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Fetalgrowthrestriction:Evaluationandmanagement

OfficialreprintfromUpToDate
www.uptodate.com2015UpToDate

Fetalgrowthrestriction:Evaluationandmanagement
Author
RobertResnik,MD

SectionEditors
CharlesJLockwood,MD,
MHCM
DeborahLevine,MD

DeputyEditor
VanessaABarss,MD,
FACOG

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jan2015.|Thistopiclastupdated:Dec03,2014.
INTRODUCTIONWhensuboptimalfetalgrowthissuspected,prenatalcareinvolvesconfirmingthesuspected
diagnosis,determiningthecauseandseverityofgrowthrestriction,counselingtheparents,closelymonitoringfetal
growthandwellbeing,consultingwithneonatalcolleagues,andselectingtheappropriatetimeforandrouteof
delivery.Akeyaspectofthisprocessisdistinguishingtheconstitutionallysmallfetusfromthegrowthrestricted
fetus.Aconstitutionallysmallfetusachievesitsnormalgrowthpotentialandhasagoodprognosis,whereasthe
fetuswhosegrowthpotentialisrestrictedisatincreasedriskofperinatalmorbidityandmortality.Fetalgrowth
restriction(FGR)thatresultsfromintrinsicfetalfactorssuchasaneuploidy,congenitalmalformations,andfetal
infectioncarriesaguardedprognosisthatoftencannotbeimprovedbyanyintervention.FGRrelatedto
uteroplacentalinsufficiencyhasabetterprognosis,butisstillassociatedwithanincreasedriskofadverse
outcome.However,theoptimaldefinitionofgrowthrestrictionandthedifferentiationbetweenphysiologicaland
pathologicalsmallfetalsizeisacommon,controversial,andcomplexprobleminmodernobstetrics[1].
INITIALEVALUATION
ConfirmingthediagnosisAccurateidentificationofthefetuswithpathologicgrowthrestrictionversusthe
constitutionallysmallfetusenablesthecliniciantoimplementinterventionstoreduceadverseoutcomes
associatedwithgrowthrestrictionandavoidunnecessaryinterventionsfortheconstitutionallysmallfetus,whois
notatincreasedriskofadverseoutcome.Althoughthisdistinctionisdifficulttomakeprenatally,considerationof
maternalfactorsandserialfetalassessmentcanimprovediagnosticperformance.Thishadledtothedevelopment
of"customized"growthcurves,whichtakeintoaccountfetalgrowthpotentialbaseduponthemother'sheight,pre
pregnantweight,parity,andethnicity,allstrongcontributorstoultimatefetalweight[2,3].Thisapproachmaymore
reliablydistinguishthosefetuseswhoaretrulygrowthrestrictedandatincreasedriskofmorbidityandmortality
fromthosewhoaresmallbutnormal[4].(See"Fetalgrowthrestriction:Diagnosis",sectionon'Customized
growthcurves'.)
Anotherimportantfactoristhethresholdusedtodefineasmallfetus/newborn.Historically,asmallfetus/newborn
hasbeendefinedas<10thpercentileweightforgestationalage,eventhoughmostfetuses/newbornswithweights
betweenthe5thand10thpercentilesareconstitutionallysmallandnormal.Conversely,somefetuses/newborns
>10thpercentileexhibitneonatalcomplicationsassociatedwithFGRbecausetheydidnotachievetheirgrowth
potential.TheneedforabetterdefinitionofFGRissupportedbyfindingsofalarge,prospectiveobservationaltrial
(PORTO)conductedinIrelandandincludingover1100pregnancieswithnonanomalousfetuseswithestimated
fetalweight<10thpercentileonultrasoundexamination[1].Only2percentoffetusesatthe3rdto10thpercentile
(5/254)experiencedadverseperinataloutcome,while6.2percentofthose<3rdpercentile(51/826)hadanadverse
outcomeandalleightmortalitieswereinthisgroup.Thecombinationofestimatedfetalweight<3rdpercentileand
abnormalumbilicalarteryDoppler(definedaspulsatilityindex>95thcentile,absentorreversedenddiastolicflow)
wasastrongandconsistentpredictorofadverseoutcome:16.7percentofthesefetusesdeveloped
intraventricularhemorrhage,periventricularleukomalacia,hypoxicischemicencephalopathy,necrotizing
enterocolitis,bronchopulmonarydysplasia,sepsis,ordeath.Inasubsequentanalysisofthisdatabase,an
abnormalgrowthtrajectoryovertimewasanotherfactorthatpredictedperinatalcomplications(eg,pretermbirth,
preeclampsia,neonatalmorbidity)[5].
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However,usingstricterthresholdsandstrategiesfordefiningFGRhasimplicationsonresourceallocationand
pregnancyoutcome[1].Themostappropriateapproachremainscontroversialmorestudiesareneededcomparing
variousdefinitionsandmanagementstrategies.Theauthorsapproach(discussedbelow)istoaccurately
determinethegestationalage,followfetalgrowtheverytwotofourweeksinthosefetuseswherethereisa
concern(ie,abnormalgrowthtrajectory),andseriallyassessfetalfunctionbymonitoringumbilicalarteryDoppler
andamnioticfluidvolume.
DeterminingthecauseAcompletehistoryandphysicalexaminationisperformedtolookformaternal
disordersassociatedwithimpairedfetalgrowth(eg,alcoholortobaccouse,maternalvasculardisease,
antiphospholipidsyndrome).Inaddition,obstetricalimagingandlaboratoryevaluationsareperformedtolookfor
fetalorplacentaletiologies.(See"Fetalgrowthrestriction:Causesandriskfactors".)
FetalsurveyAdetailedfetalanatomicsurveyisrecommendedinallcasessincemajorcongenital
anomaliesarefrequentlyassociatedwithfailuretomaintainnormalfetalgrowth.Amongmalformedinfants,
thefrequencyofFGRrangesfrom20to60percent,withthehighestriskininfantswithmultipleanomalies
[6],whileapproximately10percentofFGRisaccompaniedbycongenitalanomalies[7].Someanomalies
associatedwithFGRincludeomphalocele,diaphragmatichernia,skeletaldysplasia,andsomecongenital
heartdefectsthus,amoreformalexaminationofthefetalheart(fetalechocardiogram)isindicatedifthereis
anyquestionofcardiacabnormalityonanexpert(levelII)ultrasoundexamination.Polyhydramniosis
associatedwithtrisomy18andseveralcongenitalanomalies.(Seeindividualtopicreviewsoneachsubject).
KaryotypeFetalkaryotypingissuggestedwhenFGRisearlyonsetandsymmetric(secondtrimester),
severe(<3rdpercentile),oraccompaniedbypolyhydramnios(suggestiveoftrisomy18)orstructural
anomalies.Tento40percentofstructurallyabnormal,growthrestrictedfetuseswillhaveanabnormal
karyotype[8]thehighestriskisinthosewithmultipleanomaliesorcertaintypesofanomaly.By
comparison,only2percentofstructurallynormal,growthrestrictedfetuseshaveachromosomalabnormality
[8].EarlyonsetFGRiscommonlyobservedwithtrisomy18,trisomy13,andtriploidy(table1).Ultrasound
