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ntrauterine growth restriction: new concepts in antenatalurveillance, diagnosis, and management

rancesc Figueras, MD, PhD; Jason Gardosi, MD, FRCOG

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ntrauterine growth restriction (IUGR)is associated with stillbirth, neonatal

eath, and perinatal morbidity as well aselayed effects including cerebral palsyCP) and adult diseases.1-3 In most cases,UGR is due to placental insufficiency but

ay also be due to a number of other con-itions such as congenital anomalies, in-

ections, or drug and substance misuse.However, the study of the natural his-

ory of IUGR or fetal growth restrictionFGR) has particular challenges. First,rowth failure is often not detected ante-atally, and in routine clinical practice,s many as three-quarters of babies atisk of IUGR are not recognized as suchefore delivery.4 In low-risk pregnancy,ith a lower threshold of suspicion, theetection rate is even lower, about 15%.5

econd, when IUGR is recognized, theregnancy is likely to be interrupted if therowth failure is considered severe and ifhe babies are mature enough to have aetter chance ex utero. Therefore, mostualitative and quantitative evidence forhe significance of IUGR comes from theetrospective assessment of the birth-eight of live or stillborn babies.Studies have been hampered by theidespread practice of using the terms

mall for gestational age (SGA) andUGR synonymously. SGA simply referso a weight for gestation below a given

rom the Department of Maternal-Fetaledicine, University of Barcelona, Hospital

linic, Barcelona, Spain (Dr Figueras); andest Midlands Perinatal Institute,

irmingham, UK (Dr Gardosi).

eceived June 2, 2010; revised Aug. 10, 2010;ccepted Aug. 27, 2010.

eprints: Jason Gardosi, MD, FRCOG,irector, West Midlands Perinatal Institute,irmingham B6 5RQ, UK.

[email protected].

002-9378/$36.002010 Mosby, Inc. All rights reserved.

poi: 10.1016/j.ajog.2010.08.055

hreshold, but a significant proportion ofmallness is due to constitutional orhysiological causes, which means thathe association between pathologicalmallness and adverse outcome islurred. However, such factors can nowe adjusted for by the use of the custom-

zed growth potential, which improveshe association between low birthweightnd pathology, as explained in the nextection.

ssociation betweenUGR and outcome

ew tools and new insightsn modern epidemiological research, thetandard for birthweight for gestationas been refined to be able to assessirthweight not against the average ofhe population but against an individualrowth potential calculated for eachaby in each pregnancy.This is based on 3 principles.6,7 First,

he standard is adjusted or customizedor sex as well as maternal characteristicsuch as height, weight, parity, and ethnicrigin on the principle that one size doesot fit all.8 The stepwise improvement ofrediction through this method is illus-rated in Figure 1.

Second, pathological factors such asmoking, hypertension, diabetes, and

Intrauterine growth restriction (IUGR) remainImprovements have to start from a better dfetal growth potential. Customized standarddetection of IUGR by better distinction betwand have led to internationally applicable noinsights in the assessment of risk and survemeasurement plotted on customized charbiometry and Doppler flow are the mainsAppropriate protocols based on available esessment are essential to ensure good ma

Key words: birthweight, customized charts

reterm delivery are excluded to predict S

MONTH 2010 A

he optimum weight that a baby caneach at the end of a normal pregnancy.

Third, the term optimal weight andssociated normal range is projectedackward for all gestational age points,sing an ultrasound growth based pro-ortionality curve; this avoids basing thetandard on preterm neonatal weights,hich by definition are derived fromregnancies with a pathological (pre-erm) outcome and hence do not repre-ent the growth potential.6,7

Recent studies have shown that thisrinciple is also internationally applica-le, with striking similarities of the pre-icted birthweight of a baby born to atandard European mother in the Unitedingdom, Australasia, and the Unitedtates.9,10 In practice, the fetal growthotential, and the individually adjustedr customized normal limits (eg, the0th and 90th centile), are calculated byomputer software11 because of the infi-ite number of possible variations.

alidationhe new standard has been applied to the

esearch of birthweight as well as fetaleight and has helped to improve ournderstanding of the association be-

ween smallness and outcome.In studies of birthweight databases,

e of the main challenges in maternity care.ition of IUGR, applying the concept of ther fetal growth and birthweight improve thephysiological and pathological smallness

. Such developments have resulted in newnce during pregnancy. Serial fundal heightis a useful screening tool, whereas fetalfor investigation and diagnosis of IUGR.

ence as well as individualized clinical as-ement and timely delivery.

