Isolated hypospadias: The impact of prenatal exposure to pesticides, as determined by meconium analysis

Although endocrine-disrupting chemicals (EDCs, including pesticides) are thought to increase the risk of hypospadias, no compounds have been formally identified in this context. Human studies may now be possible via the assessment of meconium as a marker of chronic prenatal exposure. The objective of the present study was to determine whether or not prenatal exposure to pesticides (as detected in meconium) constitutes a risk factor for isolated hypospadias. In a case-control study performed between 2011 and 2014 in northern France, male newborns with isolated hypospadias (n = 25) were matched at birth with controls (n = 58). Newborns with obvious genetic or hormonal anomalies, undescended testis, micropenis, a congenital syndrome or a family history of hypospadias were not included. Neonatal and parental data were collected. Foetal exposure was assessed by determining the meconium concentrations of the pesticides or metabolites (organophosphates, carbamates, phenylurea, and phenoxyherbicides) most commonly used in the region. Risk factors were assessed in a multivariate analysis. The pesticides most commonly detected in meconium were organophosphates (in up to 98.6% of samples, depending on the substance) and phenylurea (>85.5%). A multivariate analysis revealed an association between isolated hypospadias and the presence in meconium of the phenylurea herbicide isoproturon and of the phenoxyherbicide 2-methyl-4-chlorophenoxyacetic acid (odds ratio [95% confidence interval]: 5.94 [1.03-34.11] and 4.75 [1.20-18.76]) respectively). We conclude that prenatal exposure to these two herbicides (as assessed by meconium analysis) was correlated with the occurrence of isolated hypospadias. The results of our case-control study (i) suggest that prenatal exposure to pesticides interferes with the development of the male genitalia, and (ii) emphasize the importance of preventing pregnant women from being exposed to EDCs in general and pesticides in particular.