PrenatalSAFE® test limits
The non-invasive prenatal exam that analyzes circulating fetal cell-free DNA isolated from a maternal blood sample is a screening test and not a diagnostic one. Although this test is very accurate, the results are not diagnostic and have to be evaluated in the context of the clinical picture of the pregnant woman and of the familial anamnesis. Furthermore, the assay is not a replacement of invasive prenatal diagnosis (Chorionic villus sampling or Amniocentesis). The test has been validated on singleton or twin pregnancies, monozygotic or dizygotic, with at least 10 weeks of gestation. The exam cannot exclude the presence of all fetal chromosomal abnormalities.
3 evaluates only the aneuploidies of chromosomes 13, 18, 21, PrenatalSAFE®
evaluates also the sex chromosomes aneuploidies (X and Y);
the aneuploidies of other chromosomes are detectable only with
Karyo test highlights the 92,6% of fetal chromosomal abnormalities detectable in prenatal period and the 96.2% of those observed at birth. PrenatalSAFE®
test highlights the 95,5% of fetal chromosomal abnormalities detectable in prenatal period and the 99.1%of those observed at birth.
test is not able to detect balanced chromosomal rearrangements, fetal and/or placental chromosomal mosaicisms (that is the presence of two cell lines with a different chromosomal asset), point mutations, methylation defects, polyploidy. The test doesn’t highlight other malformations or defects not specifically researched. In particular, the exam does not highlight the presence of inherited Mendelian disorders. The partial alteration of the analyzed chromosomes and the structural chromosomal abnormalities may be pointed out only with PrenatalSAFE®
Karyo tests. The estimated resolution limit of the test is consistent with that of the cytogenetic karyotype (traditional) with 400 bands (about 7-10 Mb). PrenatalSAFE®
Karyo Plus test highlights structural chromosomal abnormalities at a resolution of about 3 Mb, on the level of chromosomal regions associated to the microdeletion syndromes investigated.
In dizygotic twin pregnancies is not possible to distinguish the condition of the single fetus, nor to evaluate sex chromosomes aneuploidies. However it is possible to observe the presence/absence of chromosome Y. In the case in which is detected the presence of chromosome Y, it is not possible to discern if just one or both fetuses are male. In pregnancies that started as twin or multiple, followed by miscarriage of one or more fetuses with reabsorption of the gestational sac (vanishing twin), even the free fetal DNA of the aborted fetus could be present in maternal blood. This could interfere with the quality of the results, determining false positives in case in which the cause of the abortion was due to the presence in the aforementioned fetus of chromosomal aneuploidies on one of the chromosomes investigated. Similarly, it could determine an incongruity in gender results (es. diagnosis of male gender, in which the presence of chromosome Y is originated from the aborted DNA fetus). The existence of a tumor condition (metastasis) in the pregnant woman could determinate false positive test results. The test is based on the quantification of fragments of circulating free fetal DNA in maternal blood, which have placental origins. Therefore, due to chromosomal mosaicism condition (frequency: 1-2%) there may be discrepancies in the results (false positive or false negative) that justify the sensitivity and specificity of the test <100%. In particular, the test could produce a positive result (aneuploidy detected), but this chromosomal abnormality could be confined to the placenta due to the chromosomal mosaicism, and thus the fetus could eventually result with a normal karyotype during invasive prenatal diagnosis control (false positive). Vice versa, the test could produce a negative result (no aneuploidy detected), but because of the chromosomal mosaicism the fetal DNA without aneuploidy could be confined to the placenta, and therefore the fetus could eventually result with aneuploid karyotype during invasive prenatal diagnosis control (false negative). The fetal sex is indicated as male and female, based on the presence or absence of chromosome Y, but do not give information about the presence or absence of SRY gene. The pregnancies with ultrasound results suggesting of fetal pathology should be studied with other types of prenatal exams, such as molecular fetal karyotype on chorionic villi, or amniotic fluid, because of the higher detection rate. There is the possibility to identify with this test, sex chromosomes abnormalities present in the mother (homogeneous or mosaic) that can interfere with the accuracy of the results concerning fetal sex chromosomes. A “NEGATIVE – No Aneuploidy or structural chromosomal abnormality detected” result, reduces considerably the possibility that the fetus has an aneuploidy or a structural chromosomal abnormality on chromosomes examined, but it cannot ensure that the chromosomes are actually normal or that the fetus is healthy. It is not possible to perform this test to women carriers of aneuploidies. Because of the limits explained above, in case of a positive result, counseling with a geneticist and the confirmation of the result by karyotype analysis on amniotic fluid is recommended.
GeneSAFE™ test limits
This test screens only for the genetic diseases and the genes listed in
The test does not highlight other genetic diseases not specifically investigated.
The test also does not highlight:
mutations located in intronic regions over ± 5 nucleotides from breakpoints;
deletions, inversions or duplications superior than 20bp;
is a screening and not a diagnostic test. Although this test is very accurate, the results are not diagnostic and must be considered in the context of the clinical picture of the pregnant woman and the familial anamnesis. Furthermore, the exam is not a substitute for invasive prenatal diagnosis (Chorionic villus sampling or Amniocentesis). The test is validated for singleton or twin, monozygotic or dizygotic pregnancies with gestational age of at least 10 weeks.
In twin pregnancies is not possible to distinguish the condition of the single fetus. In pregnancies that started as twin or multiple, followed by the spontaneous abortion of one or more fetuses with resorption of the gestational sac (vanishing twin), the cell-free fetal DNA of the aborted fetus could be also present in maternal blood. This could interfere in the quality of results, determining false positives. The presence of a cancer condition (metastasis) in the pregnant woman could determinate false positive test results owed to mutations of the circulating tumor DNA (ctDNA) on the genes involved in the carcinogenesis process (ex. BRAF, KRAS, NRAS). A “NEGATIVE” – Low risk for a genetic disease” result, reduces considerably the possibility that the fetus has the genetic diseases examined, but cannot ensure the fetus is healthy. The GeneSAFE™ test detects only mutations with a known pathological significance. The test does not screen for variations with a benign significance, i.e. those detectable in normal individuals and lacking of pathological significance, and variants with uncertain significance, i.e. those not yet known or characterized by the medical-scientific community. The interpretation of the genetic variations is based on the most recent knowledge available at the time of the analysis. This interpretation may change in the future with the acquisition of new medical and scientific information on the genome structure and affect on the same evaluation of the variations. Because of the limits explained above, in case of a positive result, counseling with a geneticist and the confirmation of the result by amniotic fluid or chorionic villi genetic analysis is recommended.