胎儿泌尿系统梗阻性病变的遗传学病因及妊娠结局分析

Genetic Etiology of Fetal Urinary Tract Obstruction and Pregnancy Outcomes

目的:探讨胎儿肾积水、巨膀胱和后尿道瓣膜等泌尿系统梗阻性病变的遗传学病因、超声表征及相关预后。方法:收集广州医科大学附属第三医院2014年1月—2020年6月产前超声诊断为泌尿系统梗阻性病变的359例胎儿(其中23例为双胎之一,余均为单胎),分析其检查结果,并对其中进行介入性产前诊断的156例的遗传学检测结果进行分析,追踪所有病例的妊娠结局。结果:359例胎儿泌尿系统梗阻性病变包括肾积水314例(87.46%),巨膀胱36例(10.03%)和后尿道瓣膜9例(2.51%)。319例为单发,40例合并其他系统异常。156例胎儿样本染色体微阵列分析(CMA)检测发现10例(6.41%)染色体数目异常、3例致病性拷贝数变异(CNVs)和8例临床意义不明的CNVs,其中2例21-三体综合征胎儿超声表现为单纯肾积水。活产267例新生儿。产前超声诊断肾积水胎儿中,251例活产,其中211例产后排尿正常,40例产后诊断重度肾积水行泌尿系统梗阻解除手术,36例手术效果佳。产前超声诊断巨膀胱胎儿中,15例活产,其中9例在妊娠早期发现巨膀胱,妊娠中晚期复查超声恢复正常;1例出生后因合并左肾积水和左侧输尿管畸形行患侧输尿管切除术,术后恢复好;其余5例出生后排尿正常,未行超声检查。产前超声诊断后尿道瓣膜胎儿中,8例终止妊娠,1例活产,该病例于孕28周确诊,出生后未行手术,目前生长发育正常。结论:在泌尿系统梗阻性病变中肾积水不良妊娠率较低,预后较好;部分妊娠早期发现的巨膀胱病例在妊娠中晚期复查超声恢复正常,但巨膀胱染色体异常风险增加,若产前确诊,需行染色体核型分析和基因检测;后尿道瓣膜预后与明确诊断时的孕周有关,如妊娠24周后诊断,预后较好。

Objective:To investigate the genetic etiology,ultrasonic characterization and prognosis of obstructive diseases,such as fetal hydronephrosis,posterior urethral valve and giant bladder.Methods:The clinical data of 359 fetuses(23 of them were one of twins,others were singleton)with urinary obstructive lesions diagnosed by prenatal ultrasound from January 2014 to June 2020 were analyzed,including 156 cases with interventional prenatal diagnosis.The prognosis of all cases was tracked.Results:There were 314 cases of hydronephrosis(87.46%),36 cases of giant bladder(10.03%),and 9 cases of posterior urethral valve(2.51%).Among 359 cases of urinary obstructive diseases,319 cases were single disease and 40 cases were complicated with other system abnormalities.Chromosomal microarray analysis of fetal samples from 156 cases showed that 10 cases(6.41%)were the abnormalities of chromosome number,3 cases were pathogenic CNVs and 8 cases were CNVs of unknown clinical significance,including 2 cases of 21 trisomy with the simple hydronephrosis under ultrasonic examination.Among 267 live born newborns,251 newborns with hydronephrosis,211 newborns with hydronephrosis showed normal micturition after delivery,40 cases were diagnosed with severe hydronephrosis and underwent further urinary obstruction-relief surgery,in which 36 cases exhibited good effects after surgery.Among the giant bladder cases diagnosed by prenatal ultrasound,9 cases of 15 live births were found the giant bladder in the early pregnancy,and returned to normal in the middle and late stage of pregnancy,which suggested a transient bladder enlargement.One case recovered well from the ureterectomy surgery on the affected side due to left hydronephrosis and left ureteral malformation after birth.The other 5 cases had normal urination and did not undergo the follow-up ultrasound examination.Among 9 cases of posterior urethral valve,8 cases were terminated pregnancy and 1 case got a live birth.This case was diagnosed as posterior urethral valve at 28 weeks of pregnancy,no operation performed after birth,and the growth and development was normal.Conclusions:The rate of adverse pregnancy with hydronephrosis is low and the prognosis is good in obstructive diseases of urinary system.In some cases of the giant bladder found in the early pregnancy and with the ultrasonic imaging returned to normal in the middle and late pregnancy,the risk of chromosomal abnormalities related to giant bladder was increased.When the fetal giant bladder was found before delivery,chromosomal karyotype analysis and gene detection were needed.The prognosis of posterior urethral valve is related to the gestational age of definite diagnosis.The prognosis may be better if the posterior urethral valve happened after 24 weeks of pregnancy.