Ventral Wall Defects Research Articles

OEIS complex: prenatal ultrasound and autopsy findings

To describe prenatal ultrasound and autopsy findings in fetuses with OEIS (omphalocele, bladder exstrophy, imperforate anus, spina bifida) complex. This was a retrospective study of the nine cases with OEIS complex diagnosed at our center using detailed fetal ultrasound during the last 10 years. We summarized the fetal ultrasound findings that led to the diagnosis and compared them with the autopsy results. All affected fetuses were diagnosed using detailed fetal ultrasound after 16 weeks' gestation. The main prenatal findings were omphalocele, skin-covered lumbosacral neural tube defect, non-visualized bladder and limb defects. Prenatal sonography failed to detect the abnormal genitalia, bladder exstrophy and anal atresia. All cases had abnormalities in a 'diaper distribution', which helped in making the prenatal diagnosis. Eight of the nine couples chose to terminate the pregnancies following multidisciplinary counseling. The pregnancy that was continued was a case with dizygotic twins discordant for OEIS, and the affected fetus died in utero. The combination of the following ultrasound findings: ventral wall defect, spinal defect and a non-visualized bladder with or without limb defects, are characteristic of OEIS complex. Diagnosis can be made with confidence as early as 16 weeks' gestation, although earlier diagnosis may be possible.

Management of Gastroschisis

After completing this article, readers should be able to: 1. Describe various aspects of prenatal management for pregnancies complicated by gastroschisis, including diagnosis and counseling. 2. Know the increased risk of third trimester complications in pregnancies with gastroschisis and the need for close monitoring and vigilance during the perinatal period. 3. Discuss the controversial management strategies regarding timing and mode of delivery in gastroschisis and the resolution of some of the ongoing debates. 4. Delineate the important aspects of neonatal management of gastroschisis, including enumeration of modalities of surgical repair and postoperative complications. 5. Discuss the need for multicenter prospective controlled trials to standardize care of infants who have gastroschisis and improve outcomes. Gastroschisis is a common neonatal congenital anomaly whose global prevalence is increasing. Although survival of affected infants has improved over the past several decades, the relationship among prenatal diagnosis, the resulting perinatal management (including timing and mode of delivery), and timing and type of neonatal surgery remain uncertain. Over the past several years, a number of clinical and animal studies have clarified some aspects of the confusion. ### Diagnosis Gastroschisis is diagnosed prenatally via ultrasonography that documents the ventral abdominal wall defect through which loops of bowel protrude and float freely in the amniotic fluid. The umbilical cord insertion site usually appears normal, but it can be difficult to discern because herniated bowel loops may be pressed against it. Maternal serum alpha-fetoprotein concentrations usually are elevated and may be a marker for fetal gastroschisis, but specific diagnostic biochemical testing (eg, amniotic fluid acetylcholine esterase) is not recommended as a screening tool. Furthermore, genetic amniocentesis generally is not recommended because of the low risk of chromosomal abnormalities. Researchers have tried to identify sonographic predictors of bowel damage, such as fixed dilation of the herniated bowel and thickening of the bowel wall, but none has been …

Maternal serum alpha-fetoprotein levels in fetal hydrocephalus: a retrospective population based study

BackgroundAlthough maternal serum alpha-fetoprotein (MSAFP) is a highly sensitive marker for certain congenital malformations such as open neural tube and ventral wall defects, its usefulness as a screening test for fetal hydrocephalus is uncertain. We wished to determine the distribution of maternal serum alpha-fetoprotein levels associated with fetal hydrocephalus in a population-based screening program in Manitoba, and their potential relationship to additional anomalies.MethodsCases of fetal hydrocephalus unrelated to neural tube defects were ascertained from multiple sources and reviewed. Cross-reference with the Manitoba Maternal Serum Screening Program database determined which mothers had undergone maternal serum screening. Mean MSAFP levels in both isolated and complex hydrocephalus were calculated and compared with the general population of screened pregnancies using Independent Samples T-tests.ResultsMean MSAFP levels in 70 cases of fetal hydrocephalus were significantly higher than those of the general population of screened pregnancies (P = 0.029). This was due to the fact that mean MSAFP levels in those cases with other major anomalies were increased over those of the general population (P = 0.041); cases with hydrocephalus alone showed no significant difference (P = 0.203). Only seven cases (10%) had MSAFP levels ≥ 2.3 multiples of the median, the cut-off used in Manitoba. However, six of these (86%) had additional major and/or minor malformations.ConclusionMSAFP screening has low sensitivity for fetal hydrocephalus and is rarely elevated in isolated cases. However, when fetal hydrocephalus is detected, elevated MSAFP levels indicate that the fetus is at significant risk to have additional malformations and further investigations, including chromosome breakage studies, may be indicated.

