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Association of vasoconstrictive exposures with risks of gastroschisis and small intestinal atresia
Martha M Werler1, Jane E Sheehan, Allen A Mitchell
1Slone Epidemiology Center, Boston University, 1010 Commonwealth Avenue, Boston, MA 02215, USA. mwerler@slone.bu.edu
Insights
Maternal use of vasoconstrictive drugs and smoking during early pregnancy increases risks for gastroschisis and small intestinal atresia. Combined exposure significantly elevates the risk of these congenital defects.
Area of Science:
- Medical Genetics
- Developmental Biology
- Obstetrics
Background:
- Gastroschisis and small intestinal atresia are congenital anomalies potentially caused by vascular disruption.
- Maternal exposure to vasoconstrictive substances like cocaine, amphetamines, decongestants, and nicotine may contribute to these defects.
Purpose of the Study:
- To investigate the association between combined exposure to vasoconstrictive drugs and cigarette smoking and the risks of gastroschisis and small intestinal atresia.
Main Methods:
- A retrospective study conducted between 1995 and 1999 in 15 cities across the US and Canada.
- Interviews with mothers of 205 gastroschisis cases, 127 small intestinal atresia cases, and control groups within six months of delivery.
Main Results:
- Combined exposure to vasoconstrictive drugs and smoking in early pregnancy was reported by 9% of cases for both gastroschisis and small intestinal atresia, versus 4% in controls.
- Multivariate analysis showed increased odds ratios of 2.1 for gastroschisis and 2.8 for small intestinal atresia.
- Risk increased with smoking levels; heavy smokers (≥20 cigarettes/day) using vasoconstrictive drugs had 3.6-fold increased gastroschisis risk and 4.2-fold increased small intestinal atresia risk.
Conclusions:
- Findings support vascular disruption as a key etiological factor in gastroschisis and small intestinal atresia.
- Highlights the synergistic risk posed by combined maternal exposure to vasoconstrictive agents and smoking.
Background:
Gastroschisis and small intestinal atresia are congenital anomalies that may arise from vascular disruption. It is hypothesized that maternal exposure to cocaine, amphetamines, decongestants and nicotine, all of which have vasoconstrictive actions, can contribute to these defects. The present study examined risks of gastroschisis and small intestinal atresia associated with combined exposure to vasoconstrictive drugs and cigarette smoking.
Methods:
This was a retrospective study conducted from 1995 to 1999 in 15 cities across the United States and Canada. Mothers of 205 gastroschisis cases, 127 small intestinal atresia cases, 381 malformed controls and 416 nonmalformed controls were interviewed within 6 months of delivery.
Results:
Reported vasoconstrictive drugs included pseudoephedrine, phenylpropanolamine, ephedrine and methylenedioxymethamphetamine. Combined exposure to vasoconstrictive drugs and cigarette smoking in the first 2.5 months of pregnancy was reported by 9% of gastroschisis cases, 9% of small intestinal atresia cases and 4% of controls. Multivariate-adjusted odds ratios, controlling for the effects of age, education, income, other drug use and alcohol intake, were 2.1 (95% confidence interval = 1.0-4.4) for gastroschisis and 2.8 (1.1-6.9) for small intestinal atresia. Risks of each defect increased with increasing level of cigarettes (P for trend = 0.019 and 0.012, respectively). Vasoconstrictive drug use among smokers of 20 or more cigarettes a day increased gastroschisis risk 3.6-fold (1.3-10.3) and small intestinal atresia risk 4.2-fold (1.1-16.2).
Conclusions:
These findings provide further evidence of vascular disruption as an etiology for gastroschisis and small intestinal atresia.
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