Fetal fractions
The temporal dynamic changes of fetal fractions by three different
methods in all five pregnancies are shown in Figure 1, and detailed
information at each timepoints listed in Table S1.
In patient 1, both fetuses were female and fetal fractiosn could not be
calculated using Y-chromosome signals. However, the fetal fraction of
the reduced T18 fetus was calculated using trisomy signals, showing an
immediate decline from 3.27% to 2.01% after reduction and a mild
increase to 3.41% at eight weeks after reduction. After that, the
demised T18 fetus gradually stopped the release of cfDNA at 16 weeks
after reduction as the fetal fraction dropped to close to 0. In
contrast, after a transient decline, the overall fetal fraction
maintained stable for several weeks, and then rise when the terminated
fetus reduced the release of cfDNA at eight weeks after reduction.
In patient 2, who had a male euploidy and a male T18 fetus, the fetal
fraction of the terminated T18 fetus increased from 1.80% to the
maximum of 11.71% at nine weeks after reduction and then rapidly
declined to close to 0 at 11 weeks after reduction. Since both fetuses
were male, the male fetal fractions calculated by the Y-chromosome
method and the overall fetal fractions calculated by FF-QuantSC were
almost overlapped, which showed peak levels at nine weeks after
reduction following the quick decline afterward. At 12 weeks after
reduction when the terminated fetus stopped the release of cfDNA, the
fetal fraction of the euploid fetus quickly rebound, and kept rising
until birth. It was noted that at 15 and 20 weeks after reduction, the
overall fetal fractions were slightly higher than the fetal fractions of
male fetuses.
Both patient 3 and 4 had discordant sex twins with a female trisomy and
a male euploid fetus. The fetal fractions of the terminated female fetus
showed the increase of fetal fraction to peak levels at seven to nine
weeks after reduction. After that, the terminated fetus in patient 3
gradually reduced the release of cfDNA and stopped discharge at 22 weeks
after reduction, while the fetal fraction of the terminated fetus in
patient 4 dropped to close 0 at 15 weeks after reduction. In both
patients, once the fetal fractions of the terminated female fetuses
began to decline, the fetal fractions of the euploid male fetuses
rapidly increased, especially when the fetal fraction of the terminated
female fetus was down to nearly 0. When the terminated female fetuses in
both patient 3 and 4 still gave rise substantial amount of cfDNA to
maternal circulation, the overall fetal fractions were higher than the
fetal fractions of each co-twin. However, after the fetal fractions of
the terminated female fetuses reduced to a relatively low level, the
total fetal fractions were closely correlated with the fetal fractions
of the euploid male fetuses.
In patient 5, since a male T18 fetus was terminated in the female-male
twins, the fetal fractions calculated with trisomy signals and Y
chromosome were almost identical, both showing a transient decrease
shortly after reduction and later rise to maximum levels at eight weeks
after reduction, and finally decline to nearly 0% at 14 weeks after
reduction. Before seven weeks of post-reduction, the overall fetal
fraction maintained two to four folds higher than the fetal fraction of
the terminated fetus. Once the terminated fetus stopped the release of
cfDNA at 14 weeks after reduction, the overall fetal fraction began to
increase rapidly.