Omphalocele

The incidence of omphalocele ranges from 1 in 1100 to 1 in 3000 pregnancies, but it is less common among live births (1 and 10,000) due to deaths in utero and terminations of pregnancy. Omphalocele is twice is common in males. It is also more common in mothers over 29, maternal obesity and multiple gestations.

The incidence of omphalocele ranges from 1 in 1100 to 1 in 3000 pregnancies, but it is less common among live births (1 and 10,000) due to deaths in utero and terminations of pregnancy. Omphalocele is twice is common in males. It is also more common in mothers over 29, maternal obesity and multiple gestations.

Omphaloceles may differ in size and location. Omphaloceles that are more than 5 cm in diameter or contain the liver herniated outside of the abdomen are considered giant omphaloceles. Giant omphaloceles are at risk for associated pulmonary underdevelopment (pulmonary hypoplasia) and pulmonary hypertension. Omphaloceles may occur in the upper midline abdomen (epigastric) associated with pentalogy of Cantrell, a collection of anomalies including omphalocele, diaphragmatic defect, defect in the pericardium, defect in the sternum and intracardiac defects. The mid-abdominal omphalocele is the most common location. Abdominal location however, may be seen in association with bladder exstrophy or cloacal exstrophy, in which either the bladder or the cloaca opens up on the lower abdomen with the omphalocele above it. This may be part of the multiple malformation complex known as OEIS (omphalocele, cloacal exstrophy, imperforate anus and spinal defects).

Associated structural abnormalities occur in 25 to 97% of cases, although up to 40% of these anomalies may not be diagnosed until after the baby is born. Congenital heart defects occur in 15 to 50% of cases. Among the most common are ventricular septal defect, tetralogy of Fallot, and dextrocardia. Gastrointestinal anomalies include malrotation of the bowel, diaphragmatic hernia, intestinal atresia, imperforate anus, which collectively occur in 17 to 40% of cases. Genitourinary anomalies are seen in 10 to 40% of cases and include renal agenesis, polycystic kidney disease, ureteral stenosis or duplication, vesicoureteral reflux, urethral atresia, and bladder agenesis. Other anomalies that occur with omphalocele include spina bifida, cleft lip and palate, clubfeet, and vertebral anomalies.

Small omphaloceles are more likely to have an abnormal karyotype (23 sets of chromosomes, instead of the usual 22). When there are associated structural anomalies, chromosomal abnormalities or multiple malformation syndromes are present in 30 to 70% of cases. The most common genetic abnormalities and multiple malformation syndromes are trisomy 18, 13, 21, Beckwith-Weidemann syndrome, omphalocele-exstrophy-imperforate anus-spinal (OEIS) complex, and pentalogy of Cantrell.

Beckwith-Weidemann syndrome is an autosomal dominant condition occurs in 5 to 25% of cases of all omphaloceles. Omphaloceles associated with Beckwith-Weidemann syndrome tend to be small containing only the bowel. Beckwith-Weidemann syndrome also has associated macrosomia (excessive body growth), organomegaly (enlarged organs), macroglossia (large tongue), polyhydramnios (too much amniotic fluid) and placentomegaly (enlarged placenta), but diagnosis is rare before the third trimester as these conditions develop late in pregnancy. Preterm birth complicates Beckwith-Weidemann syndrome in 50 to 60% of cases. In Beckwith-Weidman syndrome, the enlarged pancreas can secrete excessive insulin causing severely low blood sugar after delivery. Beckwith-Weidemann syndrome is also associated with childhood cancers, such as Wilms’ tumor, neuroblastoma, and hepatoblastoma, which can be seen in 2.6 to 28% of cases.

Omphalocele is diagnosed usually on routine ultrasound when a midline abdominal wall defect is noted with a mass encased by a thin membrane. The umbilical cord does not insert on the abdominal wall as it should but rather onto the omphalocele membrane itself. The liver and bowel are present within the membrane. Doppler ultrasound will show liver vessels within the omphalocele membrane suggestive of liver herniation into the omphalocele sac.

It is important to rule out other conditions which can be confused with omphalocele. Hernia of the umbilical cord occurs in normal development in which loops of bowel may slip up into the cord at its insertion on the abdominal wall but there is no abdominal wall defect. Hernia of the cord can persist throughout the gestation. Gastroschisis is another type of abdominal wall defect in which the defect is immediately to the right of the normal umbilical cord insertion on the abdominal wall. In gastroschisis there is no membrane covering the bowel loops, which flow freely in the amniotic fluid. Unlike omphalocele, the abdominal wall defect in gastroschisis tends to be small and usually does not include liver. If the membrane in omphalocele ruptures, it may be difficult to tell omphalocele from gastroschisis, but the larger the abdominal wall defect, the more likely this represents a case of ruptured omphalocele.

The most important aspect of caring for a mother carrying a baby with omphalocele is to accurately diagnose the omphalocele, determine the size and type, rule out associated chromosomal and associated structural abnormalities, and develop a comprehensive prognostic assessment. This is done by imaging with ultrasound, fetal MRI, and fetal echocardiography. In addition to identifying the structural abnormalities that might be present, it is important to obtain measurements that help define the severity of the omphalocele. The omphalocele circumference to abdominal circumference (OC/AC) ratio and omphalocele diameter to abdominal diameter (OD/AD) ratio can identify babies at increased risk for respiratory insufficiency, the need for staged repair, and prolonged hospitalization. In addition, fetal MRI can calculate the observed-to-expected total lung volumes (O/E TLV), which can identify fetuses with omphalocele at greatest risk for pulmonary hypoplasia and pulmonary hypertension. An amniocentesis should be performed for karyotype and microarray analysis. The incidence of fetal growth restriction is 50% in omphalocele. In addition, there is a marked increase in the rate of intrauterine fetal demise in omphalocele, so twice-weekly antenatal testing should be started at 30 weeks gestation.

