Pediatric Omphalocele and Gastroschisis

Ventral body wall defects comprise a group of congenital malformations that includes gastroschisis and omphalocele, which are relatively common, and ectopia cordis, bladder exstrophy, and cloacal exstrophy, which are extremely rare. The prevalence of gastroschisis is increasing; thus, it is the congenital anomaly most frequently encountered by pediatric surgeons. ^[1]

The reported incidence of abdominal wall defects is as follows:

• Gastroschisis - 1 case in 2000 births
• Omphalocele - 1 case in 4000 births
• Bladder exstrophy - 1 case in 40,000 births
• Ectopia cordis - 1 case in 125,000 births
• Cloacal exstrophy - 1 case in 200,000 births

Although the treatment of these babies is the task of neonatologists and pediatric surgeons, it behooves pediatricians to become familiar with the clinical spectrum of abdominal wall defects so that they are prepared to care for these children later in life. Sometimes, gastroschisis is as easy to repair as a surgical incision. In such cases, routine postnatal care may suffice; however, if multiple procedures are required or if the abdominal wall defect is one component of a multifaceted anomaly, further care by specialists familiar with the child's specific problems may be required.

A baby born with gastroschisis may have malabsorption, because in utero exposure of the intestine to amniotic fluid may cause mucosal or muscularis dysfunction, or the anatomic defect may constrict the mesentery causing ischemia and diminished intestinal length. In addition, there may be luminal obstruction from adhesions or bands associated with midgut malrotation, which accompanies all the anomalies in which the intestine remains outside the nascent abdominal cavity. Midgut volvulus, the complication most feared in babies with malrotation, is theoretically possible but unlikely, because of postsurgical adhesions. Atypical appendicitis may occur, however, if the abnormally located appendix is not removed. In addition, children with gastroschisis frequently have gastroesophageal reflux, which usually responds to medical therapy; fundoplication is rarely necessary. Hirschsprung disease, also, may contribute to these babies' intestinal dysfunction.

See the Medscape Drugs & Diseases articles Omphalocele and Gastroschisis as well as information from the Children's Hospital of Philadelphia on Omphalocele and Gastroschisis.

Embryology

Initially, the embryo is a flat disk surrounded by the umbilical ring. Gastrulation proceeds in a cephalocaudal direction and converts the original two-layered disk into three germ layers. The dorsal layer is the ectoderm, which becomes either the central nervous system (CNS) or the skin and sensory organs. The middle layer is the mesoderm, which forms the skeleton, connective tissue, and the cardiovascular and urogenital systems. The ventral layer is the endoderm, which develops into the intestines, liver, gallbladder, and pancreas.

Proliferation of the neuroectoderm and the underlying mesoderm pushes the embryonic disk above the umbilical ring like a sprouting mushroom. The amnion bulges over the embryo and fuses with the yolk sac and body stalk. As the embryo elongates, longitudinal enfolding of its lateral walls creates the appearance of a ridged cylinder. Ventral enfolding separates the thoracic and abdominal cavities from the extra-embryonic space. With caudal enfolding, the embryo begins to resemble a fetus.

The yolk sac is incorporated into the hindgut and the allantois is incorporated into the urogenital sinus creating the cloaca. The cloacal membrane separates the coelom from the amniotic cavity.

The mesoderm invades the cloacal membrane and unites the genital tubercles to form the ventral wall of the urogenital sinus. As the hindgut elongates, condensation of mesoderm anteriorly forms the urorectal septum. The body folds (cephalic, caudal, and lateral) unite where the amnion invests the yolk sac and body stalk.

Fusion is a complex process that also occurs in formation of the neural tube, palate, and lip. In these areas, a surface glycoprotein promotes adhesion; then, planned cellular death (apoptosis) and migration create continuity between the opposing surfaces.

In an analogous fashion, the amnion and the lateral folds of the body wall coalesce about the attenuated yolk sac, constricting the umbilical ring. This process requires a "component separation and reorganization"” for the opposing sides to become a continuous layer. Development of the gut, suspended on its mesentery, occurs coincidentally with these events.

By the sixth week of intrauterine life, rapid growth of the liver and intestines causes herniation of the midgut through the umbilical ring.

By the tenth week, the abdominal cavity has enlarged sufficiently to accommodate the return of the midgut.

Rotation and fixation of the duodenum and the proximal colon occur as the intestine returns to the abdominal cavity.

Omphaloceles and gastroschisis

Omphaloceles

In babies with omphaloceles, this return to the abdominal never takes place; thus, the intestine stays within the confines of the umbilical ring. See the image below)

Baby with an intact omphalocele.

