comparativemorphologicaldi썒erencesbetweenumbilicalcords ...age 27.7±4.6 28.3±4.4 27.6±5.3...

ComparativeMorphologicalDierencesbetweenUmbilicalCordsfromChronicHypertensiveandPreeclampticPregnancies

SevincInan ,MuzaerSancı,DenizCan,SedaVatansever,OzgurOztekin,andSivekarTinar

DepartmentofHistology&Embryology,CelalBayarUniversity,FacultyofMedicine,Manisa,Turkey,DepartmentofObstetrics&Gynecology,AegeanSocialSecurityHospital,Izmir,Turkey,and

DepartmentofRadiology,TepecikSocialSecurityHospital,Izmir,Turkey

Tocomparemorphologicalchangesintheumbilicalcordsfrom chronichypertensiveandpree-clampticpatientshavingnormalorpathologicalumbilicalarteryDopplerultrasonographicresults.Umbilicalcordsfrom34normotensive,31chronichypertensiveand70preeclampticwomenwithnormalandabnormalDopplerflowvelocitywaveforms(FVW)at35-40gestationalweekswerestudied.Morphologicalchangesintheumbilicalcordswereexaminedonformalin-fixed,para n-embeddedsections.Thetotalumbilicalcordarea,totalvesselarea,andwallthicknessofumbilicalvesselsweremeasuredinsystematicrandom samplesusingunbiasedstereologymethods.AnANOVAtestwasusedforstatisticalanalysis.InthechronichypertensiveandpreeclampticgroupswithnormalDopplerFVW,thethicknessoftheumbilicalcordvesselsremainednearlyconstant,whereasboththetotalareaandthelumenareawerereduced.Thesechangescorrelatewiththehistopathologicalfindings,suggestingamainlyvasoconstrictiveeect.Bycontrast,analysisofthepreeclampticgroupwithpathologicDopplerFVW showedacomparablereductionofallparametersoftheumbilicalcord.Histopathologicalfindingswererelatedtosmaller,contractedsmoothmusclecellsofthevesselwall,whichissuggestiveofapredominanthypoplasticmechanism.Asaresultofreduceduteroplacentalperfusion,fetalhypoxiaandintrauterinegrowthretardationbecomeun-avoidableinpreeclampsia.ThehistopathologicalchangesintheumbilicalcordbetweenthechronichypertensiveandpreeclampticpatientsdependontheDopplerresults.Inconclusion,theumbilicalarteryDopplerFVW indicesprovidegoodvaluesforpredictingintrauterinegrowthretardationinpreeclampticpatients.

Keywords:umbilicalcord,morphometry,hypertensiveinducedpregnancy

H ypertensivedisordersinpregnancyarerespon-sibleforasignificantamountofmaternaland

perinatalmorbidityandmortality.Theetiologyofthesedisordersisstillunknown.Itcomplicatesabout6-20

ofallpregnancies.Preeclampsiaandeclampsiaconstituteabout70 ofthesedisorders,whereaschronichyperten-sionrepresentstheremaining30 ofhypertensivedis-ordersinpregnancy［1,2］.Althoughpreeclampsiaisoneofthemajorcausesof

maternaldeath,especiallyindevelopingcountries,per-inataloutcomesarealsonotfavorable.Intrauterinegrowthretardation,prematuredelivery,lowbirthweight,

ReceivedNovember12,2001;acceptedApril18,2002.Correspondingauthor.Phone:＋90-236-237-64-40;Fax:＋90-236-237-64-49E-mail:sevincinan＠yahoo.com(S.Inan)

http://www.lib.okayama-u.ac.jp/www/acta/

ActaMed.Okayama,2002Vol.56,No.4,pp.177-186

OriginalArticle

Copyrightｃ2002byOkayamaUniversityMedicalSchool.