Average gestational age at delivery is 36 weeks. Cesarean delivery may not be necessary for small omphaloceles, but it’s strongly recommended for giant omphaloceles to prevent dystocia (failure to progress through birth canal) or injury to the extracorporeal liver.

It is important to note that as long as the omphalocele membrane is intact there is no urgency to treat the omphalocele. There is time to assess the baby’s respiratory function, need for supplemental oxygen, or ventilatory support. In addition, work ups may be ordered to rule out other structural defects, such as heart defects and pulmonary hypertension. If the membrane is intact, there are 3 options: primary repair; staged repair; and delayed repair or the “paint and wait” approach. Which option is best depends on the gestational age of the baby at delivery, presence or absence and severity of pulmonary hypoplasia or pulmonary hypertension, and the presence or absence of congenital heart disease. If the omphalocele is small and isolated (no other anomalies), primary repair results in the shortest hospital stay and best outcomes. If the defect is larger and primary repair is not possible, staged reduction may be performed. In this approach, a Silastic silo is sewn to the fascia, and the silo is gradually reduced, gently displacing the bowel and liver back into the abdominal cavity. Over the course of 5 to 7 days, once complete reduction is achieved, the abdominal wall can be surgically closed (usually with a patch).

In cases in which the baby is quite premature, has significantly pulmonary hypoplasia or pulmonary hypertension, or requires mechanical ventilator support, it is best to “paint and wait” to avoid unnecessary stress of the baby. This can be done by applying antibiotic cream and sterile dressing changes daily. Alternatively, a negative pressure dressing can be applied twice weekly to encourage re-epithelialization. Once the membrane is completely re-epithelialized, Ace wrapping can be started to encourage development of the abdominal cavity, which over a period of months to a year, results in movement of the bowel and liver within the abdomen. At that point, an abdominal wall reconstruction can be formed performed.

The survival in omphalocele in general is excellent, but that prognosis is related to the presence of associated chromosomal abnormalities, cardiac defects, and the severity of pulmonary hypoplasia. The survival for prenatally diagnosed omphalocele is lower than those diagnosed after birth (23% versus 80%). With small omphaloceles, survival to 1 year is 90%. But with giant omphaloceles, the mortality increases, ranging from 50 to 89%. In the setting of chromosomal abnormalities, mortality approaches 100%. The majority of deaths occur in the first month of life from pulmonary hypoplasia, respiratory failure, and prematurity, which are all more commonly seen in giant omphalocele. There is a direct correlation between fetal MRI measurements of O/E TLV to survival. An O/E TLV greater than 50% has a 96% survival; an O/E TLV greater than 25% less but than 50% has a 92% survival; and a O/E TLV less than 25% has a 60% survival.

In general, the long-term outcome of babies with omphalocele is excellent. There is a subset of patients with severe tracheobronchomalacia who require a tracheostomy for positive end expiratory pressure (PEEP) to support their airway. This is usually resolved by 1½ to 2 years of age and the trach can be removed. There is also an increased incidence of autism spectrum disorders and learning disabilities in children with omphalocele.

The defect is thought to be caused by an abnormality that occurs during the process of body infolding at 3 to 4 weeks of gestation (Dimmick and Kalousek, 1992). At that time, 3 folds occur simultaneously, and each is associated with a distinct type of omphalocele:

• Cephalic folding defects result in a high or epigastric omphalocele. An example of this is pentalogy of Cantrell, which consists of an epigastric omphalocele, anterior diaphragmatic defect, sternal cleft, pericardial defect, and associated intracardiac defects (Cantrell et al., 1958).
• Lateral folding defects result in the classic omphalocele with a midabdominal defect.
• Caudal folding defects result in a low or hypogastric omphalocele, as seen in bladder or cloacal exstrophy (Duhamel, 1963; Meller et al., 1989; Vasudevan et al., 2006).

The spectrum of severity of abdominal wall abnormalities can vary from a small umbilical hernia to a large defect with extrusion of the abdominal viscera.

The incidence of omphalocele ranges from approximately 1 to 3.8 in 10,000 livebirths (Stallings 2019, St Louis 2017, Baird and MacDonald, 1981; Lindham, 1981; Rankin et al., 1999; Stoll et al., 2001). The incidence of omphalocele is higher in combined livebirths and stillbirths (1 in 300 to 1 in 4000), reflecting the increased risk of intrauterine fetal death in cases of omphalocele. In fact, the overall incidence of abdominal wall defects is 20 times greater in stillborn than in liveborn infants (McKeown et al., 1953; Baird and MacDonald, 1981; Lindham, 1981; Carpenter et al., 1984). While the increase in the incidence of omphalocele has not been as great as for gastroschisis, there has been an 11% increase in prevalence of omphalocele (St Louis et al 2017).

This rise in mothers with omphalocele is associated with extremes of maternal age with the rate among < 20 and > 40 years old double that of the general obstetric population (Byron-Scott et al 1998, Marshall et al 2015). Maternal risk factors for omphalocele include obesity and multiparity and mothers over 35 years of age. (Marshall 2015, Du ong 2012 Walker 2007). There is a higher prevalence among Hispanic and lower prevalence among non-Hispanic black mothers (Stallings 2019). There is a higher prevalence among male fetuses (Kirby 2017).