markerssuggestiveofaneuploidyincludeechogenicbowel,nuchalthickening,andabnormalhand
positioning.(See"Sonographicfindingsassociatedwithfetalaneuploidy".)
InfectionWhenthereisaclinicalsuspicionofviralinfection(eg,maternalorfetalsigns/symptomsof
cytomegalovirus,rubella,varicella),maternalserumshouldbeexaminedforevidenceofseroconversion.
SpecificamnioticfluidviralDNAtestingcanalsobeperformed,whenindicated.Sonographicmarkersfor
viralinfectionareoftennonspecific,butincludeechogenicityandcalcificationofthebrainand/orliver,and
hydrops.(Seeindividualtopicreviewsonviralinfectionsduringpregnancy).
MalariainpregnancycanalsocauseFGRandisreviewedseparately.(See"Overviewofmalariain
pregnancy".)
Assessmentforcongenitalandacquiredthrombophilicdisordersisnotrecommended,asevidenceforan
associationbetweentheinheritedthrombophiliasandFGRisweak.(See"Inheritedthrombophiliasinpregnancy",
sectionon'Fetalgrowthrestriction'.)
OBSTETRICALMANAGEMENT
AntepartumfetalassessmentTheoptimalapproachtomonitoringthefetuswithsuspectedgrowthrestriction
hasnotbeenestablishedthereisessentiallynoevidencefromrandomizedtrials[9].Serialultrasoundevaluation
offetalgrowth,fetalbehavior(BPP),andimpedancetobloodflowinfetalarterialandvenousvessels(Doppler
velocimetry)formthecornerstoneofevaluationofthefetalconditionanddecisionmaking.Thepurposeistotryto
identifythosefetuseswhoareathighestriskofinuterodemiseandneonatalmorbidity,andthusmaybenefitfrom
interventionbypretermdelivery.
SerialfetalweightassessmentFetalweightestimatesarecalculatedusingvariouspublishedequations
andformulae.Thecomputedweightisthenplottedonapopulationbasedorcustomizedgrowthcurve,which
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allowsthecliniciantodeterminewhentheestimatedweightisbelowthe10thpercentile(table2)andtofollow
growthvelocity.Serialsonogramsaretypicallyobtainedattwotofourweekintervals[10]persistentgrowth
deficiencyinmultipleexaminationsovermanyweeksstrengthensthelikelihoodofFGR.Conversely,normal
growthvelocityinasmallfetussuggestsaconstitutionallysmallbutnormalfetus.(See"Prenatalsonographic
assessmentoffetalweight"and"Fetalgrowthrestriction:Diagnosis",sectionon'Customizedgrowthcurves'.)
DopplervelocimetryDopplervelocimetryoftheumbilicalarteryisrecommendedastheprimary
surveillancetoolformonitoringpregnanciesinwhichFGRissuspected[11].Ithasbeenwellestablishedby
numerousrandomizedtrialsthattheuseofthistoolcansignificantlyreduceperinataldeath,aswellas
unnecessaryinductionoflaborinthepretermgrowthrestrictedfetus.ACochranereviewof18trialscomparingthe
useofDopplertonoDopplerinhighriskpregnanciesshowedareductionofperinataldeathsby29percent(OR
0.71,95%CI0.520.981.2versus1.7percentnumberneededtotreat203),andsignificantlyfewerlabor
inductionsandcesareandeliveries[12].
DopplervelocimetryisagoodtoolforfetalassessmentinFGRwhentheetiologyisplacentaldysfunctionrelated
toprogressiveobliterationofthevillousvasculature.Asplacentaldysfunctionworsens,umbilicalarterybloodflow
resistanceincreasesandtransferofsubstrates,oxygen,andfetalwasteproductsbecomesincreasinglyimpaired.
Initially,fetalcompensatoryresponsescanbeseeninthecerebralarterialcirculation,butultimatelyfetalcardiac
decompensationcanoccurandisreflectedbyafallinforwardflowintheductusvenosus.Althoughthisisthe
classicDopplerpatternassociatedwithfetaldeterioration,otherpatternshavebeenobserved[13].
UmbilicalarteryAnincreaseinumbilicalarteryresistanceleadingtoreducedenddiastolicflowis
consistentlyseenwhen30percentofthevillousvasculatureceasestofunction[14].Normalorreducedend
diastolicflowisinfrequentlyassociatedwithsignificantperinatalmorbidityormortalityandisstrongevidenceof
fetalwellbeing,thusprovidessupportfordelayingdeliverywhenitisimportanttoachievefurtherfetalmaturity.In
thePORTOstudy,perinatalmortalitywas0.3percent(2/698)amonggrowthrestrictedfetuseswithnormal
umbilicalarteryDopplercomparedwith1.4percent(6/418)amongthosewithabnormalDoppler(pulsatilityindex
>95thcentileorabsent/reversedenddiastolic),p=0.06[15].
Absentorreversedenddiastolicflowintheumbilicalarteryoccurswhen60to70percentofthevillous
vasculatureisobliteratedandisevidenceofpoorfetalcondition[14].Thesefetuseseventuallyshowthemetabolic
andbiophysicalconsequencesofworseninghypoxia,includingacidosis,lossofheartratevariability,andlossof
fetalmovement,breathing,andtone.Asmightbeexpected,reverseddiastolicflowisassociatedwithpoorer
neonataloutcomesthanabsentdiastolicflow.Forexample,astudyincluding143FGRpregnanciesthatcompared
neonatal/perinatalmortalitywithreversedversusabsentflowfoundmortalitywasoverfivefoldhigherwhen
reversedflowwasobserved[16].(See"Dopplerultrasoundoftheumbilicalarteryforfetalsurveillance".)
MiddlecerebralarteryVasodilationandhighdiastolicflowinthemiddlecerebralarteryreflect
compensatorycerebralvasodilatation(brainsparingeffect)secondarytofetalhypoxiaandresultinareduced
pulsatilityindex(MCAPI),[1719].Thesechangesmayoccuronetothreeweeksbeforedeteriorationoffetal
biophysicalparameters,buttheprognosticvalueislow.
TherehavebeenseveralreportsofnormalizationoftheMCAPIwhenfetaldeathwasimminent,butitisnota
consistentfinding,thusitsuseintimingofdeliveryislimited[20].
DuctusvenosusWithprogressivelyincreasingumbilicalarterialresistance,fetalcardiacperformance
canbecomeimpairedandcentralvenouspressureincreases,resultinginreduceddiastolicflowintheductus
venosusandotherlargeveins.Vasodilatationoftheductusvenosusfurtherdivertsnutrientandoxygenrichblood
totheheart,butenhancesretrogradetransmissionofatrialpressure.Anabsentorreversedductusvenousawave
indicatescardiovascularinstabilityandcanbeasignofimpendingacidemiaanddeath[21,22].Althoughoverall
sensitivityandspecificityforfetalpH<7.20areonly65and95percent,respectively[21],thedurationofthe
absentorreversedductusvenousawaveneedstobetakenintoaccountandappearstoimpactoutcome
independentlyofgestationalage.EachdayofthisDopplerabnormalitydoublestheoddsofstillbirth,andfetal
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survivalformorethanoneweekisunlikely[22].(See"VenousDopplerforfetalassessment".)
BiophysicalprofileThebiophysicalprofile(BPP)isausefulmethodformonitoringthefetusbecauseit
