When Is Non-Invasive Prenatal Testing Reliable in Pregnancies with a Vanishing Twin? - A Systematic Review of Case Reports

Background: Fetal demise can complicate aneuploidy screening in a multi fetal pregnancy. The cellfree DNA (CF-DNA) from a non-viable conception may be discordant with the viable fetuses. The Aim of study was to review the waiting period, follow on single fetal demise in a twin gestation before performing NIPT (Non-Invasive Prenatal Testing). Methods: In this review article we searched through online databases of CINAHL, Cochrane, Database of Abstracts of Reviews of Effects (DARE), PubMed, Medical Library, and Google Scholar for English literature between 2011 to 2020, with the following keywords: "NIPT", "non-invasive prenatal screening testing", "cell free DNA", "vanishing twin" and "co-twin demise". We included the studies regarding the duration between the twin vanishing or reduction and NIPT false results. Results: 201 studies across the eight scientific websites were detected; 178 of which were excluded for duplication or being irrelevant. And 29 studies were fully read. 4 case series, finally, met the criteria for systematic review. The findings suggested that the NIPT screening test can be falsely-positive several weeks after vanishing twins although the live fetus is normal. Therefore, the time duration in which the placenta can release CF-DNA of the vanished twin is unknown. In addition, several weeks after reduction, the fetal CF-DNA increases and then decreases, thus CF-DNA analyzing in multifetal pregnancies with reduction can be challenging as well. Conclusion: In pregnancies with vanishing twin or reduction, evaluating NIPT results is more complex than single fetal pregnancy. According to the reviewed studies, after a fetal demise, the cytotrophoblast continues to release to the CF-DNA in the maternal circulation for a variable time, which may cause a false-positive result if the demised twin is aneuploidy.