INTRODUCTION — Body stalk anomaly (also called limb-body wall complex) and cloacal exstrophy are rare abdominal wall defects. This topic will discuss prenatal diagnosis and obstetric management of pregnancies complicated by fetal body stalk anomaly or cloacal exstrophy. Management of infants with bladder exstrophy is reviewed separately. (See "Clinical manifestations and initial management of infants with bladder exstrophy".)
VALUE OF PRENATAL DIAGNOSIS — Prenatal diagnosis informs parents about the health and prognosis of their unborn child and thus helps them make informed decisions about the pregnancy within the context of their own value system. These decisions may involve pregnancy continuation/termination, choice of health care provider (eg, is specialty care needed?), birth site (eg, is a higher level of newborn care needed?), and palliative care for newborns with life-threatening conditions. Prenatal diagnosis also helps the patient prepare other family members, particularly children, for what to expect and provides an opportunity to engage with support groups. These issues apply to body stalk anomaly because it is generally considered to be lethal, with rare exceptions [1]. They apply to cloacal exstrophy because it generally requires multiple and complex surgical procedures and had long-term implications regarding continence, kidney function, fertility, and body image. (See "Surgical management and postoperative outcome of children with bladder exstrophy".)
BODY STALK ANOMALY
Definition — Body stalk anomaly is massive and generally lethal malformation of the thorax and/or abdomen, often associated with limb abnormalities and severe scoliosis. The intrathoracic and abdominal organs lie outside of the abdominal cavity and are contained within a sac comprised of amnioperitoneal membrane attached directly to the placenta (picture 1) [2,3]. The umbilical cord may be completely absent or extremely shortened.
Pathogenesis — Possible causes of body stalk anomaly include early amnion rupture resulting in amniotic bands that exert direct mechanical pressure on the developing embryo/fetus, vascular disruption of the early embryo, or an abnormality in the germinal disk [4]. Pathogenic variants in genes related to embryogenesis may play a role [5].
The germinal disk abnormality is thought to represent complete failure of body folding along all three axes (cephalic, lateral, and caudal) during the sixth postmenstrual week [6]. Normal body folding results in separation of the intraembryonic coelom (future peritoneal cavity) from the extraembryonic coelom, formation of the body stalk, and development of the umbilical cord [7]. Abnormal cephalic folding results in a defect in the thoracic wall and epigastrium, allowing development of ectopia cordis (image 1). Abnormal lateral folding results in herniation of the midabdominal contents into a large wide-based amnioperitoneal sac, which inserts peripherally onto the placental chorionic plate in lieu of an umbilical cord or with a very short umbilical cord. Due to extrusion of the intraabdominal and thoracic contents, the spine and thoracic cavity do not develop symmetrically, which results in severe kyphoscoliosis and other abnormalities of the axial skeleton. Malrotation of the spine and incomplete closure of the pelvis can lead to malrotated limbs and/or clubfeet.
In one series of 16 infants with body stalk anomaly, 10 infants had unilateral renal agenesis, as well as malformations or absence of the genitalia, urinary bladder, or both [8]. All these findings would be consistent with aberrant caudal folding, but there are also case reports describing an intact bladder retained in the abdomen, where a caudal fold defect would not likely be involved. Such heterogeneity would be consistent with select Hox gene mutations [5].
Prevalence and epidemiology — Body stalk anomaly is rare; reported prevalence ranges from 0.4 to 3.2 per 100,000 live births and stillbirths [8]. However, this range likely under-represents the true prevalence because it does not account for fetal losses due to miscarriage and termination of pregnancy. For example, four cases were noted among 6952 sonographic examinations of nuchal translucency performed at 11 to 14 weeks of gestation in a single institution (58 per 100,000 first trimester pregnancies) [9].
The prevalence appears to be increased in twins [8]. Monochorionic twins may concordant or discordant for the anomaly [10-12].
Prevalence does not appear to be affected by parental age or fetal sex.
Postnatal findings — The postnatal diagnosis of body stalk anomaly is based on characteristic findings on physical examination: a defective thoracoabdominal wall with thoracoabdominal organs outside of the abdominal cavity in a sac adherent to the placenta (picture 2 and picture 3 and picture 1). The umbilical cord is absent or very short (<10 cm) and skeletal abnormalities are common [8].
