Donald School Journal of Ultrasound in Obstetrics and Gynecology

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VOLUME 7 , ISSUE 2 ( April-June, 2013 ) > List of Articles


The End of Amniocentesis? From TriTest to PrenaTestTM

Franco Borruto, Alain Treisser, Skander Ben Abdelkrim, Ciro Comparetto

Keywords : Amniocentesis,Cell-free fetal DNA,First trimester screening,Pregnancy,Prenatal diagnosis

Citation Information : Borruto F, Treisser A, Abdelkrim SB, Comparetto C. The End of Amniocentesis? From TriTest to PrenaTestTM. Donald School J Ultrasound Obstet Gynecol 2013; 7 (2):213-218.

DOI: 10.5005/jp-journals-10009-1286

License: CC BY-NC 4.0

Published Online: 01-12-2013

Copyright Statement:  Copyright © 2013; The Author(s).



The rapid development in molecular biological technologies makes it possible to screen and to diagnosis thousands of genetic conditions, mutations and also predispositions to chronic diseases or traits, either prenatally or after birth. Clinical application of noninvasive prenatal diagnosis (NIPD) using fetal deoxyribonucleic acid (DNA) in maternal plasma has become a reality. We review the latest developments in screening and diagnosis of chromosomal diseases and a new noninvasive method of prenatal diagnosis.

Materials and methods

PrenaTest™ (LifeCodexx AG, Konstanz, Germany, patented and licensed by Sequenom Inc., San Diego, California, USA) is a molecular genetic test that can detect fetal trisomy 21 with a high precision level from maternal blood using new generation multiplex genome sequencing techniques. The test is based on the analysis of extracellular fetal DNA measured in the blood of pregnant women: Cell-free fetal DNA (cffDNA).


In the case of trisomy 21, there were found 105 specific fragments of chromosome 21, 15 of fetal origin and 90 of maternal origin. The validity of PrenaTest™ has been demonstrated by many tests (427 cases), and the sensitivity was 95%, with a false negative rate of 5% and a specificity of 99.5%. Anyway, an additional ultrasound can always be performed to assess fetal morphology.


The arrival of the molecular genetic era also leads to many new ethical, social and medicolegal problems and dilemmas that obstetricians will have to face in the near future. There is an urgent need for the development of a new model for provision of genetic screening and diagnosis.

How to cite this article

Borruto F, Treisser A, Abdelkrim SB, Comparetto C. The End of Amniocentesis? From TriTest to PrenaTestTM. Donald School J Ultrasound Obstet Gynecol 2013;7(2):213-218.

