Accuracy of cell‐free fetal DNA in detecting chromosomal anomalies in women experiencing miscarriage: systematic review and meta‐analysis

ABSTRACT Objective To report the diagnostic accuracy of cell‐free fetal DNA (cfDNA) in detecting fetal chromosomal anomalies in women experiencing miscarriage. Methods PubMed, MEDLINE, EMBASE and Cochrane databases were searched from inception to June 2024. The inclusion criteria were women experiencing miscarriage (defined as pregnancy loss before 20 weeks of gestation) who underwent cfDNA screening for trisomies 21, 18 and 13, other autosomal aneuploidies, sex‐chromosome aneuploidies and/or copy‐number variants (CNVs). The index test was cfDNA screening for each of the chromosomal anomalies listed. The reference standard was cytogenetic analysis of pregnancy tissue. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were computed using the hierarchical summary receiver‐operating‐characteristics model. Results Seven studies (887 women) were included in the systematic review and meta‐analysis. cfDNA had a sensitivity and specificity of 100% (95% CI, 81.5–100%) and 100% (95% CI, 99.1–100%), respectively, for trisomy 21, 100% (95% CI, 54.1–100%) and 100% (95% CI, 99.0–100%), respectively, for trisomy 18, and 88.9% (95% CI, 51.8–99.7%) and 100% (95% CI, 99.1–100%), respectively, for trisomy 13. The respective values for other autosomal trisomies were 75.8% (95% CI, 65.7–84.2%) and 99.4% (95% CI, 97.9–99.9%), while those for CNVs were 60.0% (95% CI, 14.7–94.7%) and 100% (95% CI, 97.4–100%). Failure of cfDNA testing was reported in 7.3% (95% CI, 5.7–9.2%) of cases. Conclusion cfDNA has high diagnostic accuracy in detecting fetal trisomies 21, 18 and 13 in women experiencing miscarriage, while its accuracy for other autosomal aneuploidies and CNVs is only moderate. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.