A vascular and thrombotic model of gastroschisis.

A binary vascular/thrombotic pathogenesis for gastroschisis, a form of congenital bowel herniation, is proposed, where normal right umbilical vein involution creates a possible site for thrombosis adjacent to the umbilical ring. If thrombosis occurs, it weakens the area, explaining overwhelmingly right-sided lesions. The model arises from the existence of two groups of risk factors with different maternal age associations. Older mothers show a greater association with vascular factors (although this may actually represent a lack of any significant maternal age effect), consistent with associations of gastroschisis with congenital heart lesions and with amyoplasia. Alternatively, other predispositions, and especially decreased maternal age, the greatest known risk factor, associate with factors raising maternal estrogen, with evidence that estrogen in turn acts here as a predisposition to thrombosis. Absorption of thrombotic by-products from the amniotic fluid can explain the unusual amniocyte inclusions that are common with gastroschisis, while a role for estrogens suggests a connection between rising gastroschisis prevalence and increasing environmental contamination with estrogen disruptors. This model explains a variety of structural and epidemiological findings, and suggests that stratification of data based on binary effects may clarify associated risks and mechanisms. The model also shows that what is often referred to as vascular disruption may actually reflect alternative or additional factors instead, including thrombosis as a primary mechanism.