Prenatal diagnostic outcomes and positive predictive values in 1,326 pregnancies with high-risk non-invasive prenatal testing results

Objective To investigate the prenatal diagnostic outcomes of pregnant women with high-risk non-invasive prenatal testing (NIPT) results and to explore factors influencing the positive predictive value (PPV) of NIPT. Methods Clinical data from 1,326 pregnant women with high-risk NIPT results who underwent invasive prenatal diagnosis at Hebei General Hospital between January 2014 and December 2023 were retrospectively analyzed. Chromosomal karyotyping, fluorescence in situ hybridization (FISH), and/or copy number variation sequencing (CNV-seq) were used as confirmatory diagnostic methods. PPVs were compared across different types of chromosomal abnormalities, maternal age groups, Z-score categories, ultrasound findings, and before and after implementation of the free NIPT screening policy. Results Among the 1,326 pregnancies with high-risk NIPT results, 648 were confirmed as true positives, yielding an overall PPV of 48.87%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), and sex chromosome abnormalities (SCAs) were 78.61%, 56.36%, 10.53%, and 47.11%, respectively. The PPVs for common autosomal trisomies were higher in the advanced maternal age group than in the non-advanced maternal age group. After implementation of the free screening program, the PPVs for T21, T18, and T13 showed a slight numerical increase, the difference between groups was not statistically significant. PPVs increased with higher Z-scores and were further elevated when multiple ultrasound soft markers or structural anomalies were present. Among SCAs, the PPV for sex chromosome gains was significantly higher than that for sex chromosome losses. Conclusion NIPT demonstrated high screening performance for T21 and T18, whereas T13 and SCAs were associated with relatively high false-positive risks. Clinical interpretation of high-risk NIPT results should integrate maternal age, Z-score, ultrasound phenotype, and confirmatory prenatal diagnostic findings to facilitate stratified genetic counseling and optimize pregnancy management.