Prenatal diagnosis
Imaging — Ultrasound examination should be performed at a center with sonographic expertise for making the diagnosis and delineating the multitude of anatomical abnormalities.
Body stalk anomaly should be strongly suspected when a massive midline thoracoabdominal wall defect is noted in a fetus with skeletal anomalies, especially severe scoliosis or lordosis (present in three-quarters of patients [4]) and an absent or extremely short umbilical cord [13-18]. The peritoneal cavity retains its communication with the extracoelomic cavity, which extends to the margins of the placenta [19]. The massive amnioperitoneal-lined sac may contain portions of the lungs, heart, liver, spleen, bowel, kidneys, and bladder; in female fetuses ovaries, tubes, and uterus may herniate [19]. Usually only two umbilical vessels are present and do not spiral while coursing along the amnioperitoneal membrane [15,19]. In the second trimester, oligohydramnios is common.
Diagnostic images:
●Body stalk malformation (image 2)
●Short umbilical cord (image 3)
●Ectopic cordis (image 1)
●Limb-body wall complex (image 4)
●Limb body wall complex (image 5)
●Limb body wall complex (image 6)
●Severe fetal scoliosis (image 7)
Alpha-fetoprotein — The second-trimester maternal serum alpha-fetoprotein (MSAFP) level is elevated in 100 percent of cases [20].
Associated abnormalities — Urogenital organs are commonly affected. In one series of 16 infants with body stalk anomaly, 10 infants had unilateral renal agenesis, as well as malformations or absence of the genitalia, urinary bladder, or both [8]. Nine infants had anal atresia and/or severe limb reduction defects (two with amelia, four with phocomelia, three with unspecified reduction defects). All of the limb defects were unilateral, only one infant had more than one limb affected, and all but one (phocomelia of an arm) involved a lower limb. Others have also reported a preponderance of lower limb defects [21].
Genetic studies — Only two cases of body stalk anomaly associated with an abnormal karyotype have been reported (confined placental trisomy 16 and uniparental disomy 16 in one case [22] and mosaic trisomy 2 on chorionic villous sampling in the other case [23]). This may be an underestimate given the small number of reported cases; however, many cases of body stalk anomaly with normal karyotype have been reported [8]. We offer microarray in all cases. (See "Prenatal genetic evaluation of the fetus with anomalies or soft markers".)
Differential diagnosis — The differential diagnosis of major abdominal wall defects is described in the table (table 1). The combination of exteriorization of thoracoabdominal organs, scoliosis, and an abnormality at the cord insertion site suggests body stalk anomaly, rather than omphalocele or gastroschisis, which are the two most common abdominal wall defects. The fetal cord insertion site is umbilical in both omphalocele and gastroschisis; however, the abdominal wall defect is at the base of the cord in omphalocele but paraumbilical in gastroschisis. In body stalk anomaly, the umbilical cord is absent or not visualized and the anterior abdominal wall is partially formed or absent. (See "Gastroschisis" and "Omphalocele: Prenatal diagnosis and pregnancy management".)
Amniotic band sequence can mimic a body stalk anomaly because the bands cause abdominal wall disruption too. However, amniotic band sequence would involve other, non-abdominal wall structures such as the limbs, face, or cranium, as well as a shredded amniotic membrane. (See "Amniotic band sequence".)
Obstetric management
●Counseling – The patient should be counseled about the likelihood of neonatal demise, since the abnormality is generally considered lethal [6,24]. Options that should be discussed include pregnancy termination, continuation of pregnancy with neonatal palliative care, and the possibility of repair, which has been performed successfully in rare cases but has severe morbidity [1]. Generally, repair is not possible because there is no abdominal cavity in which to place the organs. Normally, the abdominal cavity is formed by the organs growing inside it, thus if the abdominal organs are exteriorized, the cavity will not develop.
●Route of birth – If the pregnancy is continued, vaginal birth is desirable as there is generally no newborn benefit from cesarean birth, given the highly lethal nature of this anomaly. Cesarean birth should be considered if there are maternal contraindications to vaginal birth or plans for neonatal interventions such as resuscitation and repair of the abnormalities.
Recurrence risk — Most cases are sporadic.
CLOACAL EXSTROPHY
Definition — Cloacal exstrophy is a severe multi-system congenital malformation involving defects of the genitourinary, gastrointestinal, musculoskeletal, and neurologic systems. The disorder is also known as OEIS complex (omphalocele-exstrophy-imperforate anus-spinal dysraphism) [25].
