利用母血中的胎儿细胞检测胎儿性别和非整倍体：NIFTY I数据的分析。美国国立儿童健康与人类发展研究所胎儿细胞分离研究。

Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study.

作者信息

Bianchi D W, Simpson J L, Jackson L G, Elias S, Holzgreve W, Evans M I, Dukes K A, Sullivan L M, Klinger K W, Bischoff F Z, Hahn S, Johnson K L, Lewis D, Wapner R J, de la Cruz F

机构信息

Division of Genetics, Departments of Pediatrics, Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA, USA.

出版信息

Prenat Diagn. 2002 Jul;22(7):609-15. doi: 10.1002/pd.347.

DOI:10.1002/pd.347

PMID:12124698

Abstract

OBJECTIVES

The National Institute of Child Health and Human Development Fetal Cell Isolation Study (NIFTY) is a prospective, multicenter clinical project to develop non-invasive methods of prenatal diagnosis. The initial objective was to assess the utility of fetal cells in the peripheral blood of pregnant women to diagnose or screen for fetal chromosome abnormalities.

METHODS

Results of fluorescence in situ hybridization (FISH) analysis on interphase nuclei of fetal cells recovered from maternal blood were compared to metaphase karyotypes of fetal cells obtained by amniocentesis or chorionic villus sampling (CVS). After the first 5 years of the study we performed a planned analysis of the data. We report here the data from 2744 fully processed pre-procedural blood samples; 1292 samples were from women carrying singleton male fetuses.

RESULTS

Target cell recovery and fetal cell detection were better using magnetic-based separation systems (MACS) than with flow-sorting (FACS). Blinded FISH assessment of samples from women carrying singleton male fetuses found at least one cell with an X and Y signal in 41.4% of cases (95% CI: 37.4%, 45.5%). The false-positive rate of gender detection was 11.1% (95% CI: 6.1,16.1%). This was higher than expected due to the use of indirectly labeled FISH probes in one center. The detection rate of finding at least one aneuploid cell in cases of fetal aneuploidy was 74.4% (95% CI: 76.0%, 99.0%), with a false-positive rate estimated to be between 0.6% and 4.1%.

CONCLUSIONS

The sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple marker method for non-invasive prenatal screening. The limitations of the present study, i.e. multiple processing protocols, are being addressed in the ongoing study.

摘要

目的

美国国立儿童健康与人类发展研究所胎儿细胞分离研究（NIFTY）是一项前瞻性多中心临床项目，旨在开发非侵入性产前诊断方法。最初的目标是评估孕妇外周血中胎儿细胞用于诊断或筛查胎儿染色体异常的效用。

方法

将从母血中回收的胎儿细胞间期核的荧光原位杂交（FISH）分析结果与通过羊膜穿刺术或绒毛取样（CVS）获得的胎儿细胞中期核型进行比较。在研究的前5年之后，我们对数据进行了计划分析。我们在此报告2744份经过充分处理的术前血样的数据；1292份样本来自怀有单胎男性胎儿的女性。

结果

使用基于磁性的分离系统（MACS）比流式分选（FACS）能更好地回收目标细胞和检测胎儿细胞。对怀有单胎男性胎儿的女性样本进行的盲法FISH评估发现，41.4%的病例（95%置信区间：37.4%，45.5%）中至少有一个细胞具有X和Y信号。性别检测的假阳性率为11.1%（95%置信区间：6.1，16.1%）。由于在一个中心使用了间接标记的FISH探针，这一比例高于预期。在胎儿非整倍体病例中发现至少一个非整倍体细胞的检测率为74.4%（95%置信区间：76.0%，99.0%），估计假阳性率在0.6%至4.1%之间。