Abstract
Hypospadias (H) is a common birth defect affecting the male urinary tract. It has been suggested that exposure to endocrine disrupting chemicals might increase the risk of H by altering urethral development. However, whether H risk is increased in places heavily exposed to agricultural pesticides, such as vineyards, remains debated and difficult to ascertain. The objective of the work is to test the possible association of H with residential proximity to vineyards. Residential address at birth of 8,766 H cases born 1980–2011 was taken from 17 specialized surgery centers. The geographical distribution of vineyards was obtained from the European Land Parcel Identification System (LPIS) and the distance of address to the nearest vineyard was computed. A first estimate of the variation of H relative risk with distance to vineyards was obtained using as controls 13,105 cryptorchidism (C) cases operated during the same period in the same centers. A separate estimate was obtained from a case-control study using “virtual controls” (VC) defined as points of the map sampled to match the demographic distribution of births within the recruitment territories of the study centers. Non-exposed patients were defined as those with a residence between 5,000 and 10,000 m from the closest vineyard. The residential distance to vineyard was smaller for H than for C cases (p<10−4). We found 42/8766 H cases (0.48%) and 50/13,105 C cases (0.38%) born to mothers living within 20 m of a vineyard. The odds ratios for H were 2.48 (CI: 1.0 to 5.1) and 2.4 (CI: 1.3 to 4.4), vs C or vs VC, respectively, when pregnant mothers lived 10–20 m from a vineyard. In conclusion, our study supports that children born to mothers living close to a vineyard have a two-fold increased risk of H. For environmental research, the use of VC provides an alternative to classical case control technique.
Highlights
Hypospadias (H) is a defect in the urethral development occurring between the 8th and the 16th week of pregnancy causing the meatus to be ill-located on the ventral side of the penis
A direct way to assess the exposures of cases and controls to agricultural pesticides is offered by Geographical Information Systems (GIS) and the increasing availability of environmental data bases informing on land use [16]
H cases were more frequent than C in all classes of distances below 5,000 m to vineyards, with the exception of those located between 0 and 10 m
Summary
Hypospadias (H) is a defect in the urethral development occurring between the 8th and the 16th week of pregnancy causing the meatus to be ill-located on the ventral side of the penis. A direct way to assess the exposures of cases and controls to agricultural pesticides is offered by Geographical Information Systems (GIS) and the increasing availability of environmental data bases informing on land use [16]. Surgical centers do not usually record epidemiological information on the exposure history of their patients, but all of them record basic demographic information for billing purposes, including mother’s address at childbirth. This low-cost hospital information crossed with available geographic environmental databases was used for the current study. We did a second independent case-control analysis, where controls were “virtual” controls (VC) defined through an algorithmic approach described below
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