Genome‐Wide NIPT With Fetal‐Fraction Enrichment and BinDel: Clinical Cohort Evaluation of Microdeletion and ‐Duplication Detection
Year: 2026
Type: article
Abstract: ABSTRACT Objective To evaluate the analytical and clinical performance of fetal fraction (FF) enriched genome‐wide noninvasive prenatal testing (GW‐NIPT) for the detection of clinically relevant copy number variants (CNVs) down to 1 Mb. Methods We retrospectively analyzed 10,501 singleton pregnancies tested with FF enrichment‐based GW‐NIPT between August 2023 and July 2025. CNV analysis was performed using BinDel and WisecondorX. Results FF enrichment increased the mean FF to 24% (2.4‐fold increase). Clinically relevant CNVs, including microdeletions and microduplications, were detected down to approximately 1 Mb. Performance was robust across all maternal body mass index (BMI) categories. The retest rate was 0.95%, resulting in a final no‐call rate of 0.03% with no BMI‐attributable failures. The workflow demonstrated high observed sensitivity, specificity, and positive predictive value for common aneuploidies, rare autosomal trisomies, sex chromosome aneuploidies and subchromosomal CNVs. Conclusions FF enrichment enhances the analytical resolution of first‐trimester GW‐NIPT, extending detection of subchromosomal CNVs to approximately 1 Mb across diverse patient populations, although detection at the lower end of this range remains fetal‐fraction dependent. This approach broadens the scope of prenatal screening while maintaining low test failure rates. All positive findings require confirmatory diagnostic testing and appropriate genetic counseling.
Source: Prenatal Diagnosis
DOI: 10.1002/pd.70286
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,640
OpenAlex ID: W7222902811