Department of Surgery and Paediatrics, Division of Urology, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, London, Ontario, Canada.
Institute for Clinical Evaluative Sciences, London, Ontario, Canada.
J Pediatr Urol. 2019 Feb;15(1):41.e1-41.e9. doi: 10.1016/j.jpurol.2018.09.021. Epub 2018 Oct 10.
There are several reported risk factors for undescended testis (UDT) and hypospadias (HYP). Also, a family history of UDT or HYP has not been accounted for in prior studies, and doing so may influence these independent risk estimates.
A population-based retrospective cohort study was conducted using linked administrative databases in Ontario, Canada, to identify all live male newborns born between 1997 and 2007, and it was determined whether they underwent an orchidopexy or HYP repair within 5 years of birth. Baseline maternal and fetal risk factors were obtained using appropriate ICD codes. A statistical analysis using a generalized estimating equation with a logit link was performed, adjusting for clustering in mothers with a previous child born in the 5 years before the proband with UDT or HYP, to evaluate the adjusted risk factors of UDT and HYP.
A total of 709,968 male infants were followed up from birth for 5 years, of which 5830 underwent an orchidopexy and 2722 had an HYP repair. On multivariable analysis, factors associated with a higher risk of UDT included prematurity, small for gestational age (SGA), associated HYP, gestational hypertension, use of assisted fertility techniques, increased maternal age, Cesarean section, previous sibling with UDT, and disorders of sexual differentiation (DSDs). After adjusting for clustering in mothers with a previous baby with UDT, DSD, associated HYP (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.0-4.1), and a previous sibling with UDT (OR, 3.6; 95% CI, 2.5-5.2) remained significant risk factors. The risk factors on multivariable analysis predicting the risk of HYP included SGA, prematurity, higher income families, and associated anomalies such as UDT. After adjusting for clustering in mothers with a previous sibling with HYP, SGA (OR, 1.8; 95% CI, 1.0-3.1), higher income families (OR, 1.5-1.6), associated UDT (OR, 7.1; 95% CI, 4.9-10.0), and a previous sibling with HYP (OR, 12.8; 95% CI, 9.1-18.1) remained significant risk factors.
Studies estimating risk factors for UDT and HYP have used variable methodologies to identify index cases and perform statistical analysis. This study suggests that having an older sibling with UDT or HYP is a significant independent risk factor. Performing an analysis adjusting for clustering in mothers with a previous child with UDT or HYP leads to loss of statistical significance for other described risk factors.
Underlying genetic or similar environmental exposures may be a key risk factor for UDT and HYP, which confounds known maternal and fetal risk factors for these anomalies.
隐睾症（UDT）和尿道下裂（HYP）有几个已报道的风险因素。此外，既往研究未考虑家族史，而UDT 或 HYP 的家族史可能会影响这些独立的风险估计。
采用加拿大安大略省基于人群的回顾性队列研究，使用链接的行政数据库，对 1997 年至 2007 年间出生的所有男性活产新生儿进行了识别，并确定他们是否在出生后 5 年内接受了睾丸固定术或 HYP 修复。使用适当的 ICD 代码获取基线产妇和胎儿风险因素。使用广义估计方程（GEE）和对数链接进行统计学分析，调整了与 UDT 或 HYP 前一个孩子在 5 年内出生的母亲聚类相关的因素，以评估 UDT 和 HYP 的调整风险因素。
共对 709968 名男性婴儿进行了从出生到 5 年的随访，其中 5830 名接受了睾丸固定术，2722 名接受了 HYP 修复。多变量分析表明，早产、小于胎龄（SGA）、合并 HYP、妊娠期高血压、辅助生育技术的使用、母亲年龄增加、剖宫产、前一个同胞有 UDT 以及性分化障碍（DSD）与 UDT 风险增加相关。在调整了 UDT、DSD、合并 HYP（比值比[OR]，2.0；95%置信区间[CI]，1.0-4.1）以及前一个同胞有 UDT（OR，3.6；95% CI，2.5-5.2）的母亲聚类相关因素后，这些因素仍然是显著的风险因素。多变量分析预测 HYP 风险的因素包括 SGA、早产、高收入家庭以及 UDT 等相关异常。在调整了 HYP 前一个同胞的母亲聚类相关因素后，SGA（OR，1.8；95% CI，1.0-3.1）、高收入家庭（OR，1.5-1.6）、合并 UDT（OR，7.1；95% CI，4.9-10.0）和 HYP 前一个同胞（OR，12.8；95% CI，9.1-18.1）仍然是显著的风险因素。
估计 UDT 和 HYP 风险因素的研究使用了不同的方法来确定指数病例并进行统计分析。本研究表明，有一个患有 UDT 或 HYP 的年长同胞是一个显著的独立风险因素。在调整了 UDT 或 HYP 前一个孩子的母亲聚类相关因素的分析中，其他描述的风险因素失去了统计学意义。
潜在的遗传或类似的环境暴露可能是 UDT 和 HYP 的一个关键风险因素，这会混淆这些异常的已知母体和胎儿风险因素。
