Clinical indications and Z-score-assisted NIPT testing: a new perspective in prenatal screening

Objective We aim to explore positive predictive value (PPV) in non-invasive prenatal testing (NIPT)-positive cases and investigate the impact of diverse clinical indications and Z-scores on PPV performance. Methods From January 2021 to June 2024, 37 891 pregnant women underwent NIPT screening for fetal trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13) at our laboratory using the NextSeq CN500 platform. Positive results were verified through prenatal diagnostic karyotype analysis and fluorescence in situ hybridisation (FISH) techniques. Results The sensitivity, specificity and PPV were 95.24%, 99.95%, 67.80% for T21; 100%, 99.97%, 56.00% for T18; and 100%, 99.97%, 16.67% for T13. Across clinical indications, PPV ranged from 0% to 100% for T21 and T18 and 0% to 28.57% for T13. In the T21 group, the predominant proportion of pregnant women (45.76%) exhibited Z-scores between 5 and 10, accompanied by a PPV of 77.78%. For those with Z-scores above 10 (23.73%), the PPV was 85.71%. Pregnant women with Z-scores between 3 and 5 exhibited a PPV of 16.67%. In the T18 group, the majority of women (52.00%) exhibited Z-scores ranging from 3 to 5, with a PPV of 33.85%. In the T13 group, all women had Z-scores between 5 and 10, with a PPV of 40.00%. Conclusions NIPT exhibits elevated PPVs for T21 and T18. Moreover, the detection efficacy of NIPT differs across several clinical indication categories. The PPV performance of NIPT for T21/T18/T13 is associated with Z-scores. These results provide valuable guidance for clinicians in prenatal consultation and interpretation of NIPT results.