Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy

Objectives : First, to examine the performance of screening for fetal trisomies 21, 18 and 13 in twin pregnancies by cell free (cf ) DNA testing of maternal blood and second, to compare twin and singleton pregnancies for the distribution of fetal fraction and failure rate to obtain a result.<br /><br />Methods:<br />This was a prospective study in 438 twin and 10,698 singleton pregnancies undergoing screening for fetal trisomies by cfDNA testing at 10 +0 13 +6 weeks’ gestation.<br /><br />Chromosome selective sequencing of cfDNA was used and in twin pregnancies an algorithm was applied that relies on the lower fetal fraction contribution of the two fetuses. Multivariate<br />regression analysis was used to determine significant predictors of fetal fraction and failed result<br /><br />Results:<br />In twin pregnancies, compared to singletons, the median fetal fraction was lower (8.0, IQR 6.0 10.4% vs 11.0, IQR 8.3 14.4%; p<0.0001 ) and failure rate after first sampling was higher ( vs 2.9 %%; p<0.0001 )). Multivariate logistic regression analysis demonstrated that the risk of test failure increased with increasing maternal age and body mass index and decreased with fetal crown rump length ; t he risk was increased in women of South Asian racial origin and in pregnancies conceived by in vitro fertilization The main contributor to the higher rate of failure in twins was conception by in vitro fertilization which was observed in<br />9.5% of singletons and 56.2% of twins. In the 417 twin pregnancies with a cfDNA result after first or second sampling , the detection rate was 100% for trisomy 21 (8 of 8) and 60% for trisomy 18 or 13 (3 of 5), at false positive rate of 0.25% (1 of 404). In the 10,530 singleton pregnancies with a cfDNA result after first or second sampling, the detection rate was 98.7% for trisomy 21 (156 of 158) and 80.3% for trisomy 18 or 13 (49 of 61) 61), at false positive rate of 0.22% (23 of 10,311).<br /><br />Conclusions:<br />In twin pregnancies, compared to singletons, undergoing first trimester screening for trisomies by cfDNA testing, the fetal fraction is lower and failure rate higher.<br /><br />The number of trisomic twin pregnancies examined is too small for accurate assessment of performance of screening, but this may be similar to that in singleton pregnancies