Short Interpregnancy Interval and Gastroschisis Risk in the National Birth Defects Prevention Study

Background: The micronutrient depletion hypothesis proposes that consecutive pregnancies spaced too closely may leave insufficient time for maternal micronutrient replenishment. Short interpregnancy intervals (IPI) have been associated with an increased risk for several adverse pregnancy outcomes, but an association with gastroschisis risk has not been previously explored.

Methods: Within a population-based, case-control study, we evaluated the association between IPI length and gastroschisis risk using multivariable logistic regression models to estimate gastroschisis odds ratios for IPI <12 months and 12 to 17 months relative to those 18 to 23 months. We further evaluated the association between IPI and gastroschisis risk stratified by maternal age, periconceptional multivitamin use, preceding pregnancy outcome, study center region, and season of conception to explore whether observed associations were compatible with the hypothesis of maternal micronutrient depletion.

Results: For women with IPI <12 months, the adjusted odds ratio (aOR) was 1.7 (95% confidence interval [CI]: 1.1-2.5). The magnitude of the observed effect did not differ among strata of maternal age or periconceptional multivitamin use. However, the association was more pronounced after a miscarriage or termination (aOR: 2.5; 95% CI: 1.1-5.6) and among women who resided in northern study areas (aOR: 2.8; 95% CI: 1.3-5.9). The higher risk observed with short IPI among women in northern study areas was attenuated for spring/summer conceptions.

Conclusion: Short IPI was associated with an increased risk for gastroschisis, particularly among women whose preceding pregnancy resulted in a miscarriage or termination and among those who resided in northern study areas with winter/fall conception.