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Table of Contents
Vol. 31, No. 2, 2012
Issue release date: March 2012
Section title: Review
Free Access
Fetal Diagn Ther 2012;31:81–86
(DOI:10.1159/000333060)

Diagnostic Accuracy of Noninvasive Detection of Fetal Trisomy 21 in Maternal Blood: A Systematic Review

Verweij E.J.a · van den Oever J.M.E.b · de Boer M.A.a · Boon E.M.J.b · Oepkes D.a
aDepartment of Obstetrics and bCenter for Human and Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
email Corresponding Author

Abstract

Background: Both pregnant women and providers of obstetric care are aware of the rapid advances in noninvasive prenatal diagnosis (NIPD) of fetal trisomies, and appear to look forward to its clinical introduction. Objectives: To review and critically assess the published literature on diagnostic accuracy of NIPD using cell-free fetal DNA or RNA in maternal blood to detect fetal trisomy 21. Method: An electronic search was performed in MEDLINE, EMBASE and the Cochrane library (1997 to April 2011). Of a total of 201 citations, 9 studies were eligible for full-text analysis by 2 independent reviewers, using the QUADAS tool. Results: Two of the 9 analyzed studies complied with the criteria of the QUADAS tool. Combining the selected 2 studies, with a total of 681 pregnancies included, overall sensitivity was 125/125 (100%, 95% CI 97.5–100%) and specificity 552/556 (99.3%, 95% CI 98.7–99.3%). Conclusions: NIPD of fetal trisomy 21, using fetal nucleic acids in maternal plasma, appears to have a high diagnostic accuracy. Large-scale prospective studies are awaited before implementation in clinical practice.

© 2011 S. Karger AG, Basel


  

Key Words

  • Noninvasive prenatal diagnosis
  • Screening
  • Trisomy 21
  • Down syndrome
  • Maternal blood

References

  1. Mégarbané A, Ravel A, Mircher C, Sturtz F, Grattau Y, Rethoré MO, Delabar JM, Mobley WC: The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome. Genet Med 2009;11:611–616.

    External Resources

  2. Morris JK, Alberman E: Trends in Down’s syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008:analysis of data from the National Down Syndrome Cytogenetic Register. BMJ 2009;339:b3794.
  3. de Graaf G, Haveman M, Hochstenbach R, Engelen J, Gerssen-Schoorl K, Poddighe P, Smeets D, van Hove G: Changes in yearly birth prevalence rates of children with Down syndrome in the period 1986–2007 in the Netherlands. J Intellect Disabil Res 2011;55:5:462–473.
  4. Nicolaides KH: A model for a new pyramid of prenatal care based on the 11 to 13 weeks’ assessment. Prenat Diagn 2011;31:3–6.

    External Resources

  5. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS: Presence of fetal DNA in maternal plasma and serum. Lancet 1997;350:483–487.

    External Resources

  6. Zhong XY, Holzgreve W, Hahn S: Detection of fetal Rhesus D and sex using fetal DNA from maternal plasma by multiplex polymerase chain reaction. BJOG 2000;107:766–769.
  7. Rijnders RJP, Schoot van der E, Bossers B, Vroede de MAMJ, Christiaens GCML: Fetal sex determination from maternal plasma in pregnancies at risk for congenital adrenal hyperplasia. Obstet Gynecol 2001;98:374–378.
  8. Finning K, Martin P, Daniels G: The use of maternal plasma for prenatal RhD blood group genotyping. Methods Mol Biol 2009;496:143–157.
  9. Scheffer PG, van der Schoot E, Page-Christiaens GCML, Bossers B, van Erp F, de Haas M: Reliability of fetal sex determination using maternal plasma. Obstet Gynecol 2010;115:117–126.
  10. Whiting P, Rutjes AWS, Reitsma JB, Bossuyt PMM, Kleinen J: The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003;3:25.
  11. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group: Reprint – preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther 2009;89:873–880.

    External Resources

  12. Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR: Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci USA 2008;105:16266–16271.
  13. Chiu RWK, Chan KCA, Gao Y, Lau VYM, Zheng W, Lueng TY, et al: Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci USA 2008;105:20458–20463.
  14. Tong YK, Jin S, Chiu RWK, Ding C, Chan KCA, Leung TY, et al: Noninvasive prenatal detection of trisomy 21 by an epigenetic-genetic chromosome-dosage approach. Clinical Chemistry 2010;56:190–198.

    External Resources

  15. Tsui NBY, Akolekar R, Chiu RWK, Chow KCK, Leung TY, Lau TK, et al: Synergy of total PLAC4 RNA concentration and measurement of the RNA single-nucleotide polymorphism allelic ratio for the noninvasive prenatal detection of trisomy 21. Clin Chem 2010;56:173–181.

    External Resources

  16. Ghanta S, Mitchell ME, Ames M, Hidestrand M, Simpson P, Goetsch M: Non-invasive prenatal detection of trisomy 21 using tandem single nucleotide polymorphisms. PLoS One 2010;8:5:e13184.

