Young maternal age has been associated with an increased risk of gastroschisis, while high maternal weight status has been associated with a decreased risk. We were interested in investigating the joint effect of these two risk factors to identify thresholds in risk associated with body mass index (BMI) for a given age. Data from the National Birth Defects Prevention Study included 464 case infants with gastroschisis and 4842 healthy controls. A generalised additive model with a bivariate spline for continuous maternal age and prepregnancy BMI was used to model the probability of gastroschisis. The bivariate spline in BMI and maternal age was significantly associated with gastroschisis (P = 0.0001) after adjustment for study centre, maternal race/ethnicity, education, income and number of persons supported by income, smoking, alcohol use, vitamin use, vasoconstrictor medication use and gestational diabetes. The data indicate that women who are younger and who have lower BMI are at the greatest risk; a woman with a BMI of 17 who gives birth at age 15 has 7 times the odds (adjusted odds ratio = 7.0 [95% CI 4.2, 11.5]) of having an offspring with gastroschisis compared with a woman of age 24 with a BMI of 23. Furthermore, there was an interaction between maternal age and BMI for this risk. The increased risk of low maternal age and prepregnancy BMI associated with gastroschisis appears to suggest an aetiological role related to biological immaturity for this particular birth defect.