providesanevaluationofmultipleacuteandchronicfetalphysiologicparameters,isrelativelyeasytoperform,and
isareliabletestoffetalwellbeing(fetaldeathwithinoneweekofanormaltestscoreisrare)[23].Amnioticfluid
assessmentisacomponentoftheBPPormodifiedBPP.ChronicplacentalinsufficiencyresultsinbothFGRand
oligohydramniosandobservationalstudieshavereportedthatpregnanciescomplicatedbyFGRand
oligohydramnioshaveamodestlyincreasedriskofperinatalmortality[24,25].Conversely,normalamnioticfluid
volumeisinfrequentlyassociatedwitheitherFGRorfetaldemise,unlessthecauseisacongenitalmalformation
oraneuploidy.(See"Oligohydramnios".)
ApplicationoftheBPPtothegrowthrestrictedfetusremotefromtermmaybelessreliablesincethepretermfetus
maynothaveachievedmaturityofthebiophysiologicprocessesmeasuredbythistest.Furthermore,although
manylargeobservationalstudieshavedemonstratedtheusefulnessoftheBPPinantepartumfetalassessment,
thereisapaucityofevidencederivedfromrandomizedtrials[26].(See"Thefetalbiophysicalprofile".)
TheBPPistypicallyobtainedonceortwiceperweekhowever,morefrequenttesting,asoftenasdaily,is
indicatedforfetusesathighestrisk,including,butnotlimitedto,severeFGR(lessthanthefifthpercentile),
severeoligohydramnios,absentorreversedumbilicalarteryflowonDopplervelocimetry,orequivocalBPPscore
(ie,6/10).Severelygrowthrestrictedfetusescandeterioraterapidlytheyshouldbemonitoredcloselyusing
multiplemodalitiesifdeliveryistobedelayed[17,27,28].
OutpatientversusinpatientmonitoringWomenwithpregnanciescomplicatedbyFGRareusually
evaluatedandmonitoredasoutpatients.Therearenodataonwhichtobaseindicationsforhospitalization.Weand
otherexperts[29]considerhospitalizationforselectedwomenwhoneeddailyormorefrequentmaternalorfetal
assessment(eg,dailyBPPbecauseofreverseddiastolicflow).Hospitalizationprovidesmoreconvenientaccess
fordailyfetaltestingandallowspromptevaluationandinterventionintheeventofdecreasedfetalactivityorother
complications,butthereisnoevidencethathospitalizationimprovesfetalgrowthoroutcome[30].Decisionsabout
ambulatoryversusinhospitalcareshouldbemadeonacasebycasebasis.
TemporalsequenceoffetaldeteriorationThetemporalsequenceofDopplerchangesintheperipheraland
centralcirculatorysystemsofthegrowthrestrictedfetusissummarizedbelowandinthefigure(figure1)[17
19,3133].However,progressionthroughtheentiresequencedoesnotalwaysoccurbeforedeliveryDoppler
abnormalitiesinsomegrowthrestrictedfetusesprogressslowlyornotatall.Thesequenceismostlikelyto
progresswhenFGRandDopplerabnormalitiesareidentifiedinthesecondtrimesterandtheDopplerindices
worsenwithinthefirsttwoweeksofmonitoring[34].
Decreaseinumbilicalvenousvolumeflowoccursearlyandprecedesclinicalrecognitionofgrowthdelay[35]
Umbilicalvenousbloodflowisredistributedawayfromthefetalliverandtowardstheheart.Liversize
decreases,causingalaginfetalabdominalcircumference,whichisthefirstbiometricsignoffetalgrowth
restriction.
TheumbilicalarteryDopplerindexincreases(diminishedenddiastolicflow)duetoincreasedresistancein
placentalvasculature.
ThemiddlecerebralarteryDopplerindexdecreases(increasedenddiastolicflow),resultinginpreferential
perfusionofthebrain(brainsparingeffect).
Increasingvillousobliterationincreasesplacentalresistance,leadingtoabsentandthenreversedend
diastolicflowintheumbilicalartery.
Myocardialdysfunctionduetochronichypoxiaandnutritionaldeprivation,aswellasincreasedfetoplacental
arterialimpedance,resultsinincreasedductusvenousindices.Ascardiacperformancedeteriorates,absent
orreversedenddiastolicflowintheductusvenosusandpulsatileumbilicalvenousflowmaydevelop,which
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canbepreterminalevents.
Atthispoint,biophysicalchangesusuallybecomeapparent:thenonstresstestbecomesnonreactive,the
biophysicalprofilescorefalls,andlatedecelerationsaccompanycontractions.
However,thecardiovascular(Doppler)andbehavioral(BPP)manifestationsoffetaldeteriorationinFGRfetuses
canoccurlargelyindependentofeachother,resultingindiscordantDopplerandBPPfindings[36].Thebest
approachwhenthisoccursisnotclearandthephysicianmustanalyzeeachcaseindividually,takingintoaccount
suchfactorsastheobstetricalsituation,gestationalage,degreeofabnormality,andresultsfromothertestsof
fetalwellbeing.
FrequencyoffetalsurveillanceThefrequencyoffetalsurveillanceisbasedupontheseverityoffindingsand
whethertheexaminationsarebeingdonetomonitorfetalwellbeing,whichrequiresrelativelyfrequent
assessment,orfetalgrowth,whichisassessedoverintervalsoftwotofourweeks.
TheSocietyforMaternalFetalMedicinepublicationscommitteesuggestsumbilicalarteryDopplerstudiesevery
onetotwoweeksinitially,andifnormal,theintervalcanbedecreased[11].Ingeneral,whenumbilicalarteryend
diastolicflowispresentandstable,wefollowthefetuswithweeklyDopplerevaluationtodeterminethepatternof
progression.TheBPPisusedeitheronceweeklyasanintervaltestbetweenDopplerexaminationsortwice
weekly,withonetestatthetimeoftheDopplerexaminationtherearenodatatosupportoneapproachoverthe
other.OnetrialreportedthatgrowthrestrictedfetuseswithnormalumbilicalarteryDopplerimpedancecouldbe
safelyevaluated(andwithfewerinterventions)withfortnightly,ratherthantwiceweekly,surveillance[37].This
approachwouldbecosteffectivewithoutcompromisingclinicalefficacy,butrequiresfurthercorroboration.(See
"Dopplerultrasoundoftheumbilicalarteryforfetalsurveillance".)
WeeklyDopplershouldbecomplementedbytwiceweeklyBPPoranothercombinationoftwoantenataltests
(nonstresstestandmodifiedBPPorBPP)whenFGRiscomplicatedbyoligohydramnios,preeclampsia,
decelerationoffetalgrowth,increasingumbilicalDopperindex,orothercomplications,evenwhenumbilicalartery
enddiastolicflowispresent.
Absentorreversedenddiastolicflowintheumbilicalarteryispotentiallyasignofimpendingfetalcardiovascular
andmetabolicdeterioration.Ifeitheroftheseabnormalpatternsispresentandthefetusisnotimmediately
deliveredbecauseofextremeprematurity,thendailyBPPandDopplerarerecommended.Theabsenceof
abnormalflowpatternsintheductusvenosusmaybeusedtosupportthedecisiontoextendsuchapregnancy,
andmayenablethepregnancytobeprolongedforaslongastwoweeks.