The diagnosis of omphalocele has been made as early as 10 to 12 weeks of gestation by transvaginal sonography, when an echogenic mass nearly equal to the size of the diameter of the fetal abdomen was found anterior to the fetal abdomen (Brown et al., 1989). The use of three-dimensional transvaginal ultrasound examination may facilitate this diagnosis early in gestation (Anandakumar et al., 2002; Tonni and Centini, 2006). The ultrasonographic appearance of omphalocele varies depending on the size and location of the defect, the presence of ascites, and the organs contained within the defect. However, a principal diagnostic feature of omphalocele is the umbilical cord insertion into the membrane covering the abdominal wall defect. This contrasts with gastroschisis, in which the defect is immediately to the right of the normal umbilical cord insertion into the abdominal wall.

The cord insertion site at the caudal apical portion of the omphalocele membrane can be visualized with color flow Doppler studies on sagittal or oblique images. An additional diagnostic feature is the presence of the intraabdominal portion of the umbilical vein coursing through the central portion of the defect. Omphaloceles are characterized in utero by the presence of a membrane; however, occasionally this membrane will rupture. In cases of ruptured omphalocele, the abdominal contents are floating free in the amniotic cavity, similar to gastroschisis. However, unlike gastroschisis, in ruptured omphaloceles, the defects are usually large and have at least exposed, if not extracorporeal, liver.

Even when the diagnosis of omphalocele is not in doubt based on ultrasound findings, fetal MRI is an important adjunct to prenatal imaging. The high rate of associated anomalies in omphalocele, which may not be picked up on prenatal ultrasound, underscores the need for additional imaging. The prenatal detection rate of associated anomalies and omphalocele ranges from 30 to 70% (Faugstad 2014, Connor 2008).

On fetal MRI omphalocele appears as a central abdominal wall defect covered by a thin membrane with abdominal viscera herniating into the sac. The liver is more readily distinguished from the bowel on fetal MRI compared to ultrasound. Fetal MRI is helpful in determining not only the size of the abdominal wall defect but the degree of viscero-abdominal disproportion by virtue of its wider field-of-view compared to ultrasound. In a subset of omphaloceles, particularly those meeting criteria for giant omphalocele, fetal MRI is helpful in estimating fetal lung volumes. Danzer et al reported using measurements of total lung volume as a ratio to gestational age matched nomograms to yield an observed to expected total lung volume (O/E TLV) ratio. They found that giant omphaloceles had significantly lower than expected lung volumes compared to gestational age matched nomograms. Specifically, gestation matched O/E TLV of less than 25% predicted a significant increase in mortality and a more complicated postnatal course.

Giant omphaloceles have been defined as an anterior abdominal wall defect of greater than 5 cm or more than 50% of the liver in an extracorporeal position in the omphalocele sac (Akinkuotu 2015). There is no universal agreement on the definition of a giant omphalocele. Mantero et al suggested a ratio of the omphalocele size to the head circumference (O/HC) ratio of greater than 0.21 predicts inability to achieve a primary closure of the defect (Mantero 2011). They found that the O/HC ratio was a better predictor of prognosis than the measurement of the abdominal wall defect. Giant omphaloceles are associated with a poorer prognosis with respiratory insufficiency observed in 75% and pulmonary hypertension in 57% (Hutson 2008 ) indicating the importance of making this distinction on prenatal imaging for prenatal counseling.

Congenital heart defects are seen with omphaloceles in 15 to 50% of cases. The most commonly observed defects include ventricular septal defects and Tetralogy of Fallot. The cardiac axis can also be shifted, even in the absence of structural heart disease, particularly in giant omphaloceles. While the normal fetal cardiac index is 0 to +60o, in omphaloceles, the axis shifts in a counterclockwise fashion with the axis commonly at +90o. It is thought that the abdominal wall defect shifts the position of the liver applying traction on the heart altering the cardiac axis.

Pentalogy of Cantrell is a multiple malformation syndrome that includes complete or partial expression of 5 congenital defects: cleft or absence of the sternum; defect of the anterior diaphragm; defect in the pericardium; intracardiac defects; and epigastric omphalocele. Not every case has all 5 components, and each component may vary greatly in severity from one case to another. The prognosis depends, in large part, on the severity of the cardiac defects and the degree of associated pulmonary hypoplasia. Despite defects, which should be amenable to surgical repair, mortality of 50 to 80% is reported (Arujo 2017, Jnah 2015).

It is usually easy to distinguish sonographically between gastroschisis, with its cord insertion on the abdominal wall, and omphalocele, with the cord insertion at the apex of the membrane encompassing the abdominal wall defect. It sometimes is more difficult to distinguish between a small omphalocele and a hernia of the cord or between a ruptured omphalocele, gastroschisis, and body-stalk anomaly.

Two syndromes deserve mention in the context of omphalocele: pentalogy of Cantrell and Beckwith–Wiedemann syndrome. Pentalogy of Cantrell is characterized by the presence of an epigastric omphalocele and defects of the sternum, anterior diaphragm, and diaphragmatic pericardium, with associated intracardiac lesions (Cantrell et al., 1958; Toyama, 1972; Spitz et al., 1975). Cantrell et al. (1958) hypothesized that the syndrome might have resulted from a developmental failure of a segment of lateral mesoderm around 14 to 18 days of embryonic life. Consequently, there is a lack of development of the transverse septum of the diaphragm and a lack of migration of the two paired mesodermal folds of the upper abdomen. A defect in the lower sternal region develops, allowing for protrusion of the heart and the upper abdominal organs. The syndrome is very rare. Ghidini et al. (1988) reviewed the Yale experience with 10 cases of pentalogy of Cantrell. Five pregnant patients elected termination and the remaining five delivered infants; there were no survivors beyond 3 months of age. A number of other anomalies can be associated with pentalogy of Cantrell, including craniofacial abnormalities, chromosomal abnormalities, clubfeet, malrotation of the colon, hydrocephalus, and anencephaly (Craigo et al., 1992). The defects themselves can vary in severity, ranging from only rectus muscle diastasis to a large omphalocele. The most common cardiac abnormalities include atrial and ventricular septal defects, and tetralogy of Fallot (Bryker and Breg, 1990). The prognosis in pentalogy of Cantrell is directly related to the severity of the cardiac defect and pulmonary hypoplasia.

