Complex gastroschisis: a new indication for fetal surgery?

Gastroschisis (GS) is a congenital abdominal wall defect, in which the bowel eviscerates from the abdominal cavity. It is a non-lethal isolated anomaly and its pathogenesis is hypothesized to occur as a result of two hits: primary rupture of the 'physiological' umbilical hernia (congenital anomaly) followed by progressive damage of the eviscerated bowel (secondary injury). The second hit is thought to be caused by a combination of mesenteric ischemia from constriction in the abdominal wall defect and prolonged amniotic fluid exposure with resultant inflammatory damage, which eventually leads to bowel dysfunction and complications. GS can be classified as either simple or complex, with the latter being complicated by a combination of intestinal atresia, stenosis, perforation, volvulus and/or necrosis. Complex GS requires multiple neonatal surgeries and is associated with significantly greater postnatal morbidity and mortality than is simple GS. The intrauterine reduction of the eviscerated bowel before irreversible damage occurs and subsequent defect closure may diminish or potentially prevent the bowel damage and other fetal and neonatal complications associated with this condition. Serial prenatal amnioexchange has been studied in cases with GS as a potential intervention but never adopted because of its unproven benefit in terms of survival and bowel and lung function. We believe that recent advances in prenatal diagnosis and fetoscopic surgery justify reconsideration of the antenatal management of complex GS under the rubric of the criteria for fetal surgery established by the International Fetal Medicine and Surgery Society (IFMSS). Herein, we discuss how conditions for fetoscopic repair of complex GS might be favorable according to the IFMSS criteria, including an established natural history, an accurate prenatal diagnosis, absence of fully effective perinatal treatment due to prolonged need for neonatal intensive care, experimental evidence for fetoscopic repair and maternal and fetal safety of fetoscopy in expert fetal centers. Finally, we propose a research agenda that will help overcome barriers to progress and provide a pathway toward clinical implementation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Development of the amniote ventrolateral body wall.

In vertebrates, the trunk consists of the musculoskeletal structures of the back and the ventrolateral body wall, which together enclose the internal organs of the circulatory, digestive, respiratory and urogenital systems. This review gives an overview on the development of the thoracic and abdominal wall during amniote embryogenesis. Specifically, I briefly summarize relevant historical concepts and the present knowledge on the early embryonic development of ribs, sternum, intercostal muscles and abdominal muscles with respect to anatomical bauplan, origin and specification of precursor cells, initial steps of pattern formation, and cellular and molecular regulation of morphogenesis.

Fetal anterior abdominal wall thickness between gestational diabetes and normal pregnant women.

OBJECTIVES: To compare fetal anterior abdominal wall thickness (AAWT) between women with and without GDM during third trimester and to determine accuracy of AAWT to predict large for gestational age (LGA) infants. MATERIALS AND METHODS: A total of 250 pregnant women, including 125 women with GDM and 125 women without GDM, were enrolled. Tansabdominal ultrasonographic examinations were performed at 28-30, 32-34 and 36-38 weeks. In addition to standard fetal biometries, AAWT was measured. Patient characteristics and ultrasonographic measurements were compared between groups. Sensitivity and specificity of AAWT for identifying LGA were evaluated. RESULTS: While standard fetal biometries were comparable, mean fetal AAWT in GDM women were significantly higher than those without GDM at 28-30 weeks (2.8 ± 0.8 vs. 2.6 ± 0.6, p = 0.006) and 32-34 weeks (4.0 ± 0.9 vs. 3.5 ± 0.8, p = 0.042). LGA infants had significantly higher fetal AAWT at each time point only in GDM women. Using cut off values of AAWT of ≥2.0, 3.0, and 4.0 mm at 28-30, 32-34, and 36-38 weeks, sensitivity for LGA diagnosis in GDM women were 94.4%, 93.9%, and 89.3%, respectively. The use of abdominal circumference (AC) at >90th percentile showed lower sensitivity but higher specificity, regardless of GDM status. Combination of both measurements increased sensitivity to approximately 90% or higher in every time point, especially among GDM women. CONCLUSION: Significant increase in fetal AAWT was observed in GDM women at 28-30 and 32-34 weeks. Fetal AAWT significantly increased among LGA infants and had higher sensitivity than AC in identifying LGA during third trimester. In GDM women at 28-30 weeks, AAWT ≥2.0 mm and AC >90th percentile had 97.2% sensitivity for LGA diagnosis.

