Not to Flog the Genetic Testing Horse…

Oh, who are we kidding? We love to flog metaphorical horses. Anyway, there’s an interesting article about non-invasive genetic testing that looked at the accuracy of determining if prenatal genetic testing could accurately identify if a child would have Trisomy 21 (Down’s Syndrome), Trisomy 18 (Edward’s Syndrome) or other meiotic disjunction related diseases. It’s kind of interesting–the abstract (boldface mine):

Purpose: Recent published studies have demonstrated the incremental value of the use of cell-free DNA for noninvasive prenatal testing with 100% sensitivity for trisomies 21 and 18 and a specificity of ≥99.7% for both. Data presented by two independent groups suggesting positive results by noninvasive prenatal testing were not confirmed by cytogenetic studies.

Methods: Concordance of results among cases with noninvasive prenatal testing referred for cytogenetic prenatal and/or postnatal studies by karyotyping, fluorescence in situ hybridization, and/or oligo–single-nucleotide polymorphism microarray was evaluated for 109 consecutive specimens.

Results: Cytogenetic results were positive for trisomy 21 in 38 of the 41 noninvasive prenatal testing–positive cases (true-positive rate: 93%) and for trisomy 18 in 16 of the 25 noninvasive prenatal testing–positive cases (true-positive rate: 64%). The true-positive rate was only 44% (7/16 cases) for trisomy 13 and 38% (6/16 cases) for sex chromosome aneuploidy.

Conclusion: These findings raise concerns about the limitations of noninvasive prenatal testing and the need for analysis of a larger number of false-positive cases to provide true positive predictive values for noninvasive testing and to search for potential biological or technical causes. Our data suggest the need for a careful interpretation of noninvasive prenatal testing results and cautious transmission of the same to providers and patients.

From the paper:

To an average clinician, the claim that a test is specific leads him or her to expect that the false-positive rate will be 1%. As can been seen by the data in this report and others, the ability of NIPT to correctly predict a positive result for trisomy18 and trisomy 13 is less than 60% (Table 2). For this reason, it is crucial that providers and consumers understand that NIPT is fundamentally a screening test and cannot be used as a replacement for invasive prenatal diagnosis. For a couple with an NIPT positive for trisomy 18, it is foremost to counsel them that the likelihood their fetus actually has a trisomy 18 is 60%. A normal ultrasound result would reduce that likelihood even further. This is very different from being told that there is a 99% chance the fetus is affected and might lead to a different decision regarding an invasive prenatal diagnosis before any action is taken. Clinicians must be educated regarding the differences between published specificities and the more important statistics of PPV.

Genetic testing is a good thing, but you have to understand the limitations of your diagnostic. Not to put to fine a point on the issue, but some couples might decide to terminate a pregnancy based on the ultimate diagnosis. These are high stakes.

Seems relevant to a debate in the science bloggysphere a while ago.

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