Abstract

Objevtive: This study was performed to explore clinical significance of sex chromosome aneuploidies (SCAs) positive results in non‐invasive prenatal screening (NIPS) on both pregnant women and fetus.

Methods: We retrospective analysis pregnant women with high-risk SCAs results revealed by NIPS from January 2019 to December 2022. Clinical information and pregnancy outcomes were collected. According to the results of prenatal diagnosis, SCAs positive cases were divided into true positive (TP) Group and false positive (FP) Group. Copy number variation sequencing (CNV-seq) was performed with maternal white blood cells both on TP Group and FP Group.

Results: In total, 177 (0.63%) women with SCAs positive results were collected from 27,941 NIPS.100 women accepted prenatal diagnosis by Chromosomal microarray analysis (CMA), of them, 40 (40%) fetal SCAs were confirmed. The positive predictive value (PPV) for 45,X, 47,XXX, 47,XXY, 47,XYY and other SC abnormalities detected by NIPS was 20.00%, 47.62%, 72.22%, 66.67% and 25.00% respectively. In FP Group, 57 cases of maternal white blood cells were conducted by CNV-seq, of them, 30(30/57, 52.63%) cases of sex chromosome abnormality including 22(38.6%) cases of mosaicism monosomy X, 6(10.5%) trisomy X and 2 (3.5%) mosaicism trisomy X, 6 (10.5%) case of maternal chromosome X CNV were detected, and the remaining 22 (38.6%) case were normal. In TP Group, 30 cases of maternal white blood cells were conducted by CNV-seq, of them, no obvious abnormalities were found in the pregnant women.

Discussion: Maternal sex chromosome abnormality especially monosomy X played an important role in inconsistency between NIPT and prenatal diagnosis. Our findings showed that maternal mosaicism is an important reason for the false positive of SCAs. SCAs positive results of NIPS can indicate fetal as well as maternal chromosome X abnormality. Maternal CNV-seq examination should be recommended for SCAs false positive women so as to strengthen pregnancy health management and guidance in second pregnancy.