Main findings
Using selective reduction of a co-twin with aneuploidy as the simulation of twin demise, we demonstrated that the fetal fraction of the terminated fetus underwent dynamic changes and persistent effect throughout pregnancy. After fetal reduction, the fetal fraction of the terminated fetus took 7 to 9 weeks to reach a peak level, and then gradually dropped down to nearly 0% at 15 to 16 weeks after reduction. In one case (patient 3), the residual cfDNA of the terminated fetus even gave rise to observable fetal fraction at 20 weeks after reduction, equivalent to 37 gestational weeks in this woman. On the other hand, in patient 3 and 4, we observed that the fetal fraction of the remaining normal fetus appeared to maintain stable or mildly increase until the fetal fraction of the trisomy co-twin declined.
The influence of the residual cfDNA of a terminated fetus was apparent, as we found the persistent detection of fetal trisomy after the fetal reduction, ranging from 12 to 22 weeks post-reduction with the median of 15.8 weeks. Importantly, in all pregnancies, T-scores demonstrated close correlations to the fetal fractions of the terminated fetus, showing a rapid increase from two to three weeks after reduction and reached the maximum values at seven to nine weeks after reduction, following the gradual decline to close to 0 in the late third trimester. In patient 3 who had a very long presence of residual cfDNA of the terminated T21 fetus, NIPT showed positive results until 20 weeks after reduction, which was concordant to the fetal fraction results.