Prenatal diagnosis and analysis of fetuses with false-positive NIPT results caused by sex chromosomal abnormalities in pregnant women
10.3760/cma.j.cn511374-20250127-00053
- VernacularTitle:孕妇性染色体异常导致NIPT假阳性胎儿的产前诊断与分析
- Author:
Tingting BAI
1
;
Fengni FAN
1
;
Xiangdong LIN
1
;
Lihui YANG
1
;
Rong QIANG
1
;
Ting JIA
1
;
Rui WANG
1
Author Information
1. 西北妇女儿童医院医学遗传中心，西安 710061
- Publication Type:Journal Article
- Keywords:
Non-invasive prenatal testing;
Sex chromosome;
Aneuploidy;
Prenatal diagnosis;
Maternal factor;
Maternal chromosome
- From:
Chinese Journal of Medical Genetics
2025;42(5):525-531
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the results of prenatal diagnosis for fetuses with a high risk for sex chromosome aneuploidies (SCAs) indicated by non-invasive prenatal testing (NIPT), and to assess the influence of maternal chromosomal factors on the results of NIPT.Methods:A retrospective analysis was conducted on the clinical data of 454 pregnant women with a high risk for SCAs indicated by NIPT undergoing invasive prenatal diagnosis at the Medical Genetics Center of Northwest Women′s and Children′s Hospital from January 2022 to September 2024. The data has included prenatal diagnosis indications, results, pregnancy outcomes, and chromosomal results of the pregnant women. This study has been approved by the Ethics Committe of Northwest Women′s and Children′s Hospital(Ethics No.2024-132)Results:Among the 454 women (including 10 with twin pregnancy) with a high risk for SCAs indicated by NIPT, 149 (including 4 twin cases) were diagnosed with SCAs through invasive prenatal diagnosis. These had included 47, XXX (37 cases), 47, XXY (56 cases), 47, XYY (29 cases), 45, X (1 case), 48, XXYY (1 case), mosaicism (20 cases), sex chromosome structural abnormalities (6 cases), and small-scale pathogenic copy number variations (3 cases). 383 pregnant women (including 7 with twin pregnancy) had accepted chromosomal karyotyping analysis. In total 49 cases(including 1 twih case) of SCAs were detected. Among them, 41 cases were pregnant women with SCAs but normal fetal chromosomes, which yielded a false positive rate for NIPT caused by maternal factors by 10.7%. In addition, 9 cases (including 1 twin case) had SCAs in both the pregnant woman and the fetus. Among the 383 pregnant women, 129 cases (including 3 twin cases) of fetal SCAs were diagnosed, which yielded an overall positive predictive value (PPV) of NIPT for SCAs by 33.7% (129/383). With the 41 false positive cases caused by maternal SCAs excluded, the PPV of NIPT for SCAs will be increased to 37.7% (129/342). Among the 454 pregnant women, twin pregnancies have accounted for 2.2% (10/454). Among the confirmed cases of SCAs, twin cases accounted for 2.7% (4/149). Among the 383 pregnant women undergoing chromosomal karyotyping, twin cases accounted for 1.8% (7/383). Among the detected cases of chromosomal abnormalities, twin cases accounted for 2.0% (1/49). Among singleton pregnancies, the positive predictive value (PPV) of NIPT for sex chromosome aneuploidies (SCAs) was 32.7% (145/444), in twin pregnancies, the PPV was 40.0% (4/10).Conclusion:NIPT can improve the screening efficiency for SCAs, but its PPV is limited. Therefore, pregnant women with a high risk for SCAs indicated by NIPT need to undergo invasive prenatal diagnosis for a definite diagnosis, while the PPV in twin pregnancies may be higher than in singletons, this observation is limited by the small sample size of twins in our study. The study confirmed that chromosomal abnormalitpies in pregnant women can significantly affect the accuracy of NIPT in detecting fetal SCAs. Therefore, when NIPT indicates SCAs, it is recommended to simultaneously conduct chromosomal karyotyping for the pregnant women. The combined application of chromosomal karyotyping analysis, fluorescence in situ hybridization, and copy number variation detection techniques can significantly improve the diagnostic accuracy for SCAs, especially for the detection of mosaicisms.
