Cell‐free DNA test for fetal chromosomal abnormalities in multiple pregnancies

Introduction This study aimed to report the screening performance of cell‐free DNA (cfDNA) testing for chromosomal abnormalities in twins, triplets, and vanishing twin pregnancies. Material and Methods Data were obtained from pregnant women with a multiple pregnancy or a vanishing twin pregnancy at ≥10 weeks’ gestation who requested self‐financed cfDNA testing between May 2015 and December 2021. Those that had positive screening results had diagnostic confirmatory procedures after counseling and consent. The performance of screening of the cfDNA test was determined by calculating confirmation rate and combined false‐positive rate (cFPR). Results Data from 292 women were included after exclusion of those lost to follow‐up, with no‐result on cfDNA testing, or had reductions. Of the 292 pregnancies, 10 (3.4%) were triplets, including no cases of trisomy 21 and trisomy 18; 249 (85.3%) were twins, including 3 cases of trisomy 21 and no cases of trisomy 18 and 13; and 33 (11.3%) were vanishing twins, including 3 cases of trisomy 21 and 1 case of trisomy 18. The median (IQR) maternal age was 34 years (31–37). For triplet pregnancies, the initial no‐result rate was 10.3% (95% confidence interval [CI] 3.6–26.4), all with results after redraw. For twin pregnancies, the initial no‐result rate was 12.9% (95% CI 9.6–17.0), and the no‐result rate after redraw was 1.6% (95% CI 0.7–3.6). For vanishing twins, there were no cases with no‐result. All triplets had low‐risk cfDNA results. The confirmation rate for trisomy 21 was 100% with a FPR at 0% due to the small number of positive cases for twins. For vanishing twins, one high‐risk case for trisomy 21 and the only high‐risk case for trisomy 18 were confirmed with a cFPR of 8.3% (n = 2/24; 95% CI 2.3–25.9). Conclusions cfDNA testing in twin pregnancies has sufficient screening performance for trisomy 21 but the number of affected cases for other conditions is limited to draw any meaningful conclusion. The use of cfDNA testing in triplet pregnancies and vanishing twins remains an area for further research. cfDNA testing in twin pregnancies has sufficient screening performance for trisomy 21 but the number of affected cases for other conditions is limited to draw any meaningful conclusion. The use of cfDNA testing in triplet pregnancies and vanishing twins remains an area for further research.