Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies

ABSTRACT

Background

Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort.

Research design and methods

In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022. SCAs were diagnosed based on karyotyping or chromosomal microarray analysis (CMA). Among them, 2,084 singleton pregnancies received karyotyping and/or CMA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NIPS for fetal SCAs were evaluated.

Results

The sensitivity was 97.7% (95%CI, 87.7–99.9), 87.3% (95% CI, 76.5–94.4), 96.1% (95%CI, 86.5–99.5), and 95.7% (95% CI, 78.1–99.9), the PPV was 25.8% (95%CI, 19.2–33.2), 80.9% (95%CI, 69.5–89.4), 79.0% (95%CI, 66.8–88.3), and 53.7% (95%CI, 37.4–69.3) for 45,X, 47,XXY, 47,XXX, and 47,XYY, respectively. The specificity was 94.1% (95%CI, 93.0–95.1) for 45,X, and more than 99.0% for sex chromosome trisomy (SCT). The NPV was over 99.0% for all.

Conclusions

NIPS screening for fetal SCAs has high sensitivity, specificity and NPV. The PPV of SCAs was moderate, but that of 45,X was lower than that of SCTs. Invasive prenatal diagnosis should be recommended for high-risk patients.

KEYWORDS:

• Cell-free fetal DNA
• noninvasive prenatal screening
• sex chromosome aneuploidy
• singleton pregnancy
• performance

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Minyue Dong conceived and designed the study; Yanfei Xu, Jianbo Lou, Yeqing Qian, Pengzhen Jin, Yangwen Qian, Jiawei Hong, Yuqing Xu, Yixuan Yin and Songjia Yi acquired and analyzed the data; Yanfei Xu wrote the manuscript; Minyue Dong revised the manuscript critically for intellectual content; All the authors approved the version to be published and agreed to be accountable for all aspects of the work.

Ethics approval

IRB-20230049-R.

Additional information

Funding

This paper was funded by the National Natural Science Foundation of China (No. 82171848), the Key Projects Jointly Constructed by the Ministry and the Province of Zhejiang Medical and Health Science and Technology Project (WKJ-ZJ-2127), and Key Research and Development Program of Zhejiang Province (No. 2019C03025).