fetaldeathandneonataldeathduetoprematurebirtharecommon complications. Predicting preeclampsia isdicultinearlypregnancy,butsomeepidemiologicalriskfactorsareknown,suchasnulliparity,previouspre-eclampsia,familyhistory,blackrace,obesity,diabetesmellitus,multi-fetalpregnancies,ageofmother(＜18and＞35),andpreviousrenaldisease［3］.Althoughtheetiologyofpreeclampsiaisstillunknown,

theplacentaplaysacrucialroleinthedevelopmentofthedisease［4,5］.Preeclampsiaisassociatedwithincreasedvascularresistanceanddecreaseduteroplacentalperfusion.Accordingtothedegreeofdecreaseinuteroplacentalperfusion,fetalhypoxiaandintrauterinegrowthretarda-tioncanbecomeunavoidable［6］.Manystudieshavedemonstratedsignificantdierencesinthemorphologicalstructuresoftheplacentaandumbilicalcordvesselsbetweennormalandpreeclampticpregnantwomen［7-12］.Mostofthewomenwithpreeclampsiashowhis-tologicalandbiochemicalevidenceofpoorplacentationandischemia.Bruchetal.reportedthatgrowth-retardedfetuseswithorwithoutumbilicalarteryDopplerabnor-malitieshaveasmallerumbilicalcordcross-sectionalareaatdeliverythandonormalhealthyfetuses［10］.DiNarofoundthatthediametersandareasofumbilicalcordschangedduringgestation,andthesedierencesdependedonthereductionofWhartonjellyratherthantheumbilicalvesselsthemselves［11］.Juneketal.demonstratedthatumbilicalarterieswerethickerinthepreeclampticgroupthaninuncomplicatedpregnancies.Thesedierenceswereespeciallyobservedinthetunicaintimaandmedia.Thesedierenceswereacceptedasaresultoftheadapta-tionsystemoftheumbilicalcordarteriesunderthealteredhomodynamicconditionsinpreeclampsia［12］.Itwasobservedthatumbilicalarterialvasoconstriction

wasinducedbyanexcessofeitherendothelium orplatelet-derivedthromboxaneA2,asdescribedinIUGR［13］.AhigherproductionofendothelininIUGRwasalsodescribed［14］.Butthedegreeofdefectiveplacenta-tionandplacentalischemiamaynotadjusttotheseverityofpreeclampsia.Thereforesomeotherpreexistingfactorsmustalsobepresent.Thesealterationsintheplacentaandumbilicalcordvesselsmaydevelopasaresultofadecreaseinavasodilatorsubstanceoranincreaseinvasoconstrictorsduetoapathophysiologicevent［15-18］.Anabnormalendothelialhyperstimulationanddysfunctionmightbethemainevent,andpreeclampsiacanbeanacuteformofsuchasituation.Bothpreeclamp-siaandchronichypertensionincludesimilarriskfactors

andbiochemicalalterations.Althoughtheperinatalriskforwomenwithchronichypertensionislessthanforpreeclampticwomen,thehistopathologicaldierencesinbothgroupsmaybeimportantforthedevelopingfetus.Theaimofthisstudywastocomparethemorphologicalchangesintheumbilicalcordvesselsinnormotensivepregnancies,chronichypertensivepregnanciesandpre-eclampticpatientswithandwithoutpathologicumbilicalarteryDopplerultrasoundstudyresults.

MaterialsandMethods

TheEthicsCommitteeoftheResearchCenterofAegeanSocialSecurityHospitalapprovedtheprotocol.Studieswereperformedontheumbilicalcordsof135newborns,deliveredbetween35-40weeksofgestation.Inallcases,10cm longsectionsoftheumbilicalcordwerecut,beginningfromtheirplacentalend,formorphometricstudyoftheumbilicalcordves-sels.Patientswereseparatedinto4groups.Therewerenostatisticallysignificantdierencesinthemean(±SD)ageofthewomenamongthegroups.Patientcharacteris-ticsaregiveninTable1.Forallpatients,arterialumbilicalflowvelocitywaveforms(FVW)from24hto1weekbeforedeliverywererecordedwithToshiba250pulse-wavedDopplerUSG,usinga5MHzabdominaltransducer.NormalumbilicalDopplerindicesweredefinedasasystolic/diastolicvaluebetween5 and95 withrespecttogestationalage.Valuesoutofthisrangeweretakenasabnormal.Group1:Thecontrolmaterialwastakenfromnew-

bornsdeliveredbyhealthymothers,aged23-32,withnormalbloodpressure(systolic100-135mmHg,diastolic60-85)andhavingnormalumbilicalDopplerFVW(n＝34).Exclusioncriteriaincludedmultiplepregnancies,essentialhypertension,diabetes,chronicrenaldisease,plateletdisorders,andepilepsy.Themeanbodyweightofthenewbornswas3,261.7±418.3grams.Group2:Inthisgroup,theumbilicalcordswere

