Discordant Karyotype Results Among Non-invasive Prenatal Screening Positive Cases. K. W. CHOY1,2, K. Y. KWOK1, E. T. LAU3, M. H. TANG3, A. PURSLEY4,5, J. SMITH4,5, S. W. CHEUNG4,5, T. Y. LEUNG1, A. PETAL4,5 1) Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China; 2) CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China; 3) Department of Obstetrics and Gynaecology, Tsan Yuk Hospital, The University of Hong Kong, Hong Kong SAR, China; 4) Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; 5) Medical Genetics Laboratories, Baylor College of Medicine, Houston, TX, USA.

   OBJECTIVE: To evaluate the performance of non-invasive prenatal screening (NIPS) for detection of fetal aneuploidies in a multi-center cohort of NIPS high-risk cases referred for prenatal diagnosis. METHODS: Cases included were those referred for an invasive prenatal diagnosis procedure to verify aneuploidies (trisomies 21, 13, 18 and sex chromosomes aneuploidy) among screen positive NIPS cases. The NIPS results were reported from Ariosa, BGI, Natera, Sequenom, and Quest. Cytogenetics studies were performed by two referral prenatal diagnostic laboratories in Hong Kong and the Medical Genetics Laboratories at Baylor College of Medicine.The karyotype results were compared against the NIPS results, and validated by birth follow-up when possible. RESULTS: A total of 80 prospective NIPS positive samples were referred, among which 55 cases were indicated as high risk for trisomy 21, 12 cases for trisomy 18, 7 cases for trisomy 13, 6 cases for sex chromosomes aneuploidy. The NIPS detection rates were as follows: T21: 52 of 55 (94.5%), T18: 6 of 12 (50.0%), T13: 4 of 7 (57.1%), and sex chromosomes aneuploidy: 4 of 6 (66.7%). Overall, NIPS correctly detected 66 of the 80 (82.5%) screen positive cases, including three mosaic karyotype results: two mosaic trisomy 21 and one mosaic 47,XXX[31]/45,X[19]. CONCLUSION: Consistent with previously published studies, the detection rates vary among the different chromosomes with chromosome 21 being the highest followed by sex chromosomes, chromosome 13 and 18. More specifically, close to half of the patients with a screen positive NIPS result for trisomy 13, 18 and sex chromosomes aneuploidy had NORMAL karyotype results. These results support the recommendation that non-invasive prenatal screening should be regarded as an advanced screening test and invasive prenatal diagnosis by CVS or amniocentesis should be performed to confirm the NIPS findings. This has important implications for counseling patients with positive NIPS results.

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