Pathogenesis — The pathogenesis of cloacal exstrophy is unclear. During the fifth and sixth postmenstrual weeks, the human embryo is transformed from a flat disc-shaped organism into two tubes, one dorsal to the other, surrounded by supporting structures in the body wall [26]. Based on histopathologic studies in human embryos, cloacal exstrophy most likely results from a very early defect in the closure of the ventral body wall rather than an abnormality related to premature rupture of the cloacal membrane [27]. Greater concordance among monozygotic than dizygotic twins supports a genetic basis for the disorder [27] or an error in embryological development related to monozygotic twinning [28].
Prevalence and epidemiology — Cloacal exstrophy is a rare event, occurring in fewer than 1 in 100,000 births [27]. Epidemiology is poorly understood because of the rarity of the disorder. Prevalence appears to be higher in females. Although variability in prevalence by geographic location has been observed, this is most likely an artifact related to the small number of cases.
Postnatal findings — The postnatal diagnosis of cloacal exstrophy is based on physical examination showing the characteristic clinical findings (picture 4):
●Omphalocele
●Exstrophy of the bladder and portions of bowel
●Imperforate anus
●Spinal defects
In addition, the bladder is split into hemibladders that flank the openings of the small intestine and blind-ending large intestine and contain the orifices of the ureters and vasa deferentia in males and the uterovaginal canal in females [29]. In males, the penis and scrotum are split in two or the penis is flat and short with hypospadias. In females, the clitoris is split, there may be two vaginal openings, and the vulvae are rudimentary. Vesico-intestinal, urethral-intestinal, or ureteral-intestinal fistula may be present [30,31].
Prenatal diagnosis
Imaging — Ultrasound examination should be performed at a center with sonographic expertise for making the diagnosis and delineating the spectrum of anatomical abnormalities.
Prenatal diagnosis of cloacal exstrophy is based on ultrasound identification of the features most commonly present in the complex (image 8). The accuracy of sonographic diagnosis appears to be less than 25 percent due to the rarity of the disorder and the wide spectrum of anatomic variants, which depend upon the degree of cloacal septation completed [32,33]. There is also lack of consensus regarding its clinical components
In one of the largest series of patients with cloacal exstrophy in whom prenatal sonography was available (22 cases), major criteria for the complex were defined as findings that occurred in >50 percent of cases [34]:
●Nonvisualization of the urinary bladder (91 percent). (Note: nonvisualization of the fetal bladder requires repeated assessments because the fetal bladder normally empties every 50 to 155 minutes [35])
●Large midline infraumbilical anterior abdominal wall defect or cystic anterior wall structure (persistent cloacal membrane) (82 percent)
●Omphalocele (77 percent)
●Meningomyelocele (68 percent)
Minor criteria were defined as findings that occurred in <50 percent of cases [34]:
●Lower extremity defects (23 percent)
●Kidney abnormalities (23 percent)
●Ascites (14 percent)
●Diastasis of the pubic rami (18 percent)
●Narrow thorax (9 percent)
●Hydrocephalus (9 percent)
●Single umbilical artery (9 percent)
Malformations in other organ systems (eg, congenital heart defects, rib defects, microcephaly, tracheoesophageal fistula, encephalocele, diaphragmatic hernia) have been described in case reports and small case series compiled over decades [27]. A prolapsed terminal ileum resembling the trunk of an elephant on ultrasound has been reported as a finding unique to cloacal exstrophy [36].
Color Doppler sonography to identify the perivesical umbilical arteries at the normal bladder location can help delineate the origin of a mass (eg, bladder) in the lower abdomen [37]. Three-dimensional ultrasound and/or fetal magnetic resonance imaging (MRI) are adjunctive imaging modalities that can be used to assist in clarifying uncertain two-dimensional ultrasound findings [38,39].
Amniotic fluid volume can be low, normal, or increased [40].
Alpha-fetoprotein — Second trimester maternal serum alpha-fetoprotein (MSAFP) level is elevated; levels of 20 to 30 MoMs have been reported [41].
Genetic studies — Cloacal exstrophy has not been reported to be associated with specific aneuploidies. Nonetheless, karyotyping should be considered since it may influence the decision to terminate the pregnancy, perform a cesarean birth for fetal indications, or initiate a series of corrective operations in the newborn period versus palliative care [42].
