(1108) Diagnostic Outcomes of Sex Chromosome Abnormalities Detected on Noninvasive Prenatal Testing

To evaluate the confirmation rate of sex chromosome abnormalities (SCA) including both sex chromosome aneuploidies and atypical sex chromosomes findings on noninvasive prenatal testing (NIPT).  

Study Design:
This retrospective cohort study included patients who underwent diagnostic testing following results of SCA on NIPT between March 2020 and June 2025. Exclusion criteria included incomplete records, contraindications to NIPT (e.g. organ or bone marrow transplant, hematological malignancy) and normal NIPT results. Medical records were reviewed for demographics, diagnostic results, and ultrasound findings. The primary outcome was the diagnostic confirmation rate, defined as the proportion of SCA on NIPT results that were subsequently confirmed by diagnostic testing (Chorionic Villi Sampling and/or Amniocentesis). Chi-squared tests were used for categorical variables and Mann-Whitney U test for continuous variables. 

Results:

Of 91 patients who met inclusion criteria, NIPT predicted the type of SCA in 49 (53.8%) cases, while 42 (46.2%) were not specified. Among those with a specified SCA type, the diagnostic confirmation rate was 29% for monosomy X, 67% for triple X, 80% for XXY, and 100% for XYY (p = 0.001). Among the unspecified SCA type, only 11 (26%) were confirmed on diagnostic testing. Maternal karyotype was more likely to be normal when the SCA was confirmed on diagnostic testing compared to when it was not (100% vs. 57%, p = 0.038). Maternal demographics and ultrasound findings did not differ significantly between groups. 

Conclusion:
The diagnostic confirmation rate for monosomy X was low, whereas other SCAs (XYY, Triple X, and XXY) were more frequently confirmed. The false positive cases of SCA were often linked to abnormal maternal chromosomes. These findings underscore the importance of offering diagnostic testing, including maternal karyotyping, and providing comprehensive counseling about the risk of false positives, especially in cases of monosomy X.