    External Resources

  17. Deng YH, Yin A, He Q, Chen J, He Y, Wang H, et al: Non-invasive prenatal diagnosis of trisomy 21 by reverse transcriptase multiplex ligation-dependent probe amplification. Clin Chem Lab Med 2011;49:641–646.
  18. Papageorgiou EA, Karagrigoriou A, Tsaliki E, Velissariou V, Carter NP, Patsalis PC: Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21. Nat Med 2011;17:510–513.
  19. Chiu RWK, Akolekar R, Zheng YWL, Lueng TY, Sun H, Chan KCA, et al: Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011;342:c7401.
  20. Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R: Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol 2011;204:205.e1–e11.
  21. Go ATJI, Dikker Hupkes HW, Lomecky M, Twisk J, Blankenstein MA, Vugt van JMG: Evaluation of a programme for the prenatal screening for Down’s syndrome by ultrasonographic nuchal translucency measurement and serum determinations in the first trimester of pregnancy. Ned Tijdschr Geneeskd 2005;149:2795–2799.
  22. Caughey AB, Hopkins LM, Norton ME: Amniocentesis and the difference in the rate of pregnancy Loss. Obstet Gynecol 2006;108:612–616.
  23. Schielen PCJI, Koster MPH, Elvers LH, Loeber JG: Downsyndroom-kansbepaling met de eerstetrimester-combinatietest 2004–2006 (deels 2007). RIVM rapport 230024002/2008.
  24. Wortelboer EJ, Koster MPH, Stoutenbeek Ph, Elvers LH, Loeber JG, Visser GHA, Schielen PCJI: First-trimester Down syndrome screening performance in the Dutch population; how to achieve further improvement? Prenat Diagn 2009;29:588–592.

  

Author Contacts

Dick Oepkes
Department of Obstetrics, Leiden University Medical Centre
PO Box 9600
NL–2300 RC Leiden (The Netherlands)
Tel. +31 71 526 2896, E-Mail d.oepkes@lumc.nl

  

Article Information

Received: July 19, 2011
Accepted after revision: September 12, 2011
Published online: November 17, 2011
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 2, Number of References : 24

  

Publication Details

Fetal Diagnosis and Therapy (Clinical Advances and Basic Research)

Vol. 31, No. 2, Year 2012 (Cover Date: March 2012)

Journal Editor: Gratacós E. (Barcelona)
ISSN: 1015-3837 (Print), eISSN: 1421-9964 (Online)

For additional information: http://www.karger.com/FDT


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Both pregnant women and providers of obstetric care are aware of the rapid advances in noninvasive prenatal diagnosis (NIPD) of fetal trisomies, and appear to look forward to its clinical introduction. Objectives: To review and critically assess the published literature on diagnostic accuracy of NIPD using cell-free fetal DNA or RNA in maternal blood to detect fetal trisomy 21. Method: An electronic search was performed in MEDLINE, EMBASE and the Cochrane library (1997 to April 2011). Of a total of 201 citations, 9 studies were eligible for full-text analysis by 2 independent reviewers, using the QUADAS tool. Results: Two of the 9 analyzed studies complied with the criteria of the QUADAS tool. Combining the selected 2 studies, with a total of 681 pregnancies included, overall sensitivity was 125/125 (100%, 95% CI 97.5–100%) and specificity 552/556 (99.3%, 95% CI 98.7–99.3%). Conclusions: NIPD of fetal trisomy 21, using fetal nucleic acids in maternal plasma, appears to have a high diagnostic accuracy. Large-scale prospective studies are awaited before implementation in clinical practice.

© 2011 S. Karger AG, Basel


  

Author Contacts

Dick Oepkes
Department of Obstetrics, Leiden University Medical Centre
PO Box 9600
NL–2300 RC Leiden (The Netherlands)
Tel. +31 71 526 2896, E-Mail d.oepkes@lumc.nl

  

Article Information

Received: July 19, 2011
Accepted after revision: September 12, 2011
Published online: November 17, 2011
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 2, Number of References : 24

  

Publication Details

Fetal Diagnosis and Therapy (Clinical Advances and Basic Research)

Vol. 31, No. 2, Year 2012 (Cover Date: March 2012)

Journal Editor: Gratacós E. (Barcelona)
ISSN: 1015-3837 (Print), eISSN: 1421-9964 (Online)

For additional information: http://www.karger.com/FDT


Article / Publication Details

First-Page Preview
Abstract of Review

Received: 7/19/2011 10:25:49 AM
Accepted: 9/12/2011
Published online: 11/17/2011
Issue release date: March 2012

Number of Print Pages: 6
Number of Figures: 2
Number of Tables: 2

ISSN: 1015-3837 (Print)
eISSN: 1421-9964 (Online)

For additional information: http://www.karger.com/FDT


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Mégarbané A, Ravel A, Mircher C, Sturtz F, Grattau Y, Rethoré MO, Delabar JM, Mobley WC: The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome. Genet Med 2009;11:611–616.

