Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases

Journal name:
Genetics in Medicine
(2015)
Volume:
17,
Pages:
234–236
DOI:
doi:10.1038/gim.2014.92
Received
Accepted
Published online

Abstract

Purpose:

Recent published studies have demonstrated the incremental value of the use of cell-free DNA for noninvasive prenatal testing with 100% sensitivity for trisomies 21 and 18 and a specificity of ≥99.7% for both. Data presented by two independent groups suggesting positive results by noninvasive prenatal testing were not confirmed by cytogenetic studies.

Methods:

Concordance of results among cases with noninvasive prenatal testing referred for cytogenetic prenatal and/or postnatal studies by karyotyping, fluorescence in situ hybridization, and/or oligo–single-nucleotide polymorphism microarray was evaluated for 109 consecutive specimens.

Results:

Cytogenetic results were positive for trisomy 21 in 38 of the 41 noninvasive prenatal testing–positive cases (true-positive rate: 93%) and for trisomy 18 in 16 of the 25 noninvasive prenatal testing–positive cases (true-positive rate: 64%). The true-positive rate was only 44% (7/16 cases) for trisomy 13 and 38% (6/16 cases) for sex chromosome aneuploidy.

Conclusion:

These findings raise concerns about the limitations of noninvasive prenatal testing and the need for analysis of a larger number of false-positive cases to provide true positive predictive values for noninvasive testing and to search for potential biological or technical causes. Our data suggest the need for a careful interpretation of noninvasive prenatal testing results and cautious transmission of the same to providers and patients.

Genet Med 17 3, 234–236.

Keywords:

false positive; noninvasive prenatal testing; positive predictive value; sensitivity; specificity

References

  1. Bianchi DW, Parker RL, Wentworth J, et al.; CARE Study Group. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med 2014;370:799808.
  2. Choy KW, Kwok KY, Lau ET, et al. Discordant karyotype results among non-invasive prenatal screening positive cases. In: The Shifting Landscape of Genetic Testing: Approaches and Success Stories, Platform Session, Abstract #19, American Society of Human Genetics 2013 Annual Meeting, Boston, MA, USA, 2013.
  3. Meck JM, Dugan EK, Aviram A, et al. Non-invasive prenatal screening: a cytogenetic perspective. In: Oral Platform Presentations: Cytogenetics, Abstract #17, American College of Medical Genetics and Genomics 2014 Annual Meeting, Nashville, Tennessee, USA, 2014.
  4. Lutgendorf MA, Stoll KA, Knutzen DM, Foglia LM. Noninvasive prenatal testing: limitations and unanswered questions. Genet Med 2014;16:281285.
  5. Gardner RJ, Sutherland GR, Shaffer LG. Chromosome Abnormalities and Genetic Counseling. 4th edn. Oxford University Press: New York, 2012.

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Author information

Affiliations

  1. Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA

    • Jia-Chi Wang,
    • Trilochan Sahoo,
    • Kimberly A. Kopita,
    • Leslie Ross &
    • Charles M. Strom
  2. Current affiliation: CombiMatrix, Irvine, California, USA

    • Trilochan Sahoo
  3. Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, Chantilly, Virginia, USA

    • Steven Schonberg &
    • Kyla Patek

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