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Non-invasive prenatal test findings in 41,819 pregnant women: results from a clinical laboratory in southern China

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Abstract

Background

This paper evaluated the clinical utility of massively parallel sequencing-based non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21), T18, T13, sex chromosome aneuploidies (SCA), and rare chromosome aneuploidies (RCA) among the data collected by a clinical laboratory in southern China.

Methods

In a 3-year period between January 2017 and December 2019, over 40,000 pregnant women underwent NIPT clinical screening test for fetal T21, T18, T13, SCA, and RCA in our laboratory. NIPT samples were processed using the NextSeq CN500 platform. The positive results were confirmed by karyotyping, and chromosomal microarray analysis (CMA) or copy number variants (CNV) sequencing. Details of the pregnancy outcomes were collected via telephone interview.

Results

NIPT results were available for 41,819 cases; 691 positive cases were reported. The overall sensitivity for detection of T21, T18, T13, SCA, and RCA was 99.21, 100.00, 100.00, 98.55, and 100.00%, and the specificity was 99.95, 99.94, 99.98, 99.69, and 99.92%, respectively. The positive predictive values (PPVs) for detection of T21, T18, T13, SCA, and RCA were 85.62, 45.24, 40.00, 34.17, and 13.51%, respectively, and those for detection of 45,X, 47,XXY, 47,XXX, 47,XYY, and 46,XY(delX) 20.00, 59.18, 28.95, 61.54, and 25.00%, respectively. Regarding pregnancy outcomes, 92.38% of the pregnancies with confirmed aneuploidies were terminated, and 91.20% of those identified as having a false-positive result were carried to term. Among 252 unconfirmed cases, 24.60% of the pregnancies were terminated and 38.10% carried to term, while 37.30% declined interview.

Conclusions

NIPT is widely used to screen fetal aneuploidies based on its high sensitivity and specificity. However, in this study, the PPVs of NIPT in terms of detecting T18, T13, XO, XXX and RCA were < 50%. In addition, more than one-third of NIPT-positive women did not accept invasive prenatal diagnosis. Confirmatory diagnosis is strongly recommended for women with positive NIPT outcomes before any further decision is made.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank all of the project participants for their contributions. We also thank Textcheck (http://www.textcheck.com) for language editing.

Funding

The study was supported by Science and Technology Planning Project of Guangzhou, China (201604020104).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Siping Liu, Qingxian Chang, Fang Yang, Yushuang Xu, Bei Jia, Ruifeng Wu, Liyan Li, Ailan Yin, Weishan Chen, Fodi Huang & Fenxia Li

  2. Institute of Antibody Engineering, School of Laboratory Medical and Biotechnology, Southern Medical University, Guangzhou, China

    Xuexi Yang

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  1. Siping Liu
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  2. Qingxian Chang
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  3. Fang Yang
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Contributions

FL, QC and XY conceived the analysis. FL drafted the manuscript. SL and YX reviewed NIPT results. RW, WC, and FH performed the validation experiments. QC, FY, BJ, LL and AY performed clinical diagnosis and communication with patients. FL followed the pregnancy outcome. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Fenxia Li.

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Written informed consent was obtained from all subjects and their legal guardians.

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Liu, S., Chang, Q., Yang, F. et al. Non-invasive prenatal test findings in 41,819 pregnant women: results from a clinical laboratory in southern China. Arch Gynecol Obstet 308, 787–795 (2023). https://doi.org/10.1007/s00404-022-06908-3

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