Prenatal diagnosis and prognosis of fetal hyperechogenic kidney: a study of 65 cases

目的 探讨胎儿肾脏回声增强的产前诊断和预后. 方法 回顾性分析2009年7月至2015年5月于北京大学第一医院妇产科经产前超声检查发现的65例胎儿肾脏回声增强病例.分析其产前超声结果和妊娠结局,以及截至2015年12月的新生儿随访结果.采用独立样本t检验、x2检验或Fisher精确概率法进行统计学分析. 结果 65例胎儿肾脏回声增强的病例中,双侧48例(73.8％),单侧17例(26.2％);非单纯性肾脏回声增强34例(52.3％),单纯性31例(47.7％).非单纯性肾脏回声增强中,产前超声主要合并异常包括心脏异常14例(41.2％)、泌尿系统异常12例(35.2％)、骨骼异常9例(26.5％)、神经系统异常8例(23.5％).1例(2.9％)为Meckel-Gruber综合征.单纯性与非单纯性肾脏回声增强的产前超声表现中,羊水量、累及肾脏数目及肾脏大小差异均无统计学意义.共20例(30.8％,20/65)产前行胎儿染色体核型分析,1例行无创产前DNA检测,均未见异常;3例产前行脐血微阵列比较基因组杂交分析,均未发现异常.2例应用目标基因捕获结合高通量测序分析,其中1例胎儿脐血发现HNF1β基因杂合片段缺失变异,1例生后外周血发现TTC21B基因突变.共引产23例(35.4％),活产42例(64.6％),3例生后死亡.单纯性肾脏回声增强胎儿的活产率(87.1％,27/31)明显高于非单纯性肾脏回声增强者的44.1％ (15/34) (x2=13.101,P＜0.01).非单纯性肾脏回声增强组共14例随访时存活且生长发育正常,1例失访.单纯性肾脏回声增强共23例随访时存活且生长发育正常,1例生后失访,2例新生儿期死亡(1例新生儿肠扭转,1例死因不详),1例因肝肾功能异常于2.5岁死亡. 结论 胎儿肾脏回声增强是先天性肾脏发育异常的重要超声表现,合并其他系统异常时活产率较低.胎儿肾脏回声增强染色体异常发生率较低,应进一步提高的产前基因检测率.Objective To investigate prenatal diagnosis and prognosis of fetus with hyperechogenic kidney.Methods Clinical data of 65 cases prenatally diagnosed with fetal hyperechogenic kidney in Peking University First Hospital between July,2009 and May,2015 were retrospectively analyzed.Results of fetal ultrasound screening and pregnancy outcomes were analyzed and Growth and development status of those babies were followed up until December,2015.Independent-sample-t,Chi-square or Fisher's exact test was applied for statistical analysis.Results Among the 65 cases,including 48(73.8％) bilateral and 17 (26.2％) unilateral,34 cases (52.3％) were diagnosed as non-isolated and 31 cases (47.7％) as isolated fetal hyperechogenic kidney.The primary associated malformations with non-isolated fetal hyperechogenic kidney included cardiac abnormality (14 cases,41.2％),urinary system abnormality (12 cases,35.2％),skeletal system abnormality (nine cases,26.5％),central nervous system abnormality (eight cases,23.5％) and Meckel-Gruber sydrome (one case,2.9％).Amniotic volume,the size and numbers of affected kidney between non-isolated and isolated groups showed no significant differences (all P＞0.05).Twenty out of the 65 cases (30.8％) received fetal karyotyping and one received non-invasive prenatal testing,and no abnormality was detected.Three cases received cord blood array comparative genomic hybridization with negative results.Pathogenic genes were found in two cases who received targeted exome capture with high throughput sequencing,including a TTC21B mutation in cord blood in one case and a HNF1β deletion mutation in peripheral blood after birth in the other.There were 23 (35.4％) terminations of pregnancy and 42 (64.6％) live births among which three died after birth.The rate of live birth was significantly higher in the isolated group than in the non-isolated group[87.1％(27/31) vs 44.1％(15/34),x2=13.101,P＜0.01].Of the fifteen live births in the non-isolated group,there were fourteen survived symptomfree except that one lost to follow-up.Of the 27 live births in the isolated group,follow up study revealed 23 symptom-free survivors,one lost,two neonatal deaths (one died of volvulus neonatorum,and the other due to unknown causes) and one death of renal and liver function failures at the age of two-and-a-half.ConclusionsFetal hyperechogenic kidney is an important prenatal ultrasound marker for congenital renal anomalies,and the prognosis of non-isolated fetal hyperechogenic kidney is poor.The current rate of abnormal karyotype in fetus with hyperechogenic kidney is very low.However,the rate of prenatal genes screening should be encouraged.中国科学引文数据库(CSCD)285-902