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There is evidence to suggest that omphaloceles have a genetic etiology, as follows:

• Omphaloceles are associated with increased maternal age.
• Omphaloceles occur in twins, consecutive children, and different generations of the same family.
• Omphaloceles are associated with trisomies 13, 18, and 21 (in 25-50 % of cases) and with Beckwith-Wiedemann Syndrome

Gastroschisis

In gastroschisis, there appears to be a weakness in the body wall—perhaps caused by defective ingrowth, cellular death, or impaired cellular fusion, such that the intestines are extruded through the defective area into the amniotic cavity. See the image below.

Baby with gastroschisis.

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Gastroschisis is associated with young maternal age as well as low gravida, prematurity, and low birth-weight babies, secondary to in utero growth retardation.

Clustering of cases (number and severity) suggests a complex etiology, such as environmental factors acting upon susceptible hosts.

Other abdominal wall defects

There is a vast spectrum of body wall defects, which vary in their anatomic location and size of the defect. Issues to consider include the following:

• Is a sac is present?
• Is it ruptured?
• Are there associated anomalies (which are four times more prevalent in omphalocele than gastroschisis)?

Other associated anomalies include the following:

• Congenital heart disease
• Cleft palate
• Musculoskeletal abnormalities
• Dental malocclusion
• Intestinal Atresia
• Patent omphalomesenteric duct remnant, creating an umbilical cord stoma

Hernias of the umbilical cord

In hernias of the umbilical cord, the umbilical ring is oversized, but the relation of the amnion to the yolk sac and connecting stalk is normal. See the image below.

Baby with an umbilical cord hernia.

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Urachal remnants and omphalomesenteric duct malformations

Urachal remnants ^[2] and omphalomesenteric duct malformations ^[3] result from deficient apoptotic cell death of the epithelium of the urachus and yolk stalk. See the images below.

Omphalomesenteric duct remnant presenting as an "umbilical granuloma."

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Operative finding: patent omphalomesenteric duct, which is being excised.

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Bladder exstrophy

The bladder develops between the fifth and ninth gestational weeks (postfertilization). ^[4] By 10 weeks, urine is produced and mixes with the amniotic fluid; this is is crucial for normal lung development. In healthy babies, the bladder is visible on ultrasonography toward the end of the first trimester.

In patients with bladder exstrophy, the bladder image is a protruding, semi-solid mass inferior to an umbilical cord that is displaced caudally. The pelvis is shallow and flat; the lack of space displaces the developing bladder, urethra, vagina, and rectum anteriorly. Herniation of these organs interferes with the normal development of the lower abdominal wall. See the images below.

Baby with bladder exstrophy and epispadias; note the appearance of the bladder mucosa, indicating chronic inflammation.

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Another view demonstrating the epispadias shown in the previous image.

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Prune-belly syndrome

Prune-belly syndrome involves hydroureteronephrosis, megacystis, and undescended testes in addition to multiple other organ system defects. This syndrome is caused by increased "apoptotic" cell death in the body-wall placode or insufficient deposition of mesodermal cells with abnormal retention of the yolk sac. ^[4]

Note the following:

• There is attenuation of the abdominal musculature.
• Muscle fibers are absent and are replaced by thick collagenous aponeuroses.
• Hypoplasia of the abdominal wall contrasts with hypertrophy of the bladder wall, causing bladder neck obstruction and dilation of the ureters and renal collecting system.
• Faulty intercellular conduction of electrical impulses causes disordered muscular contraction and ineffective ureteric peristalsis.
• Approximately 95% of babies with prune belly syndrome are male; the absence of prostatic and seminal fluid precludes normal sperm development and causes infertility.

Cloacal exstrophy

The urorectal septum divides the cloacae into the urogenital sinus and the rectum. Defective enfolding of the embryo's caudal pole and deficient incorporation of the yolk sac and allantois into the urogenital sinus leads to malformation of the external genitalia.

Without ingrowth of the mesoderm, the cloaca persists; differentiation of the genitourinary system and hindgut are arrested; and development of the lower abdominal wall obstructed. The result is cloacal exstrophy.

This anomaly is associated with mutations in the homeobox genes.

See the images below.

Baby with cloacal exstrophy.

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Note the bifid genitalia in this baby with cloacal exstrophy.

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Folic acid deficiency, hypoxia, and salicylates cause rats to develop abdominal wall defects, but the clinical significance of these experiments is conjectural.

Elevation of maternal serum alpha-fetoprotein (MSAFP) is associated with omphalocele and gastroschisis. An elevated MSAFP warrants ultrasonography to determine if structural abnormalities are present in the fetus. If the study is suspicious for an omphalocele, amniocentesis is indicated to determine any associated genetic abnormality.

