High Risk for Rare Autosomal Trisomies Detected by Non‐Invasive Prenatal Testing: Prenatal Diagnosis and Pregnancy Outcomes

Objective To investigate the incidence, positive predictive value (PPV) and pregnancy outcomes of rare autosomal trisomies (RATs) identified by non‐invasive prenatal testing (NIPT). Method A retrospective analysis of pregnancies who underwent NIPT at our center between May 2020 and August 2024 and received high‐risk RATs results. A copy number (CN) ≥ 2.4 indicated high‐risk for maternal duplications, while a CN ≤ 1.6 correlated with maternal deletion. Targeted amplicon sequencing was utilized to screen for uniparental disomy (UPD)‐related imprinting disorders. Prenatal diagnosis and pregnancy outcome follow‐up were recommended for all high‐risk pregnancies. Results Among 20,796 pregnancies screened, 0.26% (55/20,796) were identified as high‐risk for RATs. Prenatal diagnosis was performed in 44 cases, with a PPV of 4.55%. Maternal copy number variations were confirmed in four cases, three of which were transmitted to the fetus. No UPD‐related imprinting disorders were detected in the 23 cases. Two cases of mosaic trisomy showed similar levels of mosaicism on chromosomal microarray analysis (CMA) but had divergent clinical outcomes. Among 36 cases with no abnormalities detected by prenatal CMA, 38.89% had adverse outcomes. Conclusion NIPT for RATs has a low PPV, but the risk of adverse outcomes is high. Mosaic RATs identified via amniocyte‐based prenatal diagnosis do not always correlate with an obvious postnatal phenotype. Integrating prenatal diagnosis with ultrasound monitoring is essential for fetal prognosis.