Meconium Concentrations of Pesticides and Risk of Hypospadias: A Case–Control Study in Brittany, France

Abstract

Background: Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. Objectives: To study risk of hypospadias in association with multiple pesticide measurements in meconium samples. Methods: The Brittany Registry of Congenital Anomalies (France) conducted a case–control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following EUROCAT guidelines (N=69). Controls (N=135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case–control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. Results: Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between detection of fenitrothion in meconium and risk of hypospadias (OR=2.6 [1.0-6.3] with ncases=13, ncontrols=21), but not the other pesticides. Conclusions: Our small study provides robust assessment of fetal exposure. Fenitrothion’s established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.