Genome-Wide Cell-Free DNA Analysis for Aneuploidy Detection in Miscarriages: Test Performance Meta-Analysis

Abstract

Objective: To conduct a systematic review and meta-analysis of published series examining the efficacy of genome-wide cell-free DNA (cfDNA) testing in identifying aneuploidy in pregnancies ending in miscarriage. Methods: A systematic review was conducted encompassing observational studies evaluating aneuploidy detection by genome-wide cfDNA testing in pregnancy losses before 22 weeks of gestation. A hierarchical summary receiver operating curve was employed to assess pooled sensitivity, specificity, and area under the curve (AUC) of genome-wide cfDNA versus genetic diagnostic studies in the detection of aneuploidy. Pooled aneuploidy rate, rate of no-calls, and concordance between cfDNA and diagnostic studies were analyzed using a single proportion meta-analysis based on the inverse of the variance. Results: Out of 25 eligible series, eight studies were included for analysis, comprising 552 miscarriages with informative results for both cfDNA and diagnostic testing. Pooled sensitivity, specificity, and AUC were 78% (95% CI: 71%–83%), 91% (95% CI: 86%–95%), and 92%, respectively. Pooled aneuploidy rate, the proportion of no-calls, and concordance were 61% (95% CI: 53%–69%), 4% (95% CI: 0%–12%), and 84% (95% CI: 81%–87%), respectively. In cases of positive cfDNA results, the risk of aneuploidy increased to 93%, whereas negative results yielded a 28% risk of aneuploidy. Conclusion: cfDNA testing demonstrates acceptable accuracy in predicting fetal aneuploidy when employed as a screening test in miscarriages. The main advantage of cfDNA testing is that it does not require the availability of products of conception or prior chorionic villi sampling.