新生儿脑室内出血英文.docx

新生儿脑室内出血英文.docx

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新生儿脑室内出血英文

Clinicalmanifestationsanddiagnosisofintraventricularhemorrhageinthenewborn

Author

LisaMAdcock,MD

SectionEditors

JosephAGarcia-Prats,MD

DouglasRNordli,Jr,MD

DeputyEditor

MelanieSKim,MD

Disclosures:

 LisaMAdcock,MD Nothingtodisclose. JosephAGarcia-Prats,MD Nothingtodisclose. DouglasRNordli,Jr,MD Nothingtodisclose. MelanieSKim,MDNothingtodisclose.

Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamulti-levelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.

Conflictofinterestpolicy

Alltopicsareupdatedasnewevidencebecomesavailableandour peerreviewprocess iscomplete.

Literaturereviewcurrentthrough:

 Feb2015. | Thistopiclastupdated:

 May22,2014.

INTRODUCTION — Intraventricularhemorrhage（IVH;alsoknownassubependymalorgerminalmatrixhemorrhage）isanimportantcauseofbraininjuryinprematureinfants.Althoughtheincidencehasdeclinedsincethe1980s,IVHremainsasignificantproblem,asimprovedsurvivalofextremelyprematureinfantshasresultedinagreaternumberofsurvivorswiththiscondition[1,2].

Theepidemiology,pathogenesis,clinicalpresentation,anddiagnosisofIVHarediscussedinthistopicreview.Themanagement,complications,andoutcomeofIVHinthenewbornarediscussedseparately.（See "Managementandcomplicationsofintraventricularhemorrhageinthenewborn".）

PATHOLOGY

Preterminfants — Inpreterminfants,thesiteoforiginofbleedingisgenerallythesubependymalgerminalmatrix,whichislocatedbetweenthecaudatenucleusandthethalamusattheleveloftheforamenofMonro[3].Neuropathologicstudiessuggestthatthehemorrhageisprimarilywithinthecapillarynetwork,whichfreelycommunicateswiththevenoussystem,althoughbleedingcanalsooccurfromthearterialcirculation[4].Vesselsinthisregionoccupyborderzonesbetweencerebralarteriesandthecollectingzoneofthedeepcerebralveins,andhaveincreasedpermeabilitywhensubjectedtohypoxia and/or increasedvenouspressure[5].（See 'Germinalmatrixfragility'below.）

SeverityandgradingofIVH — Severityofhemorrhageisbasedonwhetherthebleedingisconfinedtothegerminalmatrixregionorifitextendsintotheadjacentventricularsystemorwhitematter（intraparenchymal）.Thefollowinggradingsystemisusedtodefinetheextentofbleeding（table1）[3]:

●GradeI–Bleedingisconfinedtothegerminalmatrix（image1 and image2）

●GradeII–Intraventricularhemorrhage（IVH）occupies50percentorlessofthelateralventriclevolume

●GradeIII–IVHoccupiesmorethan50percentofthelateralventriclevolume（image3）

●GradeIV–HemorrhagicinfarctioninperiventricularwhitematteripsilateraltolargeIVH（image4）

GradeIcorrespondstomild,gradeIImoderate,andgradesIIIandIVsevereIVH.EachgradeofIVHmaybeunilateral,orbilateralwitheithersymmetricorasymmetricgradesofIVH.

Terminfants — Incontrast,theinitialsiteofbleedinginterminfantsisvariablebasedonlimiteddata,asillustratedbythefollowing:

●Inoneneuropathologicstudyof32terminfants,themajorityofIVHarosefromthechoroidplexus[6].

●Inanotherstudyofterminfants,ultrasonographicimagingshowedsubependymalgerminalmatrixandchoroidplexushemorrhagesoccurredatsimilarrates[7].

●ThalamichemorrhagemayalsocontributetoIVHinterminfants,asdescribedinaseriesof19cases,ofwhichtwo-thirdshadassociatedthalamichemorrhagedetectedbycomputedtomography[8].Thisislikelyavenoushemorrhagicinfarctioncausedbythrombosisintheinternalcerebralvein（s）,ormoreextensivevenousthrombosis,ratherthanaprimaryhemorrhage.

ThesefindingssuggestthattheoriginofintracranialbleedinginterminfantsdiffersfromthatseeninpreterminfantswithsubependymalIVH.

EPIDEMIOLOGY — Intraventricularhemorrhage（IVH）generallyoccursinpreterminfants,andtheincidenceincreaseswithdecreasinggestationalageandbirthweight.

Prematureinfants — IVHoccursmostfrequentlyininfantsbornbefore32weeksgestationorlessthan1500gbirthweight.Sincethelate1990s,thereportedrateofIVHintheUnitedStatesisabout20percentinverylowbirthweight（VLBW）infants（birthweight<1500g）and45percentinextremelylowbirthweight（ELBW）infants（birthweight<1000g）[9-12].

Apopulation-basedstudyof2896prematureinfants（<32weeksgestation）exemplifiestherelationshipbetweengestationalageandIVH,showingthatIVHratesdecreased3.5percentwitheachaddedweekofgestation[13].

