Malan V, et al. - In this randomized clinical trial, researchers compared the rates of miscarriage following invasive procedures only in the case of positive cfDNA test results vs immediate invasive testing procedures in women with pregnancies at high risk of trisomy 21 as identified by first-trimester combined screening. Findings revealed that using cell-free DNA to stratify individuals for invasive testing compared with direct invasive testing was not related to a significant reduction in the rate of miscarriage in women with pregnancies at high risk of trisomy 21. This investigation might have been underpowered to identify clinically important differences in miscarriage rates.

Methods

• This trial directed from April 8, 2014, to April 7, 2016, in 57 centers in France among 2111 women with pregnancies with a risk of trisomy 21 between 1 in 5 and 1 in 250 following combined first-trimester screening.
• Participants in the study were randomized to receive either cfDNA testing followed by invasive testing procedures only when cfDNA tests results were positive (n = 1034) or to receive immediate invasive testing procedures (n = 1017).
• Based on next-generation sequencing, the cfDNA testing was performed using an in-house validated method.
• Number of miscarriages before 24 weeks’ gestation was the primary outcome.
• cfDNA testing detection rate for trisomy 21 was the included secondary outcomes.
• The primary outcome underwent 1-sided testing.
• Secondary outcomes underwent 2-sided testing.

Results

• The study results showed that among 2051 women who were randomized and analyzed (mean age, 36.3 [SD, 5.0] years), 1997 (97.4%) completed the trial.
• It was observed that the miscarriage rate was not significantly different between groups at 8 (0.8%) vs 8 (0.8%), for a risk difference of -0.03% (1-sided 95% CI, -0.68% to ∞; P=.47).
• The present data indicated that the cfDNA detection rate for trisomy 21 was 100% (95% CI, 87.2%-100%).