takenfromnewbornsdeliveredbymothers,aged24-33,withessentialhypertensionbeforethe20thweekofpregnancyandhavingnormalumbilicalDopplerFVW(n＝31).Themeanbodyweightofthesenewbornswas3,153.2±314.8grams.Group3:Inthisgroup,theumbilicalcordswere

takenfromnewbornsdeliveredbymothers,aged22-32,withpreeclampsia.Womenwerediagnosedwithpre-eclampsiaiftheyhadbloodarterialpressureasfollows:

Inanetal. ActaMed.Okayama Vol.56,No.4178

systolic＞140mmHg,diastolic＞90mmHgmeasuredon2ormoreoccasionsatleast4hapartafterthe20thweekofgestation.Proteinuriawasconsideredpresentwhentherewasaurinedipstickvalueofatleast1＋(＞30mg/dl)on2separateoccasionsatleast6hapart.NoneofthewomenhadanMgSO4orbetamethasoneinjectionbeforethebloodsamplesweredrawn.Thisgroupwassubdividedinto2groupsaccordingtoDopplerFVW results.Group3A:WithnormalumbilicalarteryDoppler

FVW (n＝32).Themeanbodyweightofthesenew-bornswas3,015.6±426.6grams.Group3B(4):WithabnormalumbilicalarteryDop-

plerFVW (n＝38).Themeanbodyweightofthesenewbornswas2,109.2±589.9grams.

Eachumbilicalcordwasimmediatelyclampedatdelivery.Inallcases,10cm-longsectionsofumbilicalcordwerecut,beginningfromtheirplacentalend,formorphometricstudyoftheumbilicalcordves-sels.Fiveblocksofcordcross-sectionswerecut.Aroutineparanprocedurewasdone.Inbrief,tissuesampleswerefixedin10 formalinsolution.Theyweredehydratedinagradedethanolseries,cleanedinxyleneandembeddedinparan.Sectionswerecutat5μmthickness,deparanisedandhydrated.Serialsectionsoftheumbilicalcordswerestainedwithhematoxylinandeosin(H.E).Systematicrandomsamplesofumbilical

cordsectionswereidentifiedunderamicroscope(×40),andunbiasedmorphometricstudywasperformedusinganOlympusmicroscope.Theviewfromthemicroscopewasdirectlyprojectedontothecomputerscreen.Asystematicgridofcrosseswasrandomlythrownontotheviewedobject.Theinter-crossspacinginthexandydirectionisΔxandΔyunits,respectively.Thismeansthateachcrosshasanassociatedareaofa/punits.Thenumberofcrossesthathittheobjectmultipliedbya/pisanunbiasedestimateoftheobject’sarea［18］.Thefollow-ingparametersweremeasuredforeachumbilicalcord:totalcordandWhartonjellyareas,totalvesselandlumenareas,andwallthickness.Wall-thicknessmeasurementsexpressthewholethicknessofthevesselwall,fromtheendothelium totheWhartonjelly.Allmorphometricmeasurementsweredoneinablindfashion,withoutpreexistingknowledgeoftheclinicaldata.

Allresultsareexpressedasmeanvalues± SEs.StatisticalanalysisofdataandSEswascalculatedforeachparameterandestimatedineachgroup.ForcomputationweusedtheSPSSAdvancedStatisticalpackage.ThedatawasanalyzedbyanANOVA test,anddierenceswereconsideredsignificantifP＜0.05.

Pregnancy,Hypertension,UmbilicalCordAugust2002

Table1 Clinicalcharacteristicsofnormal,chronichypertensiveandpreeclampticpregnancies

GROUP GROUP1 GROUP2 GROUP3A GROUP3B

ControlChronicHTwithnormalDopplerFVW

PreeclampsiawithnormalDopplerFVW

PreeclampsiawithpathologicalDopplerFVW

n＝34 N＝31 n＝32 n＝38Age 27.7±4.6 28.3±4.4 27.6±5.3 25.5±3.8Parity(Nullipar/multipar) 21/13 10/21 23/9 26/12Gestationalage(wk) 39.0±0.5# 38.3±1.0 37.3±0.9 36.4±1.1SistolicBloodPressure(mmHg)

