The role of non-invasive prenatal testing and ultrasound in prenatal screening of fetal chromosomal abnormalities in singleton: a retrospective study.

Background: Non-invasive prenatal testing (NIPT) has good screening performance for common chromosomes, but it may have false positive (FP) and false negative (FN) results for various reasons. For abnormal NIPT results, the combination of fetal ultrasound phenotypes will provide more fetal information for prenatal diagnosis. The aim of this study was to combine NIPT and ultrasound phenotypes to analyze their complementary roles in prenatal screening of fetal chromosome abnormalities. Methods: From January 2018 to December 2021, 12,803 pregnant women with singleton who successfully underwent NIPT/expanded NIPT (NIPT-Plus) at Xiangya Hospital of Central South University, of which 111 cases were positive results and one case was FN result. We retrospectively collected the clinical features, ultrasonographic findings, prenatal diagnosis, and pregnancy outcomes of these 112 pregnant women and analyzed the ultrasonic manifestations of different chromosomal abnormalities in detail. Results: The positive predictive values (PPVs) of NIPT/NIPT-Plus for trisomy (T)21, T18, sex chromosome abnormality (SCA), microdeletion/microduplication syndrome (MMS), T13, and rare autosomal trisomy (RAT) were 100.0%, 85.7%, 57.1%, 44.4%, 40.0%, and 7.7%, respectively. The total termination rates of pregnancy for T21, T18, T13, SCA, pathogenic MMS, and RAT were 93.5%, 100.0%, 100.0%, 66.7%, 100.0%, and 100.0%, respectively. From the karyotypes of SCA live-born fetuses, 47,XYY and 47,XXX were more likely to be selected for continued pregnancy. The ultrasound phenotypes of T21 were diverse, including normal, soft marker, and structural malformation. Both T18 and T13 had structural malformations as the main phenotypes. Most ultrasound phenotypes of FP T21, T18, and T13 were normal but occasionally manifested as fetal growth restriction (FGR). The ultrasound phenotypes of SCA, MMS, and RAT were relatively mild and manifested as normal, soft marker, FGR, or polyhydramnios, and the ultrasound phenotypes were similar between FP and true positive (TP) cases. Conclusions: Ultrasound phenotypes are helpful in identifying FP NIPT/NIPT-Plus results, especially for T18 and T13. Given its mild ultrasound phenotypes, NIPT-Plus has important clinical significance in reducing the missed diagnosis of SCA, MMS, and RAT, but its screening performance needs to be further improved.