Feasibility study of using fetal DNA in maternal plasma for non‐invasive prenatal diagnosis

Liu, Fumin; Wang, Xiuying; Xu, Feng; Wang, Wen; Ye, Yue-Xian; Chen, Hong

doi:10.1080/00016340601159124

Cited by 22 publications

(11 citation statements)

References 25 publications

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“…The 7 data sets that reported results prior to 7 weeks’ gestation had poor performance. The 4 studies included in our univariate analysis 63,71,72,88 (the other 3 were excluded for insufficient sample numbers 36,65,69 ) showed low sensitivity: 74.5% (53.9%, 72.7%, 72.7%, and 88.9%, respectively). The specificity was 99.1%, which is probably artificially high as a result of no fetal DNA amplification at such early gestation (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA

Devaney

Palomaki²,

Scott³

et al. 2011

JAMA

222

142

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Context Noninvasive prenatal determination of fetal sex using cell-free fetal DNA provides an alternative to invasive techniques for some heritable disorders. In some countries this testing has transitioned to clinical care, despite the absence of a formal assessment of performance. Objective To document overall test performance of noninvasive fetal sex determination using cell-free fetal DNA and to identify variables that affect performance. Data Sources Systematic review and meta-analysis with search of PubMed (January 1, 1997–April 17, 2011) to identify English-language human studies reporting primary data. References from review articles were also searched. Study Selection and Data Extraction Abstracts were read independently to identify studies reporting primary data suitable for analysis. Covariates included publication year, sample type, DNA amplification methodology, Y chromosome sequence, and gestational age. Data were independently extracted by 2 reviewers. Results From 57 selected studies, 80 data sets (representing 3524 male-bearing pregnancies and 3017 female-bearing pregnancies) were analyzed. Overall performance of the test to detect Y chromosome sequences had the following characteristics: sensitivity, 95.4% (95% confidence interval [CI], 94.7%–96.1%) and specificity, 98.6% (95% CI, 98.1%–99.0%); diagnostic odds ratio (OR), 885; positive predictive value, 98.8%; negative predictive value, 94.8%; area under curve (AUC), 0.993 (95% CI, 0.989–0.995), with significant interstudy heterogeneity. DNA methodology and gestational age had the largest effects on test performance. Methodology test characteristics were AUC, 0.988 (95% CI, 0.979–0.993) for polymerase chain reaction (PCR) and AUC, 0.996 (95% CI, 0.993–0.998) for real-time quantitative PCR (RTQ-PCR) (P=.02). Gestational age test characteristics were AUC, 0.989 (95% CI, 0.965–0.998) (<7 weeks); AUC, 0.994 (95% CI, 0.987–0.997) (7–12 weeks); AUC, 0.992 (95% CI, 0.983–0.996) (13–20 weeks); and AUC, 0.998 (95% CI, 0.990–0.999) (>20 weeks) (P=.02 for comparison of diagnostic ORs across age ranges). RTQ-PCR (sensitivity, 96.0%; specificity, 99.0%) outperformed conventional PCR (sensitivity, 94.0%; specificity, 97.3%). Testing after 20 weeks (sensitivity, 99.0%; specificity, 99.6%) outperformed testing prior to 7 weeks (sensitivity, 74.5%; specificity, 99.1%), testing at 7 through 12 weeks (sensitivity, 94.8%; specificity, 98.9%), and 13 through 20 weeks (sensitivity, 95.5%; specificity, 99.1%). Conclusions Despite interstudy variability, performance was high using maternal blood. Sensitivity and specificity for detection of Y chromosome sequences was greatest using RTQ-PCR after 20 weeks’ gestation. Tests using urine and tests performed before 7 weeks’ gestation were unreliable.

