Article

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

Claude Hughes^1* and Obinna O. Adibe²

¹Therapeutic Science and Strategy Unit, IQVIA; Department of Obstetrics and Gynecology, Duke University Medical Center; Epidemiology and Environmental Epigenetics Laboratory, North Carolina State University, Durham, NC, USA

²Departments of Surgery and Pediatrics, Duke University Medical Center, Durham, NC, USA

Received October 23, 2018; Accepted January 28, 2019

ABSTRACT

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 the 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 signaling. 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 nutrition for younger gravidas. 3) Pre-conceptional counseling to reduce embryonic exposures to the range of implicated lifestyle, 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 therapies.

KEYWORDS

Druggable molecules; ephrin–Eph receptor; exposures; gastroschisis; mechanosensitivity and mechanotransduction; protective therapeutics; risk factors; translational toxicology

How to cite this article:

Hughes C and Adibe O. The increasing prevalence of gastroschisis: associated factors, possible mechanisms, and potential mitigative interventions. Glob Clin Transl Res. 2019; 1(1):4-20. DOI: 10.36316/gcatr.01.0002