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A prospective analysis of cell-free fetal DNA concentration in maternal plasma as an indicator for adverse pregnancy outcome.

Abstract：

OBJECTIVES:To evaluate whether cell-free fetal (cff) DNA in maternal plasma during the second trimester is a marker for developing pregnancy-associated complications. Two PCR techniques for the detection and quantitation of fetal DNA were compared. METHODS:Plasma samples were prospectively collected from 84 pregnant women carrying male fetuses before amniocentesis (14-29 weeks). We later recorded 26 pregnancies with complicated outcomes, including five cases of fetal chromosomal abnormalities. For statistical analysis, two overlapping subgroups A and B were made. Each group was separately compared for total and fetal DNA with a corresponding group considered normal using Wilcoxon rank sum test. Male fetal DNA concentration in maternal plasma was quantified using real-time quantitative polymerase chain reaction (PCR) of SRY sequences. The samples were also analyzed by quantitative fluorescent PCR (QF-PCR) using highly polymorphic short tandem repeat DNA sequences (STRs), and the percentage of relative fetal allele concentration in maternal alleles was calculated and compared to the fetal/total DNA ratio obtained by real-time PCR. RESULTS:Quantities of total and fetal circulating DNA were significantly correlated (r(2) = 0.44, P < 0.0001) with a median total DNA concentration of 522 GE/mL (range 51-3047) and a median fetal DNA concentration of 8 GE/mL (range 0-879). Neither level was correlated with gestational age in pregnancies with normal (r(2) = -0.05; P = 0.66, and r(2) = 0.02; P = 0.88, respectively) and abnormal (r(2) = 0.45; P = 0.17, and r(2) = 0.11; P = 0.76, respectively) outcomes. Although both total and fetal DNA levels were always higher in women carrying pregnancies with chromosomal aberrations or having other pregnancy complications (P-values range from 0.028 to 0.267), these differences reached statistical significance only for total DNA levels between the group A and corresponding normal pregnancies (P = 0.028). The correlation between the fetal/total DNA ratio obtained by real-time PCR and the percentage of relative fetal allele concentration in maternal alleles obtained by QF-PCR was not found to be statistically significant (r(2) = 0.04; P = 0.76). CONCLUSION:Our results confirm the clinical value of fetal DNA measurement in maternal plasma during the second trimester as a supplement for the diagnosis of aneuploidies. Its use as a screening instrument for complications that develop later in pregnancy seems to be limited but needs further investigation. Although the QF-PCR assay has the advantage of being applicable to both female and male fetuses, this approach cannot be used for quantitation of cff DNA in maternal plasma samples.

journal_name

Prenat Diagn

journal_title

Prenatal diagnosis

authors

Bauer M,Hutterer G,Eder M,Majer S,Leshane E,Johnson KL,Peter I,Bianchi DW,Pertl B

doi

10.1002/pd.1513

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

831-6

issue

eissn

0197-3851

issn

1097-0223

journal_volume

pub_type

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A prospective analysis of cell-free fetal DNA concentration in maternal plasma as an indicator for adverse pregnancy outcome.