{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:00:51Z","timestamp":1789995651321,"version":"4.0.1"},"reference-count":27,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of T\u00fcrkiye (T\u00dcB\u0130TAK) 2219 International Postdoctoral Research Fellowship Program for Turkish Citizens","doi-asserted-by":"publisher","award":["1059B192202352"],"award-info":[{"award-number":["1059B192202352"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Gastroschisis remains one of the most debated congenital abdominal wall defects with respect to its embryologic and developmental origins. Despite decades of investigation, no consensus exists regarding a single causative mechanism, and competing hypotheses variably explain laterality, bowel injury, and closing variants. This scoping review aims to synthesize historical and contemporary embryologic theories of gastroschisis and integrate them into a coherent developmental framework with direct relevance to prenatal assessment and clinical interpretation. Methods: A structured literature search was conducted in PubMed, Web of Science, and Scopus from inception through December 2025. Studies proposing original embryologic mechanisms or providing primary experimental, placental, or developmental evidence were included. Eligible publications were qualitatively synthesized and classified according to evidence strength as historical descriptive, experimental, placental pathology, or integrative synthesis. Embryologic theories were organized into mechanistic categories based on affected structures, developmental timing, and proposed pathophysiology. Results: Twenty-six publications met inclusion criteria, yielding fourteen distinct embryologic theories. These were categorized into four mechanistic categories: mesodermal and ventral body wall folding abnormalities, vascular disruption models, umbilical ring and extraembryonic attachment defects, and integrated multifactorial developmental concepts. No single mechanistic category alone consistently accounted for right-sided predominance, variability in bowel injury, and the occurrence of closing variants. Conclusions: Gastroschisis is best understood as a spectrum of periumbilical developmental disturbances arising from interacting mesodermal, vascular, and biomechanical factors. An integrated embryologic framework improves interpretation of dynamic prenatal imaging findings, supports refined risk stratification and counseling, and provides a biologic foundation for future translational research.<\/jats:p>","DOI":"10.3390\/children13020270","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:11:28Z","timestamp":1771240288000},"page":"270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Embryologic and Developmental Origins of Gastroschisis: A Scoping Review of Historical and Contemporary Theories"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8740-0679","authenticated-orcid":false,"given":"Mohamad","family":"Abi Nassif","sequence":"first","affiliation":[{"name":"The Center for Fetal and Placental Research, Cincinnati Fetal Center, Division of Pediatric General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"},{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7776-9684","authenticated-orcid":false,"given":"Emrah","family":"Aydin","sequence":"additional","affiliation":[{"name":"The Center for Fetal and Placental Research, Cincinnati Fetal Center, Division of Pediatric General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"},{"name":"Division of Maternal Fetal Medicine, Jackson Fetal Care, Department Obstetrics, Gynecology and Reproductive Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-1381","authenticated-orcid":false,"given":"Jose","family":"Peiro","sequence":"additional","affiliation":[{"name":"The Center for Fetal and Placental Research, Cincinnati Fetal Center, Division of Pediatric General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"},{"name":"NYULH Advanced Fetal Care Center, NYU Langone Health, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","first-page":"112","article-title":"Gastroschisis: Report of 2 cases treated by a modification of the Gross operation for omphalocele","volume":"33","author":"Moore","year":"1953","journal-title":"Surgery"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bhat, V., Moront, M., and Bhandari, V. (2020). Gastroschisis: A state of the art review. Children, 7.","DOI":"10.3390\/children7120302"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/BF00183727","article-title":"The pathogenesis of omphalocele and gastroschisis: An unresolved problem","volume":"11","author":"Kluth","year":"1996","journal-title":"Pediatr. Surg. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1136\/adc.38.198.142","article-title":"Embryology of exomphalos and allied malformations","volume":"38","author":"Duhamel","year":"1963","journal-title":"Arch. Dis. Child."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0022-3468(75)90285-7","article-title":"The myth of gastroschisis","volume":"10","author":"Shaw","year":"1975","journal-title":"J. Pediatr. