Scott Department of Urology, Baylor College of Medicine, Houston, Texas.
Division of Pediatric Urology, Department of Surgery, Texas Children's Hospital, Houston, Texas.
Birth Defects Res. 2019 Apr 15;111(7):345-352. doi: 10.1002/bdr2.1461. Epub 2019 Jan 29.
With the increasing birth prevalence of hypospadias, there is growing concern for pollutant exposure interfering with normal penile development. We assess the association between hypospadias and hormonally active hazardous air pollutants (HAHAPs) through a nationwide database of hazardous air pollutants and the Texas Birth Defects Registry (TBDR).
Using the TBDR, we identified 8,981 nonsyndromic isolated hypospadias cases from 1999 to 2008. Birth certificate controls were matched for birth year at a 10:1 ratio to cases. Estimated HAHAP concentrations from the 2005 U.S. EPA National-Scale Air Toxics Assessment were used to assign exposure based on maternal residence at birth. Exposure levels were categorized as quintiles based on the distribution in controls. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for each increasing exposure category of selected HAHAPs.
Of the 10 HAHAPs studied, seven were significantly associated with hypospadias risk. The HAHAP that was most strongly associated with hypospadias was phenol, which was associated with risk in all groups except the high exposure group. Cumulative HAHAP exposure demonstrated a modest increase in hypospadias risk (OR 1.15, 95% CI: 1.07-1.24, p < 0.001) in the medium and medium-high quintiles.
While maternal exposure to some HAHAPs was significantly associated with the risk of hypospadias in male offspring, the effects were modest, and no dose-response effects were observed. Future work should employ biomarkers of exposure to better delineate the relationship.
随着尿道下裂的出生率不断增加，人们越来越关注污染物暴露对正常阴茎发育的干扰。我们通过一个全国性的危险空气污染物数据库和德克萨斯州出生缺陷登记处（TBDR）评估了尿道下裂与具有激素活性的有害空气污染物（HAHAPs）之间的关联。
我们使用 TBDR 从 1999 年至 2008 年确定了 8981 例非综合征性孤立性尿道下裂病例。出生证对照病例按出生年份以 10:1 的比例与病例相匹配。使用 2005 年美国环保署国家规模空气毒物评估的估计 HAHAP 浓度来根据母亲出生时的居住地分配暴露。根据对照人群的分布，将暴露水平分为五分位数。使用逻辑回归计算每个选定 HAHAP 的暴露类别增加时的比值比（OR）和 95%置信区间（CI）。
在所研究的 10 种 HAHAP 中，有 7 种与尿道下裂风险显著相关。与尿道下裂最密切相关的 HAHAP 是苯酚，除了高暴露组外，所有组均与风险相关。HAHAP 暴露的累积量与尿道下裂风险呈适度增加（OR 1.15，95%CI：1.07-1.24，p<0.001），在中值和中高五分位数组中尤其明显。
虽然母体暴露于某些 HAHAPs 与男性后代尿道下裂的风险显著相关，但这些影响是适度的，且未观察到剂量反应关系。未来的工作应该使用暴露生物标志物来更好地阐明这种关系。
