A high Z-score might increase the positive predictive value of cell-free noninvasive prenatal testing for singleton-pregnant women

Abstract

Objective To explore the positive predictive value (PPV) in noninvasive prenatal testing (NIPT)-positive cases and analyze the effect of the Z-score intervals on PPV performance. Methods In this retrospective study, 26,667 pregnant women underwent NIPT from November 2014 to August 2022, of which 169 were NIPT-positive cases. NIPT-positive cases were divided into three groups according to the Z-score: 3 ≤ Z < 6, 6 ≤ Z < 10, and Z ≥ 10. Results The PPVs of NIPT were 91.26% (94/103) for trisomy (T) 21, 80.65% (25/31) for T18, and 36.84% (7/19) for T13. The PPVs for the 3 ≤ Z < 6, 6 ≤ Z < 10, and Z ≥ 10 groups were 50%, 84.62%, and 87.95%, respectively. A higher PPV was found in the NIPT results when the Z-score was larger, with significant differences. The PPVs for T21/T18/T13 were 71.43%/42.86%/25% for 3 ≤ Z < 6, 90.32%/85.71%/57.14% for 6 ≤ Z < 10, and 93.85%/100%/25% for Z ≥ 10. For T21, T18, and T13, the correlations between the Z-score and fetal fraction concentration in true positives were r = 0.85, r = 0.59, and r = 0.71 (all p < .001), respectively. Conclusion Z-score is associated with the PPV performance of NIPT in fetal T13, T18, and T21. The possibility of false positives caused by placental chimerism should be considered when determining whether high Z-values lead to high PPVs.