高龄孕妇产前诊断结果及其首选无创产前筛查局限性的大样本分析

Prenatal diagnosis results of advanced maternal age women and limitations of preferred non-invasive prenatal screening to them:a large sample analysis

目的探讨高龄(预产期年龄≥35岁)孕妇产前诊断应用无创产前筛查(NIPS)的价值,以及首选NIPS的局限性。方法选择2009年1月至2013年12月,于四川大学华西第二医院接受产前诊断的20 751例高龄孕妇为研究对象。采用回顾性分析方法,对其羊水穿刺胎儿细胞遗传学产前诊断结果进行分析,对胎儿染色体异常进行分类,计算各类染色体异常所占比例。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。结果这20 751例高龄孕妇产前诊断结果显示:(1)胎儿的细胞遗传学产前诊断,检出染色体异常为380例,检出率为1.83%(380/20 751)。其中,21-、18-及13-三体综合征胎儿分别为173例(45.53%,173/380),51例(13.42%,51/380)及9例(2.37%,9/380),总计为233例(61.32%);性染色体异常胎儿为78例(20.53%,78/380),染色体异常携带者为49例(12.89%,49/380),其他染色体异常胎儿为20例(5.26%,20/380),总计为147例(38.68%)。如果首先采取NIPS进行产前诊断,则检测胎儿的目标疾病为21-、18-、13-三体综合征,可检出的胎儿染色体异常仅占全部有临床表型的染色体异常胎儿总数的70.39%(233/331)。(2)2009—2013年,胎儿染色体异常检出率依次为1.49%(38/2 543)、1.44%(51/3 548)、1.87%(87/4 651)、1.85%(99/5 345)、2.25%(105/4 664),胎儿染色体异常检出率整体呈逐年上升趋势。结论 NIPS作为产前诊断的一线检测手段,首选该技术筛查胎儿染色体异常,尤其是对于高龄孕妇具有局限性,应该慎重。

Objective Based on the analysis of the cytogenetic prenatal diagnosis results,the values of non-invasive prenatal screening(NIPS)were analyzed in the detection of the advanced maternal age women(≥35 years old)and limitations of preferred to NIPS according to the fetal chromosomal abnormalities.Methods From January 2009 to December 2013,a total of 20 751 advanced maternal age women who received prenatal diagnosis in West China Second University Hospital,Sichuan University were selected as research subjects.The results of the fetal cytogenetic prenatal diagnosis by amniocentesis of those 20 751 advanced maternal age women were analyzed retrospectively.The chromosome abnormalities of the fetus were classified and the proportions of all kinds of chromosome abnormalities were calculated.This research was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013.Results①A total of 380 chromosome abnormalities were detected among those 20 751 advanced maternal age women according to the results of the cytogenetic prenatal diagnosis.The total detection rate of chromosome abnormalities in advanced maternal age women was 1.83%(380/20 751),including 173 cases of trisomy 21(45.53%,173/380),51 cases of trisomy 18(13.42%,51/380),9 cases of trisomy 13(2.37%,9/380),78 cases of sex chromosome abnormalities(20.53%,78/380),49 carriers of chromosomal abnormality(12.89%,49/380),20 cases of other chromosome abnormalities(5.26%,20/380).If NIPS was used as the preferred prenatal diagnosis method,then the aimed diseases of NIPT detecting were trisomy 21,trisomy 18 and trisomy 13,so the chromosome abnormalities which could be detected out would probably account for 70.39%(233/331)of all chromosomal abnormalities with clinical phenotypes.②From 2009 to 2013,the detection rates of fetal chromosomal abnormalities were 1.49%(38/2 543),1.44%(51/3 548),1.87%(87/4 651),1.85%(99/5 345),and 2.25%(105/4 664),respectively,and the detection rate of fetal chromosomal abnormalities was increasing year by year.Conclusion NIPS as the preferred detection method for screening of fetal chromosomal abnormalities in advanced maternal age women should be cautiously used.