The following is a summary of “Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study,” published in the October 2023 issue of Obstetrics and Gynecology by Dugoff, et al.

Cell-free DNA (cfDNA) screening in maternal blood has proven effective for trisomy 21 detection in singleton pregnancies. However, limited data were available for twin pregnancies, with many previous studies focusing on the second trimester and lacking chorionicity information. For a study, researchers sought to assess the screening performance of cfDNA for trisomy 21 in twin pregnancies within a large, diverse cohort. Additionally, the study explored the screening performance for trisomy 18 and trisomy 13.

Conducted as a retrospective cohort study, data were collected from 17 centers where cfDNA screening was performed on twin pregnancies using massively parallel sequencing technology from December 2011 to February 2020. Detailed medical record reviews were undertaken for newborns, extracting information on birth outcomes, congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing conducted prenatally or postnatally. A committee of maternal-fetal medicine geneticists reviewed cases with possible fetal chromosomal abnormalities lacking genetic test results. Cases involving vanishing twins and those with insufficient follow-up details were excluded. A minimum of 35 confirmed trisomy 21 cases was required for statistical power.

A total of 1,764 twin cell-free DNA screening samples were received, with 78 vanishing twin cases and 239 cases lacking adequate follow-up excluded. This left 1,447 cases for analysis. The median maternal age was 35 years, and the median gestational age at cfDNA testing was 12.3 weeks. Approximately 81% of the twins were dichorionic, and the median fetal fraction was 12.4%. For trisomy 21, 41 out of 42 pregnancies were accurately detected, resulting in a detection rate of 97.6% (95% CI, 83.8–99.7). The detection rate for dichorionic twin pregnancies was 97.4% (95% CI, 82.6–99.7), with 38 out of 39 cases accurately identified. Trisomy 18 was detected in all 10 affected pregnancies, with one false positive case. Trisomy 13 was detected in 4 out of 5 cases, yielding an 80% detection rate (95% CI, 11.1–99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9%.

Cell-free DNA testing demonstrates effectiveness in first-trimester screening for trisomy 21 in twin pregnancies. High detection rates were observed in dichorionic and monochorionic twins, with low nonreportable result rates. While promising for trisomy 18 and 13, the study acknowledged limited case numbers, preventing definitive conclusions on screening efficacy for these conditions. Variability in cfDNA testing performance among laboratories and screening methodologies was also acknowledged.

Source: ajog.org/article/S0002-9378(23)00229-6/fulltext