Performance Evaluation of Noninvasive Prenatal Testing in Screening Chromosome Disorders: A Single-Center Observational Study of 15,304 Consecutive Cases in China

Abstract

Qiang Ye,1 Guoping Huang,1 Qin Hu,1 Qin Man,2 Xiaoying Hao,3 Liangyan Liu,4 Qiang Zhong,1 Zhao Jin2 1Department of Clinical Laboratory, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of China; 2Department of Prenatal Diagnosis Center, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of China; 3Department of Ultrasound, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of China; 4Department of Obstetrics, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of ChinaCorrespondence: Zhao Jin, Department of Prenatal Diagnosis Center, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, No. 49 Da Huang Tong Road, Da’an District, Zigong, Sichuan, 643000, People’s Republic of China, Tel [phone], Email [email protected]: This study was to evaluate the performance of noninvasive prenatal testing (NIPT) in detecting fetal chromosome disorders in pregnant women.Methods: From October 1st, 2017, to December 31th, 2022, a total of 15,304 plasma cell free DNA-NIPT samples were collected for fetal chromosome disorders screening. The results of NIPT were validated by confirmatory invasive testing or clinical outcome follow-up. Further, NIPT performance between low-risk and high-risk groups, as well as singleton pregnancy and twin pregnancy groups was compared. Besides, analysis of 111 false-positive cases was performed.Results: Totally, NIPT was performed on 15,086 eligible venous blood samples, of which 179 (1.19%) showed positive NIPT results and 68 were further validated to be true positive samples via confirmatory invasive testing or follow-up of clinical outcomes. For common chromosome aneuploidies, sex chromosome abnormalities (SCA) and other chromosomal aneuploidies, the detection sensitivities of NIPT were all 100%, the specificities were 99.87%, 99.70%, and 99.68% and the positive predictive values (PPVs) were 65.45%, 31.82%, and 10.91%, respectively. No statistically significant variance in detection performance was observed among 2987 high-risk and 12,099 low-risk subjects, as well as singleton and twin pregnancy subjects. The concentration of cell-free fetal DNA of 111 false-positive cases ranged from 5.5% to 33.7%, which was higher than the minimum requirement of NIPT.Conclusion: With stringent protocol, NIPT shows high sensitivity and specificity for detecting fetal chromosome disorders in a large-scale clinical service, helping improving overall pregnancy management.Keywords: noninvasive prenatal testing, fetal chromosome disorders, high risk, twin pregnancy, performance evaluation

Keywords

• noninvasive prenatal testing
• fetal chromosome disorders
• high risk
• twin pregnancy
• performance evaluation.