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

Area of Science:

• Reproductive Medicine
• Genetics
• Prenatal Diagnostics

Background:

• Miscarriage is a common pregnancy complication.
• Accurate identification of fetal aneuploidy in miscarriage is crucial for understanding recurrence and guiding management.
• Current diagnostic methods often require invasive procedures or specific tissue samples.

Purpose of the Study:

• To systematically review and meta-analyze the efficacy of genome-wide cell-free DNA (cfDNA) testing in detecting aneuploidy in pregnancies ending in miscarriage.
• To compare the diagnostic performance of cfDNA testing with traditional genetic diagnostic studies.

Main Methods:

• Systematic review of observational studies on genome-wide cfDNA testing in pregnancy losses before 22 weeks gestation.
• Hierarchical summary receiver operating curve (HSROC) analysis to assess pooled sensitivity, specificity, and AUC.
• Single proportion meta-analysis for pooled aneuploidy rate, no-call rate, and concordance with diagnostic studies.

Main Results:

• Eight studies including 552 miscarriages were analyzed.
• Pooled sensitivity was 78% (95% CI: 71%-83%) and specificity was 91% (95% CI: 86%-95%) for aneuploidy detection.
• The pooled aneuploidy rate was 61% (95% CI: 53%-69%), with a 4% no-call rate and 84% concordance with diagnostic studies.

Conclusions:

• Genome-wide cfDNA testing demonstrates acceptable accuracy as a screening tool for fetal aneuploidy in miscarriages.
• A key advantage is that cfDNA testing does not necessitate the availability of products of conception or prior chorionic villi sampling.
• This non-invasive approach offers a valuable alternative for aneuploidy screening in early pregnancy loss.