Tensile Strength Comparison of Small Intestinal Submucosa Body Wall Repair

Porcine small intestinal submucosa (SIS) has been studied for body wall repair. However, the best method to implant the biological material has not been investigated. The objective of this study was to compare tensile strengths achieved after healing when SIS was placed using three implant techniques (onlay, inlay, underlay) in a porcine model of abdominal wall defect. Twenty female domestic pigs had three abdominal midline sites assigned to one of five test groups: SIS implantation using inlay, onlay, or underlay technique; sham surgery (sutured midline incision) or normal body-wall control. Full-thickness muscle/fascia midline abdominal defects (6 x 4 cm) were surgically created and then repaired using eight-layer SIS. Healing was evaluated at 1 and 4 post-operative months by tensile strength testing and histopathology. Hernias were not observed. Tensile strengths were not statistically different between the five test groups (P = 0.39) or between months 1 and 4 (P = 0.35). The caudal site was stronger than the cranial or middle sites in the 1 month group (P < 0.0001). Histologically, healing appeared to progress over time as the repair site showed remodeling towards an interlacing fibrous connective tissue pattern. No significant differences in tensile strength were found between implant techniques and were not statistically different from sham surgery and normal control tissue. This study suggested that SIS healing/remodeling provides sufficient tensile strength for the repair of ventral (anterior) abdominal wall defects when implanted using any of three common techniques.

1123: Prenatal diagnosis of ventral wall defects

Ventral wall defects are a common group of fetal anomalies and a wide variety of ventral wall defects are diagnosed. And there are various options for perinatal management of fetal ventral wall defects, which range from termination of pregnancy to normal term delivery with postnatal surgery, depending on the type and severity of the lesion and probability of associated structural and chromosomal abnormalities. The routine fetal ultrasonography with widespread use of maternal serum alpha fetoprotein (AFP) screening allows the majority of ventral wall defects to be identified prenatally. But confusion arises when the ventral wall defect is complex or has other associated abnormalities. The accurate prenatal diagnosis of ventral wall defects is important because it affects patient management and prognosis. This lecture reviews the characteristic sonographic findings with possible pathological correlation, the associated structural and/or chromosomal abnormalities and outcome of simple and complicated types of ventral wall defects, which were diagnosed on our hospital over a 10-y period.

Terminal myelocystocele

The authors describe the cases of eight patients with terminal myelocystoceles and report on their initial diagnoses, neuroimaging findings, surgical procedures, and clinical follow-up examinations. There were seven girls and one boy. The initial age at diagnosis ranged from prenatal age (determined by imaging) to 14 years. Operative correction was performed from 6 weeks to 14 years of age. One patient presented with a large prevertebral (intraabdominal) meningocele. Four patients have associated abdominal wall defects and are significantly handicapped. Two are wheelchair bound and the other two ambulate with prosthetic devices; all are incontinent. The four patients without abdominal wall defects are fully ambulatory; one wears an ankle-foot orthosis. One patient has normal bowel and bladder functions, and the other three require intermittent clean catheterization. No patient to date has had clinical evidence of retethering, although a low-set conus medullaris and residual lipoma were visible on postoperative neuroimaging. No patient in this series had hydrocephalus or Chiari malformation. It is concluded that patients with myelocystoceles without abdominal wall defects have a favorable neurological outcome when compared with those having ventral wall defects.

