Clinical performance of non-invasive prenatal served as a first-tier screening test for trisomy 21, 18, 13 and sex chromosome aneuploidy in a pilot city in China

Abstract

Background: Cell-free fetal DNA (cffDNA) has opened up new approaches for non-invasive prenatal testing (NIPT), and it is often used as the second-tier test for high-risk pregnant women in detecting trisomy (T) 21, T18, and T13 after serum biochemistry screening. This study aims to discuss the clinical performance of NIPT as an alternative first-tier screening test for pregnant women in detecting T21, T18, T13, and sex chromosome aneuploidies (SCAs) in China. Methods: A total of 42,924 samples were recruited. The cell-free plasma DNA was directly sequenced. Each of the chromosome aneuploidies of PPV was analyzed. A total of 22 placental samples were acquired, including 14 FP and 8 TP samples. The placental verification of FP NIPT results was performed. Results: Among 42,924 samples, 281 (0.65%) positive cases, including 87 of T21, 31 of T18, 22 of T13, and 141 of SCAs were detected. For the detection of T21, the positive predictive value (PPV) was 78.46%, for trisomy 18, 62.96%, for trisomy 13, 10.00%, for SCAs, 47.22% in the total samples. For trisomy 21, the PPV was 86.67%, for trisomy 18, 80.00%, for trisomy 13, 20.00%, for SCAs, 56.52% in advanced maternal age (AMA) women. The PPV of T21 increased with age. For T18, the PPV showed an overall upward trend. For T13 and SCAs, PPV was raised first and then lowered. Placental verification of false positive (FP) NIPT results confirmed confined placental mosaicism(CPM) was the reason for false positives. Conclusions: This study represents the first time that NIPT has been used as a first-tier screening test for fetal aneuploidies in a pilot city with large clinical samples in China. We propose that NIPT could replace serum biochemistry screening as a first-tier test.

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

“…Serological screening for trisomies based on maternal serum-free β-human chorionic gonadotrophin (β-HCG), pregnancy-associated plasma protein-A (PAPP-A), and αfetoprotein (AFP) levels is still widely used in China. These biochemical markers, combined with maternal age, are usually used for screening for Down syndrome and can achieve a detection rate of 70-80% but a PPV of almost 10% [19]. Compared with NIPT for detection of T21 in our study, the sensitivity and specificity of serological screening seemed unsatisfactory.…”

“…A recent study of 31,515 singleton pregnancies in southeastern China showed a high sensitivity and specificity for T21, T18, T13, and SCAs, and the positive predictive values were high for T21 and T18 and moderate for T13 and SCAs [16]. Therefore, NIPT has been implemented into public healthcare systems as either a first-line test or a supplement to the existing prenatal screening; more and more pregnant women are willing to choose NIPT [17][18][19].…”

Noninvasive prenatal detection of fetal sex chromosome abnormalities using the semiconductor sequencing platform (SSP) in Southern China

“…There is a situation in which a chromosomal abnormality that occurs only in the placenta but not in the fetus is known as CPM. Therefore, collecting placental tissue for further verification is a critical part of confirming CPM, which is reported in Liu’s latest article [ 18 ]. In this study, no placental tissue was obtained for verification, which was a limitation of the present study.…”

“…Samples were processed, and plasma was shipped frozen when necessary. Trisomies 13,18, and 21 were reported as well as other chromosomal aneuploidies. Cell-free DNA extraction, library construction, sequencing, and bioinformatics analysis were performed according to a previous study.…”

Discussing non‐invasive prenatal testing on Reddit: The benefits, the concerns, and the comradery

“…In Europe, Belgium, and the Netherlands have begun offering NIPT for all pregnant women, while numerous other countries offer NIPT for women deemed higher risk after first-tier screening. 2,3 Research shows that NIPT could increasingly be implemented as a first-tier screen for all pregnant women and many countries including Canada (http://pegasus-pegase.ca/), are exploring this option 1,[4][5][6] Barriers to increased implementation of NIPT center on costs (for individuals or healthcare systems), patient and practitioner education, as well as various social and ethical implications. 1,7,8 NIPT is seen as beneficial, as it enhances reproductive autonomy but also problematic, as it can, for example, have negative impact on disability rights.…”