The Beckwith–Wiedemann syndrome, otherwise known as exomphalos-macroglossia-gigantism (EMG) syndrome, consists of the presence of omphalocele, visceromegaly, macroglossia, and severe neonatal hypoglycemia. Cardiac abnormalities are also frequently seen in this syndrome. Greenwood et al. (1977) found that 12 of 13 patients with this syndrome had cardiovascular malformations, and 7 of the 12 had structural abnormalities. Malignant tumors can develop in 10% of patients, including Wilms’ tumor, hepatoblastoma, and adrenal tumors (Sotelo, 1977). This syndrome does not have any obligatory anomalies, and the diagnosis has been made without macroglossia or omphalocele (Cohen and Ulstrom, 1979). Evidence of macroglossia, or enlargement of adrenal glands, liver, kidneys, or pancreas, in the setting of omphalocele should alert one to the possible diagnosis of Beckwith–Wiedemann. These findings are rare and seldom seen prior to the third trimester.

In a large series of 1500 newborns with omphalocele, Beckwith-Wiedemann syndrome was the most common genetic syndrome accounting for 6% of cases followed by 3% for trisomy 13, 2% for trisomy 18 and 1% for trisomy 21 (Corey et al 2014). The prevelance of Beckwith-Wiedemann syndrome may be as high as 10-20% in fetuses with isolated omphalocele.

Omphalocele can present as part of a syndrome or as an isolated defect. A list of the syndromes associated with omphalocele is given in Table 1 (Stoll et al., 2008). The most important prognostic variable is the presence of associated malformations or chromosomal abnormalities. Visceral malformations can accompany omphalocele in 50% to 70% of cases, and chromosomal abnormalities can be seen in 30% to 69% (Paidas et al., 1994; Brantberg et al., 2005; Lakasing et al., 2006). Interestingly, the absence of the liver in the omphalocele has been correlated with fetal karyotypic abnormalities and perinatal mortality (Kline-Fath 2021).

Nyberg et al. (1989) were the first to report an association between omphalocele contents and fetal chromosomal abnormalities. Other investigators have validated the finding that small defects in omphalocele that contain only bowel are associated with an increased risk of chromosomal abnormalities (Benacerraf et al., 1990; Getachew et al., 1991). In one study, chromosomal abnormalities were present in all 8 fetuses with intracorporeal liver, as opposed to 2 of the 18 fetuses with an extracorporeal liver. They also found a significant association between advanced maternal age (33 years and older) and abnormal karyotype. Gilbert and Nicolaides (1987) found that in a series of 35 fetuses, there was a high rate of chromosomal abnormalities (54%) with a predominance of trisomy 18 (17 of 19 cases of chromosomal abnormalities). Brantberg et al. (2005) found a higher incidence of karyotypic abnormalities when the omphalocele was central (69%) as opposed to epigastric (12.5%) in location.

The constellation of other associated malformations varies greatly, ranging from single, minor, nonlethal abnormalities to multiple complex life-threatening abnormalities that influence long-term prognosis more than the omphalocele itself. The pediatric literature (as opposed to the obstetric literature) has reported a better prognosis for neonates with omphalocele, due to the fact that many of the fetuses with multiple associated anomalies die in utero or during the immediate perinatal period. The report from Rijhwani et al. (2005) from King’s College Hospital is illustrative of this point, with survival of 34 of 35 neonates undergoing primary or staged closure. The same institution reported that fewer than 10% of the 445 prenatally diagnosed cases of omphalocele survived to repair (Lakasing et al., 2006).

Several investigators have described the impact of associated anomalies on survival in cases of omphalocele. Hughes et al. (1989) reviewed a series of 46 cases detected by prenatal ultrasound examination from three high-risk obstetric referral centers. In 43 of 46 cases, adequate follow-up information was available. Twenty-nine of the 43 cases (67%) had additional malformations, with 23 (79%) considered major and 6 (21%) considered minor. Three of the 29 pregnancies were terminated. There was a total of 58 individual anomalies in the 26 fetuses in which the pregnancy was continued. Cardiac anomalies were the most common (14 cases), including ectopia cordis (4). The other systems involved were skeletal (9), gastrointestinal (6), genitourinary (6), and central nervous (7). Fetal mortality was most strongly associated with the presence of concurrent malformations. Twelve of the 15 fetuses (80%) with concurrent malformations died, and the 3 that survived had isolated minor abnormalities. This was in contrast to 7 fetuses without additional anomalies that survived. In the Hughes et al. (1989) series, the size of the omphalocele was not associated with fetal mortality. Six of the 10 survivors had a transverse omphalocele to abdomen ratio of >0.6 and two omphaloceles measured more than 10 cm. Abnormal amniotic fluid volume was present in 9 of the 12 fetuses that died spontaneously, and 3 of these had no abnormalities detected on sonographic examination.

Tucci and Bard (1990) reviewed a 5-year Canadian experience consisting of 28 cases of omphalocele. They initially divided their cases into two groups on the basis of the size of the defect, small (<5 cm) and giant (>5 cm). Of the 12 fetuses with small omphaloceles, only 1 died, whereas 10 of the 16 infants with giant omphalocele died and all except 1 had severe associated anomalies. There were five cases of congenital heart disease, three diaphragmatic hernias, and two central nervous system malformations. Of note, none of the six surviving infants had associated severe malformations. In this series, four of the survivors had liver herniation, which suggests that giant omphaloceles can have a favorable prognosis if other severe anomalies are not present.

