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.