Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis

被引:185
|
作者
Ariga, H
Ohto, H
Busch, MP
Imamura, S
Watson, R
Reed, W
Lee, TH
机构
[1] Blood Ctr Pacific, San Francisco, CA 94118 USA
[2] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA
[3] Fukushima Med Univ, Sch Med, Fukushima, Japan
[4] Odaka Municipal Hosp, Fukushima, Japan
[5] Blood Syst, Scottsdale, AZ USA
[6] Roche Mol Syst, Alameda, CA USA
关键词
D O I
10.1046/j.1537-2995.2001.41121524.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND: Fetal genetic material is detectable in the maternal circulation and has been used for noninvasive prenatal diagnosis. However, few data are available concerning its quantity and natural history during gestation. STUDY DESIGN AND METHODS: This study prospectively characterized the kinetics of cellular and cell-free fetal DNA in the circulation of 25 healthy women during and after uncomplicated pregnancy. Real-time kinetic PCR was used to quantitate human Y-chromosome sequences, and liquid oligomer hybridization with P-32-labeled probes was used to verify the identity of amplified products. RESULTS: In all male pregnancies, but no female pregnancies, low-level fetal Y-chromosome DNA was detected in both cellular and cell-free compartments beginning at 7 to 16 weeks but increasing steadily after 24 weeks and reaching a peak at parturition. The fetal DNA decreased rapidly after birth. CONCLUSION: Fetal genetic material can be detected throughout pregnancy, and its quantity is a function of gestational age and of whether the plasma or cellular compartment is examined. Both the absolute quantity of fetal DNA and its ratio to total DNA (maternal + fetal) are greater in the plasma than in the cellular compartment. Fetal DNA is cleared rapidly from both compartments after parturition, which suggests that turnover is dynamic. Because they provide prospective and quantitative data concerning fetal DNA levels, these observations and kinetic PCR methods may have implications for noninvasive prenatal diagnosis. Further studies will be needed to determine the immunologic implications of fetal-maternal DNA exchange and cellular microchimerism.
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收藏
页码:1524 / 1530
页数:7
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