The Increasing Prevalence of Gastroschisis: Associated Factors, Possible Mechanisms, and Potential Mitigative Interventions

Background: Gastroschisis has increased globally over recent decades and this increase is not explained by demographic changes in maternal age. Implicated risk factors for this increase include lifestyle behaviors, environmental exposures, low-er socioeconomic status, lower body mass index, poor nutrition, smoking tobacco, using illicit drugs, alcohol, or analgesics and genitourinary infections. Methods: Selective review of the literature. Results: Present hypotheses would only suggest avoidance of suspect exposures as protective interventions. To identify safe and efficacious protective therapies, new cellular/molecular modes-of-action need to be considered. Plausible develop-mental modes-of-action include a) changes in epigenetic programming of relevant stem or progenitor cells; b) mechanical forces (cellular mechanosensitivity and mechanotransduction) signaling; and c) ephrin–Eph receptor multimodal signali-ng. These developmental modes-of-action present plausible options for “druggable” molecules that could be developed into protective or mitigative therapeutic agents for gastroschisis. Conclusion: Possible interventions for modifiable factors in gastroschisis include 1) Delay childbearing. 2) Improve nutri-tion for younger gravidas. 3) Pre-conceptional counseling to reduce embryonic exposures to the range of implicated lifest-yle, environmental and medical factors. 4) Urge research colleagues to investigate the cellular and molecular mechanisms underlying gastroschisis and to translate those insights into one or more safe and efficacious preventive or mitigative thera-pies.