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/bjs.1800631117","article-title":"The embryology and surgical management of gastroschisis","volume":"63","author":"Thomas","year":"1976","journal-title":"Br. J. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0022-3468(80)80130-8","article-title":"The pathogenesis of gastroschisis and omphalocele","volume":"15","year":"1980","journal-title":"J. Pediatr. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"151230","DOI":"10.1016\/j.sempedsurg.2022.151230","article-title":"Anatomy and embryology of abdominal wall defects","volume":"31","author":"Khan","year":"2022","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_9","unstructured":"Moore, K.L., Persaud, T.V.N., and Torchia, M.G. (2016). The Developing Human: Clinically Oriented Embryology, Elsevier. [10th ed.]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S0022-3476(81)80640-3","article-title":"The vascular pathogenesis of gastroschisis: Intrauterine interruption of the omphalomesenteric artery","volume":"98","author":"Hoyme","year":"1981","journal-title":"J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/tera.1420500107","article-title":"Association between gastroschisis and maternal age, smoking, and alcohol consumption","volume":"50","author":"Torfs","year":"1994","journal-title":"Teratology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/ajmg.a.31578","article-title":"Development of gastroschisis: Review of hypotheses, a novel hypothesis, and implications for research","volume":"143A","author":"Feldkamp","year":"2007","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/ajmg.c.30176","article-title":"The embryology of body wall closure: Relevance to gastroschisis and other ventral body wall defects","volume":"148C","author":"Sadler","year":"2008","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1002\/ajmg.a.33636","article-title":"Examining the evidence for vascular disruption as a mechanism of birth defects","volume":"152A","author":"Sadler","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1159\/000360080","article-title":"Comprehensive developmental mechanisms in gastroschisis","volume":"36","author":"Bargy","year":"2014","journal-title":"Fetal Diagn. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1002\/ajmg.a.36370","article-title":"A vascular and thrombotic model of gastroschisis","volume":"164A","author":"Lubinsky","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1399-0004.2008.01142.x","article-title":"Escape of the yolk sac: A hypothesis to explain the embryogenesis of gastroschisis","volume":"75","author":"Stevenson","year":"2009","journal-title":"Clin. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/bdra.23130","article-title":"Gastroschisis as a defect of the umbilical ring","volume":"97","author":"Rittler","year":"2013","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/bdr2.1481","article-title":"An evolutionary and developmental biology approach to gastroschisis","volume":"111","author":"Opitz","year":"2019","journal-title":"Birth Defects Res."},{"key":"ref_20","first-page":"154","article-title":"Multifactorial models of gastroschisis pathogenesis","volume":"25","author":"Lammers","year":"2016","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_21","first-page":"145","article-title":"Embryologic and pathogenic considerations in gastroschisis: An updated review","volume":"27","author":"Muniz","year":"2024","journal-title":"J. Ultrasound"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"391","DOI":"10.2350\/13-03-1316-CR.1","article-title":"Gastroschisis, destructive brain lesions, and placental infarction suggest a vascular pathogenesis","volume":"16","author":"Folkerth","year":"2013","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1177\/1093526619875877","article-title":"Gastroschisis is associated with placental delayed villous maturation","volume":"23","author":"Ruschkowski","year":"2020","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"71","DOI":"10.4132\/jptm.2014.12.14","article-title":"Placental mesenchymal dysplasia associated with fetal gastroschisis","volume":"49","author":"Kim","year":"2015","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_25","first-page":"112","article-title":"Prenatal ultrasound markers associated with complex gastroschisis","volume":"45","author":"Caldas","year":"2025","journal-title":"Prenat. Diagn."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1111\/j.1471-0528.2000.tb11645.x","article-title":"The aetiology of gastroschisis","volume":"107","author":"Curry","year":"2000","journal-title":"BJOG"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/S0022-3468(86)80009-4","article-title":"Developmental aspects of gastroschisis","volume":"21","author":"Tibboel","year":"1986","journal-title":"J. Pediatr. Surg."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/2\/270\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:03:26Z","timestamp":1789992206000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/2\/270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,14]]},"references-count":27,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["children13020270"],"URL":"https:\/\/doi.org\/10.3390\/children13020270","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,14]]}}}