    External Resources

  2. Morris JK, Alberman E: Trends in Down’s syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008:analysis of data from the National Down Syndrome Cytogenetic Register. BMJ 2009;339:b3794.
  3. de Graaf G, Haveman M, Hochstenbach R, Engelen J, Gerssen-Schoorl K, Poddighe P, Smeets D, van Hove G: Changes in yearly birth prevalence rates of children with Down syndrome in the period 1986–2007 in the Netherlands. J Intellect Disabil Res 2011;55:5:462–473.
  4. Nicolaides KH: A model for a new pyramid of prenatal care based on the 11 to 13 weeks’ assessment. Prenat Diagn 2011;31:3–6.

    External Resources

  5. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS: Presence of fetal DNA in maternal plasma and serum. Lancet 1997;350:483–487.

    External Resources

  6. Zhong XY, Holzgreve W, Hahn S: Detection of fetal Rhesus D and sex using fetal DNA from maternal plasma by multiplex polymerase chain reaction. BJOG 2000;107:766–769.
  7. Rijnders RJP, Schoot van der E, Bossers B, Vroede de MAMJ, Christiaens GCML: Fetal sex determination from maternal plasma in pregnancies at risk for congenital adrenal hyperplasia. Obstet Gynecol 2001;98:374–378.
  8. Finning K, Martin P, Daniels G: The use of maternal plasma for prenatal RhD blood group genotyping. Methods Mol Biol 2009;496:143–157.
  9. Scheffer PG, van der Schoot E, Page-Christiaens GCML, Bossers B, van Erp F, de Haas M: Reliability of fetal sex determination using maternal plasma. Obstet Gynecol 2010;115:117–126.
  10. Whiting P, Rutjes AWS, Reitsma JB, Bossuyt PMM, Kleinen J: The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003;3:25.
  11. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group: Reprint – preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther 2009;89:873–880.

    External Resources

  12. Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR: Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci USA 2008;105:16266–16271.
  13. Chiu RWK, Chan KCA, Gao Y, Lau VYM, Zheng W, Lueng TY, et al: Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci USA 2008;105:20458–20463.
  14. Tong YK, Jin S, Chiu RWK, Ding C, Chan KCA, Leung TY, et al: Noninvasive prenatal detection of trisomy 21 by an epigenetic-genetic chromosome-dosage approach. Clinical Chemistry 2010;56:190–198.

    External Resources

  15. Tsui NBY, Akolekar R, Chiu RWK, Chow KCK, Leung TY, Lau TK, et al: Synergy of total PLAC4 RNA concentration and measurement of the RNA single-nucleotide polymorphism allelic ratio for the noninvasive prenatal detection of trisomy 21. Clin Chem 2010;56:173–181.

    External Resources

  16. Ghanta S, Mitchell ME, Ames M, Hidestrand M, Simpson P, Goetsch M: Non-invasive prenatal detection of trisomy 21 using tandem single nucleotide polymorphisms. PLoS One 2010;8:5:e13184.

    External Resources

  17. Deng YH, Yin A, He Q, Chen J, He Y, Wang H, et al: Non-invasive prenatal diagnosis of trisomy 21 by reverse transcriptase multiplex ligation-dependent probe amplification. Clin Chem Lab Med 2011;49:641–646.
  18. Papageorgiou EA, Karagrigoriou A, Tsaliki E, Velissariou V, Carter NP, Patsalis PC: Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21. Nat Med 2011;17:510–513.
  19. Chiu RWK, Akolekar R, Zheng YWL, Lueng TY, Sun H, Chan KCA, et al: Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011;342:c7401.
  20. Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R: Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol 2011;204:205.e1–e11.
  21. Go ATJI, Dikker Hupkes HW, Lomecky M, Twisk J, Blankenstein MA, Vugt van JMG: Evaluation of a programme for the prenatal screening for Down’s syndrome by ultrasonographic nuchal translucency measurement and serum determinations in the first trimester of pregnancy. Ned Tijdschr Geneeskd 2005;149:2795–2799.
  22. Caughey AB, Hopkins LM, Norton ME: Amniocentesis and the difference in the rate of pregnancy Loss. Obstet Gynecol 2006;108:612–616.
  23. Schielen PCJI, Koster MPH, Elvers LH, Loeber JG: Downsyndroom-kansbepaling met de eerstetrimester-combinatietest 2004–2006 (deels 2007). RIVM rapport 230024002/2008.
  24. Wortelboer EJ, Koster MPH, Stoutenbeek Ph, Elvers LH, Loeber JG, Visser GHA, Schielen PCJI: First-trimester Down syndrome screening performance in the Dutch population; how to achieve further improvement? Prenat Diagn 2009;29:588–592.