Omphalocele, also called exomphalos, is a rare abdominal wall defect in which

the intestines, liver and occasionally other organs remain outside of the abdomen in a sac

because of failure of the intestines and other contents to return back to the abdominal cavity
during around the sixth week of intrauterine development. Prior to this time, the intestines
protrude into the umbilical cord in utero as a normal result of rapid intestinal growth, but they
recede around the ninth week of development as the body grows.
Omphalocele occurs in 1 in 4,000 births and is associated with a high rate of mortality (25%) and
severe malformations, such as cardiac anomalies (50%), neural tube defect (40%), exstrophy of
the bladder and Beckwith–Wiedemann syndrome. Approximately 15% of live-born infants with
omphalocele have chromosomal abnormalities. About 30% of infants with an omphalocele have
other congenital abnormalities.

Contents

 1Signs and symptoms

 2Causes
o 2.1Pathophysiology
o 2.2Genetics
o 2.3Actions of the mother
 3Diagnosis
o 3.1Related conditions
 4Screening
 5Management and treatment
 6Complications
 7Society and culture
o 7.1Awareness Day
 8References
 9External links

Signs and symptoms[edit]

The sac, which is formed from an outpouching of the peritoneum, protrudes in the midline,
through the umbilicus (navel).
It is normal for the intestines to protrude from the abdomen, into the umbilical cord, until about
the tenth week of pregnancy, after which they return to inside the fetal abdomen.
The omphalocele can be mild, with only a small loop of intestines present outside the abdomen,
or severe, containing most of the abdominal organs. In severe cases surgical treatment is made
more difficult because the infant's abdomen is abnormally small, having had no need to expand
to accommodate the developing organs.
Larger omphaloceles are associated with a higher risk of cardiac defects.[1]

Causes[edit]
Diagram showing the process by which the intestine rotates and herniates during normal development.
From panel A to B (left-sided views), the midgut loop rotates 90° in a counterclockwise direction, so that its
position changes from midsagittal (A) to transverse (B1). The small intestine forms loops (B2) and slides
back into the abdomen (B3) during resolution of the hernia. Meanwhile, the cecum moves from the left to
the right side, which represents the additional 180° counterclockwise rotation of the intestine (C, central
view).[2]

Omphalocele is caused by malrotation of the bowels while returning to the abdomen during

development. Some cases of omphalocele are believed to be due to an underlying genetic
disorder, such as Edward's syndrome (trisomy 18)[3][4] or Patau syndrome (trisomy 13).
Beckwith–Wiedemann syndrome is also associated with omphaloceles.

Pathophysiology[edit]
Exomphalos is caused by a failure of the ventral body wall to form and close the naturally
occurring umbilical hernia that occurs during embryonic folding which is a process
of embryogenesis.[5] The normal process of embryogenesis is that at 2 weeks gestation the
human embryo is a flat disc that consists of three layers, the outer ectoderm and
inner endoderm separated by a middle layer called the mesoderm. The ectoderm gives rise to
skin and the CNS, the mesoderm gives rise to muscle and the endoderm gives rise to organs.
The focus areas for exomphalos are that the ectoderm will form the umbilical ring,
the mesoderm will form the abdominal muscles and the endoderm will form the gut. After the disc
becomes tri-layered, it undergoes growth and folding to transform it from disc to cylinder shaped.
The layer of ectoderm and mesoderm in the dorsal axis grow ventrally to meet at the midline.
Simultaneously, the cephalic (head) and caudal (tail) ends of these layers of the disc fold
ventrally to meet the lateral folds in the center. The meeting of both axis at the center form
the umbilical ring. Meanwhile, the endoderm migrates to the center of this cylinder.
By the fourth week of gestation the umbilical ring is formed. During the 6th week
the midgut rapidly grows from the endoderm which causes a herniation of the gut through the
umbilical ring. The gut rotates as it re-enters the abdominal cavity which allows for the small
intestine and colon to migrate to their correct anatomical position by the end of the 10th week of
development. This process fails to occur normally in cases of exomphalos, resulting in abdominal
contents protruding from the umbilical ring.[6][7][8]
Gut contents fail to return to the abdomen due to a fault in myogenesis (muscle formation and
migration during embryogenesis). During embryogenesis the mesoderm that forms muscle
divides into several somites that migrate dorso-ventrally towards the midline. The somites
develop three parts that are sclerotome which will form bone, dermatome which will form skin of
the back and myotome which will form muscle. The somites that remain close to the neural tube
at the back of the body have epaxial myotome, whilst the somites that migrate to the midline
have hypaxial myotome. The hypaxial myotome forms the abdominal muscles.
The myotome cells will give rise to myoblasts (embryonic progenitor cells) which will align to form
myotubules and then muscle fibers. Consequently, the myotome will become three muscle
sheets that form the layers of abdominal wall muscles. The muscle of concern for exomphalos is
the rectus abdominis. In the disease the muscle undergoes normal differentiation but fails to
expand ventro-medially and narrow the umbilical ring which causes the natural umbilical
hernia that occurs at 6 weeks of gestation to remain external to the body. [5]
The location of the folding defect in the embryo determines the ultimate position of the
exomphalos. A cephalic folding defect results in an epigastric exomphalos that is positioned high
up on the abdomen which can be seen in the chromosomal defect pentalogy of Cantrell. Lateral
folding defects result in a typical exomphalos that is positioned in the middle of the abdomen. A
caudal folding defect results in a hypogastric exomphalos that is positioned on the lower
abdomen.[9]

