Non-invasive prenatal test

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The acronyms NIPT or NIPD stand for non-invasive prenatal test and non-invasive prenatal diagnosis, respectively . These procedures use a (small) blood sample from the pregnant woman to identify genetic diseases in the fetus long before the birth . In current practice, a search is only made for the most frequent chromosome deviations in the child, which can be determined with a very high degree of certainty. The venipuncture in the mother is considered here as " non-invasive ", in contrast to procedures such as amniocentesis or placenta puncture . The latter are being avoided more and more because they are a burden to pregnant women and because 0.3 to 1% of such interventions lead to a miscarriage (as of 2014).

requirement

The NIPT method is based on the discovery that cell-free DNA fragments ( cfDNA ) from the entire genome of the fetus float in the bloodstream of pregnant women .

Constant remodeling processes are part of fetal growth. This is accompanied by programmed cell death , which breaks the cell nuclei and breaks up the DNA of the chromosomes. Even the embryonic erythrocytes give an example because they keep the nucleus. The fetal DNA fragments are cell free ( cfDNA ) and short so that they can cross the placental barrier and enter the mother's bloodstream. From the tenth week of pregnancy, the proportion of fetal DNA is sufficient to carry out a meaningful NIPT from a blood sample from the mother.

method

A blood sample from the mother is sufficient to carry out an NIPT.

There are three test procedures available in Germany in 2014:

  1. Whole Genome Sequencing (PrenaTest®),
  2. Digital Analysis of selected regions (DANSR) method (Harmony Test®) and
  3. Single Nucleotide Polymorphisms (SNPs) (Panorama Test®).

The tests analyze and recognize the child and maternal DNA chromosome fragments, assign them to the respective chromosomes and count them. This is done either by comparing it with maternal DNA portions or by detecting small sections of DNA that are characteristic of certain chromosomes.

If chromosomes or chromosome parts are absent or in excess, one speaks of chromosome deviations. A well-known form of chromosomal abnormality is trisomy, in which a particular chromosome is present three times instead of twice. The most common trisomies are trisomies 13 , 18, and 21 . Trisomy 21 leads to Down's syndrome and is the most common numerical chromosomal disorder. Trisomy 18 (" Edwards syndrome ") and trisomy 13 (" Pätau syndrome ") can be born alive, but usually have a life expectancy of less than twelve months.

The test methods can detect a trisomy 21 with a detection rate (ER or sensitivity or true positive rate ) of over 99%. For trisomy 18, the ER is between 98 and 100%, depending on the test method. Depending on the test procedure, the ER is between 80 and over 99% for trisomy 13.

The false positive rate (FPR) indicates the probability of a false positive . The FPR for all three trisomies is between 0.05 and 0.9%, depending on the test method.

costs

Germany

The examination costs in June 2017 were between 199 and 399 euros for the PrenaTest® or Harmony Test®, depending on the test method and scope of diagnostics. In May 2014 the examinations cost between 485 and 925 euros, depending on the test method.

Austria

Indirect information: Three-country recommendation for the use of non-invasive prenatal tests (NIPT): Analysis of cell-free DNA (cfDNA) in maternal blood for screening for fetal chromosomal disorders in clinical practice.

Switzerland

If the risk of trisomy 13, 18 or 21 is higher than 1: 1000, determined in the first trimester test (ETT), since 2015 the compulsory health insurance has covered the costs for a NIPT. The costs are around 700 to 1000 francs (2018).

Per arguments

The three most common “fetal chromosome abnormalities” can be “relatively safely determined or excluded ” by taking a blood sample without risk .

concerns

The test procedures only examine selected chromosomes for abnormalities. Rarely occurring mosaic forms, the lack of fragments and the numerical deviations of other chromosomes than 13, 18, 21 cannot be recognized. Some of the NIPT tests also examine chromosomes X and Y, X0 (Turner syndrome), and triploidy. Detection of the latter anomalies is possible, but much less precise than for trisomies.

