Peter Benn PhD, DS
Professor
Department of Genetics and Genome Sciences
University of Connecticut Health Center
Farmington, CT
Can you characterize the different laboratory techniques used to amplify cell-free DNA to determine the likelihood that the fetus has one of the common chromosome abnormalities?
How do the two methods, generally described as the traditional first generation “counting method” and the second generation “SNP (single nucleotide polymorphism)-based testing” differ from one another? Let’s start with the counting method first.
Can you go into detail with the SNP (single nucleotide polymorphism)-based testing method and describe its methodology?
From a clinical, NIPT perspective, what unique advantages and what precision-focused capabilities can be ascribed to SNP technology and its targeted approach to fetal abnormalities?
How do the sensitivities and false positive rates for aneuploidy and gender—the improved PPV for SNP in sex chromosome abnormalities, in particular—compare for the various methodologies?
Can you explain reporting and other differences between the various commercially available NIPT products?
What are the clinical implications of the reporting differences?
What are the clinical implications of the reporting differences?
Which of the NIPT reports—SNP tests, by specific laboratories—are known to have the advantage of having high positive predictive values (PPV)?
How does each of the NIPT testing products meet the laboratory guidelines for NIPT set forth by ACMG and ACOG/SMFM, especially reporting guidelines such as PPV and NPV? Are reports from any particular company consistent with the recently ...
Do companies that provide NIPT tests also report results of uncertain significance? What are the clinical implications of this?
What are microdeletions and what is the rationale for offering screening for these conditions using NIPT? Especially to detect for with a microdeletion syndrome such as 22q11.1?
What are the advantages of SNP-based technology compared with the counting method when utilizing cell-free DNA to identify women at increased risk to be carrying a fetus with a microdeletion syndrome such as 22q11.1? Which test has the most robust data?
How does the incidence of 22q11.2 deletion compare with Down syndrome in terms of incidence at various maternal ages? What is the rationale for screening for this deletion?
Why is the SNP-based approach preferred for screening for microdeletions?
Why is the SNP-based approach preferred for screening for microdeletions?
What are the ethics—on a societal and individual level—of NIPT screening, and why is it critical that we screen for these fetal abnormalities?
What is the rationale for deploying SNP-based NIPT in larger swaths of the population, especially in lower risk populations? Do studies economic and clinical studies suggest there is value using these tests in low risk patients?