AntenatalsteroidsTheefficacyofantenatalsteroidsforreducingneonatalmorbidityandmortalityinthe
pretermgrowthrestrictedneonateremainscontroversial,withtwolargestudiesshowingconflictingresults[38,39].
Untilmoreinformationisavailable,itisappropriatetoadministeracourseofantenatalsteroidsincasepreterm
deliveryoccurs.Multipleserieshavefoundthatbothspontaneousandindicatedpretermdeliveryaremore
commoningrowthrestrictedfetuses[4042].
Ideally,onecourseofsteroidsisgivenbetween24and34weeksofgestationintheweekbeforedeliveryis
expected.TimingisbasedontheseverityofFGR,Dopplerfindings,rateofprogression,andpresenceofcomorbid
conditions.(See"Antenatalcorticosteroidtherapyforreductionofneonatalmorbidityandmortalityfrompreterm
delivery".)
Threestudiesobservedthatgrowthrestrictedfetuseswithabsentenddiastolicflowoftenshowtransient
improvementinbloodflowafterglucocorticoidadministration[4345].Infact,fetusesthatdidnotshowincreased
enddiastolicflowappearedtohavepoorerneonataloutcomes.Thereasonsickerfetusesareunabletomounta
vascularresponsetoglucocorticoidadministrationisunclear.Oneactionofglucocorticoidsistoenhancethe
tropiceffectofcatecholaminesonheartmuscle.Itishypothesizedthatinotropydoesnotimproveinsicker
fetusesbecausetheyhaveimpairedcardiacwallcompliance.
FetalbloodsamplingInthepast,fetalbloodsampling(FBS)wasusedintheassessmentoffetalacidbase
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statusinseverelygrowthrestrictedfetusestoassistintheidentificationoftheoptimaltimingfordelivery.
However,FBScarriesa9to14percentrateofprocedurerelatedlossamonggrowthrestrictedfetuses,thusits
valueforlongitudinalassessmentoffetalwellbeingismitigatedbythehighriskoffetaldeath.SinceFGRcanbe
managedadequatelywithoutinvasivetechniques,FBSisnotrecommendedtofollowfetalstatus.(See"Fetal
bloodsampling".)
MedicalinterventionsThereislittleevidencethatanymaternalantenataltreatmentenhancesfetalgrowthin
growthrestrictedfetuses.Numerousapproacheshavebeentriedinsmallrandomizedtrials,includingnutritional
supplementation,maternaloxygentherapy,andinterventionstoimprovebloodflowtotheplacenta,suchas
plasmavolumeexpansion,lowdoseaspirin,heparin,bedrest,andbetamimetics,calciumchannelblockers,or
sildenafil[30,4649].Nonehaveconsistentlybeenshowntobeofvalue.Insmokers,anintensivesmoking
cessationprogrammightbeofvalue,andhasotherpregnancyandhealthbenefits[50,51].(See"Cigarette
smokingandpregnancy".)
Shortterm,maternalhyperoxiamayimprovefetalacidbasestatusatthetimeofdelivery.Althoughitslongterm
usehasbeenreportedtolowerperinatalmortalitycomparedtocontrols,thedifferencesmaybeduetomore
advancedgestationalageintheoxygentreatedgroup[52].Antihypertensivetherapyofhypertensivegravidasdoes
notimprovefetalgrowth[53].
TIMINGOFDELIVERY
GeneralprinciplesThereislittleconsensusabouttheoptimaltimingofdeliveryofthehighriskpretermgrowth
restrictedfetus[54].Thedecisionisdeterminedbybothgestationalageandfetalcondition.Thebodyof
informationapplicabletomanagementandevaluationofthesefetusesiscomplexandinevolution.Nevertheless,
thereisconsensusthatthegrowthrestrictedfetusshouldbedeliverediftheriskoffetaldeath,asdeterminedby
antepartummonitoringtests,exceedstheriskofneonataldeath,whichishighlydependentongestationalage.
Thisassessmentisdifficulttomakegiventherelativelypoorpredictivevalueofantenataltestsforfetal
surveillanceandthewidevariationinneonatalmorbidity/mortalityratesremotefromterm.Afewtrialshave
attemptedtoanswerthequestionofwhentointerveneinthesepregnancies:
TheGrowthRestrictionInterventionTrial(GRIT)randomlyassignedpregnantwomenbetween24and36
weekswithFGRtoimmediate(n=296)ordelayed(n=291)deliveryiftheirobstetricianwasuncertainabout
whentointervene[54].Fortypercentofthesepregnancieshadabsentorreversedenddiastolicumbilical
arteryflow.Inthedelayeddeliverygroup,deliveryoccurredwhentheobstetricianwasnolongeruncertain
aboutintervening,whichtookamedian4.9days.
Theimmediatedeliverygrouphadfewerstillbirths(2versus9withdelayeddelivery),butmoreneonataland
infantdeaths(27versus18),especiallywhenrandomizationoccurredbefore31weeks.Followupdataupto
age13yearsshowednodifferencesbetweengroupsincognition,language,motor,orparentassessed
behaviorscoresonstandardizedtestsfollowupwasachievedinapproximately70percentofsurvivors
[55,56].Cognitionscoreswereclosetothestandardizednormalrange.
Thesedatasuggestthatdelayingdeliveryoftheverypretermgrowthrestrictedfetusinthesettingof
uncertaintyresultsinsomestillbirths,butimmediatedeliveryproducesanalmostequalnumberofneonatal
deaths,andneitherapproachresultsinbetterlongtermneurodevelopmentaloutcome.Althoughwidelycited,
thesestudiesaredifficulttoevaluateduetothelackofstandardcriteriaforintervention.
Aprospectivemulticenterstudycametosimilarconclusions.Over600singletonfetusesatlessthan33
weeksofgestationwithnormalanatomyandkaryotype,FGR,intactmembranes,andelevatedumbilical
arteryresistancewerefollowedwithserialexaminations[57].Atverypretermgestations,gestationalage
wasthemostimportantfactorpredictingoutcome:neonatalsurvivalwaslessthan50percentbefore26
weeksofgestationintactsurvivalwaslessthan50percentbefore28weeksofgestation.
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After26to28weeks,fetalassessmenttests(ductusvenousDoppler,biophysicalprofile)wereusefulin
decidingwhethertocontinueexpectantmanagementtoallowfurthergrowthandmaturationversus
interventiontopreventinuterodemise.Abirthweightover600gwasalsoanimportantpredictorofsurvival.
TheDIGITAT(DisproportionateIntrauterineGrowthInterventionTrialAtTerm)trialrandomlyassigned650
pregnantwomenover36.0weeksofgestationwithsuspectedFGRtoinductionoflabororexpectant
monitoring[5860].Theprimaryoutcomewasacompositemeasureofadverseneonataloutcome(death
beforehospitaldischarge,fiveminuteApgarscore<7,umbilicalarterypH<7.05,oradmissiontothe
intensivecareunit)[58].NeonatalmorbiditywasanalyzedseparatelyusingMorbidityAssessmentIndexfor
Newborns(MAIN)score[59].
Theinductiongroupdelivered10daysearlierandweighed130gless(meandifference130g,95%CI188
gto71g)thantheexpectantlymanagedgroup,buthadstatisticallysimilarcompositeadverseoutcome
