Data_Sheet_2_Petroleum and Chlorinated Solvents in Meconium and the Risk of Hypospadias: A Pilot Study.pdf

Background: 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.Methods: 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).Results: 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.Conclusion: 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.

背景：隐匿性尿道下裂是一种男性先天性畸形，其发病率约为每1000例新生儿的2例。关于隐匿性尿道下裂与胎儿暴露于环境化学物质之间的关联已有研究，但其结果并不一致。尽管已有多项研究表明石油和氯化溶剂可能具有致畸作用，但其在隐匿性尿道下裂发生中的作用研究却相对较少，且尚未采用暴露生物标志物进行探究。本研究旨在评估胎儿暴露于石油和氯化溶剂（以粪便中的水平进行测量）与隐匿性尿道下裂发生之间的关联。方法：我们在法国雷恩大学医院（Rennes）的产科进行了一项试点病例对照研究。2012年10月至2014年1月期间，招募了11例隐匿性尿道下裂病例和46名对照者。收集了来自医院病历和母亲自报问卷的数据，包括社会人口学特征以及职业和非职业化学物质暴露情况。采用标准化方案收集粪便样本。通过气相色谱和液相色谱，结合串联质谱法对粪便中的石油溶剂（甲苯、苯、乙苯和p、m、o-二甲苯）、某些代谢物（苯甲酸、马尿酸、甲基马尿酸、S-苯基马尿酸、S-苄基马尿酸和苯基丙烯酸）以及两种氯化溶剂（三氯乙烯和四氯乙烯）的水平进行了测量。使用精确逻辑回归分析各化学物质的浓度与隐匿性尿道下裂发生之间的关联，同时调整了母亲的年龄、教育水平、孕前体重指数以及孕期酒精和烟草消费等因素。结果以比值比（OR）及其95%置信区间（CI）形式呈现。结果：石油和氯化溶剂或代谢物的量化率在粪便样本中范围为2.2%（甲基马尿酸）至77.1%（三氯乙烯）。我们发现粪便中苯基丙烯酸（苯乙烯和乙苯的代谢物）的量化与隐匿性尿道下裂的高风险之间存在显著关联（OR = 14.2，95% CI [2.5–138.7]）。大多数其他溶剂和代谢物的隐匿性尿道下裂风险虽有所升高，但未达到统计学显著性。结论：本项针对有限病例数的探索性研究提示，石油溶剂与隐匿性尿道下裂之间存在关联。需要进一步的研究来确认这些结果并确定这些溶剂在粪便中存在的决定因素。