Nicolaides et al. (1992) compiled their 8-year experience with omphalocele and reviewed both the obstetric and pediatric literature regarding the presence of chromosomal abnormalities and associated malformations. Of the 116 cases of omphaloceles, 87 (75%) had associated malformations. They also found a higher incidence of chromosomal abnormalities when the omphalocele contained only bowel as compared with omphaloceles that contained liver and bowel (25 of 44 vs. 17 of 72). In their summary, of 349 cases detected antenatally, 229 (65.6%) had associated malformations. Summarizing 13 studies with postnatal follow-up, an overall incidence of associated anomalies is 50%. They also noted an association with neural tube defects in chromosomally normal fetuses (Ardinger et al., 1987).

Nicolaides’ group reported their 11-year experience with 445 cases of omphalocele from the Harris Birthright Centre for Fetal Research at King’s College Hospital (Lakasing et al., 2006). In 250 cases (56%) the karyotype was found to be abnormal, and in 130 cases (30%) the karyotype was normal, with the remainder declining karyotype analysis. In the group with karyotype abnormalities, 248 (99%) underwent termination of pregnancy or died in utero. Among the 130 cases with normal karyotype, 74 (56%) were found to have associated structural anomalies. Lakasing et al. (2006) reported that during an 11-year period from 1991 to 2001, 445 cases of omphalocele experienced less than 10% survival from operative repair due to termination of pregnancy, intrauterine fetal demise, and neonatal death.

Elevated maternal serum α-fetoprotein (MSAFP) levels have traditionally been associated with open neural tube defects, but they are also associated with ventral abdominal wall defects (Brooke et al., 1979; Stiller et al., 1990; Killam et al., 1991). The sensitivity of MSAFP screening for the detection of abdominal wall defects will vary depending on whether it is omphalocele or gastroschisis and on the cutoff value of MSAFP used (Paidas et al., 1994). MSAFP screening has a much higher sensitivity for detecting gastroschisis than for detecting omphalocele. Palomaki et al. (1988) found that at each cutoff value of MSAFP, detection rates were higher for gastroschisis than for omphalocele. For example, at a cutoff value of >2.5 multiples of the median (MoM) and >3.0 MoM, the detection rates were more than 98% and 71%, and 96% and 65% for gastroschisis and omphalocele, respectively. The median MSAFP values for cases of omphalocele in this study were 4.1 MoM (Palomaki et al., 1988). The poorer detection rate for omphalocele is thought to be due to the presence of the intact amnioperitoneal membrane covering the abdominal cavity in unruptured omphalocele, as opposed to direct exposure of bowel to the amniotic fluid in gastroschisis (Paidas et al., 1994).

Once identified, a sonographic estimation of the size of the omphalocele, contents of the omphalocele sac, location of the umbilical cord insertion relative to the herniation, and the presence of an amnioperitoneal membrane should be documented. A careful sonographic search for other fetal anomalies should also be performed, including fetal echocardiography. Because of the high incidence of associated congenital cardiac disease (19%–32%), we recommend fetal echocardiography when an omphalocele is diagnosed (Greenwood et al., 1974; Carpenter et al., 1984; Crawford et al., 1985; Copel et al., 1986). The incidence of congenital heart disease is related to the embryology of the body fold defect. Ten percent of neonates with lateral fold defects have congenital heart disease, whereas the incidence approaches 100% if the cephalic fold is affected. Alternatively, if the caudal fold is involved, the incidence of associated congenital heart disease is low (Greenwood et al., 1974; Carpenter et al., 1984; Crawford et al., 1985; Copel et al., 1986).

Chromosomal analysis is strongly recommended due to the multiple studies that have documented a high rate of karyotype abnormalities. There are also other factors which may affect the prognosis in omphalocele including the presence or absence of pulmonary hypoplasia and the relative size of the omphalocele. Fetal MRI is particularly helpful in assessing pulmonary hypoplasia which may affect up to 37% of fetuses with giant omphalocele (Partridge et al 2012). The size of the omphalocele in relation to the size of the fetal abdomen is prognostically important as well. A ratio of the omphalocele diameter to the abdominal circumference <0.26 between 23 and 32 weeks is associated with a favorable prognosis with better chances of a primary closure and avoiding immediate intubation and prolonged hospitalization (Fawley et al2016). Assessing the severity of pulmonary hypoplasia offers additional prognostic information. Fetal MRI measured O/E TLV has been found to correlate with survival. If O/E TLV is less than or equal to 25%, the survival is approximately 60%. However if the old O/E TLV is greater than equal to 50%, the survival jumps up to greater than 90% (Danzer 2019). In general, neonates with an extracorporeal liver, as is typical in giant omphaloceles, have a poorer prognosis (Nicholas 2009, Tassin 2013)

We have found that a team approach provides comprehensive counseling and advice for parents with a fetus diagnosed with this anomaly. In addition to maternal and fetal medicine specialists, the parents should meet with specialists in pediatric surgery, genetics, neonatology, and pediatric cardiology. This type of approach, coordinated by the maternal and fetal medicine specialists, affords the parents the opportunity to ask questions regarding postnatal surgery, postoperative care, and long-term outcome. If chromosomal abnormalities, associated anomalies, or a particular syndrome is suspected, these issues can be further discussed in detail. After a decision has been reached regarding continuation of the pregnancy, attention is then focused on antepartum surveillance for the development of preterm labor and intrauterine growth restriction. Both of these complications are frequently associated with omphalocele. Rates for preterm delivery range from 26% to 65% and for intrauterine growth restriction from 6% to 35% (Hijkoop 2019, Carpenter et al., 1984; Sermer et al., 1987; Lafferty et al., 1989; Sipes et al., 1990 a,b). There is also a high rate of emergency cesarean delivery due to fetal distress (Moretti et al., 1990; Molenaar and Tibboel, 1993). Because of the high incidence of intrauterine growth restriction, we perform twice weekly antenatal testing and serial ultrasound examinations to assess fetal growth and amniotic fluid volume. In addition, during ultrasound assessment we observe for rupture of the omphalocele membrane, which exposes the herniated intestines to amniotic fluid.

