Gastroschisis is a congenital defect where the baby’s intestines protrude outside the body through a small opening in the abdominal wall, typically located to the right of the umbilical cord. This occurs early during pregnancy. Because the organs are exposed to the amniotic fluid, they can become irritated, swollen, and damaged. Though relatively rare, affecting an estimated one in every 2,000 to 4,000 births, the global incidence of gastroschisis has been increasing steadily over the last several decades. The precise biological event that initiates this defect remains unknown, but current evidence suggests it arises from a complex combination of developmental failure and external influences.
The Developmental Failure
Gastroschisis originates from a failure in the normal process of abdominal wall closure during the first trimester of pregnancy, specifically between the fourth and eighth week of gestation. Early in development, the lateral folds of the embryo must migrate and fuse at the midline to form the complete ventral abdominal wall. When this fusion process is incomplete, a defect forms that allows the intestines to migrate outside the abdominal cavity.
The predominant explanation for this failure is the “vascular disruption hypothesis,” which suggests an interruption of blood flow to the developing abdominal wall causes the tissue to weaken or die. One theory posits that a disruption of the right omphalomesenteric artery (vitelline artery) or an abnormal regression of the right umbilical vein may lead to localized tissue damage. This loss of blood supply prevents the formation of the mesoderm tissue that normally reinforces the abdominal wall structure. Other theories suggest the defect may be caused by an abnormal folding of the embryonic body wall itself, preventing the proper merging of structures that form the abdomen.
The critical timing of this event means the defect is established long before a pregnancy is typically confirmed. The size of the resulting opening is usually small, often only one to two inches, but it is large enough to allow the intestines and sometimes other organs to escape.
Key Maternal Risk Factors
The strongest and most consistently identified epidemiological factor is young maternal age. Mothers under 20 years old have a significantly higher risk of having a baby with gastroschisis compared to older mothers, with some studies showing the risk to be more than seven times greater. This association is a defining feature of the condition, though the biological link that explains this age-related risk is not understood.
Maternal lifestyle choices during the periconceptional period and early pregnancy are also statistically associated with the condition. Tobacco use, specifically cigarette smoking, has been shown to moderately increase the risk for gastroschisis. Pregnant women who smoke have approximately 1.5 to 1.7 times greater odds of having an affected infant. This increased risk is thought to be related to the vasoconstrictive effects of nicotine, which can restrict blood flow and potentially contribute to the vascular disruption hypothesis.
Recreational drug use, particularly substances with vasoconstrictive properties, has also been implicated as a risk factor. Drugs like cocaine and amphetamines, which cause blood vessels to narrow, show a strong statistical association with the defect. First-trimester use of vasoconstrictive recreational drugs was associated with over three times the risk of gastroschisis. These findings support the concept that any external factor compromising early embryonic blood flow may contribute to the developmental failure.
Environmental Exposure and Genetic Complexity
Research is exploring the role of environmental exposures, though definitive causal links are challenging to establish. Certain medications taken early in pregnancy, such as nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, and some decongestants, have been statistically linked to a moderately elevated risk. These medications can also have effects on blood vessel constriction, which aligns with the vascular disruption theory.
Exposure to specific chemical agents in the environment is another area of investigation. Potential associations have been studied for nitrates in drinking water, certain solvents, and pesticides, including atrazine, though the evidence remains inconsistent. The geographic clustering of gastroschisis cases in some regions suggests that a localized environmental trigger may be at play, interacting with individual susceptibility.
Regarding genetics, gastroschisis is overwhelmingly considered a non-syndromic defect, meaning it typically occurs in isolation without other major congenital anomalies and is not directly inherited. However, research suggests that gene-environment interactions may predispose some infants to the condition. Specific genetic variants in pathways that manage the body’s response to environmental toxins may make an individual more susceptible to the effects of exposure like air pollution.
Detection and Unanswered Questions
Gastroschisis is routinely detected during prenatal screening, which allows for careful planning of the delivery and immediate care. A common indicator is an abnormally high level of maternal serum alpha-fetoprotein (MS-AFP) found during routine blood tests. This occurs because the exposed intestines allow the protein to leak into the amniotic fluid and the mother’s bloodstream. The diagnosis is then confirmed with a routine fetal ultrasound, usually around the 20th week of pregnancy, which clearly visualizes the free-floating bowel loops outside the abdominal cavity.
Despite significant research, two major questions continue to challenge scientists and clinicians. First, the specific molecular trigger that causes the vascular disruption or abnormal folding in the early embryo remains elusive. Second, researchers are still working to determine the precise reason for the global increase in gastroschisis rates over the past few decades, particularly in younger mothers. Unraveling these unknowns is the focus of current epidemiological and biological studies.