【源版】NIPT无创产前诊断

NIPT

Non-InvasivePrenatalTestWhatarethegoalsofNIPT?ShouldNIPSbeofferedtoallpregnantpatients?ACMGrecommends:-InformingallpregnantwomenthatNIPSisthemostsensitiveandreliableoptionfortraditionallyscreenedaneuploidiesinvolvingchromosomes13,18and21Cell-FreeDNA(cfDNA)SmallFragments(<200bp)ofDNAInMaternalCirculationMaternalFractionAdipocytesWhiteBloodCellsFetalFractionPlacentalCells(Trophoblasts)inMaternalCirculation10-15%ofTotalcfDNAinMaternalPlasma,After10WksofGestationWhichOne:cffDNAorcfDNA?AJOG2015;SMFMPubliationCommitteeAvailablecommercialNIPTtestingEuropePrenatest-Life

CodexxIONAtest-PremaithaHealthChinaNIFTYTest–BGIUSAHarmonyTest-AriosaDiagnostic,SanjoseCaliforniaMaterniT21PlusTest–SequenomLaboratories,SanDiegoVerifiTest–VerinataHealthPanoramaTest–NateraSanCarlosCaliforniaDifferentiatingNIPTMethodologiesTrisomyDetectionbyCounting

FetalDisomyFetalTrisomyMaternal“FetalFractionofcfDNAIsKeyIn“Counting”=>HigherFetalFractions=>EasiertoDetectTrisomy(Norton,EtAl.2013)HowFetalFractionAffectsSensitivityJustVisuallyCompare!FetalFractionMattersforCounting0-4%4-8%8%+FetalFractionTooLowToReportIntermediateFetalFraction–DecreasedSensitivityWithCountingMethodologyFetalFractionAdequateToAchieveBestPerformance“AnAneuploidySampleWithALowerFetalFractionHasAHigherProbabilityOfResultingInAFalseNegativeResult.”ThomasMusci,MDPrenatalPerspectives.Volume1,No.22013.Chromosome3Chromosome21CountingSmallerChromosomeLowerFraction(e.g.Chr.21)LargerChromosomeHigherFraction(e.g.Chr.3)Chromosome3Chromosome21ExpectedAmount:20%80%CountingObservedAmount: 25%75%HowWouldYouThenAssesstheRatiosforChr.21vs.Chr.18vs.Chr.13?SNP=SingleNucleotidePolymorphismADNAsequencevariationoccurringwhenasinglebasepair(nucleotide)-A,T,C,orG–ischanged.ThesearenormalgeneticchangesthatoccurineverypersonBuffycoat=MaternalDNAPlasma=Maternal+FetalDNASNPSequencingSNPSequencingMaternalGenotypeMaternal+FetalGenotypeFetalGenotypeMaternalbloodSNPapproachUsingtheBuffyCoattoSequenceMaternalGenotypeAlgorithmNIPTTestprocedureTheNIPTTestcanbeperformedfromweek10+0ofthepregnancy.BeforecarryingoutaNIPTTest,thepatientshouldbegivenanultrasoundscantodeterminethegestationalageandtocheckwhetheritisasingletonormultiplepregnancy.Excellentdetectionrateinsingletonpregnancies

PanoramaVerifiMaternit21HarmonytestDetectionate>99%>99%>99%99.7%T2198%97%96.4%98%T1895%93%92%93%T13LowfalsepositiverateDANSRmethod5timeslowerthanrmpsReliableevenwithheparintreatment[1]AshoorG,SyngelakiA,WagnerM,BirdirC,NicolaidesKH:Chromosome-selectivesequencingofmaternalplasmacell-freeDNAforfirst-trimesterdetectionoftrisomy21andtrisomy18.AmJObstetGynecol.2012Apr;206(4):322.e1-5.[2]NicolaidesKH,SyngelakiA,AshoorG,BirdirC,TouzetG:Noninvasiveprenataltestingforfetaltrisomiesinaroutinelyscreenedfirst-trimesterpopulation.AmJObstetGynecol.2012Nov;207(5):374.e1-6.[3]NortonME,BrarH,WeissJ,KarimiA,LaurentLC,CaugheyAB,RodriguezMH,WilliamsJ3rd,MitchellME,AdairCD,LeeH,JacobssonB,TomlinsonMW,OepkesD,HollemonD,SparksAB,OliphantA,SongK:Non-InvasiveChromosomalEvaluation(NICE)Study:resultsofamulticenterprospectivecohortstudyfordetectionoffetaltrisomy21andtrisomy18.AmJObstetGynecol.2012Aug;207(2):137.e1-8.[4]SparksAB,StrubleCA,WangET,SongK,OliphantA:Noninvasiveprenataldetectionandselectiveanalysisofcell-freeDNAobtainedfrommaternalblood:evaluationfortrisomy21andtrisomy18.AmJObstetGynecol.2012Apr;206(4):319.e1-9.[5]VerweijEJ,JacobssonB,vanScheltemaPA,deBoerMA,HofferMJ,HollemonD,WestgrenM,SongK,OepkesD:Europeannon-invasivetrisomyevaluation(EU-NITE)study:amulticenterprospectivecohortstudyfornon-invasivefetaltrisomy21testing.PrenatDiagn.2013Oct;33:996-1001.[6]JuneauK,BogardPE,HuangS,MohseniM,WangET,RyvkinP,KingsleyC,StrubleCA,OliphantA,ZahnJM:Microarray-basedcell-freeDNAanalysisimprovesnoninvasiveprenataltesting.FetalDiagnTher.2014;36:282-286.[7]NortonME,JacobssonB,SwamyGK,LaurentLC,RanziniAC,BrarH,TomlinsonMW,PereiraL,SpitzJL,HollemonD,CuckleH,MusciTJandWapnerRJ(Next-Study):CellfreeDNAAnalysisforNoninvasiveExaminationofTrisomy.NEnglJMed.2015,Apr1,DOI:10.1056/NEJMoa1407349.[8]StokowskiR,WangE,WhiteK,BateyA,JacobssonB,BrarH,BalanarasimhaM,HollemonD,SparksA,NicolaidesK,MusciTJ..:Clinicalperformanceofnon-invasiveprenataltesting(NIPT)usingtargetedcell-freeDNAanalysisinmaternalplasmawithmicroarraysornextgenerationsequencing(NGS)isconsistentacrossmultiplecontrolledclinicalstudies.PrenatDiagn.2015Sep1.PanoramaVerifiMaternit21HarmonytestYESNONOYESPositivepredictivevalue(PPV)whichoptionsarepossiblewithdifferenttypesofNIPT

Tr.21/18/13sexdeterminationX/YanalysisSingletonpregnanciesincl.allIVFpregnanciesYESYESYESTwinpregnanciesincl.allIVFpregnancies/eggdonationYESYES(new)×Morethantwofetuses×××NIPTresults1.NormalResult:

NoSpecificFollowUpNecessary, UnlessUltrasoundExaminationOfTheFetusRevealsAnomalies+AFPLevel2.TestFailure:

In1.4%PregnanciesNotEnoughFetalDNA: NIPTRepeatedAtNoExtraCost.3.AbnormalNIPTResult=>

DiagnosticTests

(E.G.

AmniocentesisOrChori