Abstract
Purpose: To report the clinical experience and performance of plasma cell-free DNA sequencing-based noninvasive -prenatal testing (NIPT) as a screening method in detecting trisomy 21, 18, 13 (T21/T18/T13) as well as sex chromosome aneuploidy (SCA) in a mixed-risk population in Iran. Methods: In a 2-year period between January 1, 2015, and December 31, 2016, over 150 medical centers in Iran offered NIPT as clinical screening tests for fetal T21, T18, T13 and SCA. All NIPT positive cases were recommended to undergo invasive prenatal diagnosis. Results: 11,414 maternal blood samples were received for NIPT, for which 11,223 samples obtained NIPT results. Among 11,213 cases with confirmatory results, 94 T21, 39 T18, 8 T13, 15 XO, 6 XXX, 3 XYY, 5 XXY and 11,042 euploid cases were detected. The overall sensitivity of NIPT was 98.90, 100.00, 100.00, 90.91, 100.00, 100.00 and 100.00%, and specificities were 99.96, 99.97, 99.99, 99.96, 99.98, 100.00 and 99.99% for detecting T21, T18, T13, XO, XXX, XYY and XXY, respectively. Conclusion: With a stringent protocol, our prospective large-scale multicentric nationwide study demonstrated that NIPT showed excellent performance as screening test for the detection of fetal T21, T18, T13 and SCA in mixed-risk pregnancies in Iran.
References
1.
Strategy TBoPa
. Public Health Statistics A.D. 2013
. Ministry of Public Health
; 2013
.2.
Vatankhah
S
, Jalilvand
M
, Sarkhosh
S
, Azarmi
M
, Mohseni
M
. Prevalence of Congenital Anomalies in Iran: A Review Article
. Iran J Public Health
. 2017
Jun
;46
(6
):733
–43
.
[PubMed]
2251-60853.
Hoorsan
H
, Mirmiran
P
, Chaichian
S
, Moradi
Y
, Hoorsan
R
, Jesmi
F
. Congenital Malformations in Infants of Mothers Undergoing Assisted Reproductive Technologies: A Systematic Review and Meta-analysis Study
. J Prev Med Public Health
. 2017
Nov
;50
(6
):347
–60
.
[PubMed]
1975-83754.
Zahed Pasha
Y
, Vahedi
A
, Zamani
M
, Alizadeh-Navaei
R
, Zahed Pasha
E
. Prevalence of birth defects in Iran: a systematic review and meta-analysis
. Arch Iran Med
. 2017
Jun
;20
(6
):376
–85
.
[PubMed]
1735-39475.
Rasmussen
SA
, Wong
LY
, Yang
Q
, May
KM
, Friedman
JM
. Population-based analyses of mortality in trisomy 13 and trisomy 18
. Pediatrics
. 2003
Apr
;111
(4 Pt 1
):777
–84
.
[PubMed]
0031-40056.
Nyberg
DA
, Souter
VL
, El-Bastawissi
A
, Young
S
, Luthhardt
F
, Luthy
DA
. Isolated sonographic markers for detection of fetal Down syndrome in the second trimester of pregnancy
. J Ultrasound Med
. 2001
Oct
;20
(10
):1053
–63
.
[PubMed]
0278-42977.
Lamlertkittikul
S
, Chandeying
V
. Experience on triple markers serum screening for Down’s syndrome fetus in Hat Yai, Regional Hospital
. J Med Assoc Thai
. 2007
Oct
;90
(10
):1970
–6
.
[PubMed]
0125-22088.
Panburana
P
, Ajjimakorn
S
, Tungkajiwangoon
P
. First trimester Down Syndrome screening by nuchal translucency in a Thai population
. Int J Gynaecol Obstet
. 2001
Dec
;75
(3
):311
–2
.
[PubMed]
0020-72929.
Farshbaf Khalili
A
, Shahnazi
M
, Hajizadeh
K
, Shekari Khaniani
M
. Down syndrome screening methods in Iranian pregnant women
. J Caring Sci
. 2012
Aug
;1
(3
):145
–51
.