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Section: Resultsmentioning

confidence: 99%

Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA

Devaney

Palomaki²,

Scott³

et al. 2011

JAMA

222

142

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“…Fifty studies were located in Europe [3,7,8,20,25-27,29-32,35,37-40,42,46-48,50,52,53,57,59-81,94,98,103], 26 from Asia [4,9,23,24,28,34,36,44,54-56,58,82-86,88,89,91-93,96,100-102], eight from North America [13,21,22,43,51,87,97,99], two from multiple locations [49,90] and a further four from around the rest of the world [33,41,45,95]. Gestational ranges for the pregnant women varied across the studies, as did the amount of blood taken and the volume actually used for extracting DNA (see Additional file 2: Table S1).…”

Section: Resultsmentioning

confidence: 99%

Non-invasive prenatal diagnostic test accuracy for fetal sex using cell-free DNA a review and meta-analysis

et al. 2012

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BackgroundCell-free fetal DNA (cffDNA) can be detected in maternal blood during pregnancy, opening the possibility of early non-invasive prenatal diagnosis for a variety of genetic conditions. Since 1997, many studies have examined the accuracy of prenatal fetal sex determination using cffDNA, particularly for pregnancies at risk of an X-linked condition. Here we report a review and meta-analysis of the published literature to evaluate the use of cffDNA for prenatal determination (diagnosis) of fetal sex. We applied a sensitive search of multiple bibliographic databases including PubMed (MEDLINE), EMBASE, the Cochrane library and Web of Science.ResultsNinety studies, incorporating 9,965 pregnancies and 10,587 fetal sex results met our inclusion criteria. Overall mean sensitivity was 96.6% (95% credible interval 95.2% to 97.7%) and mean specificity was 98.9% (95% CI = 98.1% to 99.4%). These results vary very little with trimester or week of testing, indicating that the performance of the test is reliably high.ConclusionsBased on this review and meta-analysis we conclude that fetal sex can be determined with a high level of accuracy by analyzing cffDNA. Using cffDNA in prenatal diagnosis to replace or complement existing invasive methods can remove or reduce the risk of miscarriage. Future work should concentrate on the economic and ethical considerations of implementing an early non-invasive test for fetal sex.

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“…In contrast, clinical testing of selected cf-DNA fragments starts with a simple patient blood draw. In the case of fetal testing, cf-DNA can be detected in maternal blood samples from as early as 5 weeks gestational age, setting the stage for significant advances in very early prenatal diagnostics [103][104][105][106]. To date, characterization of fetal DNA, as detected in maternal blood, has proven to be the most successful clinical application of cf-DNA diagnostics [107].…”

Section: Clinical Testing Based On Fetal Cf-dnamentioning

confidence: 99%

Detecting cancer biomarkers in blood: challenges for new molecular diagnostic and point-of-care tests using cell-free nucleic acids

Lewis

Heineck

Heller

2015

Expert Review of Molecular Diagnostics

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As we move into the era of individualized cancer treatment, the need for more sophisticated cancer diagnostics has emerged. Cell-free (cf) nucleic acids (cf-DNA, cf-RNA) and other cellular nanoparticulates are now considered important and selective biomarkers. There is great hope that blood-borne cf-nucleic acids can be used for 'liquid biopsies', replacing more invasive tissue biopsies to analyze cancer mutations and monitor therapy. Conventional techniques for cf-nucleic acid biomarker isolation from blood are generally time-consuming, complicated and expensive. They require relatively large blood samples, which must be processed to serum or plasma before isolation of biomarkers can proceed. Such cumbersome sample preparation also limits the widespread use of powerful, downstream genomic analyses, including PCR and DNA sequencing. These limitations also preclude rapid, point-of-care diagnostic applications. Thus, new technologies that allow rapid isolation of biomarkers directly from blood will permit seamless sample-to-answer solutions that enable next-generation point-of-care molecular diagnostics.

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Feasibility study of using fetal DNA in maternal plasma for non‐invasive prenatal diagnosis

Abstract: Fluorescent PCR can be used for amplification of fetal SRY sequence and STRs in maternal plasma to obtain fetal genetic information, which may have implications for non-invasive prenatal diagnosis of certain hereditary diseases.

Cited by 22 publications

References 25 publications

Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA

Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA

Non-invasive prenatal diagnostic test accuracy for fetal sex using cell-free DNA a review and meta-analysis

Detecting cancer biomarkers in blood: challenges for new molecular diagnostic and point-of-care tests using cell-free nucleic acids

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