Space-Time Clustering Analyses of Trisomies 13, 18, and 21

Abstract

ISEE-183 Background: Although maternal age is an established risk factor for trisomy 21, the overall etiology and the relative contribution of genetic and environmental factors toward their prevalence remain unclear. Objective: To use high-quality fully population-based data from a geographically defined region of Northern England with low levels of in or out migration (population 2.6 million, average number of births per year 30,000, 2 main conurbations and extended rural areas) to analyze space-time clustering among cases of trisomy 13, 18, and 21 to inform the debate about their etiology. Material and Methods: The database recorded information on all pregnancy outcomes including terminations. We analyzed all cases diagnosed with trisomy 13, 18, and 21 born during the period 1985 to 2003. Both Knox and K-function tests for space-time interactions between cases were applied with fixed thresholds of close in space and close in time. The locations were taken to be the residential addresses at the time of birth. Tests were repeated using nearest neighbor thresholds to adjust for variation in population density. Results: We analyzed 124 cases of trisomy 13, 260 cases of trisomy 18, and 1151 cases of trisomy 21. There was statistically significant (P < 0.05) space-time clustering for cases of trisomy 21, but not for trisomy 13 or 18. Furthermore, there was significant space-time clustering involving cases of trisomy 21 from more densely populated areas. Conclusions: The highly novel finding of space-time clustering for trisomy 21 is suggestive of a role of environmental factors in their etiology. Future studies should investigate candidate agents such as infections in more detail.