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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2024

Open Access 01-12-2024 | Trisomy 18 | Research

Identification of copy number variations among fetuses with isolated ultrasound soft markers in pregnant women not of advanced maternal age

Authors: Yunyun Liu, Sha Liu, Jianlong Liu, Ting Bai, Xiaosha Jing, Cechuan Deng, Tianyu Xia, Jing Cheng, Lingling Xing, Xiang Wei, Yuan Luo, Quanfang Zhou, Dan Xie, Yueyue Xiong, Ling Liu, Qian Zhu, Hongqian Liu

Published in: Orphanet Journal of Rare Diseases | Issue 1/2024

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Abstract

Background

Pathogenic (P) copy number variants (CNVs) may be associated with second-trimester ultrasound soft markers (USMs), and noninvasive prenatal screening (NIPS) can enable interrogate the entire fetal genome to screening of fetal CNVs. This study evaluated the clinical application of NIPS for detecting CNVs among fetuses with USMs in pregnant women not of advanced maternal age (AMA).

Results

Fetal aneuploidies and CNVs were identified in 6647 pregnant women using the Berry Genomics NIPS algorithm.Those with positive NIPS results underwent amniocentesis for prenatal diagnosis. The NIPS and prenatal diagnosis results were analyzed and compared among different USMs. A total of 96 pregnancies were scored positive for fetal chromosome anomalies, comprising 37 aneuploidies and 59 CNVs. Positive predictive values (PPVs) for trisomy 21, trisomy 18, trisomy 13, and sex chromosome aneuploidies were 66.67%, 80.00%, 0%, and 30.43%, respectively. NIPS sensitivity for aneuploidies was 100%. For CNVs, the PPVs were calculated as 35.59% and false positive rate of 0.57%. There were six P CNVs, two successfully identified by NIPS and four missed, of which three were below the NIPS resolution limit and one false negative. The incidence of aneuploidies was significantly higher in fetuses with absent or hypoplastic nasal bone, while that of P CNVs was significantly higher in fetuses with aberrant right subclavian artery (ARSA), compared with other groups.

Conclusions

NIPS yielded a moderate PPV for CNVs in non-AMA pregnant women with fetal USM. However, NIPS showed limited ability in identifying P CNVs. Positive NIPS results for CNVs emphasize the need for further prenatal diagnosis. We do not recommend the use of NIPS for CNVs screening in non-AMA pregnant women with fetal USM, especially in fetuses with ARSA.
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Metadata
Title
Identification of copy number variations among fetuses with isolated ultrasound soft markers in pregnant women not of advanced maternal age
Authors
Yunyun Liu
Sha Liu
Jianlong Liu
Ting Bai
Xiaosha Jing
Cechuan Deng
Tianyu Xia
Jing Cheng
Lingling Xing
Xiang Wei
Yuan Luo
Quanfang Zhou
Dan Xie
Yueyue Xiong
Ling Liu
Qian Zhu
Hongqian Liu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2024
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-024-03066-4

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