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Brynn Taylor,^1,2,3 David Skelly,¹ Livia K. Demarchis,¹ Martin D. Slade,² Deron Galusha,² and Peter M. Rabinowitz²

¹School of Forestry and Environmental Studies, Yale University, New Haven, Connecticut, USA; ²Occupational and Environmental Medicine Program and ³Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA

Abstract
The cause of limb deformities in wild amphibian populations remains unclear, even though the apparent increase in prevalence of this condition may have implications for human health. Few studies have simultaneously assessed the effect of multiple exposures on the risk of limb deformities. In a cross-sectional survey of 5,264 hylid and ranid metamorphs in 42 Vermont wetlands, we assessed independent risk factors for nontraumatic limb malformation. The rate of nontraumatic limb malformation varied by location from 0 to 10.2%. Analysis of a subsample did not demonstrate any evidence of infection with the parasite Ribeiroia. We used geographic information system (GIS) land-use/land-cover data to validate field observations of land use in the proximity of study wetlands. In a multiple logistic regression model that included land use as well as developmental stage, genus, and water-quality measures, proximity to agricultural land use was associated with an increased risk of limb malformation (odds ratio = 2.26 ; 95% confidence interval, 1.42-3.58 ; p < 0.001) . The overall discriminant power of the statistical model was high (C = 0.79) . These findings from one of the largest systematic surveys to date provide support for the role of chemical toxicants in the development of amphibian limb malformation and demonstrate the value of an epidemiologic approach to this problem. Key words: agriculture, amphibian, animal sentinel, malformation, teratogen, water pollution. Environ Health Perspect 113: 1497-1501 (2005) . doi:10.1289/ehp.7585 available via http://dx.doi.org/ [Online 11 July 2005]

Address correspondence to P.M. Rabinowitz, Yale University School of Medicine, Occupational and Environmental Medicine Program, 135 College St., New Haven, CT 06510 USA. Telephone: (203) 785-5885. Fax: (203) 785-7391. E-mail: peter.rabinowitz@yale.edu

We thank the field and laboratory research staff: S. Bolden, N. Cothran, B. Fellman, K. Freidenberg, N. Freidenfelds, and N. Rabinowitz. M.R. Cullen provided assistance with study design and analysis. M. Hines of the U.S. Geological Survey assisted with the geographic information system coding of land use. R. Levey provided critical logistical support and advice.

This study was funded in part by the National Institutes of Health/National Science Foundation Ecology of Infectious Diseases Program (National Institute of Environmental Health Sciences grant 5R01ES011067) .

The authors declare they have no competing financial interests.

Received 15 September 2004 ; accepted 11 July 2005.