Polyhydramnios occurs in association with intestinal atresia, which may complicate gastroschisis. If polyhydramnios is identified by fetal ultrasonography, the mother should be referred to a tertiary care facility for optimal care of her newborn.

United States data

Allman et al evaluated retrospective discharge data (1997-2015) for the prevalence of infants with gastroschisis in US neonatal intensive care units (NICUs). Of 1,158,755 total discharges, 6,023 infants (5.2 per 1000 discharges) had gastroschisis and 1,885 (1.6 per 1000 discharges) had an omphalocele. ^[5] The rate of gastroschisis increased from 2.9 to 6.4 per 1000 discharges over a 12-year period (1997-2008), gradually declined over the next 4 years (2008-2011) from 6.4 to 4.7 per 1000 discharges, and then remained stable thereafter. The rate of omphalocele was stable over the same time periods at 1-2 per 1000 discharges. ^[5]

International data

The combined incidence of omphalocele and gastroschisis is 1 case per 3,500 births. Epidemiologic data compiled over the last 40-50 years show that the incidence of omphalocele has remained constant, whereas that of gastroschisis is increasing.

Over the past 2 decades, the incidence of gastroschisis has increased three- to four-fold, whereas the incidence of omphalocele has remained constant. See the table below.

Table 1. Incidence rates for gastroschisis and/or omphaloceles in various regions and time periods. ^{[1, 6, 7, 8]} (Open Table in a new window)

Race- and sex-related demographics

Neither gastroschisis nor omphalocele has a geographic or racial predilection. The Texas data indicate that gastroschisis occurs most commonly in Latinos, next in white persons, and least frequently in black individuals.

The male-to-female ratio is 1.5:1.

Prognosis

Omphalocele

Infants with omphaloceles are complex, with multisystem organ involvement. Their prognosis depends on the severity of the associated problems.

Giant omphaloceles can be closed; however, multiple surgical procedures are usually necessary. In addition, these infants may have additional medical problems that make caring for them quite challenging.

The critical factor affecting the survival of a baby with a giant omphalocele is the size of the thoracic cavity with associated pulmonary hypoplasia and chronic respiratory failure. Even if the baby has a small thorax, the potential for lung growth and development encourages optimism regarding the ultimate prognosis.

Gastroschisis

The patient's prognosis depends on the severity of the associated problems such as prematurity and intestinal inflammatory dysfunction, intestinal atresia, and short gut. A population-based cohort study (from 28 pediatric surgical centers in the United Kingdom and Ireland) analyzed the 1-year outcomes of infants with gastroschisis. Babies with complex gastroschisis required longer hospital stays and had more complications than babies with simple gastroschisis. Classifying infants with gastroschisis into "simple" versus "complex" (macroscopic intestinal abnormalities) may be a reliable predictor of outcome. ^[9]  A population-based study of 502 Australian infants with abdominal wall defects (166 omphalocele, 336 gastroschisis) reported similar findings of longer hospital stays and parenteral nutrition as well as higher rates of infection but lower overall mortality in infants with gastroschisis compared with those with omphalocele. ^[10]

Many pediatric surgeons believe that the prognosis has improved because of maternal sonographic diagnosis and monitoring, which allows expeditious delivery of these babies at tertiary centers.

Obtaining primary abdominal wall closure in a baby with gastroschisis rarely occurred in the past; it was usually necessary to use a silo. Primary closure is commonplace today. This progress is attributed to improvements in prenatal and obstetric care. ^{[6, 7, 11]}

Morbidity/mortality

The mortality of omphaloceles relative to gastroschisis is 8:1. Irreversible pulmonary hypertension/right heart failure is the usual terminal condition.

Factors adversely influencing the management of babies with gastroschisis are as follows:

• Prematurity and low birth weight
• Hypothermia (exposure of the intestine to the ambient environment)
• Dehydration (gastrointestinal losses, in addition to the above factors)
• Sepsis (open wound)
• Hypoglycemia (stress with little metabolic reserve)
• In utero growth restriction (protein loss from the extruded intestines)
• Oligohydramnios
• Fetal distress and birth asphyxia
• Injury to the intestines during delivery (tearing or cutting the bowel or mesentery)

Improvements in respiratory care, pharmacology (antibiotics and total parenteral nutrition), anesthesia, and surgery have increased the survival rates for these babies from 60% during the 1960s to more than 90% in more recent years. ^{[6, 7, 11]}

See the images below.

Baby with gastroschisis and associated intestinal atresia.

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Baby with gastroschisis and colon atresia. Bulbous proximal end of the atretic colon is excised, and a colostomy is created at the abdominal wall defect. An anastomosis of the proximal, dilated colon to the distal microcolon (in view of its small caliber) would not function properly. The colostomy can be closed 4-6 weeks later.

