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

Abstract

To evaluate the performance of noninvasive prenatal screening (NIPS) in the detection of common aneuploidies in a population-based study, a total of 86,262 single pregnancies referred for NIPS were prospectively recruited. Among 86,193 pregnancies with reportable results, follow-up was successfully conducted in 1160 fetuses reported with a high-risk result by NIPS and 82,511 cases (95.7%) with a low-risk result. The screen-positive rate (SPR) of common aneuploidies and sex chromosome abnormalities (SCAs) provided by NIPS were 0.7% (586/83,671) and 0.6% (505/83,671), respectively. The positive predictive values (PPVs) for Trisomy 21, Trisomy 18, Trisomy 13 and SCAs were calculated as 89.7%, 84.0%, 52.6% and 38.0%, respectively. In addition, less rare chromosomal abnormalities, including copy number variants (CNVs), were detected, compared with those reported by NIPS with higher read-depth. Among these rare abnormalities, only 23.2% (13/56) were confirmed by prenatal diagnosis. In total, four common trisomy cases were found to be false negative, resulting in a rate of 0.48/10,000 (4/83,671). In summary, this study conducted in an underdeveloped region with limited support for the new technology development and lack of cost-effective prenatal testing demonstrates the importance of implementing routine aneuploidy screening in the public sector for providing early detection and precise prognostic information.

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

“…Consistent with other reports (Ramdaney et al, 2018), the majority of pregnancies chose to continue. The overall termination rate was 56.0% in SCAs‐confirmed cases: which was relatively lower than that of other reports in the same period (61.1%–81%) (Lai et al, 2021; Scibetta et al, 2017). Reasons were mainly due to the study population, SCAs types, the parental willingness, and genetic counseling (Ge et al, 2021).…”

Validity and Utility of Non-Invasive Prenatal Testing for Copy Number Variations and Microdeletions: A Systematic Review

“…Twelve studies solely evaluated the genome-wide detection of CNVs. Most of them screened for previously undiagnosed fetal CNVs [ 4 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], but two studies obtained samples with known CNVs and retrospectively conducted NIPT analysis [ 39 , 40 ].…”

“…Most of the studies obtained plasma samples from the population of pregnant women who underwent NIPT without specifically defining referral indications for the screening [ 4 , 10 , 15 , 17 , 19 , 20 , 21 , 28 , 30 , 31 , 33 , 34 , 35 , 37 , 38 ]. Some included only samples of women with high-risk pregnancies (over 35 years of age), positive serum screening results, a history of aneuploidy, abnormal ultrasound findings, or simply maternal anxiety [ 22 , 32 , 40 ].…”

“…Only one study explicitly analyzed twin pregnancies [ 13 ]. The most common exclusion criteria in these studies were known parental chromosomal abnormalities, multiple pregnancies, known maternal malignancy, the mother receiving an allogeneic blood transfusion, organ transplantation surgery, stem cell therapy, or immunotherapy, as well as an egg donor or surrogate pregnancies [ 10 , 13 , 34 , 36 , 37 , 38 ]. Li et al also excluded samples whose transportation to the laboratory took more than 48 h, those with visible hemolysis, and a fetal fraction of less than 3% [ 40 ].…”

“…After cfDNA quantification, libraries were tag-sequenced to generate 3.5 M–32 M reads per sample and aligned to the human reference genome [ 22 , 29 ]. Reads were then allocated to continuous non-overlapping 20 kb–100 kb bins and filtered to remove bins with abnormal GC content [ 13 , 21 , 33 , 38 , 39 , 40 ]. Next, similar statistical methods were used by five teams of researchers.…”