File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study.

TitleNon-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study.
Authors
Issue Date2011
PublisherBMJ Publishing Group. The Journal's web site is located at http://www.bmj.com/
Citation
BMJ (Clinical Research Ed.), 2011, v. 342, article no. c7401 How to Cite?
AbstractTo validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling. Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples. Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands. 753 pregnant women at high risk for fetal trisomy 21 who underwent definitive diagnosis by full karyotyping, of whom 86 had a fetus with trisomy 21. Intervention Multiplexed massively parallel sequencing of DNA molecules in maternal plasma according to two protocols with different levels of sample throughput: 2-plex and 8-plex sequencing. Proportion of DNA molecules that originated from chromosome 21. A trisomy 21 fetus was diagnosed when the z score for the proportion of chromosome 21 DNA molecules was >3. Diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were calculated for trisomy 21 detection. Results were available from 753 pregnancies with the 8-plex sequencing protocol and from 314 pregnancies with the 2-plex protocol. The performance of the 2-plex protocol was superior to that of the 8-plex protocol. With the 2-plex protocol, trisomy 21 fetuses were detected at 100% sensitivity and 97.9% specificity, which resulted in a positive predictive value of 96.6% and negative predictive value of 100%. The 8-plex protocol detected 79.1% of the trisomy 21 fetuses and 98.9% specificity, giving a positive predictive value of 91.9% and negative predictive value of 96.9%. Multiplexed maternal plasma DNA sequencing analysis could be used to rule out fetal trisomy 21 among high risk pregnancies. If referrals for amniocentesis or chorionic villus sampling were based on the sequencing test results, about 98% of the invasive diagnostic procedures could be avoided.
Persistent Identifierhttp://hdl.handle.net/10722/180701
ISSN
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChiu, RWKen_US
dc.contributor.authorAkolekar, Ren_US
dc.contributor.authorZheng, YWLen_US
dc.contributor.authorLeung, TYen_US
dc.contributor.authorSun, Hen_US
dc.contributor.authorChan, KCAen_US
dc.contributor.authorLun, FMFen_US
dc.contributor.authorGo, ATJIen_US
dc.contributor.authorLau, ETen_US
dc.contributor.authorTo, WWKen_US
dc.contributor.authorLeung, WCen_US
dc.contributor.authorTang, RYKen_US
dc.contributor.authorAu-Yeung, SKCen_US
dc.contributor.authorLam, Hen_US
dc.contributor.authorKung, YYen_US
dc.contributor.authorZhang, Xen_US
dc.contributor.authorVan Vugt, JMGen_US
dc.contributor.authorMinekawa, Ren_US
dc.contributor.authorTang, MHYen_US
dc.contributor.authorWang, Jen_US
dc.contributor.authorOudejans, CBMen_US
dc.contributor.authorLau, TKen_US
dc.contributor.authorNicolaides, KHen_US
dc.contributor.authorLo, YMDen_US
dc.date.accessioned2013-01-28T01:41:16Z-
dc.date.available2013-01-28T01:41:16Z-
dc.date.issued2011en_US
dc.identifier.citationBMJ (Clinical Research Ed.), 2011, v. 342, article no. c7401en_US
dc.identifier.issn1468-5833en_US
dc.identifier.urihttp://hdl.handle.net/10722/180701-
dc.description.abstractTo validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling. Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples. Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands. 753 pregnant women at high risk for fetal trisomy 21 who underwent definitive diagnosis by full karyotyping, of whom 86 had a fetus with trisomy 21. Intervention Multiplexed massively parallel sequencing of DNA molecules in maternal plasma according to two protocols with different levels of sample throughput: 2-plex and 8-plex sequencing. Proportion of DNA molecules that originated from chromosome 21. A trisomy 21 fetus was diagnosed when the z score for the proportion of chromosome 21 DNA molecules was >3. Diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were calculated for trisomy 21 detection. Results were available from 753 pregnancies with the 8-plex sequencing protocol and from 314 pregnancies with the 2-plex protocol. The performance of the 2-plex protocol was superior to that of the 8-plex protocol. With the 2-plex protocol, trisomy 21 fetuses were detected at 100% sensitivity and 97.9% specificity, which resulted in a positive predictive value of 96.6% and negative predictive value of 100%. The 8-plex protocol detected 79.1% of the trisomy 21 fetuses and 98.9% specificity, giving a positive predictive value of 91.9% and negative predictive value of 96.9%. Multiplexed maternal plasma DNA sequencing analysis could be used to rule out fetal trisomy 21 among high risk pregnancies. If referrals for amniocentesis or chorionic villus sampling were based on the sequencing test results, about 98% of the invasive diagnostic procedures could be avoided.en_US
dc.languageengen_US
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://www.bmj.com/en_US
dc.relation.ispartofBMJ (Clinical research ed.)en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAdulten_US
dc.subject.meshCase-Control Studiesen_US
dc.subject.meshDNA - Blooden_US
dc.subject.meshDown Syndrome - Diagnosisen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshKaryotyping - Methodsen_US
dc.subject.meshMaleen_US
dc.subject.meshMaternal Ageen_US
dc.subject.meshPregnancyen_US
dc.subject.meshPrenatal Diagnosis - Methodsen_US
dc.subject.meshRoc Curveen_US
dc.subject.meshSensitivity And Specificityen_US
dc.subject.meshSequence Analysis, Dna - Methodsen_US
dc.subject.meshSex Determination Processesen_US
dc.titleNon-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study.en_US
dc.typeArticleen_US
dc.identifier.emailTang, MH: mhytang@hkucc.hku.hken_US
dc.identifier.authorityTang, MH=rp01701en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1136/bmj.c7401en_US
dc.identifier.pmid21224326en_US
dc.identifier.scopuseid_2-s2.0-78751683468en_US
dc.identifier.hkuros209006-
dc.identifier.volume342en_US
dc.identifier.spagec7401en_US
dc.identifier.isiWOS:000286384800007-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridChiu, RW=7103038413en_US
dc.identifier.scopusauthoridAkolekar, R=25724167500en_US
dc.identifier.scopusauthoridZheng, YW=36877216800en_US
dc.identifier.scopusauthoridLeung, TY=7202110959en_US
dc.identifier.scopusauthoridSun, H=14043861000en_US
dc.identifier.scopusauthoridChan, KC=13403797200en_US
dc.identifier.scopusauthoridLun, FM=16205320200en_US
dc.identifier.scopusauthoridGo, AT=7005837665en_US
dc.identifier.scopusauthoridLau, ET=7103086081en_US
dc.identifier.scopusauthoridTo, WW=7004294510en_US
dc.identifier.scopusauthoridLeung, WC=7201504435en_US
dc.identifier.scopusauthoridTang, RY=7202300287en_US
dc.identifier.scopusauthoridAuYeung, SK=36981160400en_US
dc.identifier.scopusauthoridLam, H=16022602300en_US
dc.identifier.scopusauthoridKung, YY=8569546700en_US
dc.identifier.scopusauthoridZhang, X=37039026100en_US
dc.identifier.scopusauthoridvan Vugt, JM=7006760999en_US
dc.identifier.scopusauthoridMinekawa, R=6506332729en_US
dc.identifier.scopusauthoridTang, MH=8943401300en_US
dc.identifier.scopusauthoridWang, J=37038745700en_US
dc.identifier.scopusauthoridOudejans, CB=7003663097en_US
dc.identifier.scopusauthoridLau, TK=24491963900en_US
dc.identifier.scopusauthoridNicolaides, KH=7203078780en_US
dc.identifier.scopusauthoridLo, YM=7401935391en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats