Prenatal Diagnosis of a Ventral Abdominal Wall Defect

Case Presentation:

A 12 week fetal sonogram in a 22 year-old Gravida 1 Para 0 pregnant woman was suggestive of multiple anomalies. She had previously been known to have a congenital uterine anomaly with both a vaginal septum and uterine septum that were removed three years prior to the current pregnancy. She had two cervices with one uterine cavity and normal bilateral Fallopian tubes at the time of this spontaneous pregnancy. Her initial course was uncomplicated, but fetal ultrasound at 12 weeks’ gestation showed a large anterior wall defect spanning both the chest and abdomen, with concern for possible ectopia cordis. The fetus was noted to have restricted movement within a subjectively small amniotic sac. Cell-free fetal DNA screening was low risk and amniocentesis was not performed. She was referred to the Maternal Fetal Care Center (MFCC) at 17 weeks’ gestation for further evaluation and counseling.

Imaging at the MFCC at 17 weeks and 3 days gestation included fetal ultrasound (US), magnetic resonance imaging (MRI) and fetal echocardiography. Imaging findings included the following: a small portion of the cardiac apex was outside the chest, a small anterior diaphragmatic hernia, a large abdominal wall defect with liver and bowel herniation, and significant thoracic kyphosis (Figure 1) In addition, a complete amnion-chorion separation was noted (Figure 2, US; Figure 3 MRI). Fetal echocardiogram showed a ventricular septal defect (VSD) with a mildly hypoplastic pulmonary valve and partial ectopia cordis with a small sternal defect with left cardiac ventricle herniation.

Figure 1.

Prenatal T2 MRI at 17 weeks’ gestation demonstrating herniated liver (solid green arrow) and small herniation of the apex of the heart (dotted green) through a diaphragmatic defect. Evisceration of the small bowel (solid yellow) and colon (dotted yellow) also visualized. Demonstration of kyphoscoliosis (red arrow).

Figure 2.

Ultrasound image demonstrating dilated and thickened bowel loops and amnion-chorion separation with adherent amnion to the bowel loops (purple arrows).

Figure 3.

T2 MRI demonstrating the amnion-chorion separation (purple arrows) as well as concern for club foot (white arrow).

The patient was closely followed throughout pregnancy. Imaging at 19 weeks and 2 days gestational age confirmed herniation of the entire liver with the portal vein extending outside of the abdomen, stomach, small bowel, and the majority of large bowel without an overlying membrane (Figure 4). The chest appeared small with low lung volumes, however no diaphragmatic hernia was appreciated. Final imaging at 29 weeks demonstrated a small thorax with small lung volumes and enlarged kidneys (Figure 5).

Figure 4.

T2 MRI showing axial image of abdomen with liver herniated outside of abdominal cavity with portal vein (PV) connecting liver (Liv) to the umbilicus and IVC (yellow arrow). Small bowel and colon seen outside abdomen as well.

Figure 5.

T2 MRI at 29 weeks demonstrating small thoracic cavity with small lung volumes and prominent heart (pink arrow). Kidneys (Kid) appear enlarged in abdominal cavity.

Serial sonograms showed a progressive delay in fetal biometry by a few days at 19 weeks’ gestation and then by almost 3 weeks at 24 weeks’ gestation.

Expert Opinion

The MFCC provides a multidisciplinary approach for consultation in the setting of multiple fetal congenital anomalies. Given the multiple organ systems involved in this particular patient, cardiology, surgery, maternal-fetal medicine, palliative care, and social work were all involved in the family’s consultation and guidance.

Pediatric Surgery:

Pediatric surgery was the primary consultant for the majority of the family’s visits in the MFCC. They were consulted at the first visit at 17 weeks’ gestation to provide prognosis and guidance in management decisions of the complex abdominal wall defect. They discussed with the family that the prenatal images suggested several possible diagnoses including Pentalogy of Cantrell-type defect versus a massive abdominal wall defect without an apparent membrane (complex gastroschisis vs ruptured omphalocele). The surgical team discussed that the abdominal wall defect was very large and included the entire liver and most of the intestine.

The surgical consultant emphasized to the family that there would be significant challenges to successful treatment of this extremely large defect and there was a risk of intrauterine demise or preterm delivery. Surgery recommended daytime planned delivery by Cesarean section to minimize fetal liver injury and bleeding, followed by immediate intubation. The family was also counseled that the infant would likely require prolonged ventilator support and a prolonged hospitalization of 6-12 months. Initial management would include early operation in the first few hours after birth to create a silo and begin the process of abdominal wall growth by traction. A similar case of complex gastroschisis that included total liver herniation had been successfully managed by the team in the recent past.¹

Pediatric Cardiology:

Several fetal echocardiograms performed during the pregnancy showed slightly different anatomy. However, with increasing gestational age, the defect was classified as a ventricular septal defect (VSD). Cardiology indicated that this defect could complicate postnatal care as there was deficiency of the pericardial sac, leaving the fetus at increased risk of infection given the proximity to the abdominal wall defect. The fetus maintained good cardiac function throughout pregnancy and did not develop hydrops.

