title: Fetal Aneuploidy Detection by Cell-Free DNA Sequencing for Multiple Pregnancies and Quality Issues with Vanishing Twins.
abstract: Non-invasive prenatal testing (NIPT) by random massively parallel sequencing of maternal plasma DNA for multiple pregnancies is a promising new option for prenatal care since conventional non-invasive screening for fetal trisomies 21, 18 and 13 has limitations and invasive diagnostic methods bear a higher risk for procedure related fetal losses in the case of multiple gestations compared to singletons. In this study, in a retrospective blinded analysis of stored twin samples, all 16 samples have been determined correctly, with four trisomy 21 positive and 12 trisomy negative samples. In the prospective part of the study, 40 blood samples from women with multiple pregnancies have been analyzed (two triplets and 38 twins), with two correctly identified trisomy 21 cases, confirmed by karyotyping. The remaining 38 samples, including the two triplet pregnancies, had trisomy negative results. However, NIPT is also prone to quality issues in case of multiple gestations: the minimum total amount of cell-free fetal DNA must be higher to reach a comparable sensitivity and vanishing twins may cause results that do not represent the genetics of the living sibling, as described in two case reports.
authors.affiliation: LifeCodexx AG, Konstanz 78315, Germany. s.groemminger@lifecodexx.com.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grömminger
authors.affiliation: Bahceci IVF Center, Istanbul 34330, Turkey. erbilyagmur@hotmail.com.
authors.forename: Erbil
authors.initials: E
authors.lastname: Yagmur
authors.affiliation: BioGen Medical Instruments Co. Ltd., Istanbul 34235, Turkey. sanlierkan@biogen.com.tr.
authors.forename: Sanli
authors.initials: S
authors.lastname: Erkan
authors.affiliation: Petz Aladár Country Teaching Hospital, Győr 9023, Hungary. nagysandor@gyor.net.
authors.forename: Sándor
authors.initials: S
authors.lastname: Nagy
authors.affiliation: LifeCodexx AG, Konstanz 78315, Germany. u.schoeck@lifecodexx.com.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schöck
authors.affiliation: LifeCodexx AG, Konstanz 78315, Germany. j.bonnet@lifecodexx.com.
authors.forename: Joachim
authors.initials: J
authors.lastname: Bonnet
authors.affiliation: LifeCodexx AG, Konstanz 78315, Germany. p.smerdka@lifecodexx.com.
authors.forename: Patricia
authors.initials: P
authors.lastname: Smerdka
authors.affiliation: Sequenom Center for Molecular Medicine, San Diego, CA 92121, USA. mehrich@sequenom.com.
authors.forename: Mathias
authors.initials: M
authors.lastname: Ehrich
authors.affiliation: Center for Prenatal Diagnosis and Human Genetics Kudamm-199, Berlin 10719, Germany. wegner@kudamm-199.de.
authors.forename: Rolf-Dieter
authors.initials: RD
authors.lastname: Wegner
authors.affiliation: LifeCodexx AG, Konstanz 78315, Germany. w.hofmann@lifecodexx.com.
authors.forename: Wera
authors.initials: W
authors.lastname: Hofmann
authors.affiliation: Center for Prenatal Diagnosis and Human Genetics Kudamm-199, Berlin 10719, Germany. stumm@kudamm-199.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Stumm
keywords: NIPT; aneuploidy; cell-fee fetal DNA; multiple pregnancies; random massively parallel sequencing; trisomy; vanishing twin