Abstract
INTRODUCTION: To assess the clinical efficacy of prenatal cfDNA screening for detecting sex chromosome aneuploidies (SCAs). MATERIAL AND METHODS: We conducted a retrospective study at a single center including women with singleton pregnancies who underwent prenatal cfDNA screening between January 2020 and December 2024. Cases with high-risk cfDNA screening results for SCAs were reviewed for confirmatory diagnostic results, prenatal ultrasound findings, and pregnancy outcomes. Positive predictive values (PPVs) were calculated for each SCA subtype, and associations between ultrasound findings and confirmed SCAs were analyzed. RESULTS: A total of 252 pregnancies (252/58720, 0.43%) were identified as high-risk cfDNA screening results for SCAs, including 224 fetal and 28 maternal cases. The fetal SCAs comprised 101 cases of 45,X, 37 of 47,XXX, 55 of 47,XXY, and 31 of 47,XYY. Among them, 173 underwent invasive diagnosis, confirming 90 true SCA cases with a PPV of 52.0%. For 45,X, there was a trend toward a higher detection rate in those with abnormal ultrasound findings compared to those with normal ultrasound results (4/20 vs. 8/127, p = 0.060), though it did not reach statistical significance; no significant differences were observed for sex chromosome trisomies. Of the 16 maternal SCA cases that underwent invasive testing, all fetuses had normal karyotypes. CONCLUSIONS: Our findings demonstrated prenatal cfDNA screening as a unique approach to achieve effective detection of fetal SCAs, particularly those that otherwise would be overlooked by routine prenatal ultrasound screening.