tal growth, growth potential

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otential is more strongly associatedith abnormal antenatal Doppler find-

ngs, fetal distress, cesarean section,dmission, and prolonged stay in neo-atal intensive care as well as stillbirthsnd neonatal deaths than centilesased on population standards.12-16 Inact, SGA by population centiles butormal size by customized growth po-

ential can be termed physiologicalmallness because it is not associatedith adverse outcome. Importantly,

FIGURE 1Accuracy of birthweight predictioncharacteristics (n � 313,285)

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wedish births with gestational age-controlled regainst variables added. R2 was best in the middex only, to 0.73 with all variables included. Uppeproduced, with permission, from Francis and Gardosi.152

igueras and Gardosi. Intrauterine growth restriction. Am J O

he customized standard also detects a o

American Journal of Obstetrics & Gynecology MO

ubstantial number of additional, sig-ificantly at-risk cases that were notagged up as SGA by the populationorm.12,13,16 This dual effect of identi-

ying normal-small cases not at risk,nd pathologically small cases that aret risk, is illustrated in Figure 2. Suchndings lead to the useful conclusion

hat “SGA by customized growth po-ential” represents pathological small-ess and can be used interchangeablyith “IUGR” for retrospective research

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Estimated fetal weight also varies withndividual characteristics in low- as wells high-risk pregnancies.17,18 An adjust-ble standard improves the associationith pathology, while reducing false-ositive assessments by adjusting foronstitutional smallness.19 This can havelinical relevance when seeking to reducealse-positive diagnoses of IUGR and un-ecessary intervention.20

Recent work has shown that the lengthf growth deficit is linked with perinatalorbidity,21 in that morbidity is worse

he longer the slow growth has occurredn utero. A similar principle could be in-erred from the findings of a case controltudy of birthweight and CP,2 in whichUGR at term was highly associated withn increased risk of CP, whereas it didot increase the risk in early and late pre-

erm gestations.

tillbirth and IUGRuch validation of the principles of therowth potential have allowed IUGR orGR to be introduced as an additionalategory when classifying stillbirth andound that after excluding congenitalnomalies, more than 50% of stillbirthsad preceding IUGR (�10th customizedentile). As a result, the proportion ofnexplained stillbirths drops from5-70% using the Wigglesworth classifi-ation to 15%.22 This has since been con-rmed in an independent comparativetudy.23 While IUGR is usually the resultf underlying placental pathology andot in itself the cause of the demise,24 it isclinically relevant condition. Aware-

ess of this strong link allows a renewedocus of attention on the antenatal iden-ification of IUGR as a first step towardrevention. Antenatal awareness that the

etus is not growing well is an essentialuality indicator of maternity care.

urpose of detectionirst, detection informs the clinician andhence the mother that the pregnancy ist increased risk, allowing consider-tions on the optimal timing for delivery.epending on severity, babies that areot fulfilling their growth potential have5- to 10-fold risk of dying in utero.12

Second, the information is important

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mbilical artery Doppler, which haseen shown to reduce stillbirth and in-rease preterm delivery without increas-ng neonatal mortality.25 In a large sin-le-center retrospective study, Lindqvistnd Molin26 found that antenatal detec-ion of SGA led to significantly improvedutcome.

creening for the at-risk fetusistoryrevious history of growth restriction or

tillbirth. Women with a previousrowth-restricted baby have a 50% in-reased risk of severe growth restrictionn the current pregnancy,27 and serialhird-trimester assessment for this indi-ation is common practice. A history oftillbirth is also an accepted indicationor intensive antepartum surveillanceecause more than half of normallyormed stillbirths are associated withUGR.22 Stillbirths before 32 weeks’ ges-ation have a particularly strong associa-ion with IUGR.28 Previous stillbirthould appear to be a significant risk fac-

or, especially when associated with a di-gnosis of hypertension or clinicalUGR.29

iabetes. Women with diabetes are atncreased risk of having a baby with mac-osomia as well as FGR, with increasedisk of perinatal morbidity and mortal-ty.30 Preeclampsia is observed in5-20% of pregnancies complicated byype 1 diabetes mellitus without ne-hropathy and approximately 50% inhe presence of nephropathy.31 Pre-clampsia is also more likely in womenith hypertension and poor glucose con-

rol.32 When assessed by customizedtandards, 15% of women with type 2 di-betes are found to have an SGA baby.33

Regular monitoring of fetal growth isecommended in diabetic pregnancies.34

mbilical artery Doppler seems to beore effective than biophysical profile

r cardiotocography,35-37 but its usehould be limited to women with addi-ional risk factors for placental insuffi-iency, such as SGA or preeclampsia.