Effects of cadmium on cell death and cell proliferation in chick embryos

The aim of this study was to examine cell death and cell proliferation in chick embryos destined to have ventral body wall defects as a result of cadmium (Cd) treatment. Embryos in shell-less culture were treated with 50 μL Cd acetate (8.9 × 10 −5 M Cd 2+) at Hamilton–Hamburger (H.–H.) stage 16–17, or with equimolar sodium acetate. TdT-Mediated dUTP nick end labelling (TUNEL) showed the mode of cell death to be apoptosis commencing 4 h after treatment in somites and neural tube. Desquamation also occurred in the peridermal layer of the ectoderm. Cd caused no changes in the S-phase population of any tissue except ectoderm. The peridermal layer of the latter had a 40% reduction in labeling index (LI) 5.25 h after treatment but increased thereafter, being 30% greater than control values at 25.25 h. The occurrence of gross malformation was strongly correlated with the degree of apoptosis and in turn with the extent of peridermal desquamation. Pre-treatment with zinc acetate (10× the dose of Cd) prevented gross malformation, apoptosis and the effect of Cd on peridermal proliferation. We hypothesize that the ventral body wall defect resulting from Cd treatment in chick embryos is the result of changes in the somites perhaps following interruption of a signalling pathway originating in ectoderm.

Finally, a sense of closure? Animal models of human ventral body wall defects

Malformations concerning the ventral body wall constitute one of the leading categories of human birth defects and are present in about one out of every 2000 live births. Although the occurrence of these defects is relatively common, few detailed experimental studies exist on the development and closure of the ventral body wall in mouse and human. This field is further complicated by the array of theories on the pathogenesis of body wall defects and the likelihood that there is no single cause for these abnormalities. In this review, we summarize what is known concerning the mechanisms of normal ventral body wall closure in humans and mice. We then outline the theories that have been proposed concerning human body wall closure abnormalities and examine the growing number of mouse mutations that impact normal ventral body wall closure. Finally, we speculate how studies in animal models such as mouse and Drosophila are beginning to provide a much-needed mechanistic framework with which to identify and characterize the genes and tissues required for this vital aspect of human embryogenesis.

Sonographic Signs of Midgut Malformations Due to Ventral Wall Defects

The primitive gut begins development within the fourth week of gestation. Embryonic folding toward the midline results in the fusion of the abdominal wall on the midline. Fusion failure results in an abdominal defect that allows the abdominal organs to protrude into the amniotic fluid either with or without a covering membrane. Prenatal testing includes determining the levels of •-fetoprotein (MS-AFP) and acetylcholinesterase (AChE) with abnormal levels raising suspicion for congenital defects of the brain, spine, or abdomen. Sonography is a valuable tool in diagnosing abdominal wall defects as an isolated defect or part of a syndrome.

Morphologic study of three collagen materials for body wall repair

Background The search for ideal prostheses for body wall repair continues. Synthetic materials such as polypropylene mesh (PPM) are associated with healing complications. A porcine-derived collagen-based material (CBM), small intestinal submucosa (SIS), has been studied for body wall repair. Renal capsule matrix (RCM) and urinary bladder submucosa (UBS) are CBMs not previously evaluated in this application. This is the first implant study using RCM. Materials and methods Full-thickness muscle/fascia ventral abdominal wall defects were repaired with SIS, RCM, UBS, and PPM in rats with omentum and omentectomy. A random complete block design was used to allot implant type to each of 96 rats. Healing was evaluated at 4 and 8 weeks. Adhesion tenacity and surface area were scored. Implant site dimensions were measured at implantation and necropsy. Inflammation, vascularization, and fibrosis were histopathologically scored. Data were compared by analysis of variance ( P < 0.05). Results PPM produced a granulomatous foreign body response in contrast to the organized healing of CBM implants. CBM mean scores were lower than PPM scores for adhesion tenacity, surface area, and inflammation at each follow-up time for rats with omentums ( P < 0.02). The CBMs had less tenacity and inflammation than PPM at each follow-up time in omentectomy groups ( P < 0.008). Wound contraction was greater for PPM ( P < 0.0001) for all rats. Conclusions RCM and UBS were similar to SIS invoking reduced inflammation, adhesion, and contraction compared to PPM. The fibrotic response to PPM was unique and more intense compared to CBMs. These CBM implants appear morphologically acceptable and warrant continued investigation.

