Ensuring transparency and clinical utility in SMA noninvasive prenatal diagnosis

Ensuring transparency and clinical utility in SMA noninvasive prenatal diagnosisTo the Editor, We read the article by .This first-trimester, haplotype-based approach is a significant advance.To ensure its clinical adoption, two methodological issues must be addressed.First, the Bayesian Factor (BF) framework lacks transparency, preventing independent validation.The diagnostic call depends entirely on a BF model using fixed thresholds (BF 10, 0.1), yet the manuscript omits the model's likelihood, priors, and-critically-empirical justification for these thresholds.In clinical genomics, using uncalibrated heuristic thresholds is discouraged, as it can lead to misinterpretation, especially in complex regions like *SMN1/SMN2* [2].Full disclosure of the statistical model and calibration data is essential for replication.Second, incomplete reporting overstates the 100% accuracy claim and limits clinical utility.Reporting 76/76 concordance without its 95% confidence interval (95.2-100%) omits precision.More importantly, the absence of performance stratified by fetal fraction (e.g. in the critical <4% range) or informative SNP count obscures the test's true operating limits.This contravenes STARD guidelines for diagnostic accuracy studies, which mandate such disaggregated data to define reliable clinical use [3].These issues are intrinsically linked: an opaque model and incomplete reporting together undermine the study's clinical translatability and trustworthiness for multi-center validation.Addressing them is urgent.With the 2023 FDA approval of a prenatal SMA treatment trial and global policy shifts towards early intervention [4], establishing transparent, robust NIPD methods is critical to ethically integrate diagnosis with new therapeutic pathways.