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  1. First trimester Down syndrome screening: Public health implications. Semin Perinatol 2005;29:267-71.
  2. Genetic screening and diagnosis. Curr Opin Obstet Gynecol 2005;17:163-69.
  3. Diagnosis of a trisomy 21 in the first pregnancy trimester. Value of trophoblast sampling. J Gynecol Obstet Biol Reprod 1985;14:583-85.
  4. Role of ultrasound evaluation of nuchal translucency in prenatal diagnosis. Clin Exp Obstet Gynecol 2002;29:235-41.
  5. Procedure-related complications of amniocentesis and chorionic villous sampling. A systematic review. Obstet Gynecol 2007;110:687-94.
  6. Down syndrome: Genetics, screening, and health. In: Jelinek D, Dvorak G (Eds). Handbook of Down syndrome research. New York: Nova Science Publishers 2009:1-54.
  7. Prenatal diagnosis for chromosome abnormalities: Past, present and future. Pathol Biol (Paris) 2003;5:156-60.
  8. Real-time PCR for prenatal and preimplantation genetic diagnosis of monogenic diseases. Mol Aspects Med 2006;27:176-91.
  9. Fetal DNA in maternal plasma: Biology and diagnostic applications. Clin Chem 2000;46:1903-06.
  10. Digital PCR for the molecular detection of fetal chromosomal aneuploidy. Proc Natl Acad Sci USA 2007;104:13116-21.
  11. Digital PCR for noninvasive detection of aneuploidy: Power analysis equations for feasibility. Fetal Diagn Ther 2012;31: 244-47.
  12. Détection de la trisomie 21 par l’étude de l'ADN. J Imm Biol Spec 2008;23:1-10.
  13. Noninvasive prenatal testing for aneuploidy-ready for prime time? Am J Obstet Gynecol 2012;206:269-75.
  14. Noninvasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: Large scale validity study. BMJ 2011;342:c7401.
  15. NonInvasive chromosomal evaluation (NICE) study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012;207:137.e1-8.
  16. 44 single-nucleotide polymorphisms expressed by placental RNA: Assessment for use in noninvasive prenatal diagnosis of trisomy 21. Clin Chem 2007;53:2223-24.
  17. A noninvasive test for prenatal diagnosis based on fetal DNA present in maternal blood: A preliminary study. Lancet 2007;369:474-81.
  18. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci USA 2008;105: 20458-63.
  19. Systematic search for placental DNA-methylation markers on chromosome 21. Toward a maternal plasma-based epigenetic test for fetal trisomy 21. Clin Chem 2008;54:500-11.
  20. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci USA 2008;105:16266-71.
  21. Noninvasive prenatal detection of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis: A review of the current state of the art. BJOG 2009;116:152-57.
  22. Noninvasive prenatal detection of trisomy 21 by an epigeneticgenetic chromosome-dosage approach. Clin Chem 2010;56: 90-98.
  23. Maternal plasma DNA analysis with massively parallel sequencing by ligation for noninvasive prenatal diagnosis of trisomy 21. Clin Chem 2010;56:459-63.
  24. Simultaneous detection of trisomies 13, 18 and 21 with multiplex ligation-dependent probe amplification-based real-time PCR. Clin Chem 2010;56: 1451-59.
  25. Targeted massively parallel sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles. Clin Chem 2011;57:92-101.
  26. Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood. Clin Chem 2011;57:1042-49.
  27. Noninvasive prenatal diagnosis of a case of Down syndrome due to robertsonian translocation by massively parallel sequencing of maternal plasma DNA. Clin Chem 2011;57: 917-19.
  28. 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.e1-11.
  29. Diagnostic accuracy of noninvasive detection of fetal trisomy 21 in maternal blood: A systematic review. Fetal Diagn Ther 2012;31:81-86.
  30. Refining noninvasive prenatal diagnosis with singlemolecule next-generation sequencing. Clin Chem 2012;58: 657-58.
  31. Noninvasive prenatal diagnosis empowered by high-throughput sequencing. Prenat Diagn 2012;32:401-06.
  32. Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy. Prenat Diagn 2012;32: 3-9.
  33. Noninvasive prenatal diagnostics by maternal plasma DNA sequencing. Expert Rev Mol Diagn 2012;12: 445-47.
  34. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: An international collaborative study. Genet Med 2012;14:296-305.
  35. Noninvasive fetal trisomy 21 detection using chromosome-selective sequencing: A variation of the molecular counting theme. Expert Rev Mol Diagn 2012;12:329-31.
  36. From prenatal genomic diagnosis to fetal personalized medicine: Progress and challenges. Nature Med 2012;18:1041-51.
  37. Fetal fraction in maternal plasma cell-free DNA at 11 to 13 weeks’ gestation: Relation to maternal and fetal characteristics. Ultrasound Obstet Gynecol 2013;41:26-32.
  38. Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: Impact of maternal age and prenatal screening. Eur J Hum Genet 2013;21:27-33.
  39. La fin de l'amniocentèse: Du tritest au Prénatest. Proceedings of the 42e Journeés Nationales de la Société Francaise de Médecine Périnatale (SFMP) Rev Méd Périnat 2012;4:S130.
  40. Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21. Nature Medicine 2011;17:510-14.
  41. Noninvasive prenatal measurement of the fetal genome. Nature 2012;487:320-24.
  42. Noninvasive prenatal detection and selective analysis of cellfree DNA obtained from maternal blood: Evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012;206:319.e1-9.
  43. Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X and Y, using targeted sequencing of polymorphic loci. Prenat Diagn 2012;32:1233-41.
  44. Technical concerns about immunoprecipitation of methylated fetal DNA for noninvasive trisomy 21 diagnosis. Nature Med 2012;18:1327-28.
  45. Clinical utility and cost of noninvasive prenatal testing with cfDNA analysis in high-risk women based on a US population. J Matern Fetal Neonatal Med 2013 Mar 6. [Epub ahead of print].
  46. Prenatal diagnosis: Types and techniques. Early Hum Dev 2012;88:3-8.
  47. Noninvasive prenatal diagnosis of single-gene disorders from maternal blood. Gene 2012;504:144-49.
  48. Ethical aspects arising from noninvasive fetal diagnosis. Semin Fetal Neonatal Med 2008;13:103-08.
  49. Noninvasive fetal sex determination: Impact on clinical practice. Semin Fetal Neonatal Med 2008;13:69-75.
  50. Noninvasive prenatal diagnostic test accuracy for fetal sex using cell-free DNA a review and meta-analysis. BMC Res Notes 2012;5:476.
  51. Integrating stakeholder perspectives into the translation of cell-free fetal DNA testing for aneuploidy. Genome Med 2012;4:49.
  52. The use of cell-free fetal nucleic acids in maternal blood for noninvasive prenatal diagnosis. Hum Reprod Update 2009;15:139-51.
  53. Noninvasive prenatal diagnosis of single gene disorders: How close are we? Semin Fetal Neonatal Med 2008;13:76-83.
  54. Current status in noninvasive prenatal detection of Down syndrome, trisomy 18, and trisomy 13 using cell-free DNA in maternal plasma. J Obstet Gynaecol Can 2013;35:177-81.
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