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Introduction Congenital aortic stenosis {AS} has long been known to occur predominantly in white male infants, born in rural or suburban areas. We used spatial analysis to explore hypotheses of environmental exposure that might be consistent with the original observations.

Methods Using a case control series of congenital cardiovascular malformations and population based controls, we analyzed spatial distribution of aortic stenosis, in infants diagnosed before one year of age. Statistical analysis included spatial distribution and extensive personal sociodemographic, occupational exposures, and life style exposure factors as well as family history of cardiac or other malformations. Cases and controls were mapped in the State of Maryland and the District of Columbia in the United States, including the years 1981 through 1989.

Results 60 cases of AS and 1990 controls were included in the analysis. By nonparametric analysis AS was associated with advanced maternal age, a history of previous stillbirths, maternal exposure to laboratory chemicals or solvents in pregnancy, residency in areas of orchards, and nitrate in ground water. Five clusters of aortic stenosis cases were identified by Bernoulli analysis including 15 of 60 cases of aortic stenosis. Individual clusters were not significant by Bernoulli analysis using the spatial distribution method. However, using χ2 for case control ratio within the combined cluster areas, odds of aortic stenosis compared to controls was 40, 18.9-87.7 95% CI. We assessed the characteristics of the combined clusters to determine whether these areas shared features that differentiated them from other regions of the state. Cases of aortic stenosis in these clusters differed from other aortic stenosis cases in having older mothers, mothers with high occupational grade, more frequent gestational diabetes, and, at a less significant level [p.071] residing in orchards. Exposure to pesticides sprayed from planes occurred in two cases of 15 in the clusters compared to no cases outside the clusters, p.059 chi square. To clarify the characteristics of the clusters where aortic stenosis cases were located, we compared the characteristics of controls living in and outside the clusters, using the greater power of the number of controls. The clusters are characterized by ground water risk of nitrate contamination χ2 36.996, p.000; residency in orchard χ2 46.333, p.000; residency in cropland χ2 28.893, p.002; and maternal race χ2 9.410; p.009. When analysis was made for controls in the clusters separately by race, the associations with groundwater risk, orchard, mercury exposure, and cropland were reduced in magnitude but remained highly significant and were ordered the same.

Conclusion One congenital cardiovascular malformation, aortic stenosis, shows spatial distribution consistent with possible environmental exposures and gene environment interactions that may be important in pathogenesis. Further prospective study with both genetic and environmental measures will be important in evaluating these findings.

© 2003 Lippincott Williams & Wilkins, Inc.