(6.1versus5.3percentwithexpectantmanagement)andcesareandeliveryrates(about14percent)[58].
MAINscoreswerealsosimilarforbothgroupstheonlysignificantdifferencewasahigherproportionof
hyperbilirubinemiaintheinductiongroup(10.4versus5.7percent)[59].Inaddition,developmentaland
behavioraloutcomesat2yearsofageweresimilarforbothgroups[60].Theauthorsconcludedthatboth
approacheswerereasonable,andthechoiceshoulddependonpatientpreference.
OurapproachBasedonthedatapresentedabove,datafromretrospectivestudies,expertopinion,andclinical
experience,wehavedevelopedthefollowingapproachtoevaluationandmanagementofFGR(table3).
RemotefromtermIngrowthrestrictedfetusesremotefromterm(<34weeksofgestation),evidenceof
normalumbilicalarteryflowbyDopplervelocimetryisreassuringwithregardtoimmediatefetaloutcome
prolongationofpregnancytogainfurtherfetalmaturityisreasonableinthesecases.Morbidityandmortalityof
bothconstitutionallysmallandgrowthrestrictedfetusesremainsrelativelyhighunder32weeksofgestation
[61,62].Between26and29weeksofgestation,eachdayinuterohasbeenestimatedtoimprovesurvivalby1to
2percent[57].
Ontheotherhand,absenceandparticularlyreversalofflowareominousfindingsthehighriskoffetaldemise
withexpectantmanagementinthesecasescanexceedtherisksassociatedwithpretermdelivery.Wewould
immediatelydeliveranypregnancy32weekswithreversedflowand34weekswithabsentflow,butwouldtry
todelaydeliveryinthoseunder32weekswithreversedflowandthoseunder34weekswithabsentflow.The
timingofdeliveryinthesecasesdependsupontheetiologyandseverityoftheFGR(<3rdversus<10th
percentile),theresultsofantenatalfetaltesting,andthepresence/absenceofadditionalriskfactorsforanadverse
outcome.(See"Dopplerultrasoundoftheumbilicalarteryforfetalsurveillance".)
Changesinthevenouscirculation,includingevidenceofflowreversalsintheductusvenosusorpulsatileumbilical
venousflow,generallyoccurlaterthanthoseobservedinthearterialcirculation.Theyappeartobemorepredictive
ofimpendingadverseoutcome,andthusgenerallywarrantimmediatedeliveryregardlessofgestationalage
[63,64].AlthoughtheuseofvenousDopplerinterrogationremainslargelyinvestigational,agrowingnumberof
maternalfetalmedicinespecialistsareusingtheinformationgainedfromsuchstudiestoavoidverypreterm
deliveryinfetuseswithabsentorreversedenddiastolicarterialflowandreassuringantepartumfetaltesting(non
stresstest[NST],biophysicalprofile[BPP]).Inthesepregnancies,theabsenceofabnormalflowpatternsinthe
ductusvenosusmaybeusedtosupportthedecisiontoextendthepregnancyto32to34weeks,ifothertestsof
fetalwellbeingremainreassuring.(See"VenousDopplerforfetalassessment".)
TheserecommendationsaresimilartothoseoftheSocietyforMaternalFetalMedicinepublicationscommittee,
whichsuggestsexpectantmanagementuntil34weeksofgestationforsuspectedFGRwithabsentenddiastolic
umbilicalarteryflowaslongasfetalsurveillanceremainsreassuring[11].ForFGRwithreversedenddiastolic
umbilicalarteryflowandreassuringfetalsurveillance,theysuggestdeliveryat32weeksofgestation.Whenend
diastolicumbilicalarteryflowisdecreased(butnotabsentorreversed)withreassuringfetalsurveillance,delivery
maybedelayeduntil>37weeks.
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Forfetuseslessthan32weeksofgestation,magnesiumsulfateisgivenbeforedeliveryforneuroprotection.(See
"Neuroprotectiveeffectsofinuteroexposuretomagnesiumsulfate".)
LatepretermandtermDeliveryofthelatepreterm(34to366/7thsweeks)orearlyterm(370/7thsto376/7ths
weeks)growthrestrictedfetusisrecommendedifthereareadditionalriskfactorsforadverseoutcome,suchas
maternalmedical/obstetricaldisorders,arrestofgrowthoverathreetofourweekinterval,and/orabsenceor
reversalofDopplerflowintheumbilicalartery[65].Atthisgestationalagerange,therisksofpretermbirthare
relativelylow,andthusoutweighedbytherisksestimatedtobeassociatedwiththesevariables.However,the
patientsspecificclinicalsituationmustbeassessedandmanagementindividualized.
Forpregnancieswithmildgrowthrestrictionat34to37weeks,normalumbilicalarteryDopplerflow,andno
additionalmaternal/fetalriskfactors,deliverycanbedelayeduntil38to396/7thsweeks,whenpulmonarymaturity
islikely[6568].Deliveryat37to38weeksisreasonableifumbilicalarteryflowisdecreased.
TermpregnancieswithFGRshouldbedeliveredandshouldnotextendbeyond40weeksofgestation.Theriskof
intrauterinefetaldemisesignificantlyincreasesatterm,particularlyastheseverityofFGRincreases.Asan
example,inaretrospectivecohortstudy,theriskofintrauterinefetaldeathat39weekswasestimatedas32per
10,000ongoingpregnanciesforfetalweight<3rdpercentile,23per10,000ongoingpregnanciesforfetalweight
<5thpercentile,13per10,000ongoingpregnanciesforfetalweight<10thpercentile,and2per10,000ongoing
pregnanciesforfetalweight10thpercentile[69].
INTRAPARTUMMANAGEMENTGrowthrestrictedfetusesmayexistinastateofmildtomoderatechronic
oxygenandsubstratedeprivation.Potentialconsequencesincludeantepartumorintrapartumfetalheartrate
abnormalities,passageofmeconiumwithriskofaspiration,andneonatalpolycythemia,impairedthermoregulation,
hypoglycemia,andothermetabolicabnormalities.(See"Smallforgestationalageinfant",sectionon'Outcomes'.)
Consequently,itisimperativetooptimizethetimingofdelivery(see'Timingofdelivery'above),perform
continuousintrapartumfetalmonitoringtodetectnonreassuringfetalheartratepatternssuggestiveofprogressive
hypoxiaduringlabor,andprovideimmediateskilledneonatalcare[70].Umbilicalcordbloodanalysisshouldbe
consideredasacomponentofestablishingbaselineneonatalstatus.(See"Umbilicalcordbloodacidbase
analysis",sectionon'Indications'.)
TheriskoffetalheartrateabnormalitiesrelatedtohypoxiaishighestamongfetuseswithabnormalDoppler
velocimetry.Inonelargeseries,nofetuswithnormalDopplervelocimetrywasdeliveredwithmetabolicacidemia
associatedwithchronichypoxemia[71].Comparedtogrowthrestrictedfetuseswithnormalumbilicalartery
Dopplerratios,growthrestrictedfetuseswithasystolic/diastolicratio>90thpercentileforgestationalagehad
significantlylowerumbilicalarteryandveinpHvaluesatbirth(artery7.23+/0.08versus7.25+/0.1vein,7.31
+/0.01versus7.34+/0.09),anincreasedlikelihoodofnonreassuringfetalheartratepatterns(26versus9
