Fernández Nicolas, Lorenzo Armando, Bägli Darius, Zarante Ignacio
Pontificia Universidad Javeriana, Bogota, Colombia.
Division of Urology, Hospital for Sick Children and University of Toronto, Toronto.
J Pediatr Urol. 2016 Oct;12(5):307.e1-307.e5. doi: 10.1016/j.jpurol.2016.03.015. Epub 2016 Apr 22.
Hypospadias is the most common congenital anomaly affecting the genitals. It has been established as a multifactorial disease with increasing prevalence. Many risk factors have been identified such as prematurity, birth weight, mother's age, and exposure to endocrine disruptors. In recent decades multiple authors using surveillance systems have described an increase in prevalence of hypospadias, but most of the published literature comes from developed countries in Europe and North America and few of the published studies have involved cluster analysis. Few large-scale studies have been performed addressing the effect of altitude and other geographical aspects on the development of hypospadias. Acknowledging this limitation, we present novel results of a multinational spatial scan statistical analysis over a 30-year period in South America and an altitude analysis of hypospadias distribution on a continent level.
A retrospective review was performed of the Latin American collaborative study of congenital malformations (ECLAMC). A total of 4,020,384 newborns was surveyed between 1982 and December 2011 in all participating centers. We selected all patients with hypospadias. All degrees of clinical severity were included in the analysis. Each participating center was geographically identified with its coordinates and altitude above sea level. A spatial scan statistical analysis was performed using Kulldorf's methodology and a prevalence trend analysis over time in centers below and above 2000 m.
During the study period we found 159 hospitals in six different countries (Colombia, Bolivia, Brazil, Argentina, Chile, and Uruguay) with 4,537 cases of hypospadias and a global prevalence rate of 11.3/10,000 newborns. Trend analysis showed that centers below 2000 m had an increasing trend with an average of 10/10,000 newborns as opposed to those centers above 2000 m that showed a reducing trend with an average prevalence of 7.8 (p = 0.1246). We identified clusters with significant increases of prevalence in five centers along the coast at an average altitude of 219.8 m above sea level (p > 0.0000). Reduction in prevalence was found in clusters located in two centers on the Andes mountains. Altitude of 2,000 m was associated with hypospadias (Figure), with an OR 0.59 (0.5-0.69). There are ethnic arguments to support our results supported by protective polymorphism distribution in high lands.
Altitude above 2,000 m is suggested to have a protective effect for hypospadias. Specific clusters have been identified with increased risk for hypospadias. Environmental risk factors in these areas need to be further studied given the association seen between altitude and the distribution of more severe cases.
尿道下裂是影响生殖器的最常见先天性畸形。它已被确认为一种患病率不断上升的多因素疾病。已确定许多风险因素，如早产、出生体重、母亲年龄以及接触内分泌干扰物。近几十年来，多位作者利用监测系统描述了尿道下裂患病率的上升，但大多数已发表的文献来自欧洲和北美的发达国家，很少有已发表的研究涉及聚类分析。很少有大规模研究探讨海拔高度和其他地理因素对尿道下裂发生发展的影响。认识到这一局限性，我们展示了一项对南美洲30年期间进行的跨国空间扫描统计分析的新结果以及对大陆层面尿道下裂分布的海拔分析。
对拉丁美洲先天性畸形协作研究（ECLAMC）进行回顾性分析。1982年至2011年12月期间，对所有参与中心的4,020,384名新生儿进行了调查。我们选取了所有患有尿道下裂的患者。分析纳入了所有临床严重程度等级。每个参与中心通过其坐标和海拔高度在地理上进行定位。使用Kulldorf方法进行空间扫描统计分析，并对海拔2000米以下和以上中心的患病率随时间的趋势进行分析。
在研究期间，我们在六个不同国家（哥伦比亚、玻利维亚、巴西、阿根廷、智利和乌拉圭）的159家医院发现了共计4537例尿道下裂病例，全球患病率为1:10000新生儿。趋势分析表明，海拔2000米以下的中心呈上升趋势，平均患病率为10/10000新生儿，而海拔2000米以上的中心呈下降趋势，平均患病率为7.8（p = 0 . 1246）。我们在沿海平均海拔219.8米的五个中心发现了患病率显著增加的聚类（p > 0.0000）。在安第斯山脉两个中心的聚类中发现患病率下降。海拔2000米与尿道下裂相关（图），比值比为0.59（0.5 - 0.69）。有种族方面的论据支持我们的结果，这在高地保护性多态性分布中得到体现。
建议海拔2000米以上对尿道下裂有保护作用。已确定了尿道下裂风险增加的特定聚类。鉴于海拔与更严重病例分布之间的关联，这些地区的环境风险因素需要进一步研究