Insights into embryology and development of omphalocele.

Congenital abdominal wall defects are one of the most common human birth defects with an incidence of about 1 in 2000 live births. While often discussed together abdominal wall defects consist mainly of two distinct entities namely gastroschisis and omphalocele. There is no clear consensus explaining the precise embryological mechanisms leading to the development of an omphalocele. Many clinicians and embryologists have attempted to explain congenital malformation as a result of failure of progression of normal embryonic development. This review summarizes the mechanisms involved in normal and abnormal development of the ventral abdominal wall.

An evolutionary and developmental biology approach to gastroschisis.

Recent advances have now made it possible to speak of gastroschisis narrowly in morphogenetic terms invoking the Rittler-Beaudoin (R-B) model. This proceeds from the appreciation of gastroschisis as a congenital intestinal herniation (without cover or liver) within the primordial umbilical ring, mostly to the right side of a normally formed umbilical cord. Presently, it is unresolved whether this visceral prolapse represents failure of ring closure before return of the physiological hernia into the abdomen or rupture of the delicate amniotic/peritoneal membrane at the ring's edge to the right of the cord. Animal observations and experiments will be required to address this question effectively. If gastroschisis is, in fact, a primary malformation with the primordial umbilical ring as the developmental field involved, then homology implies potential gastroschisis in all amniotes with corresponding nourishment from yolk sac (aka omphalomesenteric) vessels going into the embryo and excretory products out via the ancient umbilical connection. It also implies homology of corresponding morphogenetic signal transduction cascades. We review the history of gastroschisis, its presumed pathogenesis, and the developmental biology of the amniotic umbilical ring from this perspective. Therefore, based on the animal and human evidence to date, we propose that gastroschisis is a primary midline malformation that involves the umbilical canal from amniotic to peritoneal space and its primordial umbilical ring, either through nonclosure or rupture of the membrane covering the area, mostly to the right, between the cord and the edge of the ring.

A Nomogram of Lateral Abdominal Wall Fat Thickness in Normal Third Trimester Fetuses.

OBJECTIVES: The objective of this study is to establish a nomogram of fetal abdominal wall fat thickness in fetuses with known normal neonatal outcomes. METHODS: After IRB approval (HSD-49496), 157 ultrasound examinations in 100 patients, 41 of whom had multiple examinations during the same pregnancy were reviewed. The thickness of the fetal lateral abdominal wall fat Interreader agreement was summarized using the intraclass correlation coefficient (ICC). Fat thickness growth curve equations were estimated to quantify the relationship between fat thickness and gestational age. RESULTS: The abdominal wall fat had an intraclass correlation coefficient of 0.93 (95% confidence interval, 0.90-0.96) for 2 readers. Fat thickness increased in all 41 fetuses with multiple examinations (P < 0.001). Fat thickness increased 0.19 mm per week on average (95% confidence interval, 0.17-0.21 mm; P < 0.001) from an average of 1.7 mm at 22 weeks and 4.3 mm at 36 weeks. CONCLUSIONS: Lateral wall abdominal fat can be reproducibly measured with good inter observer correlation, and fat does increase with increasing gestational age in normal fetuses. We believe the utility of fetal fat is the documentation of its presence as a reassuring finding indicative of normal fetal health, particularly when prior dating is discrepant or not available during the third trimester.

Insights into the etiology and embryology of gastroschisis.

The development of gastroschisis has long remained an area of interest and controversy. Successive theories about its pathogenesis are herein reviewed and discussed. Two historical assumptions, that omphalocele results from a persistent umbilical hernia, and that gastroschisis does not involve the umbilical cord, are dismissed. Therefore, one can envision gastroschisis for what it is, i.e. a ruptured physiological hernia. The causal agents for this intrauterine accident to occur are yet to be determined. Further bowel damage and complications can be explained by the mesenteric insult.

Dichorionic twins discordant for body-stalk anomaly: a management challenge.

