Clinical utility of expanded non‐invasive prenatal screening and chromosomal microarray analysis in high‐risk pregnancy

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. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Next-generation sequencing: a follow-up of 36,913 singleton pregnancies with noninvasive prenatal testing in central China

“…Hence, some of the positive cases turned out to be false positive. Although our [25][26][27], several reasons contribute to having false-positive results, including maternal chromosomal abnormality [28,29], confined placental mosaicism [30,31], vanishing twin [32], maternal copy number variations [33], fetal fraction [34], and so on. In addition, a short-term telephone followup to ascertain whether the newborns are normal or not is not entirely reliable and can also contribute to false-positive results.…”

Mosaicism for copy number variations in the placenta is even more difficult to interpret than mosaicism for whole chromosome aneuploidy

“…Results from each ppCVS were categorized as fully concordant (identical to the mosaicism detected in CVS, but the level of abnormal cell line was allowed to vary), related concordant (mosaicism at the same chromosome/chromosomal region as detected in CVS), discordant abnormal (mosaicism of a different chromosome than the mosaicism detected in CVS), or normal (normal nonmosaic molecular karyotype). These categories have been modified from Zhu et al 27 …”

Performance of Cell-Free DNA Screening for Fetal Common Aneuploidies and Sex Chromosomal Abnormalities: A Prospective Study from a Less Developed Autonomous Region in Mainland China

“…The positive rate of such abnormalities by expanded NIPS ranged from 0.12 to 1.58% among all submitted cases [7,8,[10][11][12][13], with the positive predictive values (PPVs) for copy number variants (CNVs), RATs and other abnormalities as 28.99-57.14% [8,10,12,13], 6-58.82% [8,10,13,14] and 0-64% [10][11][12], respectively. Although expanded NIPS is able to provide an increased yield of the overall chromosomal abnormalities [8], it is still difficult to evaluate its sensitivity and specificity due to the differences exist in (1) types and spectrum of chromosomal abnormalities, (2) resolution (sizes) [13,15,16], (3) sequencing platforms [8,17], (4) sequencing parameters analyzed (such as sequencing read-depth and cf-DNA%) [17,18] and (5) referral indications [12,16,19,20]. In addition, as the incidence of individual aberration is low, validation in a cohort with large sample size with pregnancy outcomes is challenging but still needed.…”