For the NIPTIFY test, the doctor, midwife or nurse takes a blood sample from the pregnant woman and delivers it to the Precision Medicine Laboratory in Tartu, Estonia. In the laboratory, the blood plasma is extracted and the cell-free DNA is purified. The cell-free DNA contains both maternal and foetal origin cell-free DNA. The DNA library is then prepared and analysed by Illumina technology sequencing. Data analysis is done by original NIPTmer software and an estimation is given regarding chromosomes 13, 18, 21 and X. The foetal DNA fraction and gender are also determined (gender is only revealed if the family expresses this wish). The results are presented in an analysis report that is sent to the doctor or midwife by e-mail.
Advantages of NIPTIFY
NIPTIFY has been developed in Estonia in collaboration with KU Leuven in Belgium. Belgium and the Netherlands were the first countries in the world to offer state compensated NIPT to all pregnant women in 2017. The tests are performed in university laboratories. NIPTIFY is highly similar to Belgium NIPT method – it uses the same, high quality laboratory standards but data analysis is solved by original NIPTmer software. The software was developed by scientists from the Competence Centre on Health Technologies (Tartu, Estonia), University of Tartu and in collaboration with KU Leuven in Belgium.
The profit from testing is reinvested in R&D and in creating new genetic tests.
In Estonia, NIPT tests are offered by several companies that send samples to foreign laboratories for testing. Thus, blood samples and most of the questionable amount for the test move to foreign biotechnology companies. However, Tervise-TAK offers research-based molecular diagnostics in its laboratory in Estonia. This allows you to maintain and develop the expertise of precision medicine and to provide quality medical services in our own laboratory. The benefits of testing will be directed towards further research and development and the creation of new genetic tests. Thus, every person who has made a NIPTIFY test is able to make a conscious contribution to the development of Estonian science and biotechnology.
NIPTIFY is the most up-to-date screening method for chromosomal diseases
Although NIPT is highly accurate non-invasive prenatal genetic test, it is screening test and need diagnostic confirmation in following reasons:
Studied foetal cell-free DNA has placenta origin. The NIPT results show the risk of chromosomal disease in placental tissue. There is slight theoretical and practical probability that placenta tissue has chromosomal disease but foetus inside it is still healthy.
Foetal cell-free DNA is mixed with maternal DNA. Foetal risk of chromosomal disease is calculated in distant, through maternal DNA sample. Although NIPT methods detect 4-15% foetal origin DNA in mother blood sample, and that is sufficient for reliable analysis, it may theoretically affect the outcome. Therefore the results of NIPT should be confirmed by direct, invasive diagnostic method.
NIPT methods in general may give false-positive or false-negative results in case of mosaicism. Mosaicism may occur in foetus or mother.In general, mosaicism denotes the presence of two or more populations of cells with different number of chromosomes or part of chromosomes in one individual who has developed from a single fertilized egg. In other words, mosaicism may be normal variability in smaller or larger scale if it is not fatal.
NIPTIFY test is not developed to detect sex chromosome anomalies (except Turner syndrome, X0). The test does not detect partial chromosomal copy-number variances, chromosomal microdeletions or microduplications. NIPTIFY is valid only for single pregnancies.
Why NIPT and NIPTIFY are still screening tests?
Like other NIPT tests, NIPTIFY is a high-sensitivity prenatal testing method that evaluates the risk of certain chromosomal diseases occurring in the fetus. However, NIPTIFY is not a diagnostic test as it analyzes fetal health through a pregnant blood sample. The mother and fetal DNA are mixed in the blood sample. However, false-negative or false-positive results are still possible. The test may give false results for a variety of clinical reasons (such as placental mosaic, maternal chromosomal abnormalities, or tumors), or for technical reasons that are not dependent on the pregnant woman.
A low chromosomal risk test does not rule out other developmental abnormalities. NIPTIFY does not provide information on fetal developmental issues (such as brain or heart developmental disorders, spinal developmental disorders, fetal growth disorders, etc.). An ultrasound examination of the fetus is performed to detect such side effects.
Only a NIPTIFY result should not lead to a decision to discontinue pregnancy. In the case of a high chromosomal risk, the result is also confirmed by an invasive method (amniocentesis or chorionic biopsy). Gynecologists emphasize that despite the results of NIPT, national screening, including ultrasound, should be continued.
NIPTIFY significantly improves the quality of fetal screening.
Research behind NIPTIFY test
Bayindir et al. (2015) Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management. Eur J Hum Genet 23(10):1286-93. doi: 10.1038/ejhg.2014.282. Direct link to article.
Sauk et al. (2018) NIPTmer: rapid k-mer-based software package for detection of fetal aneuploidies. Sci Rep. 8(1):5616. doi: 10.1038/s41598-018-23589-8. Direct link to article.
Zhilina et al. (2018) Creating basis for introducing NIPT in the Estonian public health setting. bioRxiv. doi: https://doi.org/10.1101/431924. Direct link to article.