If the proportion of child DNA in the maternal blood falls below a certain value, the test can no longer be evaluated correctly. “In 3 to 4 percent of the samples”, “no result can be achieved” or “a new blood sample must be taken”.

It should also be borne in mind that a “normal” test result cannot guarantee a completely healthy child, as trisomies only make up about 10% of the children who are suspicious at birth.

Individual evidence

  1. Anupama Srinivasan et al. a .: Noninvasive detection of fetal subchromosome abnormalities via deep sequencing of maternal plasma. In: American J Human Genetics 92, 2, 2013: 167–176 doi: 10.1016 / j.ajhg.2012.12.006 ( full text ).
  2. Trisomies: blood test is superior to conventional screening in study. aerzteblatt.de, June 7, 2013; accessed on September 15, 2016.
  3. a b c d e f g h i j k Angelika Dohr, Vera Bramkamp: Non-invasive prenatal tests NIPT. (PDF; 159 kB) In: pro familiamedizin, No. 2 May 2014, accessed on 15 August 2016 .
  4. ^ YM Dennis Lo: Fetal DNA in maternal plasma: Biology and diagnostic applications. In: Clin Chem 46, 12, 2000: 1903-1906.
  5. Jump up ↑ Yuk-ming Dennis Lo, N Corbetta, PF Chamberlain, V Rai, IL Sargent, CW Redman, JS Wainscoat: Presence of fetal DNA in maternal plasma and serum. In: Lancet 350, No. 9076, 1997, pp. 485-487. doi: 10.1016 / S0140-6736 (97) 02174-0
  6. P Mandel, P Metais: Les acides nucléiques du plasma sanguin chez l'homme. In: CR Acad Sceances Soc Biol Fil, Paris 142, 1948, pp. 241-243.
  7. D Kraljevic, K Vukojevic, D Karan, B Rajic, J Todorovic, J Miskovic, V Tomic, M Kordic, V Soljic: Proliferation, apoptosis and expression of matrix metalloproteinase-9 in human fetal lung. In: Acta Histochem , 117, 4/5, 2015, pp. 444-450. doi: 10.1016 / j.acthis.2015.02.003 .
  8. ^ MA Helal, Huseyin Mehmet, NS Thomas, Phillip M Cox, DJ Ralph, Rekha Bajoria, Rohit Chatterjee: Ontogeny of human fetal testicular apoptosis during first, second, and third trimesters of pregnancy. In: J Clin Endocrinol Metab , 87, 3, 2002, pp. 1189-1193. DOI: 10.1210 / jcem.87.3.7836 .
  9. Kathleen E McGrath, Jenna M Frame, James Palis: Early hematopoiesis and macrophage development. In: Semin Immunol 27, 6, 2015, pp. 379–387, PMC 4856633 (free full text)
  10. Tobias Franz Hermle: Programmed cell death of fetal erythrocytes. Doctoral thesis at the Med Fak, University of Tübingen 2007. uni-tuebingen.de (PDF)
  11. Cenata website. Roche Diagnostics and Cenata GmbH, July 6, 2017, accessed on July 6, 2017 .
  12. Lifecodexx website. LifeCodexx AG, June 6, 2017, accessed June 6, 2017 .
  13. ^ Ulrich Bahnsen: Prenatal diagnosis: Mother's blood, baby's genes. New tests provide even more data about the genetic makeup of the fetus. Do parents really want to know everything? In: Die Zeit , No. 6/2013.
  14. M Schmid, P Klaritsch, W doctor, T Burkhardt, HC Duba, M Häusler, E Hafner, U Lang, B Pertl, M Speicher, H Steiner, S Tercanli, E Merz, KS Heling, B Eiben: Cell-free DNA testing for fetal chromosomal anomalies in clinical practice: Austrian-German-Swiss recommendations for non-invasive prenatal tests (NIPT). In: Ultrasound Med 36, 5, 2015, pp. 507-510. doi: 10.1055 / s-0035-1553804 .
  15. Health insurance reimburses non-invasive trisomy blood tests. Swissmom
  16. The first trimester test . Swissmom
  17. NIPT (non-invasive prenatal test). Swissmom