percent),moreadmissionstotheneonatalintensivecareunit(41versus31percent),andahigherincidenceof
respiratorydistress(66versus27percent).
Inthepresenceofreassuringantenataltesting,spontaneousorinducedlaborwithcontinuousintrapartum
monitoringisreasonable[72,73].However,thefrequencyofcesareandeliveryfornonreassuringfetalheartrate
tracingisincreased,giventheincreasedprevalenceofchronichypoxiaandoligohydramniosamongthesefetuses.
OUTCOMEIfthefetusissmallforgestationalage(SGA),butanatomicallynormalwithanappropriateamniotic
fluidvolumeandgrowthrate,theoutcomewillusuallybeanormal,constitutionallysmallneonate.Bycomparison,
trulyimpairedfetalgrowthisassociatedwithincreasedperinatalmortalityandmorbidity,andcanhavelongterm
effectsongrowth,development,andcardiovascularhealth.Morbidityandmortalityinthesecasesisinfluencedby
theetiologyofFGR,earlygestationalageatonsetofgrowthdelayandpretermdelivery,andseverityofgrowth
restriction.
MortalityFetal,neonatal,andperinatalmortalityareincreasedinSGAcomparedtoappropriateforgestational
age(AGA)infants[7479].Theoverallriskoffetaldemiseis1.5percentforfetuses<10thpercentileestimated
fetalweightforgestationalageand2.5percentforfetuses<5thpercentile[80,81].
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Boththeseverityofgrowthrestrictionanddegreeofprematuritycontributetotheincreasedriskofneonataldeath.
Mortalityandmorbidityriseabruptlywhenbirthweightis5thpercentile(figure2)[82].Congenitalmalformations,
perinatalasphyxia,andtransitionalcardiorespiratorydisorderscontributetothehighmortalityrateintermSGA
infants,whereascomplicationsofprematurityplayasignificantroleasgestationalagedecreases[78].(See
"Smallforgestationalageinfant"and"Shorttermcomplicationsoftheprematureinfant".)
AlthoughneonatalmortalityishigherinSGAthaninAGAinfantsateverygestationalage,neonatalmortalityis
similarforSGAandAGAinfantsatanygivenbirthweight[54].
MorbiditySGAinfantsareatincreasedriskofneonatalmorbiditycomparedtoAGAinfants,particularlywhen
veryprematureandpretermbirthsaremorecommoninpregnanciescomplicatedbyFGR[62,8386].Shortterm
morbiditiesarerelatedtobothlowbirthweightandprematurityandincludeimpairedthermoregulation,
hypoglycemia,polycythemia/hyperviscosity,hypocalcemia,hyperbilirubinemia,infection,andimpairedimmune
function.Increasedrisksofacidemia,apnea,respiratorydistress,intraventricularhemorrhage,andnecrotizing
enterocolitishavealsobeendescribed[83,87].(See"Smallforgestationalageinfant"and"Shortterm
complicationsoftheprematureinfant".)
Abroadrangeofadverselongtermoutcomeshasbeenreported,includingsmalldecreasesinIQ(whichare
statistically,butnotclinically,significant),areductioninscoresforexecutivecognitivefunctions(reflectiveness,
visualmemoryandvisualmotorcoordination,planningandsequentialprocessing),andasharplyincreasedriskof
cerebralpalsy[8894].OnereportsuggestedthatFGRhasanegativeimpactonintellectualoutcomeeveninthe
presenceofcatchupgrowth[95].Asmightbeanticipated,theworstoutcomeshavebeenobservedinthemore
severelygrowthrestrictedinfantswhoarepreterm,andwhoexhibitthemostovertevidenceofimpairedumbilical
bloodflow[9698].TermFGRinfantsarealsoatriskofneurodevelopmentaldelay[99].Thereissomeevidence
thatabnormalfetalmiddlecerebralarteryDopplerflowassociatedwithFGRispredictiveofneurobehavioral
impairmentinchildhood[100,101].
Inaninterestingstudycomparingoutcomesingrowthrestrictedversusnormallygrownmonozygotictwinpairs,
thesmallercotwinhadalowerverbalbutnotperformanceIQscore[102].Thesefindingsareuniquesincethe
studypopulationnaturallycontrolsforparentalIQandeducationandotherconfoundingvariablessuchasgender
andgenetics.(See"Smallforgestationalageinfant",sectionon'Outcomes'.)
Theprognosisforintactneurologicfunctionispresumablymorefavorableforthegrowthrestrictedfetuswhenthe
causeisrelatedtosubstratedeprivation,sincecatchupgrowthispossiblewhenthetimingofdeliveryreflects
thepointwhenfetalriskexceedsneonatalriskwhenthefetusremainswellcompensatedantepartumand
intrapartumandwhentheinfantreceivesappropriateneonatalcare.
Theremayalsobedeleteriouseffectsofinuterogrowthrestrictiononsubsequentadulthealth.TheBarker
hypothesisproposedthattheendocrinemetabolicreprogrammingthatenabledthegrowthrestrictedfetusto
compensateforthehostileintrauterineenvironmentmightleadtoametabolicsyndromeinlaterlifewith
developmentofhypertension,hypercholesterolemia,impairedglucosetolerance,andischemicheartdisease
[103,104].Asystematicreviewof80studiesfoundthatbloodpressurerose2mmHgwitheachkilogramof
decreasingbirthweightandsmallheadcircumferencewasmostconsistentlyassociatedwithhighbloodpressure
[105].OtherstudieshavereportedthatFGRisassociatedwithanincreasedriskofischemicheartdisease[104],
lownormalrenalfunction[106],andtype2diabetesinadultlife[107].Astudycomparingcardiacfunctionin80
childrenwhoweregrowthrestricted(meanage5years)and120controlsfoundthatthegrowthrestrictedchildren
hadadifferentcardiacshape,moreglobularventricles,decreasedstrokevolume,andincreasedheartrate,aswell
ashigherbloodpressure[108].(See"Possibleroleoflowbirthweightinthepathogenesisofprimary(essential)
hypertension"and"Overviewoftheriskequivalentsandestablishedriskfactorsforcardiovasculardisease".)
RECURRENCERISKThereisatendencytorepeatSGAdeliveriesinsuccessivepregnancies[109112].As
anexample,aprospectivenationalcohortstudyfromTheNetherlandsreportedthattheriskofanonanomalous
SGAbirth(<5thpercentile)inthesecondpregnancyofwomenwhosefirstdeliverywas'SGA'versus'notSGA'
was23and3percent,respectively[110].
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Furthermore,uteroplacentalinsufficiencymaymanifestindifferentwaysindifferentpregnancies.Growth
restriction,pretermdelivery,preeclampsia,abruption,andstillbirthcanallbesequelaeofimpairedplacental
function.TheassociationbetweenthebirthofaSGAinfantinafirstpregnancyandstillbirthinasubsequent
pregnancywasillustratedbyanalysisofdatafromtheSwedishBirthRegister(table4)[113]subsequentstudies
fromtheUnitedStatesandAustraliareportedsimilarfindings[114,115].Thehighestriskofstillbirthwasinwomen