107.0±10.8# 148.3±11.8 149.8±11.8 156.5±12.7

DiastolicBloodPressure(mmHg)

69.4±9.9# 95.9±6.1 101.0±11.4 105.1±10.7

Edema 1.0±0.6# 0.9±0.9 2.2±0.4 2.2±0.4Spontantdelivery/

Cesariansection25/9# 16/15 6/26 7/31

APGAR 8.3±0.6# 8.0±0.7 7.4±0.8 6.8±1.2Fetalweight(gm) 3261.7±418.3 3153.2±314.8 3015.6±426.6 2109.2±589.9

#,P＜0.05Group1vs.Group2,3A,3B;,P＜0.05Group3Avs.Group2;,P＜0.05Group3Bvs.Group3A,2.

179

Results

Demographicandclinicalfindingsofthecontrolgroup(Group1),chronichypertensive＋pregnancy(Group2),preeclampticwithnormalDoppler(Group3A)andpre-eclampticwithabnormalDoppler(Group3B)aresum-marizedinTable1.Asexpectedfromtheinclusionandmatchingcriteria,thepatients’ageswerenotsignificantlydierent,butotherparameterssuchasbloodpressureandedemaweresignificantlyelevated(P＜0.05)inthepreeclampticgroup.ThemethodofdeliverywasusuallycesareansectioninGroups3Aand3B.Wealsosawthatthegestationalageandbirthweightweresignificantlylowerinthepreeclampticgroup,especiallyinthepath-ologicDopplerflowpatterns.Relatedwiththesefindings,APGARscoresinGroups2,3Aand3Bwerefoundtobelow.TheresultsofthemorphometricparametersofumbilicalcordsaregiveninTable2.Histologicalexaminationoftheumbilicalcordshows

severaldistinctlayersunderthelightmicroscopeinthecontrolgroup(Fig.1A).Onthesurfaceisawell-definedsinglelayerofsquamoidamnioticepithelium.DeepintheepitheliumthatcomprisesthesurfaceofthecordisthesubstanceknownasWharton’sjelly.EmbeddedwithintheWharton’sjellyaretheumbilicalvessels.Thevas-

culatureoftheumbilicalcordiscomposedof2arteriesandasinglevein.Thearteriespossessnoelasticlaminaandhaveadouble-layeredmuscularwall(Fig.1B).Eachofthesemuscularlayersiscomposedofanetworkofinterlacingsmoothmusclebundles.Theveinhasaninnerelasticlamina(Fig.1C).Theumbilicalvein,whichgenerallyhasalargerdiameter,possessesathinnermuscularcoatconsistingofasinglelayerofcircularsmoothmuscle.Inthecontrolgroup,themeancordareawas63.58±2.00,thetotalareaoftheveinwas6.28±0.44andthewallthicknessoftheveinwas471.75±33.27.Thethicknessesofthearteriesweresimilartoeachother.Themeanwallthicknessofthearterieswas597.08±18.02andtheirtotalareawas2.97±0.18.WhentheumbilicalcordvesselsinGroup2(chronic

hypertensive＋pregnancy)wereexaminedunderthelightmicroscope,thehistologicalappearanceappearedtobeclosetonormal(Fig.2A).Theendotheliumandthesubendotheliumoftheumbilicalartery(Fig.2B)andvein(Fig.2C)wereseentobeintheirnormalstate.Althoughafewcontractionsinthenucleuscouldbeseen,thesmoothmusclecellsgenerallyhadtheappearanceofbeingnormalandofnormalsize(Fig.2D).Theintercellulargapshadanunnoticeablewideningbetweenthem.Themorphometricanalysesofthisgroupshowedthatthetotal

