Rouget Florence, Bihannic Adèle, Cordier Sylvaine, Multigner Luc, Meyer-Monath Marie, Mercier Fabien, Pladys Patrick, Garlantezec Ronan
CHU Rennes, Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S 1085, Rennes, France.
Brittany Registry of Congenital Anomalies, CHU Rennes, Rennes, France.
Front Pediatr. 2021 Jun 2;9:640064. doi: 10.3389/fped.2021.640064. eCollection 2021.
Hypospadias is a male congenital malformation that occurs in ~2 of 1,000 births. The association between hypospadias and fetal exposure to environmental chemicals has been studied, but the results are inconsistent. Although several petroleum and chlorinated solvents are suspected to have teratogenic effects, their role in the occurrence of hypospadias has been little studied and never using biomarkers of exposure. We aimed to evaluate the association between fetal exposure to petroleum and chlorinated solvents measured in meconium and the occurrence of hypospadias. We conducted a pilot case-control study in the maternity of the University Hospital of Rennes (France). Eleven cases of hypospadias and 46 controls were recruited between October 2012 and January 2014. Data from hospital records and maternal self-reported questionnaires, including socio-demographic characteristics and occupational and non-occupational exposure to chemicals, were collected. Meconium samples were collected using a standardized protocol. Levels of petroleum solvents (toluene, benzene, ethylbenzene, and p, m, and o xylene), certain metabolites (mandelic acid, hippuric acid, methylhippuric acid, S-phenylmercapturic acid, S-benzylmercapturic acid, and phenylglyoxylic acid), and two chlorinated solvents (trichloroethylene and tetrachloroethylene) were measured in meconium by gas and liquid chromatography, both coupled to tandem mass spectrometry. Associations between the concentration of each chemical and the occurrence of hypospadias were analyzed using exact logistic regressions adjusted for maternal age, educational level, pre-pregnancy body mass index, and alcohol, and tobacco consumption during pregnancy. Results are presented with odds ratios (ORs) and their 95% confidence intervals (CIs). Quantification rates for petroleum and chlorinated solvents or metabolites ranged from 2.2% (for methylhippuric acid) to 77.1% (for trichloroethylene) of the meconium samples. We found a significant association between the quantification of phenylglyoxylic acid (metabolite of styrene and ethylbenzene) in the meconium and a higher risk of hypospadias (OR = 14.2, 95% CI [2.5-138.7]). The risk of hypospadias was non-significantly elevated for most of the other solvents and metabolites. This exploratory study, on a limited number of cases, suggests an association between petroleum solvents and hypospadias. Additional studies are needed to confirm these results and identify the determinants for the presence of these solvents in meconium.
尿道下裂是一种男性先天性畸形，发生率约为千分之二。人们对尿道下裂与胎儿暴露于环境化学物质之间的关联进行了研究，但结果并不一致。尽管怀疑几种石油和氯化溶剂具有致畸作用，但它们在尿道下裂发生中的作用鲜少被研究，且从未使用暴露生物标志物进行研究。我们旨在评估胎粪中测量的胎儿暴露于石油和氯化溶剂与尿道下裂发生之间的关联。我们在法国雷恩大学医院妇产科开展了一项病例对照试点研究。2012年10月至2014年1月期间招募了11例尿道下裂病例和46例对照。收集了医院记录以及母亲自我报告问卷的数据，包括社会人口学特征以及职业和非职业性化学物质暴露情况。使用标准化方案收集胎粪样本。通过气相色谱和液相色谱联用串联质谱法测量胎粪中石油溶剂（甲苯、苯、乙苯以及对二甲苯、间二甲苯和邻二甲苯）、某些代谢物（扁桃酸、马尿酸、甲基马尿酸、S-苯巯基尿酸、S-苄基巯基尿酸和苯甲酰甲酸）以及两种氯化溶剂（三氯乙烯和四氯乙烯）的水平。使用精确逻辑回归分析每种化学物质的浓度与尿道下裂发生之间的关联，并对母亲年龄、教育水平、孕前体重指数以及孕期饮酒和吸烟情况进行了校正。结果以比值比（OR）及其95%置信区间（CI）呈现。石油和氯化溶剂或代谢物的定量率在胎粪样本的2.2%（甲基马尿酸）至77.1%（三氯乙烯）之间。我们发现胎粪中苯甲酰甲酸（苯乙烯和乙苯的代谢物）的定量与尿道下裂风险较高之间存在显著关联（OR = 14.2，95% CI [2.5 - 138.7]）。大多数其他溶剂和代谢物导致尿道下裂的风险虽未显著升高，但有所增加。这项针对有限病例数的探索性研究表明石油溶剂与尿道下裂之间存在关联。需要进一步研究以证实这些结果，并确定胎粪中这些溶剂存在的决定因素。
