Evaluation of the Z-score accuracy of noninvasive prenatal testing for trisomies 21, 18 and 13: a cohort study based on cell-free fetal DNA and maternal age

Objective This study aimed to evaluate the relationship between the Z-score of positive noninvasive prenatal testing (NIPT) results and the positive predictive value (PPV), as well as the correlation between Z-score and cell-free fetal DNA (cff-DNA) concentration, and the association between PPV and maternal age.Methods A total of 278 singleton pregnant women with high-risk NIPT results were included. Fetal karyotyping or copy number variation sequencing (CNV-Seq) was performed to confirm the presence of chromosomal abnormalities. The study evaluated the correlation between Z-scores of true positive NIPT results and the concentration of cff-DNA. Additionally, the study analyzed the association between NIPT Z-score and PPV, as well as the relationship between PPV and maternal age. Logistic regression analysis was used to assess the correlation between Z-scores and PPV. The diagnostic performance of Z-scores in detecting chromosomal aneuploidy was evaluated using receiver operating characteristic (ROC) curve analysis.Results Of the 242 pregnant women who opted for prenatal diagnosis through invasive amniocentesis, 184 cases were diagnosed as true positives. The total PPVs of NIPT screening for trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) were 89.82%, 67.65%, and 26.83%, respectively. The Z-scores of T18 and T21 are positively correlated with the concentration of cff-DNA. The PPVs of T18 and T21 increase with rising Z-score. When 5 < Z ≤ 20, the PPV of T21 is the highest, while that for T13 is the lowest under the same Z-score. Furthermore, the PPV was found to be higher among pregnant women aged ≥35 years compared to those younger than 35 years. The ROC curve analysis showed that the optimal cutoff value of Z-scores for T21, T18, and T13 was 9.189, 14.08, and 13.72. The logistic regression analysis revealed that Z-scores of NIPT-positive results were significantly associated with the PPV at T21 (p < 0.001), T18 (p = 0.008), and T13 (p = 0.034).Conclusion Z-score showed a positive correlation with cff-DNA concentration and PPV for T21 and T18. Based on these findings and current knowledge, we suggest that, a multi-parameter model (including Z-score, maternal age, cff-DNA%, and ultrasound markers) be evaluated in future studies to potentially improve NIPT accuracy and reduce false positives. This suggestion is speculative and requires prospective validation.