Omphalocele is a defect in the ventral abdominal wall that is characterized by an absence of abdominal muscles, fascia, and skin. The defect is covered by a membrane that consists of peritoneum and amnion. It can vary in size from a few centimeters to most of the ventral abdominal wall. Unlike gastroschisis, in omphalocele, the umbilical cord inserts into this membrane at a location distant from the abdominal wall (deVries, 1980). 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 (see Chapter 61), which consists of an epigastric omphalocele, anterior diaphragmatic defect, sternal cleft, pericardial defect, and associated intracardiac defects (Figure 62-1A) (Cantrell et al., 1958). A defect in lateral folding results in the classic omphalocele (Figure 62-1B) with a midabdominal defect. A defect in caudal folding results in a low or hypogastric omphalocele, as seen in bladder or cloacal exstrophy (see Chapters 64 and 65) (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 in 4000 to 1 in 7000 livebirths (Baird and MacDonald, 1981; Lindham, 1981; Rankin et al., 1999; Stoll et al., 2001). The incidence of omphalocele is higher in combined livebirths and still births (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). Unlike gastroschisis, there has not been a change in the incidence of this abnormality, which supports the notion that these are two separate entities with different causes (see Chapter 63). Unlike gastroschisis, omphalocele is associated with advanced, as opposed to younger, maternal age (Redford et al., 1985; Hwang and Kousseff, 2004).

The diagnosis of omphalocele was made as early as 10 to 12 weeks of gestation by vaginal 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 (Figure 62-2). 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 intrahepatic 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 (Figure 62-3).

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 than between ruptured omphaloceles, gastroschisis, and body-stalk anomalies.

Two syndromes deserve mention in the context of omphalocele: pentalogy of Cantrell and Beckwith–Wiedemann syndrome (see Chapters 27, 61, and 123). 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. Fewer than 90 cases have been described (Craigo et al., 1992). Ghidini et al. (1988) reviewed the Yale experience and found 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.

The Beckwith–Wiedemann syndrome, otherwise known as exomphalos-macroglossia-gigantism (EMG) syndrome, consists of the presence of omphalocele, visceromegaly, macroglossia, and severe neonatal hypoglycemia (see Chapters 27 and 123). 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.

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 62-1 (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.

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).

More recently, 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.