Table2 Correlation’scordparameters

GROUP1 GROUP2 GROUP3A GROUP3B

UMBILICALCORDPARAMETERS

ControlChronicHTwithnormalDopplerFVW

PreeclampsiawithnormalDopplerFVW

PreeclampsiawithpathologicalDopplerFVW

n＝34 N＝31 n＝32 n＝38

UmbilicalcordTotalcordarea 63.58±2.00# 54.09±2.65 48.99±3.18 41.84±1.58Jellyarea 51.37±1.79# 43.95±2.43 40.39±3.09 35.22±1.77Totalvesselarea 8.44±0.69# 7.01±0.29 6.07±0.22 5.01±0.19Totallumenarea 3.77±0.13# 3.11±0.28 2.58±0.10 1.61±0.11VeinTotalareamm 6.28±0.44# 4.95±0.09 3.61±0.11 2.51±0.22Lumenareamm 2.97±0.29# 2.47±0.05 1.96±0.21 1.10±0.22Wallthicknessμm 471.75±33.27 459.58±11.58 437.75±10.79 398.58±11.54ArteryTotalareamm 2.97±0.18# 2.59±0.14 2.49±0.12 2.06±0.06Lumenareamm 0.40±0.05 0.32±0.04 0.31±0.05 0.25±0.06Wallthicknessμm 597.08±18.02 544.90±17.40 547.58±12.01 426.66±19.22

#,P＜0.05Group1vs.Group2,3A,3B;,P＜0.05Group3Avs.Group2;,P＜0.05Group3Bvs.Group2,3A,1.


cordandjellyarea,andthetotalvesselareaweresignificantlyreduced(Fig.2A).ThewallthicknessoftheumbilicalvesselswasdecreasedinGroup2,butthedierencewiththecontrolgroupwasnotstatisticallysignificant.Itwasobservedthatinpreeclampticpatientshaving

normalDopplerFVW(Group3A),awideningundertheepitheliumofthearteryandbetweenthemusclelayerswaspresentduetotheedema(Fig.3B).Thecontractionofthemusclecellsoccurredwithawave-likeappearanceofthenucleus.Separationsappearedbetweenthemusclecellsduetotheincreaseinfluidbetweenthecells,whichwasassociatedwiththeedema.Thisedemainrelationtotheconnectivetissuebetweenthelayersofmusclemadeitmucheasiertodistinguishbetweenthelayers.Theveinlumenwasseentohavenarrowedduetotheedemaontheveinwallandtothevasoconstriction(Fig.3C,3D).

Macroscopically,thecordthicknesswassignificantlyreducedinthisgroupincomparisonwiththecontrolandhypertensivegroups.WhenGroup3AwascomparedwithGroup2,asignificantreductionofthetotalvesselareaofthecordwasobserved.Incontrast,nodierencewasobservedinthewallthicknessofthevessels.Theumbilicalcordvessels,whichweretakenfrom

preeclampticpatientswhohadanabnormalDoppler(Group3B),seemedtobemorphologicallyhypoplastic(Fig.4).Whenexaminedunderalightmicroscope,thediametersofthevesselsweresignificantlyreduced(Fig.4A).Themuscleareaseparatedfromtheconnectivetissues,whichledinturntothesubstantialnarrowingofthediameterofthelumen,whichwasespeciallynoticeableinthearteries(Fig.4B).Thisnarrowingofthelumenresultedinthenarrowingoftheveindiameter(Fig.4C).Themusclecellswereseentobehypoplasticandsmaller

Fig.1 Photomicrographsofumbilicalcordtakenfromanewbornwithanormotensive,healthymother(Controlgroup).Normalappearanceofumbilicalcordandvesselswereseen.Onthesurfaceisawell-definedsinglelayerofamnioticepithelium(a),embeddedwithinthesubstanceofWharton’sjelly(w)aretheumbilicalvessels.Generalviewofumbilicalcordatamagnificationof×10(A);umbilicalcordartery,×40(B);umbilicalvein(V),×40(C).H.E.

181Pregnancy,Hypertension,UmbilicalCordAugust2002

thantheirnormalsize(Fig.4D).Thecontractedsmoothmusclecellswereseentohaveseparatedtheirlinksfromeachotherinsomeparts.Theendotheliumandsuben-dotheliumofthevesselsandtheinnerlayersofmusclewereobservedtohavecompletelyjoinedeachother.Withthisobservation,hypoplasycouldbeclearlydetected.Inthisgroup,itwasobservedthatallparametersoftheumbilicalcordweresignificantlyreducedincomparisontothenormalandhypertensivegroups.Asignificantcorre-lationwasalsoobservedbetweenthethicknessofavesselwallandthepathologicDopplervalues.

