Seven-week embryo with gastroschisis, multiple anomalies, and physiologic hernia suggests early onset of gastroschisis

Gastroschisis is an increasingly common birth defect involving the development of the ventral body wall. Extrusion of the bowel is usually paraumbilical, usually right sided, and associated anomalies are less common than in omphalocele. Recently, hypotheses regarding the timing of the typical gastroschisis defect have come into question. Unlike previous theories, Feldkamp et al. (2007) has postulated that gastroschisis occurs much earlier in development, before abdominal wall closure, which is completed by about 35 days postconception. We present a case of a spontaneously aborted dysmorphic embryo which exhibits features of the normal physiologic herniation of the midgut as well as gastrochisis. The co-existence of the abdominal wall defect in this abnormal embryo with the physiologic hernia supports the early development of this defect and also illustrates the causal heterogeneity of gastroschisis.     

Risk for gastroschisis in primigravidity, length of sexual cohabitation, and change in paternity

BACKGROUND: Maternal epidemiologic similarities between gastroschisis and preeclampsia have led to the objective of evaluating the risk for gastroschisis related to primigravidity, change in paternity, and length of cohabitation, considered as risk factors for preeclampsia. METHODS: The subjects were 288 newborns with isolated gastroschisis and 576 normal controls, matched by maternal age. They were ascertained in the Estudio Colaborativo Latino Americano de Malformaciones Congenitas hospital network of 10 South American countries between 1982 and 2005. Epidemiologic variables were compared among controls, between primigravidas and multigravidas, between multigravidas who had and had not changed partners, and between mothers with short and long cohabitation times with their partners. Risks associated with primigravidity, short cohabitation time, and changing paternity, as well as their combinations, were calculated. An eventual interaction between maternal age and the three risk factors was assessed. RESULTS: Only a short cohabitation time showed a significant OR for gastroschisis (OR = 2.36, 95% CI: 1.52-3.66, p < .001), whereas ORs were not significant for primigravidity (OR = 1.40, 95% CI: 0.84-2.35, p = .192) nor for changing paternity (OR = 1.20, 95% CI: 0.49-3.10, p = .752). The risk was highest for multigravidas who had changed partners (OR = 8.71, 95% CI: 2.93-21.12, p < .001), followed by multigravidas who had not changed partners (OR = 3.99, 95% CI: 1.07-15.43, p = .049), and by primigravidas (OR = 3.02, 95% CI: 1.58-5.76, p = .001), all having cohabitated for a short time. Maternal age did not modify these risks. CONCLUSIONS: Three groups at risk for a child with gastroschisis were identified, all having in common a short cohabitation time. Antigenic or "modern" lifestyle-related factors might be involved in the origin of gastroschisis.     

Selected gene polymorphisms and their interaction with maternal smoking, as risk factors for gastroschisis

BACKGROUND: Gastroschisis is a severe birth defect in which the infant is born with a portion of the intestines extruding through a small tear in the abdominal wall, usually to the right of the umbilical cord. Its etiology is unknown, but the prevailing hypothesis is that it results from a vascular accident at the time of involution of the right umbilical vein or of the development of the superior mesenteric artery. METHODS: In a case-control study of 57 cases of gastroschisis and 506 controls, we tested DNA for polymorphisms of 32 genes representing enzymes involved in angiogenesis, blood vessel integrity, inflammation, wound repair, and dermal or epidermal strength. RESULTS: In logistic regression, controlling for maternal ethnicity, and using the homozygote wild-type as referent, the following gene polymorphisms were associated with an increased risk for a gastroschisis for heterozygotes: ICAM1 gly241arg (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1 -3.4); NOS3 glu298asp (OR, 1.9; 95% CI, 1.1-3.4); NPPA 2238T > C (OR, 1.9; 95% CI, 1.0-3.4); and ADD1 gly460trp (OR, 1.5; 95% CI, 0.8-2.8). Additionally, for the NPPA and ADD1 single-nucleotide polymorphisms (SNPs), the homozygote variants had a significantly higher risk than the heterozygotes (OR, 7.5; 95% CI, 1.7-33.5 and OR, 4.9; 95% CI, 1.9-12.9, respectively). Three SNPs showed a strong interaction with maternal smoking. The risk for smokers with 1 or 2 variant alleles compared to nonsmokers with the wild-type allele were: NOS3 (OR, 5.2; 95% CI, 2.4-11.4); ICAM1 (OR, 5.2; 95% CI, 2.1-12.7); and NPPA (OR, 6.4; 95% CI, 2.8-14.6). CONCLUSIONS: These results support the hypothesis of a vascular compromise as part of a multifactorial etiology of gastroschisis involving both genes and environmental factors.     

Interaction between maternal smoking and malnutrition in infant risk of gastroschisis

BACKGROUND: Gastroschisis is a severe birth defect characterized by a tear in the infant's abdominal wall. Young mothers have the highest risk of having an infant with gastroschisis. In an animal model, the defect resulted from exposure of pregnant mice to carbon monoxide (CO) in combination with a low protein and low zinc diet. METHODS: We evaluated this model in a study of 55 infants with gastroschisis and 94 age-matched controls that included maternal interview with a food frequency questionnaire. Smoking cigarettes (> or = 1 pack/day) or marijuana (more than once) 3 months prior to pregnancy indicated CO exposure. Low protein or zinc intake and a low body mass index (BMI) indicated maternal malnutrition. RESULTS: When assessed separately, high CO, low protein, low zinc, and low BMI were each significantly associated with an increased risk of gastroschisis. Although we observed significant CO-BMI and CO-zinc interactions after adjusting for income, only a combination of high CO exposure and low BMI yielded a synergistic adverse effect. Compared to the low risk of having an infant with gastroschisis for mothers who did not have low BMI and did not smoke, the risk of having an infant with gastroschisis was 16.3 times (95% CI, 2.49-113.4) higher for mothers who did not have low BMI but smoked, and 19.7 times (95% CI, 4.33-89.6) higher for mothers who did not smoke but had low BMI. However, the risk was 26.5 times (95% CI, 7.85-89.4) higher for mothers who had low BMI and smoked. CONCLUSIONS: Our results suggest that young mothers are at increased risk of having an infant with gastroschisis if they smoke and are also malnourished.