Differential diagnosis — Differential diagnoses are described in the table (table 1). Nonvisualization of the bladder in a fetus with abdominal and spinal defects suggests cloacal exstrophy. Simple bladder exstrophy is not typically associated with fetal anomalies in other organ systems. The bladder can be visualized in omphalocele and gastroschisis, the two most common abdominal wall defects. (See "Gastroschisis" and "Omphalocele: Prenatal diagnosis and pregnancy management".)
Obstetric management
●Counseling – Prenatal consultation with a pediatric urologist or surgeon is recommended, including descriptions of surgical repair sequencing and composite bladder augmentation with gastrointestinal tract components [43]. While counseling about prognosis depends on associated anomalies, the impact of exstrophy on genitourinary function should be discussed, including residual neuropathic bladder, bowel and urinary incontinence, and pubic bone diastasis sequelae of external genital reconstruction [44,45].
●Delivery – Delivery at a tertiary care center is recommended. As with other abdominal wall defects, cesarean birth is reserved for standard obstetric indications, although there are no studies of the optimum route of delivery for this rare disorder.
The umbilical cord should be clamped or ligated carefully to avoid injury to proximate structures.
Neonatal management — Saline-soaked sterile dressings are applied over the exposed bladder and bowel mucosa and covered with plastic wrap to minimize insensible fluid and heat loss [46]. Immediate consultation with neonatologists, pediatric surgeons, and neurosurgeons is important for operative planning, but emergency surgery is not necessary. (See "Clinical manifestations and initial management of infants with bladder exstrophy".)
Ultrasound is performed to evaluate the presence or absence of kidneys, hydroureter, and hydronephrosis [46]. The latter two abnormalities may require preoperative decompression. The newborn’s spinal cord and brain should be evaluated by ultrasound and magnetic resonance imaging to detect tethered cord, myelodysplasia, hydrocephalus, or other central nervous system abnormalities. Radiographic images provide important information about the presence or absence of vertebral or pelvic-sacral abnormalities.
Karyotype may help in assigning biologic sex, if genetic studies were not performed prenatally. There are also significant psychological-emotional concerns about gender reassignment from male to female. Decisions about gender assignment and surgery in patients with a disorder of sexual organ development are complicated by societal and family expectations, the variability of phenotype, the uncertainty of adult gender identity, and by the lack of adequately sized studies of long-term outcomes. These issues are discussed in detail separately. (See "Management of the infant with atypical genital appearance (difference of sex development)".)
Repair — The surgical management of newborns with cloacal exstrophy is technically challenging and a series of complex reconstructive operations is often necessary [46]. For example, the omphalocele needs to be repaired, a urinary bladder needs to be constructed, the separation between the pubic bones need to be reduced and the pelvis stabilized, and intestinal management of the often small and shortened colon needs to be addressed. The major goal is to help the patient achieve bowel control, urinary control, and satisfactory sexual function [47]. Patients are best served in centers that specialize in the care of newborns with this malformation sequence. The presence of motor impairments or organ dysfunction (eg, bladder overdistension/neurogenic bladder) as the result of an associated neural tube defect will impact the timing and nature of the perineal repair.
In one study that described the process of achieving continence (defined as a dry interval greater than three hours without leakage at night) in patients with cloacal exstrophy, continence procedures included bladder neck reconstruction with or without augmentation, bladder neck transection with continent urinary diversion, augmentation cystoplasty, or use of injectable bulking agents [48]. At the time of analysis, 71 percent of patients who underwent a continence procedure were dry, the median number of urologic procedures to reach urinary continence was four (range 2 to 10), and the median age when continence was achieved was 11 years.
Prognosis — Survival rates of 83 to 100 percent have been reported since the 1980s and attributed to advances in hyperalimentation, neonatal intensive care, and surgical reconstruction techniques [46,49,50]. The residual mortality rate reflects both the severity of the malformations encountered and complications associated with preterm birth [46].
Quality-of-life issues remain a concern [51,52]. Two systematic reviews of 12 studies that assessed long-term functional outcomes of patients with cloacal malformation reported the following types and frequencies of outcomes: urinary incontinence (9.1 to 85 percent), sexual function issues related to vaginal anomalies (8.3 to 71.3 percent), uterine anomalies (14.3 to 71 percent), gender identity issues in 46, XY patients raised female (11.1 to 66.7 percent), impaired ambulatory capacity (13.8 percent) [52], fecal soiling (71 percent), and constipation (51 percent) [51].
