Pregnancies with positive non-invasive prenatal testing result for sex chromosome abnormalities in a tertiary hospital in Hong Kong

Abstract

Objectives: To review medical records of pregnant women with positive non-invasive prenatal testing (NIPT) results for sex chromosome abnormalities who attended Tuen Mun hospital between 2015 and 2021. Patient decision after prenatal diagnosis, confirmatory diagnostic testing results, and pregnancy/neonatal outcomes were summarised. Methods: Medical records of women with abnormal NIPT results for sex chromosome abnormalities who attended Tuen Mun Hospital between January 2015 and December 2021 were retrospectively reviewed. Results: 56 Chinese women attended our prenatal diagnostic clinic with abnormal NIPT results for sex chromosome abnormalities involving 45,X (n=17), 47,XXY (n=10), 47,XXX (n=6), 47,XYY (n=8), disproportionate level of sex chromosomes (n=9), copy number variants of sex chromosomes (n=3), and suspected maternal sex chromosome imbalance (n=3). 53 had singleton pregnancies and three had dichorionic-diamniotic twin pregnancies. 58.9% had conventional combined Down syndrome screening; 15.2% of them were at high risk for trisomy 21. 33 (58.9%) of the patients opted for invasive diagnostic test: amniocentesis (n=29), chorionic villus sampling (n=3), and chorionic villus sampling followed by amniocentesis (n=1). Confirmatory cytogenetic test results (including postnatal results) were available in 35 cases. The overall positive predictive value of NIPT to detect fetal sex chromosome aneuploidies was 71.4%; the value was 42.9% for detecting 45,X, 100% for detecting 47,XXY, 80% for detecting 47,XXX, and 83.3% for detecting 47,XYY. False positive results were observed in three cases of confined placental mosaicism and three cases of vanishing twin pregnancies. Two women with 47,XXX and one woman with mosaic 45,X/46,XX were also incidentally discovered. Conclusion: Positive NIPT results for sex chromosome abnormalities can be caused by true fetal sex chromosome abnormalities, confined placental mosaicism/placental mosaicism, vanishing twins, and maternal X chromosome abnormalities. Multidisciplinary management can help prenatal counselling and genetic diagnosis. Follow-up confirmatory cytogenetic analysis prenatally and/or postnatally is useful to characterise the numeric or structural fetal sex chromosome abnormalities and their mosaic patterns, and can maximise the benefits of prenatal genetic screening in obtaining more genetic information to support pregnancy management and clinical care of affected unborn child.