The NIPTunegx® test combines the prior (background) risk of a trisomy with a likelihood ratio to generate a final risk score. The likelihood ratio is derived from the relative copy numbers of specific fetal genetic material (chromosome 13, 18 and 21) in a blood sample of a pregnant woman.
2. Why is NIPTuneS described as a screening test rather than a diagnostic test?
As with all NIPT tests, the NIPTuneS test analyses the chromosome ratios of cell-free DNA in the mother’s blood stream derived from the placenta. Various rare conditions associated with the placenta or with the mother’s genome can alter the chromosome ratios in the absence of a fetal trisomy; therefore, a high-risk result may not accurately represent trisomy in the fetus. For this reason, high risk results must be confirmed with a diagnostic test such as amniocentesis. In the event of a low risk result it is important to be aware that there is still a very small (but not zero) risk of trisomy. A low-risk result does not exclude the presence of other genetic abnormalities in the fetal genome. Confirmation with a diagnostic test is important.
3. What is fetal fraction and how is it used in the NIPTunegx® test?
The fetal fraction is the proportion of cell-free DNA which is derived from the placenta. The NIPTunegx® test estimates fetal fraction using a combination of sex chromosome analysis and differential sequence representation. The NIPTunegx® test requires a minimal fetal fraction of ≥2% to generate a valid result. Where the fetal fraction is between 2 and 4%, a dynamic fetal fraction method is used to assess the validity of samples, if certain additional QC criteria are met. This feature allows NIPTunegx® to maximize the number of samples available for analysis.
4. What does a high-risk result on the NIPTunegx® test mean?
All high-risk results should be reviewed by the healthcare provider and confirmed by further testing.
5. Which invasive diagnostic test is suitable for follow up testing?
Both chorionic villus sampling (CVS) and amniocentesis have been recommended as suitable sampling techniques for obtaining samples for further testing but there is no clinical consensus about which is preferred. CVS has the benefit that it can be conducted earlier in the pregnancy, but it has a disadvantage compared to amniocentesis in that it tests a sample of the placenta rather than fetal cells.
6. Which sample is required?
We recommend a Streck Blood tube (cell-free DNA BCT Streck) as this keeps the blood stable for up to 14 days. Standard EDTA tubes are also suitable if the sample can be centrifuged to separate plasma within 8 hours of blood draw.
7. What is the turnaround time for the NIPTunegx® test?
2 weeks of lab processing time.
8. What could cause inaccurate test results?
The NIPTuneS test is very accurate but as with all NIPT there are several confounding conditions and circumstances which can lead to a loss of specificity or sensitivity. These can be broadly summarized as:
- Conditions arising during pregnancy.
- Pre-existing conditions in the mother.
- Medical interventions in the mother.
- Sampling or sampling handling errors and laboratory-related failure.
9. The NIPTuneS test is very accurate but as with all NIPT there are several confounding conditions and circumstances which can lead to a loss of specificity or sensitivity. These can be broadly summarized as: 1. Conditions arising during pregnancy . 2. Pre-existing conditions in the mother . 3. Medical interventions in the mother . 4. Sampling or sampling handling errors and laboratory-related failure .
No, malignant tumors shed cell-free DNA fragments which could interfere with the NIPTune test potentially giving an erroneous result so if a pregnant woman is known to have cancer the NIPTune test is not suitable.
10. Are there rare inherited genetic conditions which can preclude the use of the NIPTune test?
The NIPTunegx® test is not suitable in cases where the mother carries a genetic condition that changes the level of chromosomes 13, 18 or 21 in her cell-free DNA fraction. Such rare conditions would include mosaicism or chimerism involving a trisomic cell line as well as partial duplications or chromosomes 13, 18 and 21 in the germline.
11. Sampling and sample handling errors and laboratory-related failure?
Inaccurate test results may occur in rare circumstances beyond our control, which include but are not limited to: sampling and sample handling errors (including courier/ shipping delay, contamination or degradation of a sample) and laboratory-related failures.