Abstract

ObjectiveTo evaluate the effectiveness of non-invasive prenatal screening (NIPS) in prenatal screening of fetal pathogenic copy number variants (CNVs).Materials and MethodsWe evaluated the prenatal screening capacity using traditional and retrospective approaches. For the traditional method, we evaluated 24,613 pregnant women who underwent NIPS; cases which fetal CNVs were suggested underwent prenatal diagnosis with chromosomal microarray analysis (CMA). For the retrospective method, we retrospectively evaluated 47 cases with fetal pathogenic CNVs by NIPS. A systematic literature search was performed to compare the evaluation efficiency.ResultsAmong the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%. In total, 10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10–97.70% and the PPVs were 36.11–80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs > 3 Mb. Finally, to intuitively show the CNVs accurately detected by NIPS, we mapped all CNVs to chromosomes according to their location, size, and characteristics. NIPS detected fetal CNVs in 2q13 and 4q35.ConclusionThe DR and PPV of NIPS for fetal CNVs were approximately 51.1% and 19.7%, respectively. Follow-up molecular prenatal diagnosis is recommended in cases where NIPS suggests fetal CNVs.

Highlights

  • Redon et al (2006) constructed the first-generation copy number variant (CNV) map and reported that copy number variants (CNVs) were ubiquitous in the human genome

  • To intuitively show the CNVs accurately detected by non-invasive prenatal screening (NIPS), we mapped all CNVs to chromosomes according to their location, size, and characteristics

  • Follow-up molecular prenatal diagnosis is recommended in cases where NIPS suggests fetal CNVs

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Summary

Introduction

Redon et al (2006) constructed the first-generation copy number variant (CNV) map and reported that CNVs were ubiquitous in the human genome. Some CNVs exist in the normal human population in the form of genetic polymorphisms, while others may be related to human traits and diseases. With developments in sequencing technology, studies have increasingly shown that CNVs can lead to genetic diseases and syndromes due to gene dosage effects, gene fracture, gene fusion, and location effects (e.g., Mendelian single-gene diseases, rare diseases, and complex diseases). Studies of prenatal diagnosis have shown that pathogenic CNVs are associated with adverse pregnancy outcomes (Watson et al, 2014; Srebniak et al, 2016). The generation of CNVs is very common and can occur randomly at any location on the chromosome. Fetal genetic diagnosis continues to rely on invasive procedures, and no effective non-invasive prenatal screening (NIPS) methods are currently available

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