Methods to increase the percentage of free fetal DNA recovered from the maternal circulation

被引:106
作者
Dhallan, R
Au, WC
Mattagajasingh, S
Emche, S
Bayliss, P
Damewood, M
Cronin, M
Chou, V
Mohr, M
机构
[1] Ravgen Inc, Columbia, MD 21045 USA
[2] York Hosp, Dept Obstet & Gynecol, York, PA USA
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2004年 / 291卷 / 09期
关键词
D O I
10.1001/jama.291.9.1114
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context Noninvasive prenatal diagnostic tests using free fetal DNA provide an alternative to invasive tests and their attendant risks; however, free fetal DNA exists in the maternal circulation at low percentages, which has hindered development of noninvasive tests. Objective To test the hypothesis that using formaldehyde to reduce cell lysis could increase the relative percentage of free fetal DNA in samples of maternal blood. Design, Setting, and Patients The first phase of the study was conducted from January through February 2002 at a single US clinical site; 2 samples of blood were collected from each of 10 pregnant women, and the percentage of free fetal DNA in formaldehyde-treated and untreated samples was determined. The second phase of the study was conducted from March 2002 through May 2003, and measured the percentage of free fetal DNA in 69 formaldehyde-treated samples of maternal blood obtained from a network of 27 US clinical sites in 16 states. Main Outcome Measure Percentage of free fetal DNA in samples of maternal blood. Results In the first phase of the study, the mean percentage of free fetal DNA in the untreated samples was 7.7% (range, 0.32%-40%), while the mean percentage of free fetal DNA in the formaldehyde-treated samples was 20.2% (range, 1.6%-40%) (P=.02 for difference). in the second phase, a median of 25% (range, 3.1% to >50%) free fetal DNA was obtained forthe 69 formaldehyde-treated maternal blood samples. Approximately 59% of the samples in this study had 25% or greater fetal DNA, and only 16% of the samples had less than 10% fetal DNA. In addition, 27.5% of the samples in this study had 50% or greater fetal DNA. Conclusion Addition of formaldehyde to maternal blood samples, coupled with careful processing protocols, increases the relative percentage of free fetal DNA, providing a foundation for development of noninvasive prenatal diagnostic tests to distinguish fetal DNA from maternal DNA in the maternal circulation.
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页码:1114 / 1119
页数:6
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