Palliative Care:

The palliative care team was also consulted at the last visit prior to delivery. Overall, the family remained very hopeful about their infant’s outcome and did not wish to pursue termination or comfort care, views that they had repeatedly expressed since the initial diagnosis. Visits were often attended by both the pregnant woman and her mother, who expressed their strong religious beliefs that guided their decisions. The family equated comfort care with termination and did not see this as an option, remaining hopeful for a good long-term outcome. The palliative care team remained very involved during the infant’s hospitalization and supported the family.

Delivery Room Plan

Delivery room management was outlined by the surgical consultants in collaboration with the post-delivery team. Recommendations included delivery by Cesarean section with immediate intubation by the neonatology team, assessment by the surgical team, who would then cover the defect in warm normal saline soaked gauze. The infant would then be admitted to the Level IV NICU and likely go to the operating room within the first 6 to 12 hours after birth for placement of a silo and to initiate the steps of abdominal wall traction.

Outcome

The patient’s last MFCC visit was at 29 weeks’ gestation. She went into preterm labor at 30 weeks and 6 days gestation. A female infant was delivered by a classical Cesarean incision. At the time of delivery, portions of the infant’s bowel were adhered to the placenta, requiring delicate separation and leading to an unplanned delayed cord clamping of about one minute. The infant was brought to the warmer, covered with warm saline soaked gauze and immediately intubated with notable copious bilious output. On physical examination, the infant was noted to be small without any dysmorphic facial features. A large ventral abdominal wall defect was noted with the entire liver, small bowel, stomach and spleen outside of the abdomen (Figure 6). There was a small diaphragmatic hernia with a sternal defect and the heart was visible through this defect. The exteriorized bowel appeared well perfused. The infant’s Apgar scores were 4, 5, and 8, at 1, 5, and 10 minutes, respectively. The infant’s birth weight was 1 kilogram (9% on the Fenton Growth Chart). Initially the infant remained on a conventional ventilator with elevated pressures.

Figure 6.

Postnatal image of infant anatomy showing liver (Liv), portal vein (PV) and small intestine (Sm Int)

The infant’s initial chest radiograph suggested significant pulmonary hypoplasia with an elongated and narrow thoracic cage 9 (Figure 7). She received two doses of surfactant and spent the majority of her hospitalization on the jet ventilator on maximum settings with a high oxygen requirement.

Figure 7.

Initial chest radiograph at time of admission demonstrating elongated and thin thoracic cavity with significant kyphoscoliosis.

The infant went to the operating room within 6 hours of admission to the NICU. A hand sewn silastic bag was placed as a silo due to the extent of the defect and the proximity of the sternal defect to the abdominal wall defect. In the operating room, the infant was extremely hypothermic to 30.3C despite multiple attempts at warming.

She was hemodynamically unstable throughout her NICU course and required vasopressor support with dopamine, epinephrine, and norepinephrine. She had significant right ventricular hypertension. A large patent ductus arteriosus (PDA) was noted on the first day after birth and the PDA was closed with Tylenol. She required stress dose hydrocortisone throughout her course because of persistent hypotension, and could not be weaned off the medication. She received an initial 48 hour course of ampicillin and gentamicin after birth and following, was placed on cefazolin prophylaxis. She had multiple evaluations for an infection, but her cultures remained negative.

The infant’s pain and discomfort were managed with a fentanyl infusion, which required increasing dosage throughout her hospital course. Given the type of traction necessary to promote abdominal wall growth, she was also paralyzed with a vecuronium infusion throughout her course.

The most significant issue during her hospitalization was fluid balance and difficulty with diuresis. She quickly became extremely edematous, likely a result of a systemic inflammatory response. Multiple strategies were attempted to manage edema, including fluid restriction (limited by the high number of required infusions), 25% albumin infusions with subsequent diuretic administration and replacement of silo output. However, despite these attempts, she remained edematous, hypoalbuminemic, and intravascularly depleted. Renal Doppler showed absent diastolic flow and increased resistive indices, often associated with recent tucking of the abdominal contents into her abdominal cavity. Ultimately, her kidney function severely worsened and she alternated between oliguria and polyuria. Urinalysis revealed large protein losses in the urine consistent with nephrotic syndrome. Peritoneal dialysis was discussed but was not seen as a real option given her size, hemodynamic instability, and open abdomen.

