Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result

Objectives:
First, to report the distribution of fetal fraction and the rate of failed result in trisomies
21, 18 and 13 , by comparison with pregnancies unaffected by these trisomies, secondly, examine the possible effects of maternal and fetal characteristics on the fetal fraction and thirdly, consider the options for the further management of pregnancies with failed cfDNA result.

Methods:
This was a cohort study of 10,698 singleton pregnancies undergoing screening for fetal trisomies 21, 18 and 13 by cfDNA testing at 10 14 weeks’ gestation There were 160 cases of trisomy 21, 50 of trisomy 18, 16 of trisomy 13 and 10,472 unaffected by these trisomies. Multivariate regression analysis was used to determine significant predictors of fetal fraction and failed result amongst maternal and fetal characteristics.

Results:
Fetal fraction decreased with increasing body m ass index and maternal age, was lower in women of South Asian racial origin than in Caucasians and in assisted than natural conceptions, and increased with fetal crown rump length, serum PAPP A and free  hCG. The median fetal fraction was 11.0% (IQR 8.3-14.4%) in the unaffected group, 10.7% (IQR 7.8-14.3%) in trisomy 21, 8.6% (IQR 5.0-10.2%) in trisomy 18 and 7.0% (IQR 6.0-9.4%) in trisomy 13. There was a failed result from cfDNA testing after first sampling in 2.9% of the unaffected group, 1.9% of trisomy 21, 8.0% of trisomy 18 and 6.3% of trisomy 13. In the cases of failed result, 7% of women had invasive testing, mainly because of high risk from the combined test and/or presence of sonographic features suggestive of trisomies 18 and 13. All cases of trisomies were detected prenatally.

Conclusions:
In cases of failed cfDNA test the rate of trisomies 18 and 13, but not trisomy 21, are higher than in those with a successful test. In the management of such cases, the decision in favor of invasive testing sh ould depend on the risk of prior screening and the results of detailed ultrasound examination.