AFAFP level among fetuses with gastroschisis, omphalocele, and thoraco-abdominal ventral wall defects

AFAFP level among fetuses with gastroschisis, omphalocele, and thoraco-abdominal ventral wall defects

Body wall repair using small intestinal submucosa seeded with cells

Background/Purpose: Prosthetic repair of large ventral abdominal wall defects has been associated with high complication rates. This study was aimed at applying tissue engineering to body wall replacement. Methods: Syngeneic Lewis rats underwent harvest of skeletal muscle specimens. Once expanded in vitro, skeletal muscle cells or fibroblasts were suspended in a collagen gel. All animals underwent creation of a 2.5- × 3-cm abdominal wall defect. The defect was repaired with the cell-seeded gel placed in between 2 pieces of small intestinal submucosa (SIS). The control group was repaired by SIS with acellular gel. Animals were killed at different time-points for histologic and mechanical examination. Statistical analysis was by analysis of variance (ANOVA). Results: Abdominal wall hernia was present in 6 of 24 fibroblast-seeded constructs (25%), 5 of 21 skeletal muscle cell-seeded constructs (23.9%), and 16 of 21 acellular grafts (76.2%), respectively ( P < .05). At harvest, cell-seeded constructs were thicker with better cellular infiltration, whereas acellular grafts were thin, low in cell density, and poor in mechanical resistance. Conclusions: Unlike acellular collagen matrices, engineered cellular constructs have better cell infiltration and mechanical performance. Tissue engineering may be a viable alternative for body-wall replacement.

Geographic and temporal analysis of folate-sensitive fetal malformations.

To identify potential geographic and temporal clustering of folate-sensitive fetal malformations as a prelude to a targeted preconception curriculum in folic acid supplementation. Our comprehensive prenatal anomaly database was queried to select fetal malformations presumed to be sensitive to preconception folate insufficiency. Evidence of geographic clustering was evaluated by distribution of individual cases using zip codes of maternal residence. Potential temporal clustering of anomalies was sought by tabulating the frequency of each anomaly category during 5 consecutive 2-year intervals between 1992 and 2001. Over a 10-year period, approximately 2000 fetal anomalies were identified, of which 400 (20%) were considered potentially folate sensitive. We found geographic clustering of ventral wall defects as well as obstructive uropathy by zip code analysis. Significant increases in the frequencies of cardiac defects (P <.001) and obstructive uropathy (P <.001) were noted during the epoch of this study. A moderate increase in anomaly frequency was also seen in the diagnostic subcategory of gastroschisis, in which 15 of 27 total gastroschisis cases occurred in 2000-2001. Geographic clustering and temporal trends in anomaly rates were noted in certain folate-sensitive malformation categories. Identification of specific, high-incidence regions may provide an opportunity for targeted interventions designed to supplement the national folic acid campaign.

Risks associated with "components separation" for closure of complex abdominal wall defects.

The reconstruction of complex abdominal wall defects can often pose a significant challenge to surgeons and their patients. Complex ventral hernias may result from large tumor resections, trauma from gunshot wounds, or infections following routine abdominal surgery. "Components separation" of the abdominal musculature uses advancement of local autologous tissue, when available, to close large ventral wall defects. The authors report on a retrospective chart review of 30 patients who underwent components separation for the closure of complex abdominal defects. The study group was 50 percent female, with a mean age of 45 years, body mass index of 33.2 kg/m2, and abdominal defect size of 240 cm2. On average, 20 percent of patients had preoperative wound infections, 30 percent had intraoperative bowel enterotomies, and 33 percent required prosthetic mesh for closure. Total surgery time averaged 4.8 hours, with a mean postoperative stay of 12.5 days and follow-up of 9.5 months. The recurrence rate was 10 percent; postoperative complications included midline ischemia, infection, and dehiscence occurring at rates of 20, 40, and 43 percent, respectively. This study provides a comprehensive review of the risks and complications associated with the treatment of complex ventral hernias and those associated with abdominal "components separation."

