Non-invasive prenatal test findings in 41,819 pregnant women: Results from a clinical laboratory in southern China

Background: This paper evaluated the clinical utility of massively parallel sequencing-based non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21), T18, T13, sex chromosome aneuploidies (SCA), and rare chromosome aneuploides (RCA) among the data collected by a clinical laboratory in southern China. Methods: : In a 3-year period between 1January 2017 and 31 December 2019, over 40,000 pregnant women underwent NIPT clinical screening tests for fetal T21, T18, T13, SCA, and RCA in our laboratory. NIPT samples were processed using the NextSeq CN500 platform. The results were confirmed by karyotype, and chromosomal microarray analysis or CNV sequencing. Details of the pregnancy outcomes were collected via telephone interviews. Results: : NIPT result were available for 41,819 cases; 691positive cases were reported. The overall sensitivity for detection of T21, T18, T13, SCA, and RCA was 99.21%, 100.00%, 100.00%, 98.55%, and 100.00%, and the specificity was 99.95%, 99.94%, 99.98%, 99.69%, and 99.92% respectively. The positive predictive value (PPVs) for detection of T21, T18, T13, SCA, and RCA were 85.62%, 45.24%, 40.00%, 34.17%, and 13.51%, respectively, and those for detection of 45,X, 47,XXY, 47,XXX, 47,XYY, and 46,XY(delX) 20.00%, 59.18%, 28.95%, 61.54%, and 25.00%, respectively. Regarding pregnancy outcomes, 92.38% of the pregnancies with confirmed aneuploidies were terminated, and 91.20% of those identified as having a false-positive result were carried to term. Among 252 unconfirmed cases, 24.60% of the pregnancies were terminated and 38.10% carried to term, while 37.30% unfollow-up. Conclusions: : NIPT is widely used to screen fetal aneuploidies based on its high sensitivity and specificity. However, in this study, the PPVs of NIPT in terms of detecting T18, T13, XO, XXX and RCA were <50%. However more than one-third of NIPT-positive women did not accept the prenatal diagnosis. Confirmatory diagnosis is strongly recommended for women with positive NIPT outcomes before any further decision is made.