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.

尽管人们认为破坏内分泌的化学物质（EDC，包括杀虫剂）会增加尿道下裂的风险，但在这种情况下尚未正式鉴定出任何化合物。现在可以通过评估作为慢性产前暴露标志物的胎粪来进行人体研究。本研究的目的是确定产前暴露于农药（如在胎粪中检测到）是否构成了孤立性尿道下裂的危险因素。在2011年至2014年之间于法国北部进行的病例对照研究中，患有孤立性尿道下裂（n = 25）的男性新生儿在出生时就与对照（n = 58）相匹配。不包括具有明显遗传或激素异常，睾丸未降，微阴茎，先天综合征或尿道下裂家族史的新生儿。收集了新生儿和父母的数据。该区域最常用的代谢物（有机磷酸盐，氨基甲酸酯，苯脲和苯氧基除草剂）。风险因素进行了多因素分析。在胎粪中最常检测到的农药是有机磷酸盐（在多达98.6％的样品中，取决于物质）和苯脲（> 85.5％）。多元分析表明，孤立性尿道下裂与胎粪中苯脲的存在有关除草剂异丙隆和苯氧除草剂2-甲基-4-氯苯氧乙酸（赔率[95％置信区间]：5.94 [1.03–34.11]和4.75 [1.20-18.76]）。我们得出的结论是，产前暴露于这两种除草剂（通过粪便分析评估）与孤立的尿道下裂的发生有关。我们的病例对照研究的结果（i）表明产前暴露于农药会干扰男性生殖器的发育，并且（ii）强调必须防止孕妇普遍暴露于EDC，尤其是农药。