Introduction
The fetal demise of a co-twin (i.e., spontaneous reduction to a singleton pregnancy) is common with an estimated prevalence of 6.2% in all twin pregnancies [1, 2]. This prevalence might be underestimated, since the fetal demise occurred in the early trimester, also known as the ‘vanishing twin’, which may affect as high as 30% of early diagnosed pregnancies [3-6]. The reasons for fetal demise could be complicated, yet chromosomal anomaly could be an important factor, given the high rate of chromosome aneuploidy in early singleton miscarriages [7-9]. It has been previously reported that the demised fetus continues to give rise residual cell-free DNA (cfDNA) to maternal circulation, which can cause false-positive results of fetal aneuploidy and fetal gender when noninvasive prenatal testing (NIPT) is conducted [10-12]. This poses technical uncertainties and counseling difficulties when providing NIPT service in twin pregnancies, or pregnancies with unaware fetus demise. So far, there is a lack of clinical guidelines in terms of the interval after fetus demise to provide NIPT, partly because the longitudinal change of residual cfDNA of demise fetus has not been extensively studied. We aimed to use dichorionic diamniotic (DCDA) twin pregnancies undergoing selective fetal reduction of an aneuploidy co-twin as a model of natural fetal demise to investigate the sequential changes of residual cfDNA of the deceased fetus, as well as the persistent effect on NIPT.