In up to 50% of cases, significant pulmonary hypoplasia and pulmonary hypertension may complicate the neonatal course, particularly in giant omphaloceles (Clark 2019, Tsakayannis et al., 1996; Lee et al., 2006). We routinely recommend MRI for total lung volume assessment at 32 to 34 weeks’ gestation to help identify fetuses at risk for these complications that, if present, become the overriding determinant of management in omphalocele.

The site and mode of delivery have been debated in the obstetric literature (Lewis et al., 1990; Lurie et al., 1999; Segel et al., 2001). The goal of the management of fetuses with omphalocele is to deliver the fetus as close to term as possible. Delivery at a tertiary care center provides optimal immediate care for the newborn (Hsieh et al., 1989; Lafferty et al., 1989; Lewis et al., 1990; Geijn et al., 1991). In addition, transporting the pregnant woman before delivery, rather than transporting the neonate after delivery, provides immediate neonatal surgical care and eliminates the risk of transporting a critically ill newborn.

Mode of delivery—vaginally or by cesarean—has been the subject of several retrospective reviews. No results from prospective randomized trials have settled this issue. Older literature advocated the use of cesarean section (Cameron et al., 1978). However, the most recent retrospective reviews do not support the idea that cesarean delivery is associated with an improved survival rate (Sermer et al., 1987; Moretti et al., 1990; Sipes et al., 1990a; Kirk and Wah, 1983; Lurie et al., 1999; Segel et al., 2001). None of the six reported series show any benefit to cesarean delivery. The outcome of giant omphaloceles was not specifically addressed in these studies. Several other authors do not support routine cesarean delivery for fetuses with omphalocele (Carpenter et al., 1984; Hasan and Hermansen, 1986; Hsieh et al., 1989; Lafferty et al., 1989; Lewis et al., 1990; How et al., 2000). Labor itself does not seem to adversely affect outcome, based on the study by Lewis et al. (1990), who compared outcome data from infants delivered via elective cesarean section with those whose delivery was preceded by labor. In cases of small omphaloceles, we currently recommend vaginal delivery and reserve cesarean delivery for routine obstetric indications. However, in isolated cases of giant omphalocele with a defect in the fetal abdomen measuring 5 cm or greater and extracorporeal liver by ultrasound examination, cesarean delivery may be necessary to avoid dystocia. Particularly in cases of extracorporeal liver, we recommend delivering by cesarean section. This approach underscores the need for re-evaluation of the defect as pregnancy progresses.

There are no fetal interventions for omphalocele.

Delivery should occur in a tertiary care center, with neonatologists available for immediate resuscitation. Initial treatment consists of airway stabilization and sterile wrapping of the abdominal defect to preserve heat and minimize insensible fluid loss. A complete physical examination should be performed to rule out syndromic diagnoses. Peripheral vascular access should be established and intravenous fluids given. Mechanical ventilation is frequently necessary, especially postoperatively, when abdominal contents replaced into a small abdominal cavity impede diaphragmatic excursion and lung expansion. Antibiotics are generally given during initial treatment of the newborn directed toward preoperative stabilization.

Significant pulmonary hypoplasia and associated pulmonary hypertension may complicate the neonatal management of omphalocele from the delivery room on. This may be the most challenging management feature of neonates with giant omphaloceles (Tsakayannis et al., 1996; Lee et al., 2006). In addition to pulmonary hypoplasia, it is not uncommon to see diffuse tracheobronchial malacia which may exacerbate the pulmonary hypertension associated with pulmonary hypoplasia. Positive end-expiratory pressure (PEEP) of 8-12 cm H2O or even higher may be necessary to stabilize the airway in cases in which tracheobronchial malacia is severe.

The surgical approaches to the treatment of omphalocele has evolved considerably over the past four decades. Until 1965, the only approach for the treatment of omphalocele was the skin flap technique described by Gross (1948). The advantage of this approach is achieving early closure of the skin over the abdominal wall defect. The principal disadvantage of this technique was the creation of a large ventral hernia that ultimately requires reoperation. This is usually not an insurmountable problem, and success has been achieved with serial wrapping with elastic bandages to stimulate growth of abdominal domain for ultimate abdominal wall reconstruction. Similar to the “paint and wait” approach, considerable time (usually 6 months to 1 1/2 years, but sometimes longer) can lapse between initial surgery and final correction of the abdominal wall defect (Swartz et al., 1985).

If at all possible, primary fascial closure is the preferred method of repair in smaller omphaloceles because of a lower incidence of sepsis, bowel obstruction, and fistula, and a reduced number of operations and rate of mortality in patients who undergo this repair (Robin and Ein, 1976; Aaronson and Eckstein, 1977; Canty and Collins, 1983; Mabogunje and Mahour, 1984; Sauter et al., 1991).

Primary repair includes reduction of the herniated organs and direct closure of the fascia and the covering skin if they do not have large viscero-abdominal disproportion. Primary repair however is feasible and only 30 to 50% of all omphalocele’s (Bauman 2016).

