohort study. BMJ 2011;343:d6749.
*[13] Kuleva M, Khen-Dunlop N, Dumez Y, et al. Is complex gastroschisis predictable by prenatal ultrasound? BJOG 2012;119:
1029.
*[14] Molik KA, Gingalewski CA, West KW, et al. Gastroschisis: a plea for risk categorization. J Pediatr Surg 2001;36:515.
[15] South AP, Stutey KM, Meinzen-Derr J. Metaanalysis of the prevalence of intrauterine fetal death in gastroschisis. Am J
Obstet Gynecol 2013;209:114e1114e13.
[16] Fratelli N, Papageorghiou AT, Bhide A, et al. Outcome of antenatally diagnosed abdominal wall defects. Ultrasound Obstet
Gynecol 2007;30:26670.
[17] Nicholas SS, Stamilio DM, Dicke JM, et al. Predicting adverse neonatal outcomes in fetuses with abdominal wall defects
using prenatal risk factors. Am J Obstet Gynecol 2009;201:383e16.
[18] Nicholas S, Tuuli MG, Dicke J, et al. Estimation of fetal weight in fetuses with abdominal wall defects: comparison of 2
recent sonographic formulas to the Hadlock formula. J Ultrasound Med 2010;29:106974.
[19] Chaudhury P, Haeri S, Horton AL, et al. Ultrasound prediction of birthweight and growth restriction in fetal gastroschisis.
Am J Obstet Gynecol 2010;203:395e15.
[20] Mousty E, Chalouhi GE, El Sabbagh A, et al. Secondary bladder herniation in isolated gastroschisis justies increased
surveillance. Prenat Diagn 2012;32:88892.
[21] Abdullah F, Arnold MA, Nabaweesi R, et al. Gastroschisis in the United States 19882003: analysis and risk categorization
of 4344 patients. J Perinatol 2007;27:505.
[22] Luton D, Guibourdenche J, Vuillard E, et al. Prenatal management of gastroschisis: the place of the amnioexchange
procedure. Clin Perinatol 2003;30:55172. viii.
[23] Goetzinger KR, Tuuli MG, Longman RE, et al. Sonographic predictors of postnatal bowel atresia in fetal gastroschisis.
Ultrasound Obstet Gynecol 2013. http://dx.doi.org/10.1002/uog.12568.
[24] Garcia L, Brizot M, Liao A, et al. Bowel dilation as a predictor of adverse outcome in isolated fetal gastroschisis. Prenat
Diagn 2010;30:9649.
[25] ClinicalTrials.gov identier: NCT00127946. Trial of Amnioechange in gastroschisis affected fetuses; http://clinicaltrials.
gov/show/NCT00127946 [last accessed 08.10.13].
[26] Brantberg A, Blaas HG, Salvesen KA, et al. Surveillance and outcome of fetuses with gastroschisis. Ultrasound Obstet
Gynecol 2004;23:413.
[27] Kuleva M, Salomon LJ, Benoist G, et al. The value of daily fetal heart rate home monitoring in addition to serial ultrasound
examinations in pregnancies complicated by fetal gastroschisis. Prenat Diagn 2012;32:78996.
[28] Logghe HL, Mason GC, Thornton JG, et al. A randomized controlled trial of elective preterm delivery of fetuses with
gastroschisis. J Pediatr Surg 2005;40:172631.
[29] Grant NH, Dorling J, Thornton JG. Elective preterm birth for fetal gastroschisis. Cochrane Database Syst Rev 2013;6:
CD009394.
[30] Anteby EY, Yagel S. Route of delivery of fetuses with structural anomalies. Eur J Obstet Gynecol Reprod Biol 2003;106:59.
*[31] Christison-Lagay ER, Kelleher CM, Langer JC. Neonatal abdominal wall defects. Semin Fetal Neonatal Med 2011;16:
16472.
*[32] Islam S. Advances in surgery for abdominal wall defects: gastroschisis and omphalocele. Clin Perinatol 2012;39:37586.
[33] Achiron R, Soriano D, Lipitz S, et al. Fetal midgut herniation into the umbilical cord: improved denition of ventral
abdominal anomaly with the use of transvaginal sonography. Ultrasound Obstet Gynecol 1995;6:25660.
*[34] Kagan KO, Staboulidou I, Syngelaki A, et al. The 1113-week scan: diagnosis and outcome of holoprosencephaly,
exomphalos and megacystis. Ultrasound Obstet Gynecol 2010;36:104.
[35] Iacovella C, Contro E, Ghi T, et al. The effect of the contents of exomphalos and nuchal translucency at 1114 weeks on the
likelihood of associated chromosomal abnormality. Prenat Diagn 2012;32:106670.
[36] Khalil A, Arnaoutoglou C, Pacilli M, et al. Outcome of fetal exomphalos diagnosed at 1114 weeks of gestation. Ultrasound
Obstet Gynecol 2012;39:4016.
[37] Shaffer LG, Rosenfeld JA, Dabell MP, et al. Detection rates of clinically signicant genomic alterations by microarray
analysis for specic anomalies detected by ultrasound. Prenat Diagn 2012;32:98695.