Female patients have a high incidence of gynecologic problems at menarche and in early adult life [53]. Reassessment at early puberty by ultrasound, magnetic resonance imaging, and vaginoscopy has been recommended as additional surgery may be necessary to improve sexual/reproductive function [54]. Paternity has not been documented among males [52]. Expert management is crucial to achieve optimum quality of life, particularly as children transition into adulthood.
Recurrence risk — The genetics of the malformation sequence are not well defined, but there is a higher incidence of cloacal exstrophy in families in which one member is affected as compared with the general population [46]. Greater concordance among monozygotic twins than dizygotic twins also supports a genetic basis for the disorder [27].
SUMMARY AND RECOMMENDATIONS
●Body stalk anomaly
•Postnatal diagnosis – The postnatal diagnosis of body stalk anomaly (also called limb-body wall complex) is based on characteristic findings on physical examination: a defective thoracoabdominal wall with thoracoabdominal organs outside the abdominal cavity in a sac adherent to the placenta (picture 2 and picture 3 and picture 1). The umbilical cord is absent or very short (<10 cm) and skeletal defects are common. (See 'Postnatal findings' above.)
•Prenatal diagnosis – Prenatal diagnosis of body stalk anomaly is based on ultrasound examination showing a massive midline thoracoabdominal wall defect in a fetus with skeletal anomalies, especially severe scoliosis or lordosis and a short or absent umbilical cord. The peritoneal cavity retains its communication with the extracoelomic cavity, which extends to the margins of the placenta. The massive amnioperitoneal-lined sac may contain portions of the lungs, heart, liver, spleen, bowel, kidneys, and bladder; in female fetuses, ovaries, tubes, and uterus may herniate. Usually only two umbilical vessels are present. Second-trimester maternal serum alpha-fetoprotein (MSAFP) is always elevated and fetal karyotype is usually normal. (See 'Prenatal diagnosis' above.)
•Prognosis – Body stalk anomaly is almost always lethal. For this reason, we suggest offering the patient termination of pregnancy or vaginal delivery with palliative care at birth. (See 'Obstetric management' above.)
●Cloacal exstrophy
•Postnatal diagnosis – The postnatal diagnosis of cloacal exstrophy is based on physical examination showing the characteristic clinical findings of omphalocele, exstrophy of the bladder and portions of bowel, imperforate anus, and spinal defects. The bladder is split into hemibladders that flank the openings of the small intestine and blind-ending large intestine and contain the orifices of the ureters and vasa deferentia in males and the uterovaginal canal in females. In males, the penis and scrotum are split in two or the penis is flat and short with hypospadias. In females, the clitoris is split, there may be two vaginal openings, and the vulvae are rudimentary. (See 'Postnatal findings' above.)
•Prenatal diagnosis – The prenatal diagnosis of cloacal exstrophy is based on ultrasound identification of the features most commonly present in the complex. Findings present in >50 percent of cases include:
-Nonvisualization of the urinary bladder
-Large midline infraumbilical anterior abdominal wall defect or cystic anterior wall structure
-Omphalocele
-Meningomyelocele
A prolapsed terminal ileum resembling the trunk of an elephant on ultrasound is a finding unique to cloacal exstrophy. Amniotic fluid volume can be low, normal, or increased. Malformations may also occur in other organ systems. Cloacal exstrophy has not been reported to be associated with chromosomal aneuploidy. (See 'Prenatal diagnosis' above.)
•Delivery – Although there are no studies of the optimum route of delivery for this rare disorder, cesarean delivery is generally reserved for standard obstetric indications. The umbilical cord should be clamped or ligated carefully to avoid injury to proximate structures. (See 'Obstetric management' above.)
•Newborn care – At delivery, saline-soaked sterile dressings should be applied over the exposed bladder and bowel mucosa and covered with plastic wrap to minimize insensible fluid and heat loss. (See 'Neonatal management' above.)
•Prognosis – Survival rates of 80 to 100 percent have been reported, but quality of life (eg, bowel, urinary, and sexual function) is a concern. (See 'Prognosis' above.)
