Clinical evaluation of target capture sequencing technique for noninvasive prenatal diagnosis of β-thalassemia: A prospective case series

This study evaluated the clinical utility of a target capture sequencing technique with a “pseudotetraploid” model for noninvasive prenatal testing of β-thalassemia in high-risk pregnancies. A prospective case series included 24 pregnant women with confirmed β-thalassemia carrier status. Cell-free DNA from maternal plasma was analyzed using a custom panel targeting common β-thalassemia mutations. Fetal genotypes were estimated using the “pseudotetraploid” model, and results were compared with invasive diagnostic findings. All 24 samples met DNA quality criteria, with 19 confirmed fetal thalassemia cases (13 β-thalassemia, 5 carriers, 1 unaffected). The detection rate was 79.17%, with a sensitivity of 89.47% (95% confidence interval [CI]: 77.56%–95.67%), specificity of 90.00% (95% CI: 69.77%–97.94%), positive predictive value of 97.14% (95% CI: 84.28%–99.94%), and negative predictive value of 69.23% (95% CI: 42.06%–88.43%). No fetal aneuploidies were detected. The findings support the clinical applicability of this noninvasive prenatal testing method for β-thalassemia, demonstrating high diagnostic accuracy and potential for multiplex genetic screening in a single assay, improving prenatal care efficiency.