The Effect of Screening for Down Syndrome with cfDNA on Miscarriage Rates


Women with pregnancies at high risk for
trisomy 21, also known as Down syndrome, are often referred for fetal karyotyping
procedures like amniocentesis and CVS. Both of these are invasive
and have been associated with an additional 1% risk of miscarriage. Cell-free DNA, or cfDNA, tests are
increasingly being offered to women to reduce the number of required
invasive procedures. Those at high would first undergo
the non-invasive cfDNA test, and only if the results are positive, would
then be referred for invasive procedures. But the effect of this strategy
has yet to be evaluated. So researchers in France designed a randomized
clinical trial with the objective of determining if this strategy reduces the rate of miscarriage
compared with immediate invasive testing. So let’s review the study. The trial was conducted over two
years in 57 centers in France. The participants included just over 2100 women
whose risk of trisomy 21 was estimated to be between 1 in 5 and 1 in 250 following
combined first-trimester screening. About half the women were referred to receive
a cfDNA test followed by invasive testing only if the cfDNA results were positive,
while the other half were referred to receive immediate invasive testing. The primary outcome was the number of
miscarriages before 24 weeks gestation. Okay, onto the results. The miscarriage rate in both groups was 0.8%,
for a risk difference of negative 0.03%. Not statistically significant. But the trial did turn up some
interesting secondary outcomes. 11 chromosomal abnormalities other
than Trisomy 21 were found in the group that underwent immediate invasive procedures, some of these requiring dedicated
follow-up and management. That’s 1.5% of pregnancies in that group. Given the randomized nature of the study,
a similar incidence of abnormalities in the cfDNA group would be expected, but
only one abnormality, or 0.1%, was detected. The main conclusion is that among women
with pregnancies at high risk of trisomy 21, using cfDNA tests to stratify women
for invasive testing did not result in a significant reduction in
miscarriage rates before 24 weeks. But the researchers note that the
study may have been underpowered to detect clinically important
differences in miscarriage rates.

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