whodeliveredapretermSGAinfant.AnotherseriessuggestedasiblingdeliveredafterthebirthofaSGAinfant
(evenifmildlySGA)wasatincreasedriskofsuddeninfantdeathsyndrome[116].
PREVENTIONINSUBSEQUENTPREGNANCIESInsubsequentpregnancies,weaddressanypotentially
treatablecausesofFGR(eg,cessationofsmokingandalcoholintake,chemoprophylaxisandmosquitoavoidance
inareaswheremalariaisprevalent,balancedenergy/proteinsupplementationinwomenwithsignificantnutritional
deficiencies).(Seeindividualtopicreviews).Avoidingashortorlonginterpregnancyintervalmayalsobe
beneficial.(See"Interpregnancyintervalandobstetricalcomplications".)
Althoughsomerandomizedtrialsreportedthatlowdoseaspirinprophylaxisduringpregnancyreducedtheriskof
recurrentFGRinwomenathighrisk(eg,FGRinapreviouspregnancy)[117,118],largerrandomizedtrialsdidnot
confirmsignificantriskreduction[119].AspirinmaybeeffectivewhenFGRisrelatedtopreeclampsia.Ina
systematicreviewof36randomizedtrialsincluding23,638womenathighriskofdevelopingpreeclampsia,useof
antiplateletagentscomparedtoplacebowasassociatedwitha17percentreductionintheriskofpreeclampsia
anda10percentreductionintheriskofSGAbirths(RR0.90,95%CI0.830.98)[120].Furtherstudyisneeded.
Dietarychangesandsupplements,antihypertensivetherapyofhypertensivewomen,betamimetics,andbedrest
donotpreventFGR[30,53,121,122].
MANAGEMENTOFSUBSEQUENTPREGNANCIESAccuratedatingbyearlyultrasonographyisimportant
toestablishgestationalageandintermittentultrasoundexaminationsareusedtomonitorfetalgrowth.Otherwise,
prenatalmanagementisroutine.Iffetalgrowthisnormal,FGRinapreviouspregnancyisnotanindicationfor
antepartumfetalsurveillancewithNSTs,BPPs,orumbilicalarteryDopplervelocimetry[123].
SELECTEDGUIDELINES
AmericanCollegeofObstetriciansandGynecologists
RoyalCollegeofObstetriciansandGynaecologists
AmericanCollegeofRadiology
SUMMARYANDRECOMMENDATIONSEvaluationandmanagementofsuspectedfetalgrowthrestriction
involvesaccuratedeterminationofgestationalage,distinguishingbetweentheconstitutionallysmallandthe
growthrestrictedfetus,monitoringthefetalgrowthtrajectory,andserialassessmentoffetalwellbeing(umbilical
arteryDopplerandamnioticfluidvolume),withappropriatelytimedintervention,whenindicated.
Initialapproach
(See'Initialevaluation'above.)
Initiatetheprocesstodistinguishbetweentheconstitutionallysmall,normalfetusandthatwithFGR.
Adetailedfetalanatomicsurveyisrecommendedinallcasesoffetalgrowthrestrictionsincemajor
congenitalanomaliesarefrequentlyassociatedwithfailuretomaintainnormalfetalgrowth.
Fetalkaryotypingissuggestediftherearestructuralanomalies,earlyorseveresymmetrical(<3rdpercentile)
growthrestriction,orpolyhydramnios(suggestiveoftrisomy18)sinceeachofthesefindingsisassociated
withanincreasedfrequencyofkaryotypicabnormality.
Maternalserumshouldbeexaminedforevidenceofseroconversioniftherearematernalorfetalsigns
suggestiveofviralinfection.
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Antepartummanagement
Serialultrasoundevaluationoffetalgrowth,fetalbehavior(FPP),amnioticfluidvolume,andimpedanceto
bloodflowinfetalarterialandvenousvesselsformthecornerstoneofevaluationofthefetalconditionand
decisionmaking.Thefrequencyisbasedupontheseverityoffindingsandwhethertheexaminationsare
beingdonetomonitorfetalwellbeing(onetoseventimesperweek)orfetalgrowth(everytwotofour
weeks).(See'Obstetricalmanagement'above.)
Dopplervelocimetryoftheumbilicalarteryisrecommendedformonitoringpregnanciesinwhichgrowth
restrictionisdiagnosedbecausedeliverypromptedbyabnormalDopplerultrasonographyreducesthe
frequencyofperinataldeath.NormalDopplerfindingsarereassuringandthuspotentiallyallowprolongation
ofpregnancyandreductioninthenumberofunnecessarypreterminductions.Dopplerassessmentofthe
venouscirculationmayprovideadditionalinformationfordecisionmakingintheverypretermfetus.(See
'Dopplervelocimetry'above.)
Acourseofantenatalglucocorticoidsisrecommendedforpretermgestations.
Delivery
Timingofdeliveryisdeterminedbybothgestationalageandfetalcondition:
Remotefromterm,evidenceofnormalumbilicalarteryflowbyDopplervelocimetryisreassuringwith
regardtoimmediatefetaloutcomesocontinuedfetalmonitoringisreasonabletoachievefurtherfetal
maturity.Wewouldimmediatelydeliveranypregnancy32weekswithreversedflow,butwouldtryto
delaydeliveryinthoseunder32weekswithreversedflowandthoseunder34weekswithabsentflow.
Thetimingofdeliveryinthesecasesdependsupontheetiologyandseverityofthefetalgrowth
restriction,theresultsofantenatalfetaltesting,andthepresence/absenceofadditionalriskfactorsfor
anadverseoutcome.(See'Timingofdelivery'above.)
Thetermorlatepretermgrowthrestrictedfetusisdeliveredifthereisevidenceofmaternal
hypertension,failureofapparentgrowthoveratwotofourweekinterval,thebiophysicalprofilescore
islow(lessthan6),and/orumbilicalarterialDopplervelocimetryrevealsabsenceorreversalofflow.
However,thespecificclinicalsituationineachcasemustbeconsideredandmanagement
individualized.
Whengrowthrestrictionismildanduncomplicated(nofetalabnormalitiesorcontributingmaternal
disorders),enddiastolicflowispresent,andantepartumfetaltestingresultsarereassuring,delivery
canbedelayeduntilatleast37weekswhenpulmonarymaturityislikely.(See'Latepretermandterm'
above.)
Laborandvaginaldeliveryisareasonableapproachinthepresenceofnormalantenataltesting.Duringlabor,
continuousintrapartumfetalmonitoringisrecommendedtolookfornonreassuringfetalheartratepatterns
suggestiveofprogressivehypoxiaduringlabor.Theclinicianshouldbepreparedforrapidinterventionifthere
isanyevidenceoffetalintolerancetolabor.
Recurrence
Thereisatendencytorepeatsmallforgestationalageorlowbirthweightdeliveriesinsuccessive
pregnancies.Growthrestriction,pretermdelivery,preeclampsia,abruption,andstillbirthcanallbesequelae
ofimpairedplacentalfunctionthatmaymanifestindifferentwaysindifferentpregnancies.(See'Recurrence
risk'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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122. GlmezogluAM,HofmeyrGJ.Betamimeticsforsuspectedimpairedfetalgrowth.CochraneDatabaseSyst
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Topic6768Version43.0

