Service de Chirurgie et Urologie Pédiatrique, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, Montpellier, France; Service d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, Montpellier, France.
Service d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, Montpellier, France; Unité d'Endocrinologie et Gynécologie Pédiatriques, Service de Pédiatrie, Hôpital Arnaud de Villeneuve et Université Montpellier 1, CHU de Montpellier, Montpellier, France.
Eur Urol. 2015 Dec;68(6):1023-30. doi: 10.1016/j.eururo.2015.05.008. Epub 2015 May 23.
Numerous studies have focused on the association between endocrine-disrupting chemicals (EDCs) and hypospadias. Phenotype variability, the absence of representative comparison groups and concomitant genetic testing prevent any definitive conclusions.
To identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias.
DESIGN, SETTING, AND PARTICIPANTS: A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009-2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery.
In patients without AR, SRD5A2, and MAMLD1 mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs. Environmental exposure was estimated using the zip code, the type of surrounding hazards, and distance from these hazards. Multivariate analysis was performed.
Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias (40.00% vs 17.55%, odds ratio 3.13, 95% confidence interval 2.11-4.65). The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys (19.73% vs 10.26%, p=0.0019), especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias (40.13% vs 27.48%, p=0.02). Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys (13.29% vs. 6.64%, p<0.00005). Association of occupational and environmental exposures increases this risk.
This multicenter prospective controlled study with a homogeneous cohort of hypospadiac boys without genetic defects strongly suggests that EDCs are a risk factor for hypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk.
Our multi-institutional study showed that parental professional, occupational, and environmental exposures to chemical products increase the risk of hypospadias in children.
许多研究都集中在环境内分泌干扰物（EDCs）与尿道下裂之间的关联上。表型的可变性、缺乏代表性的对照组以及同时进行的基因检测，使得任何明确的结论都难以得出。
确定职业和环境暴露于 EDC 对非遗传性孤立性尿道下裂的作用。
设计、地点和参与者：2009 年至 2014 年，在法国南部进行了一项多机构研究，共纳入 408 例连续的孤立性尿道下裂患儿和 302 例正常男孩。该地区是尿道下裂手术患病率最高的法国地区。
在没有 AR、SRD5A2 和 MAMLD1 突变的患者中，根据欧洲问卷 QLK4-1999-01422 和针对 EDC 的经过验证的职业暴露矩阵，评估了父母职业和专业接触 EDC 的情况。使用邮政编码、周围危险类型和与这些危险的距离来估计环境暴露。进行了多变量分析。
在生殖器分化窗期间胎儿暴露于 EDC 更常见于尿道下裂病例（40.00% vs 17.55%，优势比 3.13，95%置信区间 2.11-4.65）。这些物质是油漆/溶剂/粘合剂（16.0%）、清洁剂（11.0%）、杀虫剂（9.0%）、化妆品（5.6%）和工业化学品（4.0%）。尿道下裂男孩的母亲中从事有暴露工作的情况更常见（19.73% vs 10.26%，p=0.0019），尤其是清洁工、理发师、美容师和实验室工人。父亲的工作暴露在尿道下裂病例中更为常见（40.13% vs 27.48%，p=0.02）。在尿道下裂男孩的母亲中，工业区域、焚化炉和废物区域在 3 公里半径内更为常见（13.29% vs. 6.64%，p<0.00005）。职业和环境暴露的联合增加了这种风险。
这项多中心前瞻性对照研究纳入了一组无遗传缺陷的同质尿道下裂男孩队列，强烈表明 EDC 通过胎儿期的职业和环境暴露成为尿道下裂的危险因素。各种类型的暴露的联合可能会增加这种风险。
我们的多机构研究表明，父母的专业、职业和环境接触化学产品会增加儿童尿道下裂的风险。
