Noninvasive Prenatal Testing (NIPT) is a new test which uses cell-free fetal DNA of placental origin in maternal serum to screen for fetal aneuploidy (trisomy 21, trisomy 18, trisomy 13 and monosomy X).
In the past two 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.
NIPT uptake in other countries has been extremely rapid and it is now being commercially offered in Australia and New Zealand by overseas-based laboratories. At present, maternal serum screening using NIPT is costly and time consuming (taking approximately 10-14 days to return results).
The clinical applicability and test utility are currently evolving. Specifically it has not been validated in low-risk populations and in multiple pregnancy.
NIPT should not be routinely offered to low-risk women or in multiple pregnancy as it has not been sufficiently evaluated in these groups. Its use as a primary screening modality in the general pregnant population requires more clinical and economic evaluation. This situation may change in the future with the results from ongoing studies and the expected decline in the price of NIPT.
At this stage, NIPT is a screening, not a diagnostic test and a positive NIPT test result still requires the detail and precision of the genetic information available via amniocentesis or chorionic villus sampling.
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. Pre-test counselling should include a discussion on the limitations of the test, including its inability to detect atypical chromosome abnormalities. All women with an abnormal result on NIPT should have genetic counseling and be offered invasive testing for confirmation of the diagnosis.
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.
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.
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.
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