Morphologic Study of Small Intestinal Submucosa as a Body Wall Repair Device

Background. The extracellular matrix (ECM) derived from porcine small intestinal submucosa (SIS) has been used as a constructive scaffold for tissue repair in both preclinical animal studies and human clinical trials. Quantitative characterization of the host tissue response to this xenogeneic scaffold material has been lacking.Materials and methods. The morphologic response to a multilaminate form of the SIS–ECM was evaluated in a chronic, 2-year study of body wall repair in two separate species: the dog and the rat. Morphologic response to the SIS–ECM was compared to that for three other commonly used bioscaffold materials including Marlex mesh, Dexon, and Perigard. Quantitative measurements were made of tissue consistency, polymorphonuclear cell response, mononuclear cell response, tissue organization, and vascularity at five time points after surgical implantation: 1 week, 1, 3, and 6 dmonths, and 2 years.Results. All bioscaffold materials functioned well as a repair device for large ventral abdominal wall defects created in these two animal models. The SIS–ECM bioscaffold showed a greater number of polymorphonuclear leukocytes at the 1-week time point and a greater degree of graft site tissue organization after 3 months compared to the other three scaffold materials. There was no evidence for local infection or other detrimental local pathology to any of the graft materials at any time point.Conclusions. Like Marlex, Dexon, and Perigard, the SIS–ECM is an effective bioscaffold for long-term repair of body wall defects. Unlike the other scaffold materials, the resorbable SIS–ECM scaffold was replaced by well-organized host tissues including differentiated skeletal muscle.

Management of cloacal exstrophy.

The exstrophy complex represents a spectrum of congenital abnormalities that includes the following conditions: epispadias, classic bladder exstrophy, and cloacal exstrophy. These three deformations comprise a continuum with epispadias representing the least severe, classic bladder exstrophy the most common, and cloacal exstrophy the most severe. Cloacal exstrophy is extremely rare, occurring in approximately 1 in every 200,000 to 400,000 live births (Ziegler et al, 1986). Although primarily a ventral abdominal wall defect, cloacal exstrophy is associated with varying degrees of abnormalities in the genitourinary tract, bowel, spine, and lower extremities. Until recently, most children with cloacal exstrophy did not survive infancy because of the complex multiple system abnormalities resulting in fluid and nutritional defects. In 1960, Rickham reported the first survivor with cloacal exstrophy (Rickham, 1960). Primarily due to advances in perinatal care and total parenteral nutrition, survival is now feasible in greater than 90% of patients born with cloacal exstrophy. Thus, the focus is now directed at quality of life issues in these complex patients.KeywordsIdeal TrackMullerian DuctUrethral PlateCloacal Exstrophy46XX GenotypeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Effects of cadmium on formation of the ventral body wall in chick embryos and their prevention by zinc pretreatment

Cadmium (Cd) is an established experimental teratogen whose effects can be reversed by pretreatment with zinc. Mesodermal development is a frequently reported target for Cd teratogenicity. The aim of this study was to examine the mechanisms of Cd induced body wall defects in chick embryos. Chick embryos in shell-less culture were treated with 50 microl of cadmium acetate (8.9 x 10(-5) M Cd(2+)) at 60-hr incubation (H.-H. stages 16-17). Controls received equimolar sodium acetate. Other embryos were treated with various concentrations of zinc acetate and then with Cd or NaAc 1 hrs later. Development was evaluated 48 hrs later. Resin-embedded 1-microm sections were examined at earlier stages. Cd caused embryolethality (35%), ventral body wall defect with malpositioned lower limbs (40%), and weight reduction in survivors. After 4-hr treatment with Cd, breakdown of junctions between peridermal cells with rounding up and desquamation occurred. Shape changes were also seen in the basal layer of the ectoderm. At 4 hr, cell death was evident in lateral plate mesoderm, somites, and neuroepithelium; the lateral plate mesoderm began to grow dorsally, carrying the attached limb buds with it. Zn pretreatment protected against the lethal, teratogenic, and growth-retarding effects of Cd, as well as ectodermal changes and cell death. Cd disrupts peridermal cell adhesion and induces cell death in the mesoderm. This may result in abnormal growth of lateral plate mesoderm and in a body wall defect. Zn pretreatment prevents both the gross teratogenic effects and the cellular changes, most likely by competition with Cd.

