Letter to the editor: Regarding 'Noninvasive prenatal testing: A new standard of care?'

TO THE EDITOR:

The article “Noninvasive prenatal testing: A new standard of care?” [September 2014 Contemporary OB/GYN] covered the important topic of noninvasive prenatal testing (NIPT) in ob/gyn practice today, but contained factual inaccuracies, omitted data, and conveyed a general confusion regarding the overall technology used today.

Specifically, the authors use the term massively parallel genomic sequencing (MPGS) throughout the document, a term that confuses next generation sequencing and massively parallel sequencing. Today, there are two approaches to NIPT: whole genome sequencing (WGS) and targeted sequencing. Both approaches use massively parallel sequencing. WGS is used in the verifi^® prenatal test and MaterniT21; targeted sequencing in Panorama and Harmony. While targeted sequencing requires less DNA, the assay failure rate is substantially higher.^1-5

As the industry quickly evolves to improve both speed and performance, the table used in the article was dated 2013. Importantly for the verifi^® prenatal test, time to report is 2-4 days, the fastest time in the industry. In addition, while the authors note the sensitivity and specificity as well as range of testing for other tests, the facts regarding the verifi^® prenatal test were not included. Providing that information for your readers, in clinical experience with more than 34,000 verifi^® tests, observed specificity was 99.79% and observed sensitivity 98.89% for trisomies 21, 18 and 13 taken together.⁶ To clarify the scope, the verifi^® test detects trisomy 21, 18 and 13, and sex chromosome aneuploidies (Turner syndrome, Jacobs syndrome, Klinefelter syndrome and triple X).

Finally, important peer-reviewed publications demonstrating the performance of the verifi^® test in both all-risk and high-risk populations were not footnoted within the article, and provide critical information regarding the inclusion of NIPT into ob/gyn practice today, and have been published in major medical journals including TheNew England Journal of Medicine.^7,8

While we appreciate the coverage of prenatal testing, we believe it is critically important to present updated information for all testing options to enable optimal patient care today.

References

1. McCullough RM, Almasri EA, Guan X, et al. Non-invasive prenatal chromosomal aneuploidy testing -clinical experience: 100,000 clinical samples. 2014;PLoS ONE 9(10) e109173.

2. Norton ME, 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. 2012;207(2):137.e1-8.

3. Nicolaides KH, Syngelaki A, Ashoor G, Birdir C, Touzet G. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol. 2012;207(5):374.e1-6.

4. 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. 2014;124(2 Pt 1):210–218.

5. Dar P, Curnow KJ, Gross SJ et al. Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing. Am J Obstet Gynecol. 2014;211(5):527.e1-527.e17.

6. Bhatt S, et al. Clinical laboratory experience with noninvasive prenatal testing:  update on clinically relevant metrics. Poster presented at 2014 International Congress on Early Prenatal Diagnosis, Brisbane, Australia.

7. Bianchi DW, Parker RL, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014;370(9):799–808.

8. Bianchi DW, Platt LD, Goldberg JD, Abuhamad AZ, Sehnert AJ, Rava RP; MatErnal BLood IS Source to Accurately diagnose fetal aneuploidy (MELISSA) Study Group. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol. 2012;119(5):890–901.

Vance K. Vanier, MD

Reproductive and Genetic Health

Illumina

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IN REPLY:

Dear Dr. Vanier:

Thank you for your response to our September article, “Noninvasive prenatal testing: A new standard of care?” Non-invasive prenatal testing (NIPT) is becoming an important part of ob/gyn practice and we have really enjoyed hearing comments and questions from our readers. With that said, it is important to recognize that the goal of this article was to serve as an introduction to the concept of NIPT and the available technologies. We understand that as a consequence of the brevity of the article that we were not able to fully describe each technology in breadth and depth. As such, we appreciate you taking the time to identify evidence-based references for our readers and we will surely pass them along through our online resources.

Thank you again for response and for your readership.

Brian A. Levine, MD