Body-stalk anomaly is a sporadic and rare maldevelopment disorder characterised by large abdominal wall defect, spinal deformity and rudimentary umbilical cord. It is considered a lethal condition as there are only few reports of survival but there was at least one case of long-term survival after neonatal surgery.Differential diagnosis includes isolated omphalocele or gastroschisis, short umbilical cord, amniotic band, limb body-wall complex and other polymalformative syndromes.There are few reports about the expectant prenatal management of the body stalk anomaly as the majority of prenatal diagnosed cases undergo early elective termination. Twin pregnancies discordant for the anomaly represent a challenge to prenatal management as a healthy fetus should also be considered.We describe a case of dichorionic-diamniotic twins discordant for body stalk anomaly which underwent selective feticide of the affected fetus late in pregnancy, in accordance with parents' decision focused on the neonatal well-being of the unaffected twin.

CHALLENGES AND MANAGEMENT OF CONGENITAL ABDOMINAL WALL DEFECTS (REVIEW).

Management of congenital abdominal wall malformations is still a challenge in paediatric surgery due to visceroabdominal disproportion, large defects of abdominal wall and immature abdominal cavity. Most of the patients treated with primary closure need artificial substitutes like patches or biomaterials for non-permanent abdominal wall closure. Patches represent the source of constant infections and complications like separation of prosthesis from fascia. Removal of these patches and ventral hernia repair is essential afterwards. As for component separation technique, this method helps to restore normal anatomy of anterior abdominal wall, results in good cosmetic appearance, requires only one-stage operation procedure, minimal skin flap advancement and is associated with lower infection risk. Although, while performing component separation technique, perforator branches of epigastric artery (periumbilical perforators) are damaged and puts the vascularization of the skin at the risk. Only pudendal artery branches and intercostal arteries are left to supply the skin with the blood, which from our point of view is insufficient. Accordingly, for successful treatment of congenital abdominal wall defects, further research in order to develop new operation techniques, as well as search for the ideal biomaterials for the closure of the large defects of anterior abdominal wall is essential. These biomaterials should possess unique biological properties that are important for tissue repair, including anti-inflammatory, antimicrobial, antifibrosis, antiscarring, as well as a reasonable cost and low immunogenicity.

Paradigm shift regarding the transversalis fascia, preperitoneal space, and Retzius' space.

BACKGROUND: There has been confusion in the anatomical recognition when performing inguinal hernia operations in Japan. From now on, a paradigm shift from the concept of two-dimensional layer structure to the three-dimensional space recognition is necessary to promote an understanding of anatomy. ANATOMY AND EMBRYOLOGY: Along with the formation of the abdominal wall, the extraperitoneal space is formed by the transversalis fascia and preperitoneal space. The transversalis fascia is a somatic vascular fascia originating from an arteriovenous fascia. It is a dense areolar tissue layer at the outermost of the extraperitoneal space that runs under the diaphragm and widely lines the body wall muscle. The umbilical funiculus is taken into the abdominal wall and transformed into the preperitoneal space that is a local three-dimensional cavity enveloping preperitoneal fasciae composed of the renal fascia, vesicohypogastric fascia, and testiculoeferential fascia. The Retzius' space is an artificial cavity formed at the boundary between the transversalis fascia and preperitoneal space. In the underlay mesh repair, the mesh expands in the range spanning across the Retzius' space and preperitoneal space.

Stage specific requirement of platelet-derived growth factor receptor-α in embryonic development.

BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures. PURPOSE: To address the temporal requirement of Pdgfra in embryonic development. METHODS: We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies. RESULTS: Current study showed that (i) conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5) resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii) the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives. CONCLUSION: Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a) the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b) if mutations / sequence variations of these regulatory elements cause these anomalies.

Predicting Adverse Neonatal Outcome Especially When Gestational Age Is Uncertain: Utility of Sonographic Measurement of Fetal Abdominal Wall Thickness.