besity. Obesity has been considered arotective factor for growth restric-ion,38,39 but such findings are likely to
e artifactual because of the use of unad- m
usted population standards. When SGAs defined by customized centiles, obesityncreases the risk of SGA by 50%.15 Suchelative smallness is pathological: a largeopulation-based study40 reported that

n obese women, higher perinatal mor-ality is associated with higher rates ofGA but only when SGA is defined byustomized growth potential (Figure 3).lthough obesity affects the accuracy ofltrasound biometry, it makes palpationnd fundal height measurement evenore difficult. A small series including

2 obese women showed that ultrasoundstimation of fetal weight was more ac-urate than abdominal palpation in pre-icting birthweight.41

ultiple pregnancy. Compared withingletons, twin pregnancies have in-reased risk of mortality and morbid-ty.42 Because growth restriction andeight discordance are responsible for a

arge part of this higher risk of mortalitynd morbidity,43 optimal monitoring ofetal growth is essential. Clinical assess-

FIGURE 2Stillbirth and SGA status by custom

mall for gestational age was defined accordingGA by customized centiles (all SGA by Cust) (blue

Pop and Cust SGA), by the population method onCust only SGA) (red markers) are shown. Odds rGA, small for gestational age.eproduced, with permission, from Gardosi and Francis.15


ent does not allow individual fetal c

MONTH 2010 A

valuation, and therefore, serial fetaleight estimation by ultrasound from8 weeks is considered best practice.rowth standards for multiple pregnan-

ies have been published,44 but singletonomograms are more commonly usedith good accuracy.45

Customized charts for estimated fetaleight (EFW) can also be used for twinsecause the growth potential up to 37eeks is similar to that in singleton preg-ancy.46 There is no consensus on theest definition of weight discordancend its correlation to clinical events,43

ut discordance greater than 20-25% isertainly considered significant.

In addition, the clinical meaning ofrowth discordance may differ greatlyetween monochorionic and dichori-nic pregnancies.42 Although it mayeem reasonable to incorporate umbili-al artery Doppler for an earlier detec-ion of growth restriction, there is insuf-cient evidence to support its use inichorionic multiple pregnancies not

ed and population-based centiles

population-based centiles (Popn only SGA) andrkers). Subgroups that are SGA by both methodsGA Pop only), or by the customized method onlys and 95% confidence intervals are shown.

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creening in early pregnancyiochemical markers. In the first trimes-

er, an unexplained low pregnancy-asso-iated plasma protein A or human cho-ionic gonadotropin (hCG) is associatedith an increased risk of placental-re-

ated diseases such as IUGR or pre-clampsia.49,50 In the second trimester,n unexplained elevation of serum al-ha-fetoprotein, hCG, or inhibin-A

s also associated with these adverseutcomes.51-54

In general, the association is morearked for early-onset IUGR or pre-

clampsia.55 Despite these associations,he performance in terms of sensitivity/pecificity and predictive values of these

arkers individually or combined doesot support their use. Moreover, no clearenefit of intensive surveillance56 or pro-

FIGURE 3Perinatal mortality rate and SGA byand population-based centiles

erinatal mortality rate (PMR) and SGA by cusSGApop), according to maternal body mass indMR vs SGAcust: P � .753; PMR vs SGApop: PGA, small for gestational age.eproduced, with permission, from Gardosi et al.40


hylactic strategies57 in women with ab- n


ormal biochemical markers has beenemonstrated.

arly growth restriction. Low first-tri-ester measurement of crown-rump

ength in pregnancies dated by the lastenstrual period is also linked with

GR.58,59 However, practical applicabil-ty is limited in spontaneously conceivedregnancies because the exact date ofonception is usually not known, and arown-rump length measurement can-ot be used simultaneously for establish-

ng gestational age and for assessing fetalize for gestation.

More recently, it has been demon-trated that slow growth between therst and second trimester is able to

dentify a subgroup of slow-growingabies that are at increased risk of peri-

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ized (SGAcust) and population-based centilesBMI). Comparison test for difference of slopes:.007.