TheriskofsevereIVHalsoincreaseswithdecreasinggestationalageandbirthweightasnotedbythefollowingstudies（see 'SeverityandgradingofIVH' above）:

●InastudyfromtheNationalInstituteofChildHealthandHumanDevelopment（NICHHD）neonatalresearchnetworkof9575infantswithgestationalagebetween22and28weeksandbirthweight401to1500g,theoverallincidenceofIVHwas36percentforallgradesofIVH,whichincreasedwithdecreasinggestationalage[12].TheprevalenceofsevereIVH（definedasgradesIIIandIV）alsoincreasedwithdecreasinggestationwithratesof38,36,26,21,14,11,and7percentofsurvivorsforinfantswithgestationalages22,23,24,25,26,27,and28weeks,respectively[12].

●Inapopulation-basedprospectivestudyofallpreterminfantswithgestationalagebelow27weeksborninSwedenfrom2004to2007,theincidenceofIVHincreasedfrom5.2percentofsurvivorsbornat26weeksgestationto19and20percentforthosebornat22and23weeksgestation,respectively[14].

AlthougholderliteraturehassuggestedthatVLBWinfantswhoweresmallforgestationalage（SGA）werelesslikelytohaveIVH[15],subsequentdatahaveshownnodifferenceintheincidenceofIVHbetweenSGAandappropriatesizeforgestationalageprematureinfants[16,17].

InaprospectivestudyfromtheGenetargetsofIntraventricularHemorrhageStudy,whichincludesprematureinfantswithbirthweightsbetween500and1250g,infantsborntomothersofAfricanancestryappearedtobeatincreasedriskforgradeIItoIVIVHcomparedwiththoseborntomotherswhowerewhite,aftercontrollingforconfoundingvariables[18].However,theriskwasreducedbymaternalattendanceatasingleprenatalvisit,suggestingthatracemaystillbeamarkerforhealthcaredisparities,whichincreasestheriskofIVH,ratherthanatrulyindependentfactor.

Terminfants — SevereIVHoccursinfrequentlyinterminfants,althoughminorhemorrhagesarenotuncommon.Inastudyof505healthyasymptomaticterminfantswhounderwentheadultrasonographywithin72hoursoflife,theincidenceofIVHwas4percent[19].Intheterminfant,IVHmaybeassociatedwithtrauma（eg,abdominalcompression）,alloimmunethrombocytopenia,ruptureofavascularmalformation,sinovenousthrombosis（particularlyininfantswiththalamicinvolvement）,andadiagnosisofhemophiliaandothercoagulationabnormalities[20-22].Insomecases,itisunclearwhetherthecoagulationabnormalityiscausalorisaresultofIVH[22].

PATHOGENESIS — Thepathogenesisofintraventricularhemorrhage（IVH）in premature infantsisdueto[23]:

●Germinalmatrixfragilityfromalackofstructuralsupportduetoimmaturity.

●Disturbancesofcerebralbloodflow（CBF）,particularlyrelatedtohypoxia-ischemiaandreperfusion,elevatedarterialflow,orelevatedvenouspressure.

Germinalmatrixfragility — Inpreterminfants,IVHgenerallyoriginateswithinthegerminalmatrix,thehighlycellularandrichlyvascularizedlayerinthesubependymal,subventricularzonethatgivesrisetoneuronsandgliaduringfetaldevelopment[24].Asthefetusmatures,thegerminalmatrixbeginstoinvolutestartingat28weeksasitscellularityandvascularitydecrease,andbytermitisgenerallyabsent[25].

Inthegerminalmatrix,thecapillarynetworkconsistsofnumerousthin-walled,largebloodvesselsthatlackstructuralsupport,whichcontributestotheincreasedriskofhemorrhageinthisareaofthebraincomparedwithotherregions[3,23,26-28].Themicrovasculatureofthegerminalmatrixisparticularlyfragilebecauseoftheabundanceofangiogenicbloodvesselsthathaveapaucityofpericytes,haveimmaturebasallamina,andhavedeficiencyoftightjunctionsandglialfibrillaryacidicprotein（GFAP）intheastrocyteendfeet（whicharecomponentsofacompetentblood-brainbarrier）[23].Glialfibersnormallydevelopwithincreasingmaturation,asdemonstratedinastudyshowingminimalimmunocytochemicalstainingofGFAPat27weeksgestation,whichbecamemoreprominentwithincreasinggestationalage,especiallyafter31weeksgestation[29].Thedeficientstructuralsupportmakesthegerminalmatrixvulnerabletoinjuryprimarilyduetohemodynamicinstabilityinpreterminfants,relatedtoalteredCBFcausedbyavarietyof perinatal/neonatal eventsordisorders（eg,hypoxia-ischemia）.

Thisfragilecapillarynetworkdrainsintoawell-developeddeepvenoussystemthatformstheterminalvein,whichchangesdirectioninaU-turnfashionasitemptiesintotheinternalcerebralvein.Itispostulatedthatthevenoussystemispronetocongestionandstasis,resultinginincreasedcerebralvenouspressure,whichcontributestogerminalmatrixIVH[22].

Cerebralbloodflowinstability — FluctuationsofCBFinpreterminfantsareassociatedwithIVH[30-33].PreterminfantsareparticularlyvulnerabletoalterationsinCBFbecausetheyhaveimpairedautoregulationofCBFcomparedwithterminfants.T