Prevalence threshold and positive predictive value of noninvasive prenatal testing

Abstract

ObjectiveNoninvasive prenatal testing (NIPT) has increased the number of conditions that can be screened. However, the prevalence of conditions assessed by NIPT has remained stable. The “prevalence threshold,” a novel epidemiological concept, uses a test's sensitivity and specificity to determine the prevalence below which a test's positive predictive value declines most sharply relative to disease prevalence. In this article, we calculated the prevalence threshold for common conditions assessed through NIPT and compared the value with the actual prevalence of each condition to best ascertain the reliability of NIPT results.MethodsSix databases and PubMed were searched from January 2010 to March 2023 for sensitivity and specificity parameters of common conditions tested through NIPT. Using an equation previously derived by the authors of the current paper, the prevalence threshold for each condition was calculated. The theoretical number of test iterations required to reach the prevalence threshold was also reported.ResultsNone of the conditions tested through the NIPT had a prevalence rate that met or exceeded the calculated prevalence threshold. Trisomy 21 had the greatest concordance between the prevalence rate and the prevalence threshold. In contrast, Angelman, Cri‐du‐chat, and Prader‐Willi syndromes had the most significant discordance. Apart from trisomy 21 and XXY, all remaining conditions required more than one test iteration to reach their respective prevalence threshold.ConclusionWe conclude that at the current prevalence levels, the positive predictive value of NIPT remains low, with the prevalence of disease levels significantly lower than the prevalence threshold for each condition tested.