Diagnostic accuracy of cell‐free DNA in maternal blood in detecting chromosomal anomalies in twin pregnancies: systematic review and meta‐analysis

ABSTRACT Objective To report the diagnostic accuracy of cell‐free fetal DNA (cfDNA) in maternal blood in detecting fetal chromosomal anomalies in twin pregnancy. Methods PubMed, MEDLINE, EMBASE and Cochrane databases were searched from inception to November 2023. The inclusion criteria were twin pregnancy undergoing cfDNA screening for trisomies 21, 18 and 13, monosomy X and/or other sex‐chromosome aneuploidies (SCA). The index test was cfDNA screening. The reference standard was pre‐ or postnatal karyotyping (in the case of a positive cfDNA result) or neonatal phenotypic assessment (in case of a negative cfDNA result). The quality of included studies was assessed using the revised quality assessment of diagnostic accuracy studies (QUADAS‐2) tool. Summary estimates of diagnostic accuracy were computed using a bivariate random‐effects model. Results Thirty‐five studies were included in the systematic review and meta‐analysis. cfDNA had a high accuracy in detecting trisomy 21 in twin pregnancy, with a sensitivity of 98.8% (95% CI, 96.5–100%) and specificity of 100% (95% CI, 99.9–100%). Sensitivity and specificity were 94.9% (95% CI, 75.9–99.1%) and 100% (95% CI, 99.9–100%), respectively, for trisomy 18 and 84.6% (95% CI, 54.6–98.1%) and 100% (95% CI, 99.9–100%), respectively, for trisomy 13. We could not compute the diagnostic accuracy of cfDNA in detecting monosomy X, owing to an absence of positive cases, while cfDNA had a sensitivity of 100% (95% CI, 71.5–100%) and specificity of 99.8% (95% CI, 99.7–99.9%) for other SCA. The accuracy of cfDNA in detecting the common trisomies was similar in dichorionic and monochorionic twin pregnancies. Conclusions cfDNA has high diagnostic accuracy in detecting trisomies 21 and 18 in twin pregnancy, irrespective of chorionicity. Estimation of diagnostic accuracy for trisomy 13 and other SCA was limited by the small number of affected cases and the difficulty associated with detecting false‐negative cases of other SCA, and thus requires confirmation in larger studies. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.