Discussion

Theumbilicalcordappearstoplayanimportantroleininteractionsbetweenthemotherandfetusduringpreg-nancy.Pregnancieswithgrowthretardationareassociat-

edwithsmallerplacentasandthinumbilicalcords［7-10］.Inthisstudy,thehistopathologicalandmorphometricdierencesassociatedwithpregnancy-inducedhyperten-sion(preeclampsia)andchronichypertensionwereobserv-ed.AbnormalumbilicalcordarterialDopplerFVW wasassociatedwiththereducedumbilicalcorddiameter.ItwasalsoassociatedwithbothreducedtotalcordareasandreducedWhartonjellyareas.Chronichypertensionischaracterizedbyanincreased

vascularresistanceandmodificationsinthemechanicalpropertiesofbloodvessels［20］.Vesselscontractviaavarietyofpharmacologicalagentsincludingserotonin,potassiumchloride,bradykinin,angiotensine,oxytosinandothers［21,22］.Thesepropertieshavenotbeenfullyinvestigatedinpregnancy-inducedhypertension.Butlikechronichypertensioninpreeclampsia,theinhibitionofprostacyclinesynthesis,hypersensitivitytovasocon-

Fig.2 Photomicrographsofumbilicalcordtakenfromchronichypertensivemother(Group2).Theendotelandsubendotelseemedtolookclosetonormal,thesmoothmusclecellsonthevesselwallswerealsoseentobeontheirnormalstate.Althoughitcouldbeseenthatafewvasocontrictionshadapatchedstateinthenucleus(arrow).Generalviewofumbilicalcordatamagnificationof×10(A);umbilicalcordartery,×40(B);umbilicalvein(V),×40(C);highermagnificationoftheveinwall,×200(D).H.E.


strictorsandendothelialcelldeathwereobserved［23］.Dobrinreportedthatbloodvesselsexhibitedcharacter-

isticchangesduringfetaldevelopment［24］.Thewiden-ingofthemedia,anincreasednumberandathickeningofelasticlamella,decreasedcellularityandaugmentedcol-lagencontentcharacterizethemorphologicdevelopmentduringthisperiod.Itwasreportedthattheumbilicalperfusiondecreasedinpreeclampsia［25］.Thevesselwallscouldreactwiththealterations,buttheircomposi-tiontomaintaintheirtransmuralpressureatanoptimallevelwouldhavetobesustained.Inasituationofin-creasedplacentalresistance,anincreaseinintralumenpressureintheumbilicalarterywilltendtoincreasecomplianceinordertokeeptransmuralpressurerelativelyconstant.Conversely,theintrauterinelumenpressureintheumbilicalveinwilldecrease,andthecomplianceofthe

vesselwilldiminish,againtokeeptransmuralpressureconstant.Romanowiczetal.demonstratedthattheinsolubleelastincontentdecreasedintheumbilicalcordveinsofnewbornsdeliveredbymotherswithpreeclampsia［26］.Reconstructingtheumbilicalcordveinwallmaydisturbfetalbloodflowandaectthevascularsysteminadulthood［27］.Ourmorphometricresultswereinagreementwiththe

resultsofpreviousstudiesinthecontrolandpreeclampticgroups［10-23］.OurresultsshowthatwhenGroups2and3Awerecompared,thethicknessoftheumbilicalcordvesselsremainednearlyconstant,whereasbothtotalareasandlumenareaswerereducedwithrespecttothecontrolgroup.Thesechangescorrelatewithourhis-topathologicalfindings,whichincludedawideningundertheepithelium,thecontractionofthemusclecells,and

Fig.3 PhotomicrographsofumbilicalcordtakenfrompreeclampticmotherhavingnormalDopplerFVW(Group3A).Awideningundertheepitheliumbetweenthemusclelayersandthecontractionofthemusclecellswasseenwithawavedlikeappearanceofthenucleus.Separationsappearedinbetweenthemusclecellsandinbetweenthelayersofmuscle(arrow).Theveinlumenwasseentohavenarrowed.Generalviewofumbilicalcordatamagnificationof×10(A);umbilicalcordartery,×40(B);umbilicalvein(V),×40(C);highermagnificationoftheveinwall,×200(D).H.E.


