Noninvasive prenatal testing in the general obstetric population: clinical performance and counseling considerations in over 85000 cases


  • P. A. Taneja Illumina, Redwood City, CA, United States
  • H. L. Snyder Illumina, Redwood City, CA, United States
  • E. de Feo Illumina, Redwood City, CA, United States
  • K. M. Kruglyak Illumina, Redwood City, CA, United States



aneuploidy, noninvasive prenatal testing, positive predictive value


The article contains the results of the research, which set two main goals. The first is the determination of the actual indicators of the effectiveness of noninvasive prenatal studies and the development of counseling tools about the predictability of a positive outcome, taking into account certain clinical indicators and the a priori age risk of the mother. The second is the assessment of changes in the clinical and demographic population after the introduction of testing.

Objective: The primary goal of this study was to provide clinically relevant information for appropriate patient counseling.

Method: Demographics and test metrics were reviewed for 86 658 clinical cases. Outcome information was requested for samples reported as aneuploidy detected or suspected for chromosomes 21, 18, or 13; voluntary outcome reporting was encouraged for all discordant outcomes.

Results: Of 86 658 cases, 85 298 (98.4%) met inclusion criteria for result reporting. Of the 1360 (1.6%) cancellations, only 101 (0.1%) were for technical reasons. Average time to result was 3.3 business days. Aneuploidy was detected or suspected in 2142 (2.5%) samples. For aneuploidy detected cases with known clinical outcomes, the overall positive predictive value was 83.5% (608/728); observed positive predictive values for trisomies 21, 18, and 13 ranged from 50.0 to 92.8%. As individual positive predictive values are determined by a patient’s prior risk, we developed a chart for counseling patients on positive predictive value based on maternal age.

Conclusion: This large-scale report reinforces that noninvasive prenatal testing is a highly accurate screen for fetal aneuploidy in the general obstetric population. Test improvements have facilitated a reduction in failure rates, time to result, and borderline results/unclassifiable results. We have developed a positive predictive value counseling tool to ensure appropriate patient education, counseling, and clinical utilization.

Funding sources: This study was funded by Illumina.

Conflicts of interest: Authors of article are employees of and hold equity in Illumina.


