Hypothesis: Estrogen related thrombosis explains the pathogenesis and epidemiology of gastroschisis

A three‐part hypothesis is proposed to explain the unusual epidemiology of gastroschisis, a congenital abnormality of the abdominal wall, which has a rising frequency, a higher rate in first and young mothers in whites but not blacks, and a unique negative correlation with obesity. The hypothesis involves: (1) An early estrogenic thrombophilia, (2) racial differences in thrombosis, and (3) thrombotic by‐products interfering with early developmental signaling. For the first: (1) An estrogenic thrombophilia is a known effect. (2) A mouse model links excess estrogen to thromboses affecting the fetus. (3) Young and first mothers have higher first trimester estrogen levels. (4) A negative correlation between body mass index and pregnancy estradiol accounts for the weight relationship. (5) Maternal alcohol raises estrogen levels in premenopausal women. (6) A link with atrazine, an estrogenic endocrine disruptor, has been found, and rising frequencies of gastroschisis make this and other such chemicals a particular concern if estrogen is indeed involved. For the second: Blacks have a different thrombophilic gene background and less of a thrombotic response to estrogen than whites, explaining racial differences. For the third: Protein palmitoylation affects cell signaling in development, and lipid rafts, a major aspect of thromboses, facilitate this process. Such thrombotic byproducts could be the source of palmitic acid rich amniotic vacuoles with gastroschisis. Similar vacuoles can occur with limb‐body wall defects, another early developmental anomaly associated with decreased maternal age that may have a similar pathogenesis. Later thrombotic related anomalies with a similar epidemiology seem to primarily involve vascular disruptions, but localized signaling anomalies may also occur. © 2012 Wiley Periodicals, Inc.