Article
The Increasing Prevalence of Gastroschisis: Associated Factors, Possible
Mechanisms, and Potential Mitigative Interventions
Claude Hughes1
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, lower
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
developmental 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
Copyright © 2019 by Global
Clinical and Translational Research
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.
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