[PubMed]
2251-992010.
Dan
S
, Wang
W
, Ren
J
, Li
Y
, Hu
H
, Xu
Z
, et al. Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies with mixed risk factors
. Prenat Diagn
. 2012
Dec
;32
(13
):1225
–32
.
[PubMed]
0197-385111.
Allyse
M
, Minear
MA
, Berson
E
, Sridhar
S
, Rote
M
, Hung
A
, et al. Non-invasive prenatal testing: a review of international implementation and challenges
. Int J Womens Health
. 2015
Jan
;7
:113
–26
.
[PubMed]
1179-141112.
Chiu
RW
, Chan
KC
, Gao
Y
, Lau
VY
, Zheng
W
, Leung
TY
, et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma
. Proc Natl Acad Sci USA
. 2008
Dec
;105
(51
):20458
–63
.
[PubMed]
0027-842413.
Bianchi
DW
, Parsa
S
, Bhatt
S
, Halks-Miller
M
, Kurtzman
K
, Sehnert
AJ
, et al. Fetal sex chromosome testing by maternal plasma DNA sequencing: clinical laboratory experience and biology
. Obstet Gynecol
. 2015
Feb
;125
(2
):375
–82
.
[PubMed]
0029-784414.
Bevilacqua
E
, Ordóñez
E
, Hurtado
I
, Rueda
L
, Mazzone
E
, Cirigliano
V
, et al. Screening for Sex Chromosome Aneuploidy by Cell-Free DNA Testing: Patient Choice and Performance
. Fetal Diagn Ther
. 2018
;44
(2
):98
–104
.
[PubMed]
1015-383715.
Gil
MM
, Accurti
V
, Santacruz
B
, Plana
MN
, Nicolaides
KH
. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis
. Ultrasound Obstet Gynecol
. 2017
Sep
;50
(3
):302
–14
.
[PubMed]
0960-769216.
Hui
L
, Teoh
M
, da Silva Costa
F
, Ramsay
P
, Palma-Dias
R
, Richmond
Z
, et al.; Australian NIPT collaboration
. Clinical implementation of cell-free DNA-based aneuploidy screening: perspectives from a national audit
. Ultrasound Obstet Gynecol
. 2015
Jan
;45
(1
):10
–5
.
[PubMed]
0960-769217.
Willems
PJ
, Dierickx
H
, Vandenakker
E
, Bekedam
D
, Segers
N
, Deboulle
K
, et al. The first 3,000 Non-Invasive Prenatal Tests (NIPT) with the Harmony test in Belgium and the Netherlands
. Facts Views Vis Obgyn
. 2014
;6
(1
):7
–12
.
[PubMed]
2032-041818.
Shaw
SW
, Chen
CP
, Cheng
PJ
. From Down syndrome screening to noninvasive prenatal testing: 20 years’ experience in Taiwan
. Taiwan J Obstet Gynecol
. 2013
Dec
;52
(4
):470
–4
.
[PubMed]
1028-455919.
Sago
H
, Sekizawa
A
; Japan NIPT consortium
. Nationwide demonstration project of next-generation sequencing of cell-free DNA in maternal plasma in Japan: 1-year experience
. Prenat Diagn
. 2015
Apr
;35
(4
):331
–6
.
[PubMed]
0197-385120.
Nicolaides
KH
, Syngelaki
A
, Ashoor
G
, Birdir
C
, Touzet
G
: Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population.
Am J Obstet Gynecol 2012
;207:374 e371-376. 21.
Zhang
H
, Gao
Y
, Jiang
F
, Fu
M
, Yuan
Y
, Guo
Y
, et al. Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146,958 pregnancies
. Ultrasound Obstet Gynecol
. 2015
May
;45
(5
):530
–8
.
[PubMed]
0960-769222.
McCullough
RM
, Almasri
EA
, Guan
X
, Geis
JA
, Hicks
SC
, Mazloom
AR
, et al. Non-invasive prenatal chromosomal aneuploidy testing—clinical experience: 100,000 clinical samples
. PLoS One
. 2014
Oct
;9
(10
):e109173
.
