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DNA-based Noninvasive Prenatal Testing for Fetal Aneuploidy

28 April 2015

This College communiqué on DNA-based Noninvasive Prenatal Testing for Fetal Aneuploidy reflects emerging clinical and scientific advances as of the date issued and is subject to change.

Noninvasive Prenatal Testing (NIPT) is a test which uses cell-free fetal DNA of placental origin in maternal serum to screen for fetal aneuploidy.


In the past three years, multiple independent studies have demonstrated the clinical validity of maternal plasma DNA sequencing for the detection of fetal trisomy 21 in high-risk women.1-10 DNA-based NIPT is a highly accurate screening method for trisomy 21 with an overall sensitivity of 99.5% and specificity of 99.8%. 11

However, NIPT is not a diagnostic test and abnormal results still require confirmation with an invasive test such as amniocentesis or CVS.

NIPT is now commercially available in Australia and New Zealand via several overseas-based laboratories. Preliminary estimates indicate that over 2000 Australian women have already chosen to have NIPT since its local introduction in late 2012. All current labs routinely combine testing for trisomy 21 with testing for trisomy 18 and trisomy 13. They also offer optional fetal gender and sex chromosome aneuploidy testing. There are no studies directly comparing the different NIPT assays with each other but published data show similar test performances for trisomy 21 alone. At present, aneuploidy screening with NIPT has significant direct costs to the patient (at least $500-900 at the time of publication) and has a long turn-around time (taking approximately 10-14 days to return results).  There is currently no Medicare funding or private health insurance rebate for this test.

The use of NIPT as an advanced screening test for trisomy 21 in high risk women has been endorsed by several professional bodies.12,13 Data have recently emerged suggesting equal test performance of NIPT as a primary screening test for trisomy 21 in average risk women.14-16 The most appropriate implementation strategy for NIPT in the Australian context is still to be determined.11 Presently, combined first trimester screening with nuchal translucency measurement and serum markers remains an acceptable standard of care in high risk or average risk women. NIPT is an option for those women who are able to self-fund their testing, after appropriate pre-test genetic counselling.

Pre-test counselling should include a discussion on the limitations of the test, including its inability to detect atypical chromosome abnormalities. Pre-test counselling should also include informed decision making regarding the optional testing for fetal gender and sex chromosome aneuploidy. All women with an abnormal result on NIPT should have genetic counseling and be offered invasive testing for confirmation of the diagnosis.

Due to the public awareness of this technology and widespread advertising, many of the consultations regarding NIPT are likely to be initiated by pregnant women themselves. The College does not support direct-to-consumer marketing of prenatal tests for fetal abnormalities, including NIPT. Prenatal screening tests are best implemented in the context of a therapeutic relationship and a comprehensive program that co-ordinates pre-test counselling, testing, post-test interpretation, support during decision-making, and where indicated, follow-up consultations and diagnostic testing.

At present, the College is reviewing and updating its statement on prenatal screening tests for trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and neural tube defects (C-Obs-4), which will address NIPT.

References

  1. Sehnert AJ, B Rhees, D Comstock et al. Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood. Clin Chem 2011; 57: 1042-1049.
  2. Sparks AB, CA Struble, ET Wang et al. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012; 206: 319 e311-319.
  3. Lau TK, MK Chan, PS Lo et al. Clinical utility of noninvasive fetal trisomy (NIFTY) test--early experience. J Matern Fetal Neonatal Med 2012; 25: 1856-1859.
  4. Chiu RW, R Akolekar, YW Zheng et al. Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011; 342: c7401.
  5. Ehrich M, C Deciu, T Zwiefelhofer et al. 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 e201-211.
  6. Palomaki GE, EM Kloza, GM Lambert-Messerlian et al. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med 2011; 13: 913-920.
  7. Bianchi DW, LD Platt, JD Goldberg et al. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol 2012; 119: 890-901.
  8. Ashoor G, A Syngelaki, M Wagner, et al. Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimster detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012; 206: 322.e321-325.
  9. Norton ME, H Brar, J Weiss 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: 137.e131-138.i
  10. Zimmermann B, M Hill, G Gemelos et al. Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Prenat Diagn 2012; 32: 1233-1241.
  11. Hui L & Hyett J. Noninvasive prenatal testing for trisomy 21: Challenges for implementation in Australia. Aust NZ J Obstet Gynaecol 2013; 53(5): 416-24.
  12. Benn P, Borell A, Chiu R IPosition statement from the Aneuploidy Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn 2013; 33(7):622-9.
  13. American College of Obstetricians and Gynecologists. Committee Opinion No. 545. Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol 2012; 120: 1532-4.
  14. Nicolaides KH, Syngelaki A, Ashoor G et al. Noninvasive prenatal testing for fetal trisomies in a routinely screened first trimester population. Am J Obstet Gynecol 2012; 207: 374. e371–376.
  15. Bianchi DW, Parker RL, Wentworth J et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med 2014; 370(9): 799-808.
  16. Lau TK, Cheung SW, Lo, PSS et al. Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center. Ultrasound Obstet Gynaecol 2014; 43: 254-64.

Other suggested reading
RCOG scientific impact paper Non-invasive Prenatal Testing for Chromosomal Abnormality using Maternal Plasma DNA. March 2014.




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