|
  What is the purpose of testing for microdeletion syndromes?
Recent data suggest that up to 1.6% of all fetuses may be affected by a copy number variant, otherwise known as a microdeletion or microduplication syndrome. The purpose of testing for these deletions, therefore, is to provide women with as much information as possible about the genetic status of their fetus, particularly when there is an abnormal finding on ultrasound. This is typically done through invasive testing with microarray as there are hundreds of microdeletions and microduplications known to cause clinically relevant syndromes. Testing for only a few of these with an NIPT panel will not significantly reduce the overall residual risk for these conditions.
How does adding a microdeletion panel to an NIPT platform impact the test?
Any time conditions are added to the test menu, the cumulative false positive rate (FPR) will increase. There is currently no published data on the anticipated FPR for microdeletion panels with NIPT, but adding these conditions has the potential to increase the FPR significantly, possibly as high as conventional serum screening (4-5%). This may result in the need for far more invasive tests to clarify the results of microdeletion syndromes that are as rare, in some cases, as 1/50,000.
Isn't it better to test for more conditions with NIPT rather than just a few?
More is not necessarily better. When exceedingly rare conditions are added to a screening test, the concern is that "false positives" may be more common than "true positives". The potential benefit of this testing is that we may identify a fraction of affected cases. This must be weighed against the potential harm of "false positive" results, which may include increased patient anxiety, unnecessary invasive diagnostic testing, and in some cases, loss of a healthy fetus.
What is the expected sensitivity for microdeletion syndromes with an expanded NIPT panel?
The sensitivity of microdeletion syndromes using an NIPT panel has not been studied in pregnant women. The sensitivity information that has been released was derived from testing on synthetic samples mixed in a laboratory. These unpublished data suggest that sensitivity for smaller deletions may be as low as 60%. In fact, for 22q11 deletion, the expected sensitivity for 3-6Mb deletions ranges from 60-84%, but approximately 15% of patients with this condition have deletions smaller than that, meaning the overall false negative rate could be as high as 55%.
What will the positive predictive value be for these microdeletion panels?
Positive predictive value (PPV) answers the question, "if the test is positive," what is the chance that the fetus is actually affected by the condition. PPV is influenced by the prevalence of the condition being tested and the false positive rate of the test. With the extremely low prevalence of some of these microdeletion syndromes, the PPV for these panels is likely to be extremely low, leaving providers to question the validity of a "Positive" result.
How will the addition of a microdeletion panel change the informed consent process for NIPT?
In order to provide truly informed consent, patients will need to be counseled about each of the conditions on the microdeletion panel. The patient will also need to understand the ranges of sensitivity and the fact that a "Negative" result may not significantly reduce their risk to have a baby with that condition. Similarly, the patient should be informed of the false positive rate for these conditions and that an invasive procedure with a microarray will be needed to confirm any "Positive" result. Is your practice prepared to add this degree of pre-test counseling to your current NIPT protocol?
What will Ariosa's approach be toward expanding the Harmony panel?
Ariosa is constantly evaluating the clinical utility of expanding our testing platform to provide improved services and products to our partners and patients. We are confident that our directed sequencing technology is well positioned to become a best-in-class test for many clinically relevant conditions. Moreover, Ariosa believes that the expansion of non-invasive prenatal testing should reflect a responsible strategy with the goal of effectively using the technology for the general pregnancy population.
|
Information for Clinical Utility
