False Negative NIPT Results: Risk Figures for Chromosomes 13, 18 and 21 Based on Chorionic Villi Results in 5967 Cases and Literature Review

PloS One
D van OpstalRobert-Jan H Galjaard

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.

References

Oct 1, 1990·American Journal of Medical Genetics·E S SachsJ W Wladimiroff
Oct 1, 1987·Human Genetics·D K KalousekR D Wilson
Jan 1, 1994·Pediatric Pathology·D K Kalousek, I Barrett
Jun 15, 1993·American Journal of Medical Genetics·D W BianchiE D Hay
Mar 16, 2006·Prenatal Diagnosis·Cardi van den BergRobert Jan Galjaard
Feb 28, 2008·Prenatal Diagnosis·John WolstenholmeCarol English
Mar 1, 2012·Obstetrics and Gynecology·Diana W BianchiUNKNOWN MatErnal BLood IS Source to Accurately diagnose fetal aneuploidy (MELISSA) Study Group
Apr 6, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Anthony R GreggM S Watson
Jun 15, 2013·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·P BennE Pergament
Sep 21, 2013·Clinical Chemistry·Richard P RavaDiana W Bianchi
Nov 5, 2013·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·Y GaoW Wang
Feb 12, 2014·Fetal Diagnosis and Therapy·M M GilK H Nicolaides
Feb 15, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Francesca R GratiGiuseppe Simoni
Mar 4, 2014·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·M I SrebniakD van Opstal
Mar 19, 2014·Prenatal Diagnosis·Paola BattagliaMaria Carla Pittalis

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Citations

Mar 13, 2017·Best Practice & Research. Clinical Obstetrics & Gynaecology·Francesca Romana GratiGiuseppe Simoni
Feb 2, 2018·Prenatal Diagnosis·Nathalie BrisonJoris R Vermeesch
Nov 10, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Diane Van OpstalErik A Sistermans
Feb 13, 2018·Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology·Lv-Yin HuangDong-Zhi Li
Nov 11, 2017·The Cochrane Database of Systematic Reviews·Mylène BadeauFrançois Rousseau
Mar 4, 2017·Biomedicine Hub·Thomas LiehrAnja Weise
Apr 20, 2020·Acta Obstetricia Et Gynecologica Scandinavica·Olav B PetersenMalgorzata I Srebniak
Sep 10, 2016·Molecular Cytogenetics·Malgorzata I SrebniakDiane Van Opstal
Oct 18, 2016·Prenatal Diagnosis·Dick OepkesUNKNOWN and for the Dutch NIPT Consortium
Apr 26, 2019·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Li-Li XuDong-Zhi Li
Mar 17, 2021·Molecular Cytogenetics·Justyna DomaradzkaBeata Anna Nowakowska
Aug 4, 2021·Annals of the Academy of Medicine, Singapore·Poh Ting LimWei Ching Tan

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