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GRAPHICS
Partiallistofgeneticabnormalitesassociatedwithfetalgrowth
restriction
Trisomy21(Downsyndrome)
Trisomy18(Edwardssyndrome)
Trisomy13(Patausyndrome)
Trisomy9qmosaic
WolfHirschhornsyndrome(partialdeletion4q)
Criduchatsyndrome(partialdeletion5q)
Turnersyndrome(45,XO)
Triploidy
CorneliadeLangesyndrome
BrachmanndeLangesyndrome
Mulibreynanismsyndrome
RubensteinTaybisyndrome(deletion16p13.3)
RussellSilversyndrome
Dubowitzsyndrome
Seckelsyndrome
Bloomsyndrome
JohansonBlizzardsyndrome
Fanconisyndrome
Robertssyndrome
DeSanctisCacchionesyndrome
Skeletaldysplasias
Adaptedfrom:Gross,SJ.ClinObstetGynecol199740:730.
Graphic72782Version1.0

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Smoothedpercentilesofbirthweight(grams)bygestationalage:
UnitedStates,1991,singlelivebirthstoresidentmothers
Gestational
age,weeks

5th
percentile

10th
percentile

50th
percentile

90th
percentile

24

435

498

674

977

25

480

558

779

1138

26

529

625

899

1362

27

591

702

1035

1635

28

670

798

1196

1977

29

772

925

1394

2361

30

910

1085

1637

2710

31

1088

1278

1918

2986

32

1294

1495

2203

3200

33

1513

1725

2458

3370

34

1735

1950

2667

3502

35

1950

2159

2831

3596

36

2156

2354

2974

3668

37

2357

2541

3117

3755

38

2543

2714

3263

3867

39

2685

2852

3400

3980

40

2761

2929

3495

4060

41

2777

2948

3527

4094

42

2764

2935

3522

4098

Notethatthe10thpercentilebirthweightatthelowerlimitfortermpregnancy(37weeksof
gestation)correspondstoapproximately2500grams,whichisalsotheupperlimitfordefining
lowbirthweight.
Adaptedfrom:Alexander,etal.UnitedStatesNationalReferenceforFetalGrowth.InObstetGynecol
199687:163168.
Graphic56847Version5.0

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Progressionoffetalgrowthrestriction

Graphic73075Version4.0

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EvaluationandmanagementoftheIUGRfetus

Growthrate
andpattern

Constitutionally
smallfetus

Usuallybelowbut
paralleltonormal

Fetuswith
structural
and/or
chromosome
abnormality
fetalinfection

Substratedeprivation
uteroplacental
insuffiency

Markedlybelownormal
symmetric

Variableusuallyasymmetric

symmetric
Anatomy

Normal

Usuallyabnormal

Normal

Amnioticfluid
volume

Normal

Normalorhydramnios
decreasedinthe
presenceofrenal
agenesisorurethral
obstruction

Low

Additional
evaluation

None

Karyotypespecific
testingforviralDNAin
amnioticfluidas
indicated

Fetallungmaturitytestingas
indicated

Additional
laboratory
evaluationof
fetalwell

NormalBPP/UAV

BPPvariablenormal
UAV

BPPscoredecreasesUAV
showsevidenceofvascular
resistance

Noneanticipateterm
delivery

Dependentupon
etiology

BPPandUAVdeliverytiming
requiresbalanceofgestational
ageandBPP/UAVfindingsfetal

being
Continued
surveillance
andtimingof
delivery

lungmaturitytestingoften
helpful

IUGR:intrauterinegrowthrestrictionBPP:biophysicalprofileUAV:umbilicalarteryvelocimetry.
Reproducedwithpermissionfrom:Resnik,R.IntrauterineGrowthRestriction.Obstetrics&Gynecology
200299:490.Copyright2002AmericanCollegeofObstetricsandGynecology.
Graphic68553Version1.0

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Morbidityandmortalityin1560smallfor
gestationalagefetuses

Datafrom:ManningFA.Intrauterinegrowthretardation.In:FetalMedicine:
PrinciplesandPractice,Appleton&Lange,Norwalk,CT1995.p.312.
Graphic56263Version5.0

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Relationshipbetweenselectedfirstandsecondpregnancyoutcomes
Outcomeoffirst
pregnancy,livebirths
only

Oddsratioforstillbirthin
secondpregnancy(95%CI)

Stillbirthrate
per1000births

AGA,term

1.0

2.4

SGA,term

2.0(1.5to2.6)

4.8

SGA,moderatelypreterm

4.0(2.5to6.3)

9.5

SGA,verypreterm

8.0(4.7to13.7)

19.0

Analysisadjustedforfactorssuchascigarettesmoking,maternalage,interpregnancy
interval,andpresenceofhypertensionorantepartumbleeding.
AGA:weightappropriateforgestationalageSGA:weightsmallforgestationalage(ie,birthweight>2
standarddeviationsbelowthemeanforgestationalage[<2.5 thpercentile])moderatelypreterm:32to
36weeksofgestationverypreterm:<32weeksofgestation.
Adaptedfrom:SurkanPS,StephanssonO,DickmanPW,CnattingiusS.Previouspretermandsmallfor
gestationalagebirthsandthesubsequentriskofstillbirth.NEnglJMed2004350:777.
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Disclosures
Disclosures:RobertResnik,MDNothingtodisclose.CharlesJLockwood,MD,MHCM
Consultant/AdvisoryBoards:Celula[Aneuploidyscreening(PrenatalandcancerDNAscreeningtestsin
development)].EquityOwnership/StockOptions:Celula[Aneuploidyscreening(PrenatalandcancerDNA
screeningtestsindevelopment)].DeborahLevine,MDNothingtodisclose.VanessaABarss,MD,
FACOGEmployeeofUpToDate,Inc.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmust
conformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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