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atal death before 34 weeks’ gestation, fi

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n most cases with growth restriction.60

n early indication of an increased riskould allow more intensive fetal as-

essment and surveillance. Therefore,erial ultrasound evaluation of fetalrowth in the third trimester seemsustified in these cases.

terine artery. Uterine Doppler evalua-ion in the second or first trimester haseen proposed as a screening tool forarly-onset IUGR, with detection rates ofbout 75% and 25%, respectively, for aalse-positive rate of 5-10%.61,62 Theseensitivities are higher for predictingarly IUGR associated with preeclampsiand lower for late IUGR. Different strat-gies combining maternal risk factors,lood pressure, and biochemical mark-rs have been published with detectionates greater than 90% for early-onsetreeclampsia,63,64 and associated IUGR.A metaanalysis65 of 5 randomized

tudies including 1052 women with ab-ormal uterine Doppler in the second

rimester treated with aspirin showed a0% reduction in the incidence of pre-clampsia, without reaching statisticalignificance (relative risk, 0.8; 95% con-dence interval, 0.61–1.06). Only 2 ran-omized studies (n � 225) have evalu-ted the efficacy of aspirin in womenith abnormal uterine Doppler in therst trimester,66,67 showing a pooled1% reduction in the incidence of pre-clampsia. The limited number of casesncluded a high incidence of preeclamp-ia in the control group, and there is un-ertainty whether the standard of careould be extrapolated between countrieso draw reliable conclusions.

Thus, so far, there is no evidence inavor of any prophylactic strategy inases of abnormal uterine artery Dopp-er. However, it could be useful in de-ning the standard of prenatal care byssessing the woman’s risk at the be-inning of the pregnancy. This is ingreement with the recommendationsade by the UK National Institute onlinical Excellence for risk-adjustedrenatal care.68

creening in the third trimestererial fundal height measurement. The

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ial assessment as well as the baseline forubsequent measurements, which are in-erpreted on the basis of the slope or ve-ocity of growth. Indications for referralor further investigations include cases inhich the first fundal height measure-ent is below the 10th centile or consec-

tive measurements suggest static orlow growth, meaning that the serial

easurements do not follow the ex-ected slope of the growth curve. An au-it on the population in the catchmentrea of a referral hospital in the Westidlands (UK) showed that the detec-

ion rates for SGA fetuses are improved ifeferral recommendations are fully ad-ered to, highlighting the need for a con-inuous program of education andraining.69

Not all pregnancies are suitable forrimary surveillance by fundal heighteasurement and require ultrasound bi-

metry instead. In most instances, theseregnancies fall into the following cate-ories: (1) fundal height measurementnsuitable (eg, due to fibroids, high ma-

ernal body mass index) or (2) preg-ancy considered high risk (eg, due torevious history of SGA).Fundal height measurement is more ofsurveillance than a screening tool be-

ause its strength lies in serial assess-ent. However, most clinicians are not

ormally taught how to measure fundaleight and use a variety of differentethods. This reduces accuracy and in-

reases interobserver variation. Not sur-risingly, the evidence on fundal heightssessment is mixed, with some studieseporting that it is a good predictor forUGR,70-73 whereas others fail to find

uch benefit.74-78

A recent review has summarized thefforts being made to standardize thisool to improve its reliability and effec-iveness.79 The name symphysis-funduseight is in fact misleading because the pre-erred direction of measurement is fromhe variable (the fundus) to the fixed pointthe top of the symphysis). The measure-ent should be along the fetal axis, with no

orrection of the fundus to the midline, us-ng a nonelastic tape.

One of the main problems has beenhe assumption that has crept into com-

on clinical practice, without any good 6

vidence, that 1 cm fundal height shouldqual 1 week of gestation and the defini-ion of normal as fundal height � 2 or �cm of gestational age. But as with birth-eight and ultrasound growth, one sizeoes not fit all, and different-sized moth-rs have different normal fundal heightrowth curves.80 As a serial assessment,he emphasis with fundal height mea-urement is on the slope of the curve. Re-erral guidelines for further investigationy ultrasound biometry and Doppler in-lude a single fundal height measurementhich plots below the 10th customized

entile, and serial measurements whichross centiles (ie, are slower than the pre-icted growth velocity).79

A controlled study of 1200 patientsompared measurement and plotting ofundal height on customized growthharts against routine clinical assessmenty palpation and found that it resulted insignificant increase in antenatal detec-

ion of SGA babies from 29% to 54%.81

urthermore, there was a significant re-uction of false-positive rates (ie, small-ormal babies being referred unneces-arily for investigation). The study wasot powered to assess the effect on peri-atal mortality, and there is a paucity ofrospective trials large enough to be ableo assess the effect on hard outcome

easures. However, the antenatal iden-ification of IUGR is already of provenenefit in itself and allows further inves-igations and interventions that arenown to improve outcome. Serial mea-urement of fundal height and plottingn customized growth charts are recom-ended by the Royal College of Obste-

ricians and Gynaecologists guidelines.82

outine/intermittent third-trimester ul-rasound biometry. The effectiveness ofhird-trimester ultrasound biometryor the diagnosis of growth restrictionnd its impact on perinatal outcome isncertain. Sensitivity of abdominalircumference for detecting a birth-eight less than the 10th centile ranges

rom 48% to 87%, with specificity from9% to 85%.83-88 For estimated fetaleight, sensitivities of 25-100% haveeen reported, with a specificity of
9-97%.84,87-89 c
MONTH 2010 A