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003
12 F. Prefumo, C. Izzi / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (2013) 112

[38] Cantrell JR, Haller JA, Ravitch MM. A syndrome of congenital defects involving the abdominal wall, sternum, diaphragm,
pericardium, and heart. Surg Gynecol Obstet 1958;107:60214.
[39] Restrepo MS, Cerqua A, Turek JW. Pentalogy of Cantrell with ectopia cordis totalis, total anomalous pulmonary venous
connection, and tetralogy of Fallot: a case report and review of the literature. Congenit Heart Dis 2013. http://dx.doi.org/
10.1111/chd.12101.
[40] Carmi R, Barbash A, Mares AJ. The thoracoabdominal syndrome (TAS): a new X-linked dominant disorder. Am J Med
Genet 1990;36:10914.
[41] Chen CP. Syndromes and disorders associated with omphalocele (I): Beckwith-Wiedemann syndrome. Taiwan J Obstet
Gynecol 2007;46:96102.
[42] Williams DH, Gauthier DW, Maizels M. Prenatal diagnosis of BeckwithWiedemann syndrome. Prenat Diagn 2005;25:
87984.
[43] Shuman C, Beckwith JB, Smith AC, et al. BeckwithWiedemann syndrome. In: Pagon RA, Adam MP, Bird TD, et al., editors.
GeneReviews. Seattle (WA): University of Washington, Seattle; 3 March 2000. pp. 19932013. updated 14 December
2010, http://www.ncbi.nlm.nih.gov/books/NBK1394/ [last accessed 08.10.13].
[44] Calvello M, Tabano S, Colapietro P, et al. Quantitative DNA methylation analysis improves epigenotype-phenotype cor-
relations in BeckwithWiedemann syndrome. Epigenetics 2013:8 [Epub ahead of print].
[45] Ben-Neriah Z, Withers S, Thomas M, et al. OEIS complex: prenatal ultrasound and autopsy ndings. Ultrasound Obstet
Gynecol 2007;29:1707.
[46] Wax JR, Pinette MG, Smith R, et al. First-trimester prenatal sonographic diagnosis of omphalocele-exstrophy-imperforate
anus-spinal defects complex. J Clin Ultrasound 2009;37:1714.
[47] Chen CP. Syndromes and disorders associated with omphalocele (III): single gene disorders, neural tube defects, dia-
phragmatic defects and others. Taiwan J Obstet Gynecol 2007;46:11120.
[48] Cohen-Overbeek TE, Tong WH, Hatzmann TR, et al. Omphalocele: comparison of outcome following prenatal or postnatal
diagnosis. Ultrasound Obstet Gynecol 2010;36:68792.
[49] Porter A, Benson CB, Hawley P, et al. Outcome of fetuses with a prenatal ultrasound diagnosis of isolated omphalocele.
Prenat Diag 2009;29:66873.
*[50] Kleinrouweler CE, Kuijper CF, van Zalen-Sprock MM, et al. Characteristics and outcome and the omphalocele circum-
ference/abdominal circumference ratio in prenatally diagnosed fetal omphalocele. Fetal Diagn Ther 2011;30:609.
*[51] Lakasing L, Cicero S, Davenport M, et al. Current outcome of antenatally diagnosed exomphalos: an 11 year review.
J Pediatr Surg 2006;41:14036.
[52] Danzer E, Gerdes M, DAgostino JA, et al. Prospective, interdisciplinary follow-up of children with prenatally diagnosed
giant omphalocele: short-term neurodevelopmental outcome. J Pediatr Surg 2010;45:71823.
[53] Murphy A, Platt LD. First-trimester diagnosis of body stalk anomaly using 2- and 3-dimensional sonography. J Ultrasound
Med 2011;30:173943.
[54] Paul C, Zosmer N, Jurkovic D, et al. A case of body stalk anomaly at 10 weeks of gestation. Ultrasound Obstet Gynecol
2001;17:1579.
[55] Hunter AG, Seaver LH, Stevenson RE. Limb-body wall defect. Is there a defensible hypothesis and can it explain all the
associated anomalies? Am J Med Genet A 2011;155A:204559.
[56] Tonni G, Ida V, Alessandro V, et al. Prune-belly syndrome: case series and review of the literature regarding early prenatal
diagnosis, epidemiology, genetic factors, treatment, and prognosis. Fetal Pediatr Pathol 2013;31:1324.
[57] Gearhart JP, Ben-Chaim J, Jeffs RD, et al. Criteria for the prenatal diagnosis of classic bladder exstrophy. Obstet Gynecol
1995;85:9614.
*[58] Goyal A, Fishwick J, Hurrell R, et al. Antenatal diagnosis of bladder/cloacal exstrophy: challenges and possible solutions.
J Pediatr Urol 2012;8:1404.
*[59] Bischoff A, Calvo-Garcia MA, Baregamian N, et al. Prenatal counseling for cloaca and cloacal exstrophy-challenges faced
by pediatric surgeons. Pediatr Surg Int 2012;28:7818.

Please cite this article in press as: Prefumo F, Izzi C, Fetal abdominal wall defects, Best Practice & Research
Clinical Obstetrics and Gynaecology (2013), http://dx.doi.org/10.1016/j.bpobgyn.2013.10.003