X Zhu1,2,3, M Chen4, H Wang5, Y Guo3, M H K Chau1,2, H Yan4, Y Cao1,6, Y K Y Kwok1, J Chen4, A S Y Hui1, R Zhang5, Z Meng5, Y Zhu5, T Y Leung1,2,6, L Xiong5, X Kong3, K W Choy1,2,6. 1. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, SAR, China. 2. Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. 3. Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 4. Department of Fetal Medicine and Prenatal Diagnosis, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 5. Department of Central Laboratory, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Guangdong, China. 6. The Chinese University of Hong Kong, Baylor College of Medicine Joint Center for Medical Genetics, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Abstract
OBJECTIVE: To evaluate the utility of expanded non-invasive prenatal screening (NIPS), compared with chromosomal microarray analysis (CMA), for the detection of chromosomal abnormalities in high-risk pregnancies. METHODS: This was a multicenter retrospective study of singleton pregnancies at high risk for chromosomal abnormality. Patients who underwent expanded NIPS and CMA sequentially during pregnancy from 2015 to 2019 were included in the analysis. Pregnancies with a positive result for sex chromosome aneuploidy were excluded as the full details could not be retrieved. The utility of expanded NIPS and CMA for detection of chromosomal abnormalities in this cohort was compared by assessing the concordance between the results. RESULTS: Of the 774 included high-risk pregnancies, 550 (71.1%) had a positive NIPS result, while a positive CMA result was detected in 308 (39.8%) cases. The rate of full or partial concordance between NIPS and CMA was 82.2%, 59.6% and 25.0% for trisomies 21, 18 and 13, respectively. For rare aneuploidies and segmental imbalances, NIPS and CMA results were fully or partially concordant in 7.5% and 33.3% of cases, respectively. Copy-number variants < 5 Mb were detected more often by CMA, with an incidence of 7.9% (61/774) compared with 3.1% (24/774) by NIPS. A genetic aberration was detected by CMA in 1 in 17 (5.8%) high-risk pregnancies that had a negative or non-reportable NIPS result. CONCLUSION: CMA allows for comprehensive detection of genome-wide chromosomal abnormalities in high-risk pregnancies. CMA should be offered instead of expanded NIPS for high-risk pregnancies.
OBJECTIVE: To evaluate the utility of expanded non-invasive prenatal screening (NIPS), compared with chromosomal microarray analysis (CMA), for the detection of chromosomal abnormalities in high-risk pregnancies. METHODS: This was a multicenter retrospective study of singleton pregnancies at high risk for chromosomal abnormality. Patients who underwent expanded NIPS and CMA sequentially during pregnancy from 2015 to 2019 were included in the analysis. Pregnancies with a positive result for sex chromosome aneuploidy were excluded as the full details could not be retrieved. The utility of expanded NIPS and CMA for detection of chromosomal abnormalities in this cohort was compared by assessing the concordance between the results. RESULTS: Of the 774 included high-risk pregnancies, 550 (71.1%) had a positive NIPS result, while a positive CMA result was detected in 308 (39.8%) cases. The rate of full or partial concordance between NIPS and CMA was 82.2%, 59.6% and 25.0% for trisomies 21, 18 and 13, respectively. For rare aneuploidies and segmental imbalances, NIPS and CMA results were fully or partially concordant in 7.5% and 33.3% of cases, respectively. Copy-number variants < 5 Mb were detected more often by CMA, with an incidence of 7.9% (61/774) compared with 3.1% (24/774) by NIPS. A genetic aberration was detected by CMA in 1 in 17 (5.8%) high-risk pregnancies that had a negative or non-reportable NIPS result. CONCLUSION: CMA allows for comprehensive detection of genome-wide chromosomal abnormalities in high-risk pregnancies. CMA should be offered instead of expanded NIPS for high-risk pregnancies.