Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases

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. Genet Med 17 3, 234–236.