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

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. 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 ≤ <i>Z</i> &lt; 6, 6 ≤ <i>Z</i> &lt; 10, and <i>Z</i> ≥ 10. 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 ≤ <i>Z</i> &lt; 6, 6 ≤ <i>Z</i> &lt; 10, and <i>Z</i> ≥ 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 ≤ <i>Z</i> &lt; 6, 90.32%/85.71%/57.14% for 6 ≤ <i>Z</i> &lt; 10, and 93.85%/100%/25% for <i>Z</i> ≥ 10. For T21, T18, and T13, the correlations between the Z-score and fetal fraction concentration in true positives were <i>r</i> = 0.85, <i>r</i> = 0.59, and <i>r</i> = 0.71 (all <i>p &lt; .</i>001), respectively. 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.

本研究旨在探讨无创产前基因检测（noninvasive prenatal testing, NIPT）阳性病例的阳性预测值（positive predictive value, PPV），并分析Z值区间对阳性预测值性能的影响。本回顾性研究纳入2014年11月至2022年8月期间接受NIPT检测的26667名孕妇，其中169例为NIPT阳性病例。研究人员根据Z值将NIPT阳性病例分为三组：3≤Z<6、6≤Z<10及Z≥10组。21-三体综合征（trisomy 21, T21）、18-三体综合征（trisomy 18, T18）、13-三体综合征（trisomy 13, T13）的NIPT阳性预测值分别为91.26%（94/103）、80.65%（25/31）及36.84%（7/19）。按Z值分组的整体阳性预测值分别为：3≤Z<6组50%、6≤Z<10组84.62%、Z≥10组87.95%，可见Z值越高，NIPT结果的阳性预测值越高，组间差异具有统计学意义。细分各三体类型的分组阳性预测值：3≤Z<6组的T21、T18、T13阳性预测值分别为71.43%、42.86%及25%；6≤Z<10组分别为90.32%、85.71%及57.14%；Z≥10组分别为93.85%、100%及25%。真阳性病例中，T21、T18、T13的Z值与胎儿游离组分浓度的相关系数分别为r=0.85、r=0.59及r=0.71（均p<0.001）。Z值与NIPT针对T21、T18及T13的阳性预测值性能显著相关。在判断高Z值是否对应高阳性预测值时，需考虑胎盘嵌合现象导致假阳性的可能性。