Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of the Fetal Medicine Foundation results and meta-analysis.

Abstract

Objective: To report on the routine clinical implementation of cell-free (cf)DNA analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancies and to define the performance of the test by combining our results with those arising from systematic review of the literature. Methods: The data for the study were derived from prospective screening for trisomies 21, 18 and 13 in twin pregnancies at 10+0-14+1 weeks’ gestation. Two populations were included; first self-referred women to the Fetal Medicine Centre in London or Brugmann University Hospital in Brussels and second, women selected for the cfDNA test after routine first-trimester combined testing in one of two National Health Service hospitals in England. This dataset was used to determine the performance of screening for the three trisomies. Search of Medline, Embase, CENTRAL (The Cochrane Library), ClinicalTrials.gov and ICTRP (World Health Organization) was carried out to identify all peer-reviewed publications on clinical validation or implementation of maternal cfDNA testing for trisomies 21, 18 and 13 in twin pregnancies. Meta-analysis was then performed using our data and data from the studies identified by the literature search. Results: In our dataset of 997 twin pregnancies with a cfDNA result and known outcome, the test classified correctly 16 (94.1%) of the 17 cases of trisomy 21, 9 (90.0%) of 10 of trisomy 18, 1 (50.0%) of 2 of trisomy 13 and 963 (99.5%) of 968 cases without any of the three trisomies. The literature search identified 7 relevant studies, excluding our papers because their data are included in the current study. In the combined total of our study and the 7 studies identified by the literature search there were 56 trisomy 21 and 3,718 non-trisomy 21 twin pregnancies; the pooled weighted detection rate (DR) and false positive rate (FPR) were 98.2% (95% CI 83.2, 99.8%) and 0.05% (95% CI 0.01, 0.26%), respectively. In the combined total of 18 cases of trisomy 18 and 3,143 non-trisomy 18 pregnancies the pooled weighted DR and FPR were 88.9% (95% CI 64.8, 97.2%) and 0.03% (95% CI 0.00, 0.33%), respectively. For trisomy 13, there were only 3 affected cases and 2 (66.7%) of these were detected by the cfDNA test at FPR of 0.19% (5/2,569). Conclusions: Performance of cfDNA testing for trisomies 21 in twin pregnancies is similar to that reported for singleton pregnancies. The number of cases of trisomies 18 and 13 is too small for accurate assessment of predictive performance of the cfDNA test.