High false‐positive non‐invasive prenatal screening results for sex chromosome abnormalities: Are maternal factors the culprit?

Objective To explore the impact of maternal sex chromosome aneuploidies (SCAs) and copy number variation (CNV) on false‐positive results of non‐invasive prenatal screening (NIPS) for predicting foetal SCAs. Methods In total, 22 844 pregnant women were recruited to undergo NIPS. Pregnant women with h...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Prenatal diagnosis 2020-03, Vol.40 (4), p.463-469
Hauptverfasser: Zhang, Bin, Zhou, Qin, Chen, Yingping, Shi, Ye, Zheng, Fangxiu, Liu, Jianbing, Yu, Bin
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Objective To explore the impact of maternal sex chromosome aneuploidies (SCAs) and copy number variation (CNV) on false‐positive results of non‐invasive prenatal screening (NIPS) for predicting foetal SCAs. Methods In total, 22 844 pregnant women were recruited to undergo NIPS. Pregnant women with high‐risk of SCAs underwent prenatal diagnosis and maternal copy number variation sequencing (CNV‐seq). Results Among 117 women with high‐risk of SCAs, 72 accepted prenatal diagnosis, 86 accepted maternal CNV‐seq, and 21 had maternal sex chromosome abnormalities. The abnormality rate was significantly higher than women at low‐risk of SCAs (24.42% vs 3.51%). Using a novel parameter cffDNA (ChrX)/cffDNA, when the ratio was greater than 2, all foetuses had normal karyotype, and 75.0% (6/8) had abnormal maternal chromosome X. If the ratio was less than or equal to 2, only 10% (4/40) of the mothers had chromosome X CNV alterations, while 33.3% (13/40) of their foetuses had sex chromosomes CNV abnormalities. Conclusions Approximately 25% of pregnant women with SCAs predicted by NIPS had sex chromosome abnormalities as determined by CNV‐seq. The ratio of cffDNA (ChrX)/cffDNA can tentatively distinguish the maternal or foetal origin of abnormal cell‐free DNA. In a reanalysis of previous NIPS data, false‐positive results caused by maternal CNV might be elucidated. What's already known about this topic? Non‐invasive prenatal screening (NIPS) for the detection of foetal chromosomal aneuploidy by analysing cell‐free foetal DNA (cffDNA) in the plasma of pregnant women was quickly introduced to clinical practice. The positive predictive value (PPV) of sex chromosome aneuploidies (SCAs) is significantly lower compared with autosomal trisomies. There are various possible causes of a false‐positive NIPS result, including a vanished twin, maternal tumours, maternal mosaicism, confined placental mosaicism, and maternal copy number variation (CNV). What does this study add? In this study, our data show maternal sex chromosome abnormalities (including aneuploidy and CNV) might be an important factor contributing to false‐positive SCAs among 86 pregnant women with foetal SCAs predicted by NIPS, and 20% of false‐positive SCA results were caused by maternal sex chromosome abnormalities. In addition, 23.08% of foetal chromosome X (ChrX) CNV was inherited from the mother. Using the ratio of cffDNA (ChrX)/cffDNA, the SCAs predicted by NIPS were initially distinguished to be maternal or foe
ISSN:0197-3851
1097-0223
DOI:10.1002/pd.5529