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The authors used a case-control design to evaluate the risk of central nervous system and musculoskeletal birth defects relative to exposure to solvents, metal, and pesticide contaminants from hazardous waste sites. Cases included 473 central-nervous-system-defect births and 3 305 musculoskeletal-defect births to residents of 18 counties in New York State; controls comprised 12 436 randomly chosen normal births. For each address at birth, the authors assigned a probability of exposure to solvents, metals, and pesticides from hazardous waste sites in the study area(n = 643). They also rated residences by proximity to air releases from industrial facilities and by contamination of community water supplies. Compared with individuals for whom a low probability of exposure existed, mothers who resided in areas assigned a medium or high probability of exposure to hazardous waste contaminants did not show an increased risk of either type of birth defects. After adjusting for mother's race and age, prenatal care initiation, and population density, the resulting relative risks were as follows: central nervous system defects and exposure to solvents, 0.8 (95% confidence interval [CI] = .4, .6); central nervous system and metals, 1.0 (95% CI = 0.7, 1.7); musculoskeletal defects and solvents, 0.9 (95% CI = 0.5, 1.3); and musculoskeletal defects and pesticides, .8 (95% CI = .5, 1.3). With respect to central nervous system defects, there was an elevated risk associated with living near industrial facilities that emitted solvents (odds ratio = 1.3 [95% CI = 1.0, 1.7]) or metals (OR = 1.4, [95% CI = 1.0, 1.8]) into the air. The low proportion of individuals who had a medium or high probability of residential exposure to hazardous waste-site contaminants limited the investigation of particular pathways, disease subgroups, and/or geographic areas. Associations between central nervous system defects and industrial releases of solvents and metals need to be investigated further.