Surgical Management:

The post surgical repair of this patient has been reported in the literature by Sventenoff et al.¹ A brief summary is provided below.

• 1 day after birth: Hand sewn Silastic bag placement

• 3-21 days after birth: Multiple bedside tucking procedures of abdominal contents while traction applied to the abdominal wall and fascia

• 6 days after birth: bedside fascial opening and silo repositioning

• 12 days after birth: Silo washout

• 14 days after birth: Right internal jugular central line placement

• 16 days after birth: Silo revision, washout

• 21 days after birth: Tucking, which was subsequently released for low urine output and decreased perfusion to the kidneys

• 27 days after birth: Silo revision, washout

• 31 days after birth: Decision for no further tension/tucking

• 33 days after birth: Silo exchange for alloderm placement and wound vac with peritoneal dialysis catheter placement

During the hospitalization, many conversations occurred with the infant’s mother, aunt, and grandmother and the multidisciplinary team regarding her prognosis. Ultimately, her mother made the difficult decision to redirect the goals of the infant’s care when she suffered acute and irreversible renal failure. After 38 days in the NICU, no further diagnostic testing was performed. Vasopressors and sedation were continued and the vecuronium infusion was discontinued. The mother held the infant and she passed away.

Autopsy:

The family consented to a restricted autopsy of the kidneys, intestines, and liver. The autopsy revealed generalized visceral ischemia with multiple hemorrhagic infarctions in the liver and intestines. There was hepatomegaly with congestion and multiple subcapsular infarctions as well as marked serosal/capsular adhesions. The small and large intestines had focal ischemic changes and bloody contents with marked serosal adhesions. The infant had marked anasarca (weight of 2.5kg with expected weight of 2.195kg). She had bilaterally enlarged kidneys with a soft appearance.

Genetic Testing:

Chromosomal microarray analysis (GeneDx, Gaithersburg, MD) returned with a 206 kb copy number gain on 10p26.11 interpreted as a variant of uncertain significance. The neonate and mother were enrolled in the Manton Center for Orphan Disease research, an Institutional Review Board-approved protocol at Boston Children’s Hospital. Exome sequencing was performed at the Broad Institute’s Center for Mendelian Genomics for the patient and mother using methods as previously described² and was non-diagnostic.

Discussion

This case of a complex abdominal wall defect presents multiple challenges from prenatal diagnosis and management to postnatal surgical and medical management and family decision-making. A definitive diagnosis of the cause of the defect was never determined in this case, however, the consensus was that the defect was likely a complicated gastroschisis with total liver herniation, though this was on the spectrum of Pentalogy of Cantrell to complex gastroschisis or ruptured omphalocele, including a potential body-stalk anomaly.

Pentalogy of Cantrell is a rare diagnosis with a prevalence of 1:65,000 births to 1:200,000 births with a slight male predominance and consists of sternal and anterior diaphragm defects, abdominal wall defects, ectopia cordis, and congenital heart disease. It was first described by Cantrell and colleagues in 1958³. This diagnosis has an overall poor prognosis with some literature quoting a 37% overall survival rate. Mean age at delivery is typically < 37 weeks in many case series.

Embryology of development

Normal development of the abdominal wall results from fusion of four ectomesodermic foldsIf these four folds (cephalic, caudal, and two lateral folds) do not fuse, the spectrum of many ventral abdominal wall defects may result. Pentalogy of Cantrell is thought to occur during the third week of embryonic life. If all four mesodermic folds do not fuse, then an omphalocele results. When the cephalic folds do not fuse, Pentalogy of Cantrell results. When the lateral folds are more affected, exstrophy of the bladder or cloaca results. Normally, there is a physiologic herniation of the midgut into the umbilical cord around 10-12 weeks of gestation, but failure of these contents to return leads to gastroschisis.^4–7 Pentalogy of Cantrell is much more commonly associated with omphalocele as the abdominal wall defect rather than gastroschisis as seen in this case.

Pentalogy of Cantrell has been proposed to occur between 14 to 18 days of embryonic life and includes a defect in the septum transversum development as well as the failure of migration and fusion of the primordial septum, which results in improper attachment of the anterior abdominal musculature. Currently, there are no known specific genetic abnormalities associated with Pentalogy of Cantrell though there are a few familial cases that appear to be X-linked in nature.⁷

Differential diagnosis

As described above, ventral abdominal wall defects can occur along a spectrum as a result of variation in closure of the ectomesodermal folds during embryonic development. When suspected on early prenatal imaging, a large differential should be considered. These diagnoses include gastroschisis, omphalocele, Pentalogy of Cantrell, bladder exstrophy or cloacal deformity, and body-stalk complex. In addition, Pentalogy of Cantrell can be classified as a complete or incomplete syndrome depending on the number of features present on imaging.