Key steps in primary repair of omphalocele include excision of the omphalocele membrane from the fascia and skin circumferentially while leaving it attached to the liver to avoid hemorrhage by breaking into Glisson’s capsule. In addition, if the liver must be reduced into the abdominal cavity, the hepatic veins should be dissected to free up the suprahepatic IVC to avoid kinking following repair. Once the viscera have been reduced, a decision must be made regarding fascial closure. It is important that closure of the fascia not significantly increase the peak inspiratory pressures the anesthesiologist requires to adequately ventilate the baby. If there is little tension, a primary interrupted closure can be performed. If there is too much tension, a component separation can be performed in which relaxing incisions are made in the external oblique fascia laterally allowing the fascial layers to slide more easily toward the midline allowing 2 cm or more from each side to provide additional fascial coverage (Teen 2019). If the fascia is under too much tension and would put the baby at risk for abdominal compartment syndrome, one should revert to either a skin closure only or a fascial substitute to allow closure without excessive tension. Non-absorbable synthetic patches (Gore-Tex, Marlex, Prolene) may be used as a patch. The use of non-absorbable synthetic patches is prone to infection, mesh extrusion, and erosion into organs which requires their removal (Skarsgard 2019).

The use of biocompatible patches have become more common as these materials become incorporated into the child’s fascia. These grafts include human acellular dermis (AlloDerm LifeCell Corporation Bridgewater, NJ), non-cross-linked porcine dermal collagen (Permacol, Medtronic Fridley, MN), and cross-linked porcine dermal collagen (Stratus LifeCell Bridgewater, NJ). These patches undergo ingrowth and over time create neo-fascia which grows with the child. Because it becomes perfused, it’s less prone to infection (Filisetti 2016). There have been some reports of loss of tensile strength of these fascial substitutes especially a non-cross-linked porcine dermal collagen (Beres 2012).

Larger omphalocele’s usually are associated with significant viscero-abdominal disproportion making primary repair untenable. The first described staged reduction for a large omphalocele used a Silastic silo sewn to the rectus abdominis fascia and tightened to gradually reduce the viscera (Shuster 1967). A variation of this approach called amnio inversion preserves the omphalocele membrane during the silo reduction (deLorimier 1991). The advantages of this approach are that no intra-abdominal adhesions form and if reduction is not tolerated, the silo can be removed and converted to a paint and wait approach. If successful, once the viscera have been reduced, closure of the fascia usually requires a patch as described above. This staged approach is helpful in larger omphaloceles but is associated with increased risk of infection, sepsis and dehiscence, which all increase in incidence after 7 days.

There have also been anecdotal reports of the use of tissue expanders implanted either intra abdominally or in the intermuscular plane of the abdominal wall to allow slow expansion of the capacity of the abdominal cavity to allow reduction of the organs and fascial closure (Skarsgard 2019).

In cases of infants who are significantly premature, neonates with giant omphaloceles and neonates that are critically ill with respiratory insufficiency and/or severe pulmonary hypertension, surgical options may not be feasible. The safest approach in these cases is the paint wait approach, which depends on re-epithelialization of the entire omphalocele membrane. The process of re-epithelialization can take 3 to 6 months to complete. During this time, the infant grows and develops and usually impressive wraps can be applied to gradually build abdominal domain and the abdominal wall reconstruction usually be performed by 1 to 1 ½ years of age.

In recent years, negative pressure wound therapy has been used as an adjunct to the delayed repair technique of pain and weight in giant omphalocele (Bauman 2016). This technique consists of using a nonadhesive dressing on the omphalocele membrane covered by foam (VAC Whitefoam, KCI San Antonio TX) with a second layer of foam (VAC Granufoam, KCI San Antonio TX). This is sealed by an adhesive film allowing continuous negative pressure to be applied to the surface of the omphalocele. There is no agreement on the safe level of negative pressure, especially in neonates. Reports have ranged from using -25 to -125 cm of water pressure. We have used the mean arterial pressure blood pressure as a goal for negative pressure wound therapy. A major advantage is that dressing changes are only every 3 to 7 days instead of daily. The negative pressure wound therapy may also accelerate re-epithelialization of the omphalocele membrane with time to completion down to 1 to 2 months.

A special circumstance is the case of a giant omphalocele whose membrane ruptures in utero or during delivery. This significantly increase the risks of mortality and is a surgical emergency. In some cases, a small tear in the membrane may be sutured closed and the omphalocele managed nonoperatively with the paint and wait approach or using negative pressure wound therapy. Extensive disruption of the omphalocele membrane however, requires replacement with a biocompatable patch, such as AlloDerm, combined with paint and wait or negative pressure wound therapy to accelerate re-epithelialization.

For very large omphaloceles, a staged reduction using a prosthetic silo is preferred (Schuster, 1967; Allen and Wrenn, 1969; Othersen and Smith, 1986). This procedure consists of suturing a Silastic mesh to the rim of fascial defect, which then covers the herniated contents of the omphalocele. This technique consists of paralysis with neuromuscular blocking agents, enlargement of the fascial defect, and gradual stretching of the abdominal wall. Despite the success of the silo (Allen and Wrenn, 1969), there remains a significant subset of patients in whom complete reduction is not achieved before complications of wound/fascial dehiscence, infection, enterocutaneous fistula, or sepsis develop (Stringel and Filler, 1979; Towne et al., 1980; Hershenson et al., 1985; Hatch and Baxter, 1987; Adam et al., 1991; Lee et al., 2006). In this setting, attaining skin coverage with the use of biomaterials such as AlloDerm may be the best option to reduce the great metabolic demands a large abdominal wall defect creates.

