Analysis of 17,428 pregnant women undergoing non-invasive prenatal testing for fetal chromosome in Northeast China

Abstract

Non-invasive prenatal testing (NIPT) is an incomparable prenatal screening technology, but we should undergo amniocentesis to confirm fetal chromosome when pregnancies receive a positive result via NIPT. We aimed to investigate the detection rate and positive predictive value of NIPT results in pregnancies from Northeast China, and to determine the reasons for false positive and false negative NIPT results.This study evaluates 17,428 singleton pregnancies had undergone NIPT detection. 202 samples were NIPT positive with the detection rate was 1.16% (202/17,428). Among all the positive samples, 160 samples (79.21%) were referred for an amniocentesis procedure to investigate the fetal chromosome. The positive predictive value of T21, T18, and T13 was found to be 75% with a 0.07% false positive rate. Positive predictive value from high to low was as follows: trisomy 21 (84.38%), followed by trisomy 18 (61.54%), autosomal abnormalities (52.94%), sex chromosomal abnormalities (38.46%), and trisomy 13 (33.33%). The positive predictive values for sex chromosome abnormalities turned out to be mosaic sex chromosome aneuploidies (83.33%), followed by XYY (57.14%), XXY (37.50%), XXX (36.36%), and Monosomy X (28.95%). Out of the 160 samples had amniocentesis, the true positive cases in trisomy 21 had a higher percentage of Z-scores compared with the false positive cases in trisomy 21 (P < .05). And the true positive cases in trisomy 18 had a significantly higher percentage of Z-scores compared with the false positive cases in trisomy 18 (P < .01).These findings indicate that the positive predictive value of T21, T18, and T13 was found to be 75% with a 0.07% false positive rate. It is worth noting that the positive predictive value of NIPT for autosomes and sex chromosomes. Moreover, if women receive a positive result via NIPT, they should pay attention to the results with undergoing further prenatal diagnosis.

Figure 1

The positive trisomy examples of fetal CNVs detection. A: Trisomy 21. B: Trisomy 18. C: Trisomy 13. Model I: The Z-score distribution map generated by CNV detection is based on Reads count. The black dot (or red dot) indicates that the corresponding Z-score of each alignment window bins. The orange solid line indicates that GC bias of window bins. The blue solid line indicates that Z-score smoothing line is lower than normal. The red solid line indicates Z-score smoothing line is higher than normal. Model II: The Z-score distribution map generated by CNV detection is based on Real unique Reads count. The red line is the Z-score smoothing line generated according to the Z-score of each window bin. The red solid line fluctuates upwards indicates that Z-score is higher than normal. The red solid line fluctuates downwards indicates that Z-score is lower than normal. The 3rd picture is chromosomal diagram generated from Model I and Model II. Red, grey and green bars represent duplication, normal and deletion, respectively. The y-axis shows the chromosomal copy number variations.

Figure 2

The comparison of Z-scores between true and false positive cases for Trisomy 21 and Trisomy 18.