利用母血中胎儿有核红细胞结合血清筛查和三维超声无创性产前诊断唐氏综合征

Noninvasive prenatal screening of Down's syndrome by fetal nucleated erythrocytes detection in maternal blood combined with serum screening and three-dimensional ultrasound

目的:利用母外周血中胎儿有核红细胞结合血清三联筛查及三维超声,建立快速无创性产前诊断唐氏综合征的有效模式。方法:早、中期孕妇共670例,采取血清三联筛查结合三维超声和病史选取唐氏高危孕妇,抽取高危孕妇的外周血,流式细胞术富集母血中的胎儿有核红细胞(Fetal Nucleated Red Blood Cells,FNRBCs);次日进行多重引物原位杂交(muti-primed in situ labeling,multi-PRINS)检测胎儿细胞21号染色体与Y染色体。结果:通过血清三联筛查和三维超声结合病史筛选出高危孕妇24例,高危孕妇在两日内即可确诊,24例中诊断23例染色体正常胎儿,包括男胎12例、女胎11例;诊断1例男性唐氏综合征胎儿。24例标本检测结果和实际胎儿核型符合。结论:血清三联筛查、超声检查结合病史筛选出高危孕妇,然后利用母血中胎儿有核红细胞进行多重引物原位杂交检测细胞染色体,可作为快速、无创性产前诊断唐氏综合征的有效模式,并可为其他胎儿染色体基因异常或者宫内感染的无创性产前诊断提供参考。

Objective：To establish a rapid and effective noninvasive prenatal diagnostic model of Down＇s syndrome by fetal nucleated erythrocytes detection in maternal blood combined with serum triple screening and three-dimensional ultrasound. Methods：670 pregnant women of early,middle and late pregnancy were selected,the high risk pregnant women of Down＇s syndrome were chosen by serum triple screening combined with three-dimensional ultrasound and medical history;the peripheral blood samples of high risk pregnant women were abstracted,flow cytometry was used to enrich fetal nucleated erythrocytes in maternal blood;on the following day,multiple-primer in situ hybridization was used to detect Y chromosome and 21 chromosome in fetal cells. Results：24 high risk pregnant women of Down＇s syndrome were screened out by serum triple screening combined with three-dimensional ultrasound and medical history,and they were diagnosed definitely within two days,23 fetuses were diagnosed with normal chromosomes,including 12 boys and 11 girls;one fetus were diagnosed as Down＇s syndrome;the detection results of 24 samples were coincidence with the actual fetal karyotypes. Conclusion：Serum triple screening combined with three-dimensional ultrasound and medical history can screen high risk pregnant women of Down＇s syndrome,then multiple-primer in situ hybridization is carried out to detect the karyotypes by fetal nucleated erythrocytes detection in maternal blood,which can be used as a rapid and effective noninvasive prenatal diagnostic model of Down＇s syndrome,and the method can provide a basis for noninvasive prenatal diagnosis of other fetal chromosomal or gene abnormalities and intrauterine infection.