Residential Proximity to Agricultural Herbicides during Pregnancy and Childhood Leukemia in the Danish National Birth Cohort

摘要

Background The majority (61%) of Denmark's land cover is agricultural. Cereals and grains are the major crops, and almost all acres of these crops are treated with herbicides. Based mostly on case-control studies, parental exposure to pesticides during pregnancy has been associated with increased risk of childhood cancer. Methods The Danish National Birth Cohort (DNBC) enrolled over 100,000 pregnant women 1996-2003. For childhood leukemias (diagnosed <15 years) through 2014 and 10% of the cohort (N=9,362, excluding non-singleton births and children with Down Syndrome), we linked addresses during the pregnancy to crop maps and crop-specific pesticide sales data to estimate the amount (g) of herbicides applied at distances within 100, 250, 500,1000m of homes. We used Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for 18 herbicides with the highest use. Results There were 191 children diagnosed with childhood cancer, including 61 leukemia cases. Some herbicides were used on the same crops or applied as mixtures, resulting in high correlations (Spearman's rho: 0.46-1.00). For the highest tertile (vs. no pesticide use) within 500m from the home, we found increased risk of leukemia for MCPA+methabenzthiazuron (HR: 2.08, 95%CI: 1.06-4.07), dichlorprop-p/mecoprop-p (HR: 2.10, 95%CI: 1.07-4.11), benzonitrile herbicides (HR: 2.21, 95%CI: 1.14-4.29), thifensulfuron-methyl (HR: 2.09, 95%CI: 1.07,4.09), bentazone (HR: 2.20, 95%CI: 1.13-4.27), and phenmedipham (HR: 2.16, 95%CI: 1.10-4.23), without significant trends. Risk patterns at other distances from the home were similar but attenuated. There was no association with leukemia and use of glyphosate, clopyralid, 2,4-D, and 6 other herbicides. Conclusions This is the first prospective study to evaluate residential proximity to pesticide applications and childhood cancer, and provides additional evidence that pesticide exposures during pregnancy may increase childhood leukemia risk.