Journal Article

Clinical value of positive CNVs results by NIPT without fetal ultrasonography‐identified structural anomalies

Wang, Changhong, Luan, Shanshan, Li, Hong, Mei, Li, Wen, Liu, Li, Xiaona, Zhang, Ningzhi, Wan, Yang, Lu, Jali, Wang, Pei, Han, Xue

2024

Overview

Objective To evaluate the clinical value of positive copy number variations (CNVs) results by non‐invasive prenatal testing (NIPT) without fetal ultrasonography‐identified structural anomalies, especially with several known CNVs results. Methods A total of 135,981 results of NIPT performed between April 1, 2017, and March 31, 2020, enrolled in the free NIPT service program implemented by the local government were retrospectively analyzed. Of these, 87 cases with positive NIPT screens for CNVs and no fetal ultrasonography‐identified anomalies were recalled and provided genetic counseling. After obtaining full informed consent, these cases were provided invasive prenatal diagnosis by karyotyping and chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV‐seq) with follow‐up. One case was lost, while 86 cases were successfully followed up. Results A total of 44 (50.6%) cases underwent invasive prenatal diagnosis, of which six cases were detected with abnormal karyotype. CMA/CNV‐Seq revealed 11 fetuses with positive results for CNVs, among whom eight were consistent with NIPT results, two were partially consistent, one was inconsistent, and positive predictive value (PPV) was 22.7% (10/44). For known CNVs, PPVs were 20% (15q11.2‐q13 microdeletion) and 33.3% (5p end deletions). Among 11 pregnant women with positive prenatal diagnosis, seven were confirmed to have pathogenic CNVs in their fetuses; four had CNVs of unknown clinical significance. Conclusions Even in pregnancies without ultrasonography‐identified anomalies, a positive NIPT screen for CNVs must be interpreted with caution and validated by additional diagnostic study. The 135,981 results of NIPT performed from April 1, 2017, to March 31, 2020, enrolled in the free NIPT service program implemented by local government were analyzed retrospectively. In total, 87 cases with positive NIPT screens for CNVs and no fetal ultrasonography‐identified anomalies were recalled and provided genetic counseling with follow‐up. 44 (51.2%) underwent invasive prenatal diagnosis, and CMA/CNV‐Seq revealed 11 fetuses with positive results for CNV, among whom 7 were confirmed to have pathogenic CNVs in their fetuses; 4 had CNVs of unknown clinical significance.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Amniocentesis / Anomalies / Chromosome Aberrations / Chromosomes / Chromosomes, Human, Pair 15 / Clinical Report / Clinical Reports / Copy number / copy number variations / Diagnosis / Diagnostic tests / DNA Copy Number Variations / Female / Fetuses / Genetic counseling / Genetic screening / Genomes / Gestational age / Humans / Informed consent / Intellectual Disability / Karyotypes / Local government / non‐invasive prenatal testing / Pregnancy / Prenatal diagnosis / prenatal screening / Retrospective Studies / Sequences / Ultrasonic imaging / Ultrasonography, Prenatal / Womens health