Omphaloceles are often associated with multiple other syndromes including Beckwith-Wiedemann syndrome, Pentalogy of Cantrell, Meckel-Gruber syndrome, and lethal cleft palato-omphalacele syndrome.⁸ Prenatally, when ectopia cordis is seen in addition to an abdominal wall defect, Pentalogy of Cantrell should be considered in the differential.

Detection rates of omphalocele and gastroschisis are now as high as 100%, in the second and third trimester. However, due to herniation of the midgut during weeks 10-12 of gestation, detection of gastroschisis or omphalocele is often delayed until after 12 weeks of gestation. If the liver is seen outside of the abdominal cavity, this often will not recede and can be suggestive of early omphalocele.^8,9

Gastroschisis occurs in 1/4000 births. The umbilical cord insertion site is seen laterally and typically to the right of the defect. This defect can be diagnosed as early as 12 weeks’ gestation, but often not earlier than this because of the physiologic midgut herniation that occurs during weeks 10-12.⁶

Prenatal diagnosis (imaging complications)

Imaging and antenatal diagnosis can be complex, particularly if defects are on the mild end of the spectrum. Ultrasound, MRI and fetal echocardiography can detect and characterize the defect, and all may be necessary for an accurate diagnosis. Chromosomal analysis is often suggested for families to consider. Postnatal echocardiography can assist in determining the precise cardiac defect and both a multidetector computerized tomography (MCDT) and cardiac MRI can assist in surgical planning and prognosis.^7,10,11

Outcomes of varying diagnosis

One study examined the outcomes of omphalocele and gastroschisis after prenatal diagnosis. Of 67 diagnosed cases of omphalocele, 26 had an abnormal karyotype and 22 of those underwent termination of pregnancy. In pregnancies with a normal karyotype, only 14 resulted in a live birth and of those, 12 lived through the neonatal period. Of 42 diagnosed cases of gastroschisis, 36 resulted in a live birth with 29 surviving through the neonatal period and 3 infants lost to follow-up. The majority of both of these diagnoses were made at the time of the nuchal translucency scan around 12 to 13 weeks’ gestation.¹²

For neonates with gastroschisis, survival is generally favorable except in the case of gastroschisis with associated liver herniation. In one study of 117 patients with gastroschisis, 6% had liver herniation. There was a 57% mortality with liver herniation and only 3% mortality without liver herniation.¹³

Survival of patients with Pentalogy of Cantrell is as low as 37% and this varies based on the variation in presentation. Reported survival rates vary depending on the penetrance of the syndrome. It is thought that incomplete penetrance may lead to more successful outcomes.⁷

Complications

Many of the complications of the Pentalogy complex are associated with prematurity, increased risk of infection, the extent of the cardiac defect, and surgical complications. Causes of death include sepsis, renal failure, and multisystem organ failure. There often is pulmonary hypoplasia leading to an increased risk of pulmonary hypertension, which can be difficult to manage in premature patients. In the patient presented here, capillary leak syndrome from a significant systemic inflammatory response led to difficulties with diuresis and hypotension. The severe capillary leak syndrome resulted from the open abdomen (even though covered by a silo), and would be unusual with an omphalocele defect with membrane and/or skin coverage, even with significant liver herniation. Such cases of covered abdominal wall defect have the substantial benefit of allowing delayed surgical repair of the omphalocele, often by months or even years.

In this patient who presented prenatally with concern for a ventral abdominal wall defect including possible Pentalogy of Cantrell, it was important to have a multidisciplinary approach to prenatal consultation and postnatal management. Cardiology, surgery, radiology, neonatology, maternal-fetal-medicine, and palliative care support are all essential to help families understand the anomaly and to make the best decision for their fetus and family. Outcomes of this defect depend very much on the penetrance of the syndrome and whether it is complete, with a severe cardiac malformation, versus incomplete. Diagnosis of Pentalogy should also include within the differential all other ventral abdominal wall defects, as this defect is less common than others, including omphalocele and complicated gastroschisis. Surgical management must be coordinated with cardiology as prognosis often depends on the extent of the cardiac malformation. Finally, management of this condition in a Level IV NICU is essential.

American Board of Pediatrics Neonatal-Perinatal Content Specification.

• Know the pathogenesis and anomalies associated with omphalocele

• Know the approach to management, clinical manifestations, the differential diagnosis of, and the complications of treatment of omphalocele in neonates

Abbreviations:

MFCC

Maternal Fetal Care Center

US

ultrasound

MRI

Magnetic resonance imaging

VSD

ventricular septal defect

NICU

neonatal intensive care unit

PDA

patent ductus arteriosus