title: False Negative NIPT Results: Risk Figures for Chromosomes 13, 18 and 21 Based on Chorionic Villi Results in 5967 Cases and Literature Review.
abstract: Non-invasive prenatal testing (NIPT) demonstrated a small chance for a false negative result. Since the "fetal" DNA in maternal blood originates from the cytotrophoblast of chorionic villi (CV), some false negative results will have a biological origin. Based on our experience with cytogenetic studies of CV, we tried to estimate this risk. 5967 CV samples of pregnancies at high risk for common aneuplodies were cytogenetically investigated in our centre between January 2000 and December 2011. All cases of fetal trisomy 13, 18 and 21 were retrospectively studied for the presence of a normal karyotype or mosaicism < 30% in short-term cultured (STC-) villi. 404 cases of trisomies 13, 18 and 21 were found amongst 5967 samples (6,8%). Of these 404 cases, 14 (3,7%) had a normal or low mosaic karyotype in STC-villi and therefore would potentially be missed with NIPT. It involved 2% (5/242) of all trisomy 21 cases and 7.3% (9/123) of all trisomy 18 cases. In 1:426 (14/5967) NIPT samples of patients at high risk for common aneuploidies, a trisomy 18 or 21 will potentially be missed due to the biological phenomenon of absence of the chromosome aberration in the cytotrophoblast.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Diane
authors.initials: D
authors.lastname: Van Opstal
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Malgorzata I
authors.initials: MI
authors.lastname: Srebniak
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: Polak
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: de Vries
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Lutgarde C P
authors.initials: LC
authors.lastname: Govaerts
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Joosten
authors.affiliation: Department of obstetrics and prenatal medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Attie T J I
authors.initials: AT
authors.lastname: Go
authors.affiliation: Department of obstetrics and prenatal medicine, Erasmus Medical Center, Rotterdam, the Netherlands.|Stichting Prenatale Screening Zuidwest Nederland, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Maarten F C M
authors.initials: MF
authors.lastname: Knapen
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Cardi
authors.initials: C
authors.lastname: van den Berg
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Karin E M
authors.initials: KE
authors.lastname: Diderich
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Robert-Jan H
authors.initials: RJ
authors.lastname: Galjaard
mesh_terms: D002824:Chorionic Villi / Q000378:metabolism*; D002904:Chromosomes, Human, 21-22 and Y / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D005260:Female; D006801:Humans; D011247:Pregnancy