Genetics[edit]
The genes that cause exomphalos are controversial and subject to research. Exomphalos is
greatly associated with chromosomal defects and thus these are being explored to pinpoint the
genetic cause of the disease. Studies in mice have indicated that mutations in the fibroblast
growth factor receptors 1 and 2 (Fgfr1, Fgfr2) cause exomphalos. [5] Fibroblast growth
factor (FBGF) encourages the migration of myotubules during myogenesis. When FBGF runs
out myoblasts stop migrating, cease division and differentiate into myotubules that form muscle
fibers. Mutations in homeobox genes such as Alx4, that direct the formation of body structures
during early embryonic development cause exomphalos in mice. [10] Mutations in the Insulin like
growth factor-2 gene (IGF2) and its associated receptor gene IGF2R cause high levels of IGF-2
protein in humans which leads to exomphalos in the associated disease Beckwith Wiedemann
syndrome (BWS). IFG2R is responsible for degradation of excess IGF-2 protein. BWS disease is
caused by a mutation in chromosome 11 at the locus where the IGF2 gene resides.
[11]
 Observance of the inheritance patterns of the associated anomalies through pedigrees show
that exomphalos can be the result of autosomal dominant, autosomal recessive and X-linked
inheritance.[9]

Actions of the mother[edit]

It is not well known if actions of the mother could predispose or cause the disease. Alcohol use
during the first trimester, heavy smoking, use of certain medications like the selective serotonin-
reuptake inhibitors and methimazole (anti-thyroid drug) during pregnancy, maternal febrile
illness, IVF, parental consanguinity and obesity elevate the risk of a woman giving birth to a baby
with exomphalos.[9][12] Preventive methods that could be utilised by mothers include ingestion of a
preconception multivitamin and supplementation with folic acid. Termination of pregnancy may
be considered if a large exomphalos with associated congenital abnormalities is confirmed during
prenatal diagnosis.[9]

Diagnosis[edit]
Related conditions[edit]
Gastroschisis is a similar birth defect, but in gastroschisis the umbilical cord is not involved and
the intestinal protrusion is usually to the right of the midline. Parts of organs may be free in the
amniotic fluid and not enclosed in a membranous (peritoneal) sac. Gastroschisis is less
frequently associated with other defects than omphalocele.
Omphaloceles occurs more frequently with increased maternal age.
Other related syndromes are Shprintzen Goldberg, pentalogy of Cantrell, Beckwith–
Wiedemann and OEIS complex (omphalocele, exstrophy of the cloaca, imperforate anus, spinal
defects).
After surgery a child with omphalocele will have some degree of intestinal malrotation. Due to
intestinal malrotation 4.4% of children with omphalocele will experience a midgut volvulus in the
days, months, or years after surgery. Parents of children with omphalocele should seek
immediate medical attention if their child displays signs and symptoms of an intestinal obstruction
at any point in their childhood to avoid the possibility of bowel necrosis or death. [13]
Some experts differentiate exomphalos and omphalocele as 2 related conditions, one worse than
the other; in this sense, exomphalos involves a stronger covering of the hernia (with fascia and
skin), whereas omphalocele involves a weaker covering of only a thin membrane. Others
consider the terms synonymous names for any degree of herniation and covering.

