Purpose Prior research has suggested gastroschisis, a congenital malformation, may be linked to environmental or infectious factors and cases can occur in clusters. after adjustment (p-value=0.02; OR=1.3 and 1.2). Texas had sufficient data to assess the combination of space and time, which identified an increased risk in 2003 and 2004. Conclusion This study suggests there were areas of elevated gastroschisis risk in Massachusetts and Texas that cannot be explained by the risk factors we assessed. Additional exploration of underlying artifactual, environmental, infectious, or behavioral factors may further our understanding of gastroschisis. Keywords: Gastroschisis, Congenital Abnormalities, Spatial Analysis, Spatio-Temporal Analysis Introduction Gastroschisis is a rare congenital malformation where loops of bowel are protruding from the abdominal wall of an infant [1]. The recurrence risk of gastroschisis in siblings is small and concordance is low in monozygotic twins suggesting that genetics does not play a large role in the etiology of gastroschisis [2-4]. In addition, gastroschisis often occurs in the absence of other congenital anomalies and is rarely associated with chromosomal anomalies or syndromes further suggesting that environmental or infectious factors are involved [3, 5]. From 1964 to 2004 the prevalence of gastroschisis has Bryostatin 1 IC50 increased 10 to 20-fold worldwide, leading some to call it a pandemic [6]. The prevalence of gastroschisis in the US is estimated to be 1 per 2,700 [7]; however, when stratified by maternal age the prevalence changes to 1 1 per 800 in mothers <20 years old, 1 per 1900 in 20-24 year olds, 1 per 4900 in 25-29 year olds, and 1 per 17,600 in 30 year olds [8, 9]. No other risk factor has consistently been associated with gastroschisis. One possible clue in understanding the etiology of gastroschisis is that it has been observed to occur in clusters [10-15]. Only a few studies to date have used systematic methods for assessing clustering of gastroschisis. One case-control study of gastroschisis used interview data [16]. They employed an arbitrary definition of a spatio-temporal Bryostatin 1 IC50 cluster (defined as at least 3 cases within a 30-day period within one study site) and found that 35% of cases occurred in a cluster. Comparing cases that occurred in a cluster to those that did not, the authors found that clustered cases had higher odds of having a fever versus non-clustered cases. Because this study was not population based, systematic identification of clusters was not possible. Another study using data from the Metropolitan Atlanta Congenital Defects Program found a temporal cluster in 1988, with 3 times more cases than expected [14]. In response, a case-control study was conducted to further assess if cocaine use could account for the cluster. However, the study was limited by small numbers (15 cases) and did not report other risk factors besides cocaine use. The third Prox1 study to examine clustering of gastroschisis used the North Carolina Birth Defect Registry and a sample of controls from birth certificate data [15]. This study used the most rigorous method of Bryostatin 1 IC50 any study to date utilizing cases from the entire state and individual level data to control for confounding. They identified one spatial cluster in the rural southern Piedmont area. No study to date has formally assessed the interaction of space and time for clustering of gastroschisis using population-based data. The objective of the present study was to use rigorous systematic methods to identify areas of elevated gastroschisis risk in space and time using population-based data from Massachusetts and Texas. The different population characteristics of the two states allow us to account for social and ethnic variables that may explain underlying patterns of risk. Any remaining spatial variation may suggest hypotheses for further investigation. Materials and Methods Data were obtained from the Texas Birth Defects Registry and the Massachusetts Birth Defects Monitoring Program. Both data sources are population-based registries that actively ascertain cases with congenital malformations.