Currently, there are three major commercially-available cfDNA NIPTs for detection of aneuploidy:
MaterniT21 PLUS test, developed and validated by Sequenom CMM, is a laboratory-developed test (LDT) that analyzes circulating cell-free DNA extracted from a maternal blood sample. This test is offered by Sequenom Center for Molecular Medicine and utilizes the MPSS technology to identify increased numbers of chromosomes. In the test, circulating cell-free DNA is purified from maternal plasma and the DNA is analyzed for chromosomal material and converted into a genomic DNA library for the determination of chromosome 21, 18, 13 and Y representation based on massively parallel DNA sequencing. The MaterniT21 Plus test has a reported performance characteristics of 99.1% sensitivity and 99.9% specificity for the detection of Down syndrome trisomy. Test results are reported as "negative" or "positive" for trisomies.
Verifi™ Prenatal Test
This test, offered by Verinata Health Inc., also utilizes MPSS technology. Verifi™ Prenatal Test uses a normalized chromosome value (NCV) calculation for each chromosome tested. This NCV calculation removes variation within and between sequencing to optimize the test precision. Test results are reported as “no aneuploidy detected”, “aneuploidy suspected" for borderline cases, and “aneuploidy detected” for the respective chromosome tested. The test claims to have a >99.9% sensitivity and 99.8% specificity for detection of Down syndrome.
Harmony Prenatal Test™
This test is offered by Ariosa Diagnostics and utilizes directed DNA analysis sequencing of specific cell-free DNA (cfDNA) fragments using digital analysis of selected regions (DANSR). It is a laboratory-developed test that analyzes cfDNA in maternal blood. As with other cfDNA tests, the Harmony prenatal test is best performed anytime after the tenthweek of pregnancy. Using the DANSR methodology, the Harmony Prenatal Test™ analyzes sequencing results of selected, targeted genomic regions on chromosome 21 (for Down syndrome assessment). The test results will yield an assessment of the risk for trisomy 21. Using a specific algorithm, the test results are reported out as an individualized risk for each trisomy. The test claims to have a >99% sensitivity and 99% specificity for Down syndrome detection.
All of the aforementioned cfDNA tests are considered laboratory-developed tests and are not FDA-approved. Moreover, it must be stressed that at this time the cfDNA tests are not considered diagnostic and a “low-risk” test result does not suggest an unaffected pregnancy while a “high-risk” test result still requires an invasive confirmatory test.
In addition, all cfDNA tests are typically intended for use in women 18 years or older with a singleton pregnancy at a minimum of 10 weeks gestation and who have been determined by their physician to be at risk for fetal trisomy. Such risks include advanced maternal age, positive results of prenatal screening tests (serum and/or NT ultrasound), the presence of ultrasound soft or hard markers, previous family history of genetic disorders, or a previous affected pregnancy for fetal aneuploidy.
It is important to remember that at present, invasive prenatal diagnostic tests, such as CVS and amniocentesis, should be considered the most accurate and comprehensive way to assess fetal abnormalities.