P01.04: Cell‐free DNA analysis in twin pregnancies after reduction because of fetal aneuploidy

In multifetal pregnancies, cell-free DNA from a non-viable conception may lead to a non-invasive prenatal test result that is discordant with the viable fetus. However, few studies have examined changes in cell-free DNA over time in pregnancies with an aneuploid fetal demise. Using elective fetal reduction as a model for natural demise, we examine the results of targeted cell-free DNA analysis at multiple points after reduction of an aneuploid twin. Two twin pregnancies, each with one aneuploid fetus (one trisomy 21 and one monosomy X), were included in the study. Maternal blood was collected at multiple time points prior to and following reduction and studied using targeted cell-free DNA analysis. Proportion values were calculated for chromosomes 21, X, and Y. The chromosome 21 and X aneuploidy values represent the relative signal from the chromosome of interest compared to that expected in disomy. The chromosome Y value represents the presence of Y signal. Fetal fraction was also determined for all samples. In the first pregnancy with a male fetus with trisomy 21 and one female euploid fetus, the aneuploidy values from chromosome 21 moved towards the expectation for euploidy over 13 weeks following reduction. The chromosome Y value followed a similar pattern. In the second pregnancy with a fetus with monosomy X, the aneuploidy value from chromosome X moved towards the expectation for euploidy over the 8 weeks following reduction. However, the trends were not linear: both cases showed a transient increase in the level of aneuploidy 3 to 8 weeks following reduction. Fetal fraction also increased and then decreased again over several weeks. Notably, the aneuploidy values never reached 0 (the euploid state) even months after the reduction. These study results demonstrate the complexity of cell-free DNA analysis in multifetal pregnancies with reduction. The unpredictable patterns for both aneuploidy and fetal fraction after fetal reduction do not support cell-free DNA testing at any given interval following a fetal demise. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.