Advancing Obstetric Care: The Role of Targeted Next-Generation Sequencing in Pregnancies with Structurally Normal Fetuses [RETRACTED]

In Brief Background: This study aimed to establish a targeted fetal next-generation sequencing (NGS) panel and evaluate its diagnostic yield in sonographically normal fetuses. Methods: A retrospective analysis was conducted on 1,820 cases of sonographically normal fetuses who underwent fetal NGS targeted panel testing, based on parental requests, between June 2021 and June 2023. Results: Among the 1,820 cases analyzed, 833 cases (45.8%) showed no anomalies, 893 cases (49.1%) were identified with abnormal carrier statuses, and 94 cases (5.2%) exhibited pathogenic condition. The most frequently identified condition was glucose-6-phosphate dehydrogenase (G6PD) deficiency, with hemizygous mutations observed in 35 cases. This was followed by homozygous pathogenic variants in the GJB2 gene, identified in 19 cases. Additionally, 83 cases exhibited G6PD gene mutations, and 344 cases were identified as carriers of GJB2 gene variants. Other notable findings included 15 cases of familial hypercholesterolemia, 5 cases of Noonan syndrome, and 2 cases of osteogenesis imperfecta. Rare disorders identified were Wilson's disease, cystic fibrosis, Cockayne syndrome, and ototoxic hearing loss, each occurring in a single case. Conclusion: The study demonstrated that the fetal NGS targeted panel yielded critical findings in 5.16% of sonographically normal fetuses, emphasizing its potential in prenatal diagnostics. Effective screening requires careful variant selection and detailed pre- and post-test genetic counseling to ensure clinical relevance and informed decision-making for parents. Lay summary: This study explored the value of using a targeted genetic test, called next-generation sequencing, in pregnancies where the baby appeared normal on ultrasound. Researchers analyzed 1,820 such cases between June 2021 and June 2023. Although no physical abnormalities were seen, about 5% of the fetuses were found to have genetic conditions, such as G6PD deficiency and hearing loss due to GJB2 gene mutations. Nearly half of the cases were also identified as carriers for various inherited conditions.These findings show that genetic testing can uncover important health information even when the fetus appears normal, potentially helping families prepare for future medical needs.