To assess the positive predictive value (PPV) of extended noninvasive prenatal testing (NIPT-plus) for fetal chromosomal abnormalities. This retrospective research enrolled 511 cases of pregnant women with positive NIPT-plus results at the Obstetrics and Gynecology Hospital of Fudan University from May 2017 to January 2021. Karyotype analysis and chromosome microarray analysis (CMA) techniques was applied for verification. All cases were followed to determine their pregnancy outcome. The Chi-square test was used in PPV. 63 out of 511 refused prenatal diagnosis after counseling, 448 pregnant women with prenatal diagnosis showed that the PPVs of NIPT-plus test for fetal trisomy 21, 18 and 13 (T21, T18, T13), sex chromosome aneuploidy (SCAs) and chromosome microdeletion/microduplication syndrome (MMS) were 86.0% (92/107), 79.5% (35/44), 54.5% (12/22), 39.5% (75/190), and 41.7% (30/72), respectively. The results revealed that the PPV was higher among older pregnant women compared to young pregnant women (77.8% vs. 51.9%,P<0.01). With increasing maternal age, the PPV of NIPT-plus presented increasing trends for T21, T13, and composite PPV except for T18 or SCAs. In addition, the termination rates for confirmed SCAs fetal karyotypes 45, X; 47, XXX; 47, XXY and 47, XYY were 11/11, 3/15, 91.7% (22/24) and 1/14, respectively. NIPT-plus can safely and effectively detect fetal chromosomal abnormalities and can be extended to MMS screening, significantly reducing the proportion of interventional prenatal diagnoses, and those with positive screening still require further confirmation.

Down syndrome; Karyotyping; Sex chromosome aberrations; Extended non-invasive prenatal genetic testing; Chromosome microarray analysis; Chromosome microdeletion/microduplication