separationsbetweenthemusclecellsassociatedwiththeedema.Thesefindingssuggestamainlyvasoconstrictiveeect.Bycontrast,acomparisonofGroup3BtoGroups2and1showedacomparablereductionofallparametersofthevessels.InGroup3B,ourhistopath-ologicalfindingsarerelatedtothenarrowinglumenofthevesselsandthecontractedsmoothmusclecellsthatweresmallerthantheirnormalsize.Thesefindingsaresugges-tiveofapredominanthypoplasticmechanism.These2mechanisms,vasoconstrictionandahypoplasticeect,maybedierenteventsormayfolloweachother［10］.Thefirstresponsetohypoxemiaisvasoconstrictionofthevessels.Ifhypoxemiacontinues,itmaycausemor-phologicalchangessuchashypoplasia.ChangesofthecompositionofWhartonjellysuchas

theglycosaminoglycans,watercontent,andextracellular

matrixcomponentswerethemainresultsofthereductionofthediameteroftheumbilicalcord［11,26-27］.Thesechangesmightberesponsibleforthegrowthfactors,whichmodifymyofibroblastproliferationgeneexpression,proteinbiosynthesisand/orotherprocesses.RecentstudieshavesuggestedthatDopplerwaveform

indicesfromtheumbilicalartery,fetalaortaandfetalmiddlecerebralarteriesareusefulinidentifyingIUGRanddeterminingtheriskofsubsequentperinatalmorbidity［28,29］.Anabnormalumbilicalartery Dopplerwaveform isastrongpredictorofadverseperinataloutcomeinpatientswithpreeclampsia.A correlationbetweentheumbilicalarteryDopplerindicesandadverseperinataloutcomewasfoundinpreviousstudies［24,29］.TheumbilicalarteryDopplerindicesarerelatedtoplacentalvascularresistance. Theseearlierstudies

Fig.4 PhotomicrographsofumbilicalcordtakenfrompreeclampticmotherhavingabnormalFVW(Group3B).Themuscleareawasseentohaveseparatedfromtheconnectivetissues.Themusclecellswereseentobehypoplasticandsmallerthantheirnormalsize.Therewasasignificantdecreaseinthelumenareainthisgroup,comparedtothenormalandchronichypertensivegroup.Generalviewofumbilicalcordatamagnificationof×10(A);umbilicalcordartery,×40(B);umbilicalvein(V),×40(C);highermagnificationoftheveinwall,×200(D).H.E.


showedtheuseofumbilicalarteryDopplerwaveformindicesinthepredictionofabnormalneonatalmor-phometry.Dopplerultrasonographyoftheumbilicalarteriesisincreasinginimportanceintheantenataldiagno-sisoffetalwellbeing.Theumbilicalvasculararchitectureisinterestingnotonlyfromamorphologicpointofviewbutalsoasabasisforfunctionalinterpretation.Itissuggestedthatwaveformsreflectplacentalimpedancetobloodflow,andthatchangesofflowpatternsmaybecausedbyhistomorphologicalterationsofthefetoplacentalvesseltree.AbnormalDopplersystolic/diastolicratiosmightreflectapathologicfetalcirculationresultinginintrauterinegrowthretardation,whereasnormalvaluesreflectanormalfetoplacentalcirculationassociatedwithsmallfetalsize［30-34］.Inconclusion,theumbilicalarteryDopplerFVW

indicesprovidegoodvaluesforpredictingintrauterinegrowthretardationinpreeclampticpatients.Wealsoobservedthattheumbilicalvessel’swallthicknesseswerereducedinthegroupofpreeclampticpatientswithpatho-logicalDoppler.Itisnotclearwhetherthemorphologicalchangesdisturbtheflowinthevesselsorifareductionoftheflowcausesthemorphologicalchanges.Ifaprogres-siveincreaseinbloodflowwasakeyfactorcontributingtotheembryonicdevelopmentofthevasculartree,aninitialumbilicalvasoconstrictioninresponsetoahypoxicstressproducedareductionintheumbilicalbloodflowandinturnledtoaless-developedarterialtreewithanexpectedincreaseintotalplacentalvascularresistance［10］.Chronichypertensionandpreeclampsiamaysharesimilarpathophysiologicevents.Furtherstudiesarenecessarytoelucidatetheexactmechanisms.

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comparativemorphologicaldi썒erencesbetweenumbilicalcords ...age 27.7±4.6 28.3±4.4 27.6±5.3...

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