Glypican-3 Controls Cellular Responses to Bmp4 in Limb Patterning and Skeletal Development

Glypicans represent a family of six cell surface heparan sulfate proteoglycans in vertebrates. Although no specific in vivo functions have thus far been described for these proteoglycans, spontaneous mutations in the human and induced deletions in the mouse glypican-3 (Gpc3) gene result in severe malformations and both pre- and postnatal overgrowth, known clinically as the Simpson–Golabi–Behmel syndrome (SGBS). Mice carrying mutant alleles of Gpc3 created by either targeted gene disruption or gene trapping display a wide range of phenotypes associated with SGBS including renal cystic dysplasia, ventral wall defects, and skeletal abnormalities that are consistent with the pattern of Gpc3 expression in the mouse embryo. Previous studies in Drosophila have implicated glypicans in the signaling of decapentaplegic, a BMP homolog. Our experiments with mice show a significant relationship between vertebrate BMP signaling and glypican function; GPC3-deficient animals were mated with mice haploinsufficient for bone morphogenetic protein-4 (Bmp4) and their offspring displayed a high penetrance of postaxial polydactyly and rib malformations not observed in either parent strain. This previously unknown link between glypican-3 and BMP4 function provides evidence of a role for glypicans in vertebrate limb patterning and skeletal development and suggests a mechanism for the skeletal defects seen in SGBS.

Is vaginal delivery preferable to elective cesarean delivery in fetuses with a known ventral wall defect?

Objective: We sought to test the hypothesis that vaginal delivery compared with elective cesarean delivery results in improved neonatal outcome in fetuses with a known isolated ventral wall defect. Study Design: We performed a retrospective chart review. Results: Between 1989 and 1999, we identified 102 infants with a confirmed antenatal diagnosis of an isolated ventral wall defect with either the diagnosis of an omphalocele or gastroschisis. Sixty-six infants were delivered by cesarean and 36 were delivered vaginally. There were no significant demographic differences between the study groups or between the two sites except that one center (Cincinnati) usually delivered these fetuses by cesarean whereas the other (Louisville) usually delivered such fetuses vaginally. Overall, there were a greater number of infants with gastroschisis than omphalocele (gastroschisis, n = 71; omphalocele, n = 31). After we controlled for primary versus staged closure of ventral wall defect and gestational age at delivery; the medians and interquartile ranges for cesarean and vaginal delivery were 39 (25, 63) days versus 42 (26, 75) days, respectively (P =.32), for neonatal length of stay and 13 (9, 18) days versus 13 (9, 26) days, respectively (P =.16), for days to enteral feeding. After we controlled for the size of the defect and the amount of bowel resected, the odds of primary closure given a vaginal delivery was about half that given a cesarean delivery (odds ratio, 0.56; 95% confidence interval, 0.18-1.69), but this was not statistically significant. There was no statistically significant difference in the rates of neonatal death (2 [3%] vs 2 [6%]; P =.61) and neonatal sepsis (2 [3%] vs 4 [11%]; P =.18) for cesarean versus vaginal delivery. Maternal length of stay after delivery was found to be 1 day less after vaginal delivery [vaginal, 2 (2, 2) days; cesarean, 3 (2, 3) days; P =.0001]. There were 5 instances of maternal complications, and all 5 pregnancies were delivered by cesarean (P =.16). Conclusion: Fetuses with an antenatal diagnosis of an isolated ventral wall defect may safely be delivered vaginally, and cesarean delivery should be performed for obstetric indications only. (Am J Obstet Gynecol 2000;182:1527-34.)

First trimester maternal serum AFP and total hCG in aneuploidies other than trisomy 21.

Total human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) were measured in maternal serum at 10-14 weeks of gestation from 53 pregnancies affected by trisomy 18, 42 cases with trisomy 13, 46 with Turner's syndrome and 13 with other sex aneuploides. The only significant association was the finding of reduced levels of total hCG in cases of trisomy 18 and 13. The association of increased levels of AFP in cases of trisomy 18 with ventral wall defects and the slight increase in AFP in cases of sex chromosomal anomalies other than Turner's syndrome was found. AFP and total hCG are not likely to replace the markers free beta-hCG and PAPP-A in first trimester screening for chromosomal anomalies.