False-positives and false-negatives in non-invasive prenatal testing (NIPT): what can we learn from a meta-analyses on > 750,000 tests?

Abstract

Background: Non-invasive prenatal testing (NIPT) has had an incomparable triumph in prenatal diagnostics in the last decade. Over 1400 research articles have been published, predominantly praising the advantages of this test.

Methods: The present study identified among the 1400 papers 24 original and one review paper, which were suited to re-evaluate the efficacy of > 750,000 published NIPT-results. Special attention was given to false-positive and false-negative result-rates. Those were discussed under different aspects-mainly from a patient-perspective.

Results: A 27: 1 rate of false-positive compared to false-negative NIPT results was found. Besides, according to all reported, real-positive, chromosomally aberrant NIPT cases, 90% of those would have been aborted spontaneously before birth. These findings are here discussed under aspects like (i) How efficient is NIPT compared to first trimester screening? (ii) What are the differences in expectations towards NIPT from specialists and the public? and (iii) There should also be children born suffering from not by NIPT tested chromosomal aberrations; why are those never reported in all available NIPT studies?

Conclusions: Even though much research has been published on NIPT, unbiased figures concerning NIPT and first trimester screening efficacy are yet not available. While false positive rates of different NIPT tests maybe halfway accurate, reported false-negative rates are most likely too low. The latter is as NIPT-cases with negative results for tested conditions are yet not in detail followed up for cases with other genetic or teratogenic caused disorders. This promotes an image in public, that NIPT is suited to replace all invasive tests, and also to solve the problem of inborn errors in humans, if not now then in near future. Overall, it is worth discussing the usefulness of NIPT in practical clinical application. Particularly, asking for unbiased figures concerning the efficacy of first trimester-screening compared to NIPT, and for really comprehensive data on false-positive and false-negative NIPT results.