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

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.

To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples.

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 European Surveillance of Congenital Anomalies 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.

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 the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides.

Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.