These guidelines are necessary to understand the potentiality and limitations of the NON-INVASIVE PRENATAL TEST (NIPT). In every Informed Consent, these principles summarized here very briefly, will be clarified in an extremely complete and exhaustive way.
- NIPT is a non-diagnostic screening test that analyzes free DNA fragments circulating in maternal blood, called fetal FreeDNA or FfDNA and derived from trophoblast (the cell structure that forms the placenta). In the vast majority of cases, these DNA fragments trace the composition of fetal DNA. NIPT is a screening test that evaluates the risk of the fetus being a carrier of chromosomal anomalies.
- The NIPT was born mainly for the screening of Down syndrome. Over time, new technical elements have been added that have led to the exploration of other chromosomal problems (chromosome 18, 13 and sex aneuploidies), other rare aneuploidies of all the remaining chromosome (karyotype screening or even Kario) and genetics, such as small chromosomal rearrangements (such as microdeletions). All these new aspects of the screening have limits, reported in informed consents, which must be well understood when choosing the exam. Clinical studies are currently being carried out applied to the maternal blood recognition of several fetal monogenic diseases (such as cystic fibrosis, congenital hearing loss, Mediterranean anemia, etc.). Even for these surveys, as for the other investigations, there is no unique scientific consensus and they are not provided for by the Official Guidelines. The application of these latest methodologies, however of extraordinary importance, must be well understood by pregnant women in its diagnostic limits.
- The FetalDNA provides a very recent investigation model called Total Screen FetalDNA, which includes, in a single test, all the best research specified in the previous point and also, on the basis of the most recent and accredited International Scientific Literature, goes to research the gene mutations that today are considered to be responsible for the predisposition to more than half of the preterm birth.
- The current Ministry of Health Guidelines require that all NIPT screening tests be preceded, or accompanied, by a careful ultrasound examination aimed at verifying the presence of fetal anomalies. In this case, the pregnancy should be addressed directly to the invasive prenatal diagnosis (CVS Test and Amniocentesis).
- NIPT presents a very low number of false negatives and a high number of false positives which, in the international literature is reported between 0.1-0.3% of cases.
- It is absolutely recognized by medical science and by the guidelines that the diagnostic certainty is provided exclusively by prenatal invasive diagnosis tests (Amniocentesis and CVS Test). Parents must therefore be well informed that the results of this test do not guarantee full diagnostic accuracy.
- NIPT is a molecular analysis based test using both Next Generation Sequencing and Digital PCR. The existing international literature on such methods of NIPT is so vast that it cannot be fully reported in informed consents. An essay of this will be available to us on request or can be seen on the major international MEDLINE (eg. https://www.ncbi.nlm.nih.gov/pubmed/). They are however authentic for the NIPT procedures, the indications given in the main guidelines in use and that will be indicated below.
- Although NIPT is performed through the use of the most innovative molecular technologies, it is possible that the survey does not give a result and should be repeated. In the literature it is reported that this happens in about 1% of cases. This also occurs when a low percentage of fetal DNA (typically less than 2/4%) is found. In this case, an invasive diagnosis should be performed since the low amount of fetal DNA in maternal blood can indicate an increased risk of chromosomal abnormality.
- The NIPT, according to the International Guidelines, should not be performed, as it does not have any diagnostic value in the case of an ultrasound suspected fetal disease, especially if there is an increase in nuchal translucency (above 3 mm) or appears Hydrops or Hygroma.
- The NIPT, according to the International Guidelines, should not be performed in case of dichorionic twin pregnancy, and in particular in multiple pregnancies. This is because NIPT is unable to distinguish the DNA of twins.
- When the screening test provides a pathological result, this must be confirmed by prenatal invasive diagnosis (Amniocentesis/CVS Test). These procedures will be programmed at our center in Rome in a totally free form, both for the sampling technique and for the genetic examination.
The reporting times vary depending on the type of examination required and may be subject to slippages based on technical problems or the need for further analytical feedback.
Below are the references of the major guidelines and official statements of reference:
- LLGG Position joint statement SIGU and SIEOG 2004 (Proper use of CMA techniques –Chromosomal Microarray Analysis– in prenatal diagnosis).
- LLGG Position joint statement SIGU and SIEOG 2017 (Proper use of CMA techniques –Chromosomal Microarray Analysis– in prenatal diagnosis).
- LLGG Canadian Society “Prenatal genomic microarray and sequencing in canadian medical practice: towards consensus” (April 2015).
- LLGG joint document of the “Royal College of PathologyCand the “British Society for Genetic Medicine” [Gardiner et al., 2015].
- Position Paper American Society of Ultrasound in Ob/Gyn: Cut-off value of nuchal translucency as indication for chromosomal microarray analysis, e coll Maya, Ultrasound in Ob Gyn 26 July 2017.
- Ministry of Health. Guidelines Noninvasive prenatal screening based on DNA (Non Invasive Prenatal Testing – NIPT). May 2015 2.
- Committee Opinion No. 640: Cell-free DNA Screening for Fetal Aneuploidy. Obstet Gynecol 2015; 126:e31-7. 6. Society for Maternal-Fetal Medicine (SMFM) Publications Committee #36.
- ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Gregg AR, Gross SJ, Best RG, et al. Genet Med 2013;15:395-8. 10. Canick JA, Palomaki GE, Kloza EM, et al.