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Long-term morbidity from gastroschisis is related to intestinal dysmotility (pseudo intestinal obstruction), malabsorption (mucosal injury), short gut, and gastroesophageal reflux disease. Difficulties in obtaining wound closure usually are reflected in intestinal morbidity. Poor healing of the abdominal wound causes an incisional hernia, which may require surgical repair. ^{[12, 13, 14, 15]}

The following scenarios may eventuate in short-gut syndrome, with which the baby has inadequate intestinal length:

• An antenatal mesenteric vascular accident may cause intestinal atresia.
• Constriction of the mesentery of the extruded intestine by a small abdominal wall defect may cause gut infarction ("closing gastroschisis").
• An excessively tight closure of the abdominal wall defect may impede splanchnic blood flow and result in intestinal ischemia or necrosis.

Closed-loop obstructions, in which both efferent and afferent limbs of the intestine are blocked, occur in volvulus (rotation) of the entire midgut around its mesentery (the superior mesenteric artery and vein) or when a single loop of intestine flips on its mesentry or around an external point of fixation, such as an adhesion to the abdominal wall. This causes tense distention and ischemic injury of the intestines (ie, "strangulation obstruction"). ^[16]

The injury produced by antenatal exposure of the intestine to amniotic fluid (mucosal and muscular) leads to diminished absorptive and propulsive capacity of the gut and compounds the crippling effect of diminished length.

The care of babies with short-gut syndrome has improved with innovations in parenteral and enteral nutrition, venous access devices, prevention and early treatment of catheter sepsis, innovative surgical procedures to optimize gut length, and aggressive treatment of bacterial overgrowth in stagnant loops of intestine. Babies with short-gut syndrome from gastroschisis account for a substantial number of children undergoing intestinal transplantation. ^{[17, 18]}

See the images below.

Gastroschisis complicated by jejunal atresia and loss of the entire distal small bowel = the grey tissue.

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Following lysis of adhesions, tubularization of the viable, mesenteric portion of the proximal jejunum, the eviscerated viscera are reduced and the gastroschisis abdominal wall defect closed.

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Baby with a small omphalocele sac whose contents were liver and gall bladder.

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The omphalocele sac contains liver and gall bladder.

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Completed repair; simulating an umbilicus.

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Babies with giant omphaloceles usually have small, bell-shaped thoracic cavities and minimal pulmonary reserve. Repair of the omphalocele may precipitate respiratory failure, which may be chronic and require a tracheotomy and long-term ventilator support. The author recently treated (unsuccessfully) a baby with a giant omphalocele and a diaphragmatic hernia. Both conditions are associated with pulmonary hypoplasia, and, occurring together, they were of such severity as to preclude survival, despite extracorporeal membrane oxygenation (ECMO) support.

Even with successful repair of a giant omphalocele, the liver remains located in the midepigastrium, where it lacks the normal protection afforded by the lower rib cage and where it is more vulnerable to injury. See the image below.

Baby with a giant omphalocele, in which the liver assumes an ectopic position in the epigastrium.

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A study by Corey et al indicated that compared with infants with gastroschisis, those with omphalocele have a higher incidence of other anomalies, are more likely to have pulmonary hypertension, and have a higher mortality rate. In the study, which involved 4687 infants with gastroschisis and 1448 with omphalocele, the investigators found that 35% of the patients with omphalocele had at least one other anomaly, compared with 8% of those with gastroschisis. The odds ratios for pulmonary hypertension and mortality in infants with omphalocele compared with those with gastroschisis were 7.78 and 6.81, respectively. ^[19]

Complications

Nutritional depletion is inevitable in a baby with an omphalocele treated conservatively, because of the large open wound. Positive nitrogen balance is restored following skin closure.

Prolonged parenteral nutrition can cause hepatotoxicity, manifested by cholestasis and hepatomegaly, which may complicate staged closure of a giant omphalocele. Omega 3 fatty acids (Omegaven) reportedly may reverse "intestinal failure associated liver disease."

Infants with giant omphaloceles have pulmonary insufficiency (hypoplasia consequent upon the small thoracic cavity) and may require a tracheotomy and prolonged ventilator support. Staged abdominal wall closure gradually increases the intra-abdominal pressure; this elevates the diaphragm and may make ventilation more difficult.

Infants with giant omphaloceles have an increased risk of sepsis because they are depleted nutritionally by the open wound and because of their prolonged need of ventilator support and central vascular access.

Parents should be instructed regarding the significance (ominous) of bilious emesis, because this may indicate that adhesive small-bowel obstruction or midgut volvulus has occurred.

They should be informed that their child's appendix is located in an unusual location and that computed tomography scanning is the most reliable way to diagnose acute appendicitis.