  1. Norton, M.E., Brar, H., Weiss, J., et al. “Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18.” Am J Obstet Gynecol 207.2 (2012):137.e1–8.
  2. Palomaki, G.E., Deciu, C., Kloza, E.M., et al. “DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study.” Genet Med 14.3 (2012): 296–305.
  3. Palomaki, G.E., Kloza, E.M., Lambert-Messerlian, G.M., et al. “DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study.” Genet Med 13.11 (2011): 913–20.
  4. Bianchi, D.W., Platt, L.D., Goldberg, J.D., et al. “Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing.” Obstet Gynecol 119.5 (2012): 890–901.
  5. Devers, P.L., Cronister, A., Ormond, K.E., et al. “Noninvasive prenatal testing/noninvasive prenatal diagnosis: the position of the National Society of Genetic Counselors.” J Genet Couns 22.3 (2013): 291–5.
  6. Gregg, A.R., Gross, S.J., Best, R.G., et al. “ACMG statement on noninvasive prenatal screening for fetal aneuploidy.” Genet Med 15.5 (2013): 395–8.
  7. Soothill, P.W., Lo, Y.M.D. “Scientific Impact Paper No. 15: non-invasive prenatal testing for chromosomal abnormality using maternal plasma DNA.” Royal Coll Obstet Gynaecol (2014): 1–14.
  8. Committee Opinion No. 640. “Cell-free DNA screening for fetal aneuploidy.” Obstet Gynecol 126.3 (2015): e31–e7.
  9. Benn, P., Borrell, A., Chiu, R.W., et al. “Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis.” Prenat Diagn 35.8 (2015): 725–34.
  10. Futch, T., Spinosa, J., Bhatt, S., et al. “Initial clinical laboratory experience in noninvasive prenatal testing for fetal aneuploidy from maternal plasma DNA samples.” Prenat Diagn 33.6 (2013): 569–74.
  11. Bianchi, D.W., Parsa, S., Bhatt, S., et al. “Fetal sex chromosome testing by maternal plasma DNA sequencing: clinical laboratory experience and biology.” Obstet Gynecol 125.2 (2015): 375–82.
  12. Dar, P., Curnow, K.J., Gross, S.J., et al. “Clinical experience and follow-up with large scale single-nucleotide polymorphism-based non-invasive prenatal aneuploidy testing.” Am J Obstet Gynecol 211.5 (2014): 527.e1–17.
  13. McCullough, R.M., Almasri, E.A., Guan, X., et al. “Non-invasive prenatal chromosomal aneuploidy testing– clinical experience: 100,000 clinical samples.” PLoS One 9.10 (2014): e109173.
  14. Beamon, C.J., Hardisty, E.E., Harris, S.C., et al. “A single center’s experience with noninvasive prenatal testing.” Genet Med 16.9 (2014): 681–7.
  15. Fairbrother, G., Johnson, S., Musci, T.J., et al. “Clinical experience of noninvasive prenatal testing with cell-free DNA for fetal trisomies 21, 18, and 13, in a general screening population.” Prenat Diagn 33.6 (2013): 580–3.
  16. Wang, J.C., Sahoo, T., Schonberg, S., et al. “Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases.” Genet Med 17.3 (2014): 234–6.
  17. Willems, P.J., Dierickx, H., Vandenakker, E., et al. “The first 3,000 noninvasive prenatal tests (NIPT) with the harmony test in Belgium and the Netherlands.” Facts Views Vis Obgyn 6.1 (2014): 7–12.
  18. Wax, J.R., Cartin, A., Chard, R., et al. “Noninvasive prenatal testing: impact on genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection.” J Clin Ultrasound 43.1 (2015): 1–6.
  19. National Society of Genetic Counselors. “Abnormal non-invasive prenatal testing results: what do they mean? 2015.” Available from: [ invasive-prenatal-testing-results], last accessed Apr 3, 2017.
  20. Gardner, R.J.M., Sutherland, G.R., Shaffer, L.G. Parental age counseling and screening for fetal trisomy. In Chromosome abnormalities and genetic counseling, 4th ed. New York, NY. Oxford University Press (2012): 403–16.
  21. Curnow, K.J., Wilkins-Haug, L., Ryan, A., et al. “Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism-based noninvasive prenatal test.” Am J Obstet Gynecol 212.1 (2015): 79.e1–9.
  22. American College of Obstetricians and Gynecologists. “Committee Opinion No. 545: noninvasive prenatal testing for fetal aneuploidy.” Obstet Gynecol 120.6 (2012): 1532–4.
  23. Pergament, E., Cuckle, H., Zimmermann, B., et al. “Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort.” Obstet Gynecol 124 2 Pt 1 (2014): 210–18.
  24. Norton, M.E., Jacobsson, B., Swamy, G.K., et al. “Cell-free DNA analysis for noninvasive examination of trisomy.” N Engl J Med 372 (2015): 1589–97.
  25. Bianchi, D.W., Parker, R.L., Wentworth, J., et al. “DNA sequencing versus standard prenatal aneuploidy screening.” N Engl J Med 370.9 (2014): 799–808.
  26. Grati, F.R., Malvestiti, F., Ferreira, J.C., et al. “Fetoplacental mosaicism: potential implications for falsepositive and false-negative noninvasive prenatal screening results.” Genet Med 16.8 (2014): 620–4.
  27. Society for Maternal Fetal Medicine. “Cell free DNA screening is not a simple blood test 2014.” Available from: [ dna-screening-is-not-a-simple-blood-test], last accessed Apr 3, 2017.
  28. Benn, P., Borell, A., Chiu, R., et al. “Position statement from the Aneuploidy Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis.” Prenat Diagn 33.7 (2013): 622–9.
  29. Benn, P., Borrell, A., Cuckle, H., et al. “Prenatal detection of Down syndrome using massively parallel sequencing (MPS): a rapid response statement from a committee on behalf of the Board of the International Society for Prenatal Diagnosis, 24 October 2011.” Prenat Diagn 32.1 (2012): 1–2.



How to Cite

Taneja, P. A., Snyder, H. L., de Feo, E., & Kruglyak, K. M. (2017). Noninvasive prenatal testing in the general obstetric population: clinical performance and counseling considerations in over 85000 cases. REPRODUCTIVE ENDOCRINOLOGY, (34), 89–94.



Laboratory diagnosis