Performance Metrics of Noninvasive Prenatal Testing Panels for Dominant Single-Gene Disorders: A Systematic Review...

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.

From database inception through April 2025, we explored PubMed, EMBASE, Cochrane Library, and Web of Science.

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.

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 ( I2 =96%). In contrast, heterogeneity was low ( I2 =16%) for PPV but with publication bias being detected ( P =.004).

Noninvasive prenatal testing panels for dominant single-gene disorders achieve a high PPV with high sensitivity and specificity.

PROSPERO, CRD42024571768.