Screening[edit]
An omphalocele is often detected through AFP screening or a detailed fetal ultrasound. Genetic
counseling and genetic testing such as amniocentesis are usually offered during the pregnancy.

Management and treatment[edit]

There is no treatment that is required prenatally unless there is a rupture of the exomphalos
within the mother. An intact exomphalos can be delivered safely vaginally and C-sections are
also acceptable if obstetrical reasons require it.[8] There appears to be no advantage for delivery
by C-section unless it is for a giant exomphalos that contains most of the liver. In this case
vaginal delivery may result in dystocia (inability of the baby to exit the pelvis during birth) and
liver damage.[9] Immediately after birth a nasogastric tube is required to decompress the
intestines and an endotracheal intubation is needed to support respiration. The exomphalos sac
is kept warm and covered with a moist saline gauze and plastic transparent bowel bag to prevent
fluid loss. The neonate also requires fluid, vitamin K and antibiotic administration intravenously.[6]
[7]
 After management strategies are applied, a baby with an intact sac is medically stable and
does not require urgent surgery. This time is used to assess the newborn to rule out associated
anomalies prior to surgical closure of the defect.[9] Studies show there is no significant difference
in survival between immediate or delayed closure.[14]
Surgery can be performed directly for small omphaloceles, which will require a short stay in the
nursery department, or in a staged manner for large omphaloceles, which will require several
weeks stay. Staged closure requires a temporary artificial holding sac (a silo) to be placed over
the abdominal organs and sutured to the abdominal wall. This can be made of non-adhesive
dressing. The silo is gradually reduced in size at least once daily until all of the viscera have
been returned to the abdominal cavity. This is repeated for several days to a week until surgical
closure of the fascia/skin can be done. Closure may require a patch that can be rigid or non-rigid
and made of natural biomaterials such as a bovine pericardium or artificial materials. The skin is
then closed over the patch and it is re-vascularised by the body's liver blood vessels post-
surgery.[15][16][6] The staged surgery is required, as rushed reduction of the exomphalos
compromises venous return and ventilation, as it raises intra-abdominal pressure. [17] In some
cases, stretching of the abdominal wall to accommodate intestinal contents may be required. [6][9]
Infant before and after surgical treatment for exomphalos.

Non-operative therapy uses escharotic ointments. This is used for infants with large

omphaloceles that have been born prematurely with respiratory insufficiency and associated
chromosomal defects, as they would not be able to tolerate surgery. The ointment causes the
sac to granulate and epithelialize, which leaves a residual large ventral hernia, which can be
repaired later with surgery when the baby is more stable. [6][7][17] After surgery, for larger
omphaloceles, mechanical ventilation and parenteral nutrition is needed to manage the baby.[6]

Complications[edit]
Complications may occur prenatally, during birth, management, treatment or after surgery. Both
prenatally and during birth, the exomphalos can rupture. During birth there may be trauma to the
liver for giant omphaloceles. During management exomphalos can act as a metabolic drain
affecting nitrogen balance which can lead to failure to thrive, as well as hypothermia.[18][9] Use of a
non-absorbent patch during surgery can lead to wound sepsis post-surgery. Herniation from the
patch is also a possibility.[6] Intestinal dysfunction for a few weeks after the surgery is common,
therefore parenteral feeding is continued post-surgery, however prolonged use of this may lead
to hepatomegaly and cholestasis. If intestinal dysfunction persists it can lead to
intestinal necrosis.[16] Intestinal atresia can occur, which is where the mucosa and submucosa of
the intestine form a web that obstructs the lumen which leads to malabsorption. Obstruction of
the bowel can occur which results in short bowel syndrome. For the first few years of life there is
a high incidence of gastroesophageal reflux which can be complicated by oesophagitis.[9]
Post-surgery the umbilicus (navel) is deficient or abnormally placed that causes dislike amongst
many patients. Umbilical reconstruction can be difficult due to scar tissue and lack of extra skin
for surgical use, though this can be overcome by using tissue expanders below the skin
and umbilicoplasty.[17]
Ultimately, prognosis depends on the size of the defect and whether associated abnormalities
are present or complications develop. Mortalities and morbidities still occur, with the mortality
rate for large omphaloceles with associated abnormalities being higher. Most surviving
omphalocele infants have no-long term problems and grow up to be normal individuals. [19]