Performance Metrics of Noninvasive Prenatal Testing Panels for Dominant Single-Gene Disorders

OBJECTIVE: To evaluate the clinical utility and methodologic validity of noninvasive prenatal testing (NIPT) for dominant single-gene disorders by performing a systematic review and meta-analysis. DATA SOURCES: From database inception through April 2025, we explored PubMed, EMBASE, Cochrane Library, and Web of Science. METHOD OF STUDY SELECTION: Studies that reported NIPT panels to screen for dominant single-gene disorders with confirmation testing and involved at least 50 cases were included. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used for study appraisal. Clinical utility was evaluated by using positivity rate and positive predictive value (PPV), with pooled estimates calculated through fixed- or random-effects models. Methodologic validity was assessed through sensitivity and specificity by using a bivariate random-effects model and summary receiver operating characteristic curve analysis. TABULATION, INTEGRATION AND RESULTS: Ten articles comprising 12,577 cases were included. Positivity rate and PPV were calculated from nine studies, with sensitivity and specificity from seven studies. The pooled positivity rate was 2.2% (95% CI, 0.8–5.6%), and pooled PPV was 93.8% (95% CI, 86.4–97.3%). The bivariate model yielded a pooled sensitivity of 94.5% (95% CI, 85.7–98.0%) and specificity of 99.7% (95% CI, 98.8–99.9%), with an area under the curve of 0.98 (95% CI, 0.94–0.99). Subgroup analysis revealed positivity rates of 0.3% in low-risk populations, 1.2% in mixed-risk populations, and 6.0% in high-risk populations. High heterogeneity was observed in the positivity rate analysis ( I 2 =96%). In contrast, heterogeneity was low ( I 2 =16%) for PPV but with publication bias being detected ( P =.004). CONCLUSION: Noninvasive prenatal testing panels for dominant single-gene disorders achieve a high PPV with high sensitivity and specificity. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42024571768.