Early and accurate prenatal diagnosis of intrauterine growth restriction is important. Commonly used biometric parameters have limited specificity and require accurate dating. Fetal abdominal wall thickness (AWT) could be a useful supplemental parameter. We performed a retrospective study of 100 third trimester ultrasound exams and compared the sensitivity and specificity of AWT to those of weight percentile (WP) in predicting adverse perinatal outcome.There is a statistically significant difference between the AWT of patients with normal perinatal outcome and that of patients with adverse outcome (P < 0.01). When compared with WP across the entire range of the receiver operating characteristics curve, AWT [area under the curve (AUC), 0.76] has an efficacy similar to that of WP (AUC, 0.72; P = 0.30). However, AWT has superior performance over WP (AUC, 0.72 vs AUC, 0.61, respectively, P = 0.04) in the high specificity range (70%-100%) of the receiver operating characteristics curve, where the consequences of a false negative greatly outweigh those of a false positive. In our study population, with a cutoff value of 4 mm, AWT was a useful and more specific predictor of adverse perinatal outcome than WP. Abdominal wall thickness may be more useful in situations when dating is uncertain.

Transgelin-expressing myofibroblasts orchestrate ventral midline closure through TGFß signalling.

Ventral body wall (VBW) defects are among the most common congenital malformations, yet their embryonic origin and underlying molecular mechanisms remain poorly characterised. Transforming growth factor beta (TGFß) signalling is essential for VBW closure, but the responding cells are not known. Here, we identify in mouse a population of migratory myofibroblasts at the leading edge of the closing VBW that express the actin-binding protein transgelin (TAGLN) and TGFß receptor (TGFßR). These cells respond to a temporally regulated TGFß2 gradient originating from the epithelium of the primary body wall. Targeted elimination of TGFßR2 in TAGLN+ cells impairs midline closure and prevents the correct subsequent patterning of the musculature and skeletal components. Remarkably, deletion of Tgfbr2 in myogenic or chondrogenic progenitor cells does not manifest in midline defects. Our results indicate a pivotal significance of VBW myofibroblasts in orchestrating ventral midline closure by mediating the response to the TGFß gradient. Altogether, our data enable us to distinguish highly regulated epithelial-mesenchymal signalling and successive cellular migration events in VBW closure that explain early morphological changes underlying the development of congenital VBW defects.

Further evidence of the etiology of prune belly syndrome provided by a transient massive intraabdominal cyst in a female.

We present a female neonate born with prune belly syndrome (PBS) in whom a large intraabdominal cyst was diagnosed at 12weeks of gestation. Rapid and exponential growth of the cyst caused pressure effects on the intraabdominal organs and stretching of the anterior abdominal wall by 19weeks of gestation. This led to drainage of the massive cyst at 20weeks of gestation to prevent fetal demise. This case provides further clues to the likely etiology of PBS: transient stretching and attenuation of the fetal abdominal wall secondary to gross fetal abdominal distension - from any cause.

De la embriogénesis a la prevención de cardiopatías congénitas, defectos del tubo neural y de pared abdominal / From embryogenesis to the prevention of congenital cardiopathies, defects of the neural tube and the abdominal wall

Introducción: Los defectos congénitos constituyen una causa importante de mortalidad infantil y discapacidad. Las cardiopatías y los defectos del tubo neural y de la pared abdominal son de los más frecuentes. Objetivo: sistematizar los referentes teóricos sobre la embriogénesis y la epidemiología de estas anomalías del desarrollo, que contribuyan a la capacitación de médicos y estudiantes como promotores de salud. Materiales y Métodos: se realizó la revisión de 32 artículos científicos, búsqueda en la Biblioteca Virtual de Salud de Infomed, en las bases de datos Medline Complete, Pubmed Central, Clinical Key, Scielo regional y Scielo Cuba. La búsqueda se realizó entre los meses de octubre de 2014 y febrero de 2015, y quedó limitada a los últimos 8 años. Resultados: los defectos cardiacos se producen por fallas en la embriogénesis, entre la quinta y décima semanas de embarazo; los del tubo neural en la tercera y cuarta semana de embarazo y los de pared anterior entre la cuarta y la duodécima semana de embarazo. La etiología obedece a factores genéticos, ambientales y multifactoriales, y el riesgo de recurrencia depende de la causa. Existen tres niveles de prevención: preconcepcional, prenatal y postnatal. Conclusiones: el más importante es el preconcepcional, pues es el más eficaz, humano y económico(AU)

