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

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.

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.

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.

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.