[PubMed]
1932-620323.
Kazemi
M
, Salehi
M
, Kheirollahi
M
. MeDIP Real-Time qPCR has the Potential for Noninvasive Prenatal Screening of Fetal Trisomy 21
. Int J Mol Cell Med
. 2017
;6
(1
):13
–21
.
[PubMed]
2251-963724.
Office
NS
. The 2013 Household Socio-Economic Survey
. Ministry of Information and Communication Technology
; 2013
.25.
Yuan
Y
, Jiang
F
, Hua
S
, Du
B
, Hao
Y
, Ye
L
, et al. Feasibility study of semiconductor sequencing for noninvasive prenatal detection of fetal aneuploidy
. Clin Chem
. 2013
May
;59
(5
):846
–9
.
[PubMed]
0009-914726.
Zhang
R
, Zhang
H
, Li
Y
, Han
Y
, Xie
J
, Li
J
. External Quality Assessment for Detection of Fetal Trisomy 21, 18, and 13 by Massively Parallel Sequencing in Clinical Laboratories
. J Mol Diagn
. 2016
Mar
;18
(2
):244
–52
.
[PubMed]
1525-157827.
Jiang
F
, Ren
J
, Chen
F
, Zhou
Y
, Xie
J
, Dan
S
, et al. Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies
. BMC Med Genomics
. 2012
Dec
;5
(1
):57
.
[PubMed]
1755-879428.
Salomon
LJ
, Alfirevic
Z
, Audibert
F
, Kagan
KO
, Paladini
D
, Yeo
G
, et al.; ISUOG Clinical Standards Committee
. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice
. Ultrasound Obstet Gynecol
. 2014
Jul
;44
(1
):122
–3
.
[PubMed]
0960-769229.
Gregg
AR
, Gross
SJ
, Best
RG
, Monaghan
KG
, Bajaj
K
, Skotko
BG
, et al. ACMG statement on noninvasive prenatal screening for fetal aneuploidy
. Genet Med
. 2013
May
;15
(5
):395
–8
.
[PubMed]
1098-360030.
Wilson
KL
, Czerwinski
JL
, Hoskovec
JM
, Noblin
SJ
, Sullivan
CM
, Harbison
A
, et al. NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy
. J Genet Couns
. 2013
Feb
;22
(1
):4
–15
.
[PubMed]
1059-770031.
Song
Y
, Liu
C
, Qi
H
, Zhang
Y
, Bian
X
, Liu
J
. Noninvasive prenatal testing of fetal aneuploidies by massively parallel sequencing in a prospective Chinese population
. Prenat Diagn
. 2013
Jul
;33
(7
):700
–6
.
[PubMed]
0197-385132.
Dey
M
, Sharma
S
, Aggarwal
S
. Prenatal screening methods for aneuploidies
. N Am J Med Sci
. 2013
Mar
;5
(3
):182
–90
.
[PubMed]
2250-154133.
Atri Barzanjeh
S
, Behshid
M
, Hosseini
MB
, Ezari
M
, Taghizadeh
M
, Dastgiri
S
. Community genetic services in iran
. Genet Res Int
. 2012
;2012
:129575
.
[PubMed]
2090-316234.
Ghaffari
SR
, Tahmasebpour
AR
, Jamal
A
, Hantoushzadeh
S
, Eslamian
L
, Marsoosi
V
, et al. First-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency, nasal bone, tricuspid regurgitation and ductus venosus flow combined with maternal serum free β-hCG and PAPP-A: a 5-year prospective study
. Ultrasound Obstet Gynecol
. 2012
May
;39
(5
):528
–34
.
[PubMed]
0960-769235.
Seyyed Kavoosi
E
, Younessi
S
, Farhud
DD
. Screening of Fetal Chromosome Aneuploidies in the First and Second Trimester of 125,170 Iranian Pregnant Women
. Iran J Public Health
. 2015
Jun
;44
(6
):791
–6
.
[PubMed]
2251-6085© 2019 S. Karger AG, Basel
2019
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
