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    Noninvasive prenatal testing: A new standard of care?


    Option 4: Panorama Prenatal Test

    In 2012, California-based Natera released the Panorama Prenatal Test, which is the only test to analyze single nucleotide polymorphisms (SNP). The advantage of using a SNP-based technology is that it requires less cfDNA and, unlike other noninvasive methods, can detect genetic abnormalities such as short insertions/deletions/aberrations that cause Mendelian disorders.

    At the time of this article, Panorama is able to detect trisomies 21, 18, and 13 as well as 45,X (Turner syndrome). Studies have shown that the test has high sensitivity and specificity in high-risk and low-risk cohorts (>99% detection rate for trisomies 21, 18, and 13 and a >90% detection rate for 45,X).15,16

    It is important to note, however, that while SNP-based analyses are powerful tools, they have discrete limitations. Because SNP-based sequencing utilizes a reference sample of the maternal blood to distinguish maternal from fetal DNA, although such cases are rare, Panorama cannot be used for pregnancies conceived with an egg donor or those that used a gestational carrier, and cannot be performed on women who have received a bone marrow transplant.


    Taking all of these advances together, the field of NIPT is incredibly exciting. In less than 2 years, 4 distinct robust technological tools have been added to the obstetrical armamentarium. Each tool has its strength and weakness, and it is important to know which tool to use for which clinical scenario (twins, singleton, donor egg, etc.).

    We also need to recognize that while NIPT is widely available and likely will soon become the standard of care, as obstetricians and gynecologists, we still have to practice within the guidelines and recommendations of the American College of Obstetricians and Gynecologists. The 2012 ACOG Committee Opinion on Noninvasive Prenatal Testing for Fetal Aneuploidy cautioned that the use of cfDNA testing should be an active, informed choice and not part of routine prenatal laboratory testing (Table).


    Lastly, we will all have to learn how to best utilize the new information that this testing generates. For many of us, NIPT will forever change how we practice medicine. Many of us have become facile in using technology such as ultrasound to help identify potential pregnancy complications. But in the recently released International Society of Ultrasound in Obstetrics and Gynecology consensus statement on the impact of NIPT on prenatal ultrasound practice, the authors caution that “so-called ‘genetic sonogram,’” which includes looking for soft markers of trisomy 21, should not be performed in women with a normal NIPT result due to ultrasound’s high false-positive rate and poor positive predictive value.17

    Therefore, as uptake of NIPT increases, we will not only have to learn how and when to use NIPT, but we will also have to unlearn to use many older technologies.


    1. Lo YM, Corbetta N, Chamberlain PF, et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350(9076):485–487.

    2. Lo YM, Tein MS, Lau TK, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet. 1998;62(4):768–775.

    3. Akolekar R, Beta J, Picciarelli G, Ogilvie C, D’Antonio F. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2014. doi: 10.1002/uog.14636.

    4. Bischoff FZ, Nguyen DD, Marquéz-Do D, Moise KJ Jr, Simpson JL, Elias S. Noninvasive determination of fetal RhD status using fetal DNA in maternal serum and PCR. J Soc Gynecol Investig. 1999;6(2):64–69.

    5. 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(42):16266–16271.

    6. Chiu RW, Akolekar R, Zheng YW, et al. Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ. 2011;342:c7401.

    7. Nicolaides KH, Syngelaki A, Gil M, Atanasova V, Markova D. Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Prenat Diagn. 2013;33(6):575–579.

    8. Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF, Canick JA. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med. 2011;13(11):913–920.

    9. Palomaki GE, Deciu C, Kloza EM, 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. 2014;14(3):296–305.

    10. Canick JA, Kloza EM, Lambert-Messerlian GM, et al. DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations. Prenat Diagn. 2012;32(8):730–734.

    11. Verifi Prenatal Test. http://www.verifitest.com/verifi-advantage/. Accessed August 14, 2014.

    12. Ashoor G, Syngelaki A, Wagner M, Birdir C, Nicolaides KH. Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012;206(4):322.e1–5.

    13. Science Daily. Noninvasive method accurately and efficiently detects risk of Down syndrome, researchers say. http://www.sciencedaily.com/releases/2012/02/120221125151.htm. Accessed August 14, 2014.

    14. 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.

    15. Zimmermann B, Hill M, Gemelos G, et al. Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Prenat Diagn. 2012;32(13):1233–1241.

    16. American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol. 2012;120(6):1532–1534.

    17. Salomon LJ, Alfirevic Z, Audibert F, Kagan KO, Yeo G, Raine-Fenning N; ISUOG Clinical Standards Committee. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice. Ultrasound Obstet Gynecol. 2014;44(1):122–123.

    Brian A. Levine, MD, MS, FACOG
    Dr. Levine is Practice Director at the Colorado Center for Reproductive Medicine, New York, New York.
    Dan Goldschlag, MD, FACOG
    Dr. Goldschlag is an assistant professor of Clinical Obstetrics and Gynecology and Assistant Professor of Clinical Reproductive Medicine ...


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