Analysis of Prenatal Diagnosis and Pregnancy Decisions of 767 Singleton Pregnancies With Positive Prenatal Cell‐Free DNA Screening Results in Southwest China

Background This study explored the associations between positive cell‐free DNA (cfDNA) screening results and the decisions made by pregnant women regarding invasive diagnosis and continuation of pregnancy. Methods We collected follow‐up invasive diagnosis results, pregnancy decisions, and related clinical information for 767 singleton pregnancies with positive cfDNA screening results for common trisomies and genome‐wide copy number variants (CNVs) from a cohort of 113,654 singleton pregnancies. Results A total of 547 (0.48%) cases of high‐chance common trisomies and 220 (0.19%) cases of high‐chance CNVs (≥ 3 Mb) were identified through cfDNA screening. The acceptance rate for invasive prenatal diagnosis (IPD) was 89.8% (474/520) in high‐chance common trisomies and 75.9% (151/195) in those with high‐chance CNVs. The positive predicted value of cfDNA screening was 65.4% for common trisomies (310/474) and 29.1% for CNVs (44/151) in this study. After IPD through SNP array‐based chromosomal microarray analysis (CMA), 15.2% (23/151) of high‐chance CNVs were classified as pathogenic. Eighty‐three percent of pathogenicity (23/24) was observed in concordant high‐chance CNVs driven by fetal signals only; 97.1% of parents chose to terminate their pregnancies with confirmed fetal common trisomies, and 95.7% of parents chose to terminate their pregnancies with confirmed pathogenic CNVs. Conclusions Currently, the vast majority of cases with positive prenatal cfDNA screening findings underwent IPD. While the technical PPVs were satisfactory, the parental pregnancy choices were largely dependent on the confirmation results. Our findings further demonstrate the clinical utility of prenatal cfDNA screening for CNVs.