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.

Keywords:

• Noninvasive prenatal testing
• trisomy
• positive predictive value
• false positive reactions
• Z-score

Acknowledgments

We thank all those who participated in this study. We are also grateful to the staff who collected information and blood from pregnant women, without whose efforts we could not have conducted the study successfully.

Author contributions

Li Ma and Yulan Li carried out the studies and drafted the manuscript. Lei Li and Hong Wu participated in collecting data. Yongming Liu performed the statistical analysis and participated in its design. Xin Yang and Aimin Lin participated in the acquisition, and interpretation of data. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

This article includes all the relevant data generated or analyzed during this study.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.