Background: congenital defects are an important cause of infantile mortality and disability. Cardiopathies and defects of the neural tube and the abdominal wall are among the most frequent ones. Aim: systematizing theoretical referents on embryogenesis and epidemiology of these developmental anomalies, to contribute to physicians and students´ training as health promoters. Materials and methods: 32 scientific articles were reviewed, searching in the Health Virtual Library of Infomed, in the databases Medline Complete, Pubmed Central, Clinical Key, regional Scielo and Scielo Cuba. The search was made from October 2014 to February 2015, and was restricted to the last 8 years.Outcomes: heart defects are produced by failures in embryogenesis, between the fifth and the seventh weeks of pregnancy; the neural tube ones, between the third and fourth weeks of pregnancy, and the ones of the front wall, between the fourth and the twelfth weeks of pregnancy. Etiology is due to genetic, environmental and multifactorable reasons; the recurrence risk depends on the cause. There are three prevention levels: pre-conceptional, prenatal and postnatal. Conclusions: the most important level is the pre-conceptional one, because it is the most efficacious, human and economic(AU)

Development of the ventral body wall in the human embryo.

Migratory failure of somitic cells is the commonest explanation for ventral body wall defects. However, the embryo increases ~ 25-fold in volume in the period that the ventral body wall forms, so that differential growth may, instead, account for the observed changes in topography. Human embryos between 4 and 10 weeks of development were studied, using amira reconstruction and cinema 4D remodeling software for visualization. Initially, vertebrae and ribs had formed medially, and primordia of sternum and hypaxial flank muscle primordium laterally in the body wall at Carnegie Stage (CS)15 (5.5 weeks). The next week, ribs and muscle primordium expanded in ventrolateral direction only. At CS18 (6.5 weeks), separate intercostal and abdominal wall muscles differentiated, and ribs, sterna, and muscles began to expand ventromedially and caudally, with the bilateral sternal bars fusing in the midline after CS20 (7 weeks) and the rectus muscles reaching the umbilicus at CS23 (8 weeks). The near-constant absolute distance between both rectus muscles and approximately fivefold decline of this distance relative to body circumference between 6 and 10 weeks identified dorsoventral growth in the dorsal body wall as determinant of the 'closure' of the ventral body wall. Concomitant with the straightening of the embryonic body axis after the 6th week, the abdominal muscles expanded ventrally and caudally to form the infraumbilical body wall. Our data, therefore, show that the ventral body wall is formed by differential dorsoventral growth in the dorsal part of the body.

A chicken embryo model for the study of umbilical and supraumbilical body wall malformations.

UNLABELLED: BACKGROUND/PURPOSE; The embryology of ventral body wall malformations is only partially understood, although their incidence is relatively common. As only few experimental data exist on the development of those defects, the aim of our study was to compare the teratogenic effect of trypan blue (TB) and suramin (SA) in their capability to induce umbilical and supraumbilical abdominal wall malformations in a chicken egg model. MATERIALS AND METHODS: A total of 255 fertilized chicken eggs were incubated at 38 °C and 75% relative humidity. Embryos were treated in ovo on incubation day 2.5 (Hamburger/Hamilton (HH) stage 13). The eggshell was windowed, and solutions of TB or SA were injected into the coelomic cavity at the region of the umbilicus. The window was closed and the embryos reincubated until examination on day 8 (HH 34). RESULTS: A total of 60 embryos survived in each group. The largest number of embryos presented with defects in the umbilical and supraumbilical region (25% in the SA group and 40% in the TB group). A combination of both defects (thoracoabdominoschisis) was seen in 20% of the TB and 8.3% of the SA groups, respectively. Associated anomalies found in both groups were head and eye defects, abnormal pelvic configurations, leg deformities, and mild forms of cloacal exstrophies. CONCLUSIONS: TB and SA have both a high potential to induce umbilical and supraumbilical ventral body wall malformations in chicken embryos. This novel animal model might help to establish a more profound understanding of the developmental steps in ventral body wall formation and the embryology for its malformations.