BackgroundClose residential proximity to powerlines and high magnetic fields exposure may be associated with elevated childhood leukemia risks as reported by prior studies and pooled analyses. Magnetic fields exposure from high-voltage powerlines is associated with proximity to these powerlines and consequently with any factor varying with distance. Areas underneath powerlines in California may be sites for commercial plant nurseries that can use pesticides, a potential childhood leukemia risk factor. ObjectivesAssess if potential pesticide exposure from commercial plant nurseries is a confounder or interacts with proximity or magnetic fields exposure from high-voltage powerlines to increase childhood leukemia risk. MethodsA comprehensive childhood leukemia record-based case-control study with 5788 cases and 5788 controls (born and diagnosed in California, 1986–2008) was conducted. Pesticide, powerline, and magnetic field exposure assessment utilized models that incorporated geographical information systems, aerial satellite images, site visits and other historical information. ResultsThe relationship for calculated fields with childhood leukemia (odds ratio (OR) 1.51, 95% confidence interval (CI) 0.70–3.23) slightly attenuated when controlling for nursery proximity (OR 1.43, 95% CI 0.65–3.16) or restricting analysis to subjects living far (>300 m) from nurseries (OR 1.43, 95% CI 0.79–2.60). A similar association pattern was observed between distance to high-voltage powerlines and childhood leukemia. The association between nursery proximity and childhood leukemia was unchanged or only slightly attenuated when controlling for calculated fields or powerline distance; ORs remained above 2 when excluding subjects with high calculated fields or close powerline proximity (OR 2.16, 95% CI 0.82–5.67 and OR 2.15, 95% CI 0.82–5.64, respectively). The observed relationships were robust to different time periods, reference categories, and cut points. DiscussionClose residential proximity to nurseries is suggested as an independent childhood leukemia risk factor. Our results do not support plant nurseries as an explanation for observed childhood leukemia risks for powerline proximity and magnetic fields exposure, although small numbers of subjects concurrently exposed to high magnetic fields, close powerline proximity and plant nurseries limited our ability to fully assess potential confounding.