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

Abstract

Purpose To evaluate the noninvasive prenatal testing (NIPT) results of 36,913 cases in Jiangxi province of central China and explore its application value in prenatal screening and diagnosis. Methods This retrospective analysis included 36,913 singleton pregnant women who underwent NIPT because of moderate-/high-risk pregnancy or voluntary requirements between January 2017 and December 2019 in our hospital. Chromosomal abnormalities such as trisomies 21, 18, and 13 (T21, T18, T13) and sex chromosome aneuploidies (SCAs) were judged by standard Z-score analysis. Positive NIPT results were confirmed by amniocentesis and karyotyping. Pregnancy outcomes were followed up via telephone interview. Results A total of 1.01% (371/36,913) positive cases were detected by NIPT, comprising 137, 46, 31, and 157 cases of T21, T18, T13, and SCAs, respectively. A total of 116 of T21, 27 of T18, 13 of T13, and 51 of SCAs were confirmed to be true positive; all normal cases that had been followed up were verified to be true negative. The NIPT sensitivity in T21, T18, T13, and SCAs was 100.00% individually, whereas the specificity was 99.94% (36,488/36,509), 99.95% (36,579/36,598), 99.95% (36,594/36,612), and 99.72% (36,472/36,574), respectively. Furthermore, the negative predictive values of T21, T18, T13, and SCAs were all 100%, while the positive predictive values were 84.67%, 58.70%, 41.94%, and 33.33%, respectively. Conclusion NIPT is highly sensitive and has a low false positive rate in testing clinically significant fetal aneuploidies of general reproductive women. However, this technique cannot substitute for amniocentesis and karyotyping, and detailed genetic counseling is also essential for the high-risk group of NIPT.

The accuracy and feasibility of noninvasive prenatal testing in a consecutive series of 20,626 pregnancies with different clinical characteristics

“…Recently, the detection range of NIPT has been expanding and has been extended to the screening of fetal chromosome microdeletion/microduplication syndrome (MMS), namely NIPT‐plus. Our results are consistent with previous domestic studies 30–32 . It is too early to judge the true sensitivity and false‐negative rate of SCAs in this study, because these clinical symptoms are not easily identified in neonatal examination and require long‐term prospective follow‐up 33 .…”

Positive predictive value estimates for noninvasive prenatal testing from data of a prenatal diagnosis laboratory and literature review

“…These data were mostly from China [ 8 – 10 , 13 – 20 ] and the United States [ 23 , 27 ], the Netherlands [ 24 ], Japan [ 22 ], Iran [ 25 ], and Italy [ 21 , 26 ]. The PPVs presented in this study were consistent with those in previous reports (Table 5 ) [ 9 , 15 – 17 , 19 , 20 ]. PPVs for T21 were higher than 84% in most reports, while only two reports had PPVs lower than 80% [ 10 , 14 ].…”

Clinical Application of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies in Central China

“…In contrast, limited methods can be used to screen SCAs, as the clinical features of most SCAs are not detectable during prenatal ultrasound examination because many develop after birth with the exception of structural anomalies more commonly seen in the Turner syndrome ( 1 , 5 – 7 ). With the discovery of circulating cell-free fetal DNA (cffDNA) in the blood samples of pregnant women and the advent of massively parallel genomic sequencing (MPS) technology, NIPT has been widely applied for the clinical screening for fetal chromosomal aberrations and has already expanded beyond the three common autosomal trisomies to include SCAs ( 8 , 9 ).…”

“…An increasing number of reports have proven that NIPT is the most accurate screening test for trisomy 21, trisomy 18, and trisomy 13 with high sensitivity and specificity ( 9 – 22 ). However, limited studies have evaluated the accuracy of NIPT for screening SCAs ( 7 , 8 , 23 ).…”