Nonoperative (conservative) approaches to the treatment of omphalocele, the so called “paint and wait” approach, has grown in popularity with greater success rates in cases of severe visceroabdominal disproportion and much lower mortality rates, but they have the disadvantages noted above, as well as prolonged hospitalization (Mabogunje and Mahour, 1984; Hatch and Baxter, 1987; Nuchtern et al., 1995; Tsakayannis et al., 1996). The “paint and wait” approach allows the baby to gradually re-epithelialize the omphalocele membrane and avoids the stress of primary repair in a baby with significant respiratory compromise. Nutritional support can be challenging as it is difficult to provide enough calories by enteral feedings alone, and supplemental TPN is usually necessary to allow the baby to grow and meet the increased metabolic demands of healing the large skin defect. Once re-epithelialization has been achieved and the respiratory status is stable, wrapping the newborn with elastic bandage wraps will gradually reduce the size of the omphalocele and enlarge the peritoneal cavity. A delayed primary repair can be performed once sufficient abdominal domain has been developed. We have found this approach particularly useful in premature infants with giant omphaloceles, and in cases in which there is significant pulmonary hypoplasia or diffuse tracheobronchial malacia with concomitantly difficult ventilatory management. In those cases with severe pulmonary hypoplasia or tracheobronchial malacia, this approach is particularly appealing, as improvement in the respiratory status may take 1 to 2 years.

Although the presence of multiple associated anomalies accounts for the majority of deaths in cases of omphalocele, respiratory complications also account for a significant percentage of the morbidity and mortality due to this lesion (Danzer 2021, Paidas et al., 1994; Tsakayannis et al., 1996; Lee et al., 2006). Newborns with omphalocele, particularly giant omphalocele, have a high incidence of respiratory insufficiency and chest-wall deformity. Some evidence suggests that impaired lung growth and pulmonary hypoplasia may be evident on prenatal MRI lung volumes (Danzer 2021, Clark 2019Hershenson et al., 1985; Argyle, 1989; Thompson et al., 1993, Danzer et al2012).

Neonates may require prolonged mechanical ventilation because of the need for positive pressure to expand a chest compressed by a large abdominal mass. Bronchopulmonary dysplasia and chronic lung disease are potential long-term complications. Tracheostomy may be necessary, either due to pulmonary hypoplasia complicated by the development of bronchopulmonary dysplasia, or for PEEP to stent the airway open in cases of tracheobronchial malacia. It is not uncommon for severe tracheobronchial malacia to be associated with giant omphaloceles and requires positive end-expiratory pressures (PEEP) of 10 or even 12 cm of H2O to keep the airway open. There should be a low threshold for bronchoscopic assessment of the airway to exclude this complication in cases of giant omphaloceles.

Even with primary repair of omphalocele, a protracted stay in the newborn nursery should be anticipated. Under the best circumstances, except for hernias of the umbilical cord, some period of mechanical ventilation following omphalocele repair may be required. In some cases of giant omphaloceles, there may be underlying pulmonary hypoplasia or tracheo-bronchial malacia that complicates ventilatory management. Following extubation most infants have feeding difficulties because of the prolonged period without oral stimulation and poor coordination of sucking and swallowing. In addition, many infants have high respiratory rates following omphalocele repair. Because of the compromised diaphragmatic excursion and chest wall motion, these infants maintain their minute ventilation by shallow, rapid breathing patterns. This rapid breathing often interferes with suckling, and gavage feeding may be necessary. Gastroesophageal reflux in these infants is common and may be severe, which may require medical therapy, transpyloric feeding, or antireflux surgery.

As mentioned previously, the particular anomalies associated with omphalocele have a major impact on long-term outcome. This is especially true of chromosomal and cardiac defects. As survival rates of patients with omphalocele improve, more outcome data will become available, particularly with respect to other aspects that have an impact on the quality of life. Preliminary studies suggest that there are higher rates of behavioral problems and musculoskeletal abnormalities in children with abdominal wall defects (Ginn-Pease et al., 1991; Loder and Guiboux, 1993).

Kaiser et al. (2000) suggest that a favorable long-term outcome can be anticipated, except in cases associated with severe congenital anomalies. Danzer et al., reported the long-term neurodevelopmental follow-up in a cohort of giant omphaloceles (Danzer 2019). Surprisingly, they found a substantial risk of neurodevelopmental and psychosocial dysfunction in pre-school-aged children with a history of giant omphalocele. The rate of autism spectrum disorders was observed to be 23.4%, which is 16 times the rate in the general population. This group also observed a high prevalence of neurodevelopmental delays with significantly more children being mildly or severely delayed in at least 1 developmental domain or being diagnosed with intellectual disability (Danzer 2019, 2010, 2015). These authors speculated that the increase of autism spectrum disorders and neurodevelopmental delays may have more to do with accumulated risk factors than the abdominal wall defect itself. The accumulated risk factors could include prematurity, prolonged and complicated neonatal course, neurologic injury, and the presence of other structural or genetic abnormalities. All parents of children with giant omphalocele should be counseled about the potential for neurodevelopmental delays, autism spectrum disorder, and the need for specialized care beyond infancy.

The recurrence risk depends on the cause of the omphalocele. If the fetus has a chromosomal abnormality due to aneuploidy, such as trisomy 18, the recurrence risk is 1% or the age-related maternal risk, whichever is higher. If a syndrome is diagnosed, the recurrence risk is that of the syndrome (Stoll et al., 2008). Familial cases of Beckwith–Wiedemann syndrome may have as high as a 50% recurrence risk. Nonsyndromal (isolated) omphalocele is generally considered to be a sporadic event, with a negligible recurrence risk. However, at least 17 cases of familial omphalocele have been described (Osuna and Lindham, 1976; DiLiberti, 1982; Pryde et al., 1992). Most of these families appear to transmit the gene as an autosomal dominant gene. In one asymptomatic patient, five consecutive pregnancies by two different nonconsanguineous partners were complicated by fetuses with isolated omphalocele (Pryde et al., 1992).

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