The high heterogeneity between stud-es does not allow the calculation ofooled values. The largest study,88 fromhe United Kingdom, included 3616ow-risk women on whom a third-tri-

ester (28-36 weeks) ultrasound waserformed with abdominal circumfer-nce measurement. Sensitivity for birth-eight less than the 10th centile was8%, with a false-positive rate of 7%.indqvist and Molin26 introduced a pol-

cy of a routine scan at 32 weeks and ob-erved a detection rate of 54% for SGAdefined as birthweight deviation of ateast 22% from the mean, equivalent tohe third centile). Hedriana and Moore89

ompared serial vs single scan in low-riskomen between 28 and 42 weeks and

ound that multiple ultrasonographicxaminations provided little improve-ent in the prediction of birthweight

ompared with a single observation.cKenna et al90 tested randomly a pol-

cy of 2 scans at 30 and 36 weeks andbserved that fewer babies were bornGA as a result of increased interventionn the study group, although no dataere given on actual detection rates.The impact of routine third-trimester

ltrasound on perinatal outcome is alsonclear. Seven trials83,85,86,91-94 haveeen included in a recently updatedetaanalysis95 that showed that routine

ate pregnancy ultrasound in low-risk ornselected populations does not conferenefit on mother or baby. Furthermore,

t may be associated with a small increasen cesarean section rates.

However, it could be argued that theesults of this metaanalysis have limitedalidity for contemporary practice be-ause it included studies that used out-ated surrogates of fetal growth suchs biparietal diameter measurement83

r protocols in which the diagnosis ofUGR was not followed by a change in

anagement. A Swedish population-ased study96 compared the perinatalutcome of 56,371 unselected women inhom routine third-trimester ultra-

ound was performed with the outcomef 153,355 women with no such screen-

ng. No differences in perinatal mortalityr early neonatal morbidity were found.There is currently therefore insuffi-

ient evidence to support routine third-


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6 American Journal of Obstetrics & Gynecology MONTH 2010

rimester ultrasound in all pregnancies.management trial to investigate the

mpact of third-trimester ultrasoundould be feasible in terms of maternalillingness to participate97 but will re-uire a large sample size to test effect onard outcomes such as perinatal mortal-

ty. Further trials will also need to in-lude growth scans in the late third tri-ester because most cases of IUGR

eliver at term.98

erial ultrasound biometry. For preg-ancies at risk, serial assessment of esti-ated fetal weight or abdominal cir-

umference is the best predictor of FGRs assessed by neonatal morphometry.99

herefore, serial biometry is the recom-ended gold standard for assessing

regnancies that are high risk,82 eithern the basis of past history or because ofomplications that arose during the cur-ent pregnancy. In the absence of clearvidence and consensus about the fre-uency and timing of scans, protocolsnd individual management plans areften limited by the resources available.owever, more than fortnightly scans

re not indicated because the scan errors likely to exceed the increment in sizeecause of growth during the interval.82

iagnosis of IUGRurrent thinking on the natural his-

ory of growth restriction differentiatesetween early-onset and late-onsetorms,100 which have different biochem-cal, histological, and clinical features.101

hereas the former is usually diagnosedith an abnormal umbilical arteryoppler and is frequently associated withreeclampsia, the latter is more prevalent,hows less change in umbilical flow pat-ern, and has a weaker association withreeclampsia.101

mbilical artery Dopplerost instances of growth restriction cor-

espond with cases of placental insuffi-iency.102 Evaluation of placental func-ion by umbilical artery Doppler is alinical standard to distinguish betweenGA and IUGR.103-105 The pathophysio-ogical progression of this parameter isllustrated in Figure 4. As suggested by

FIGURE 4Insonation of the umbilical artery Doppler

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, Site of insonation of the umbilical artery Doppler. Progressive waveform patterns with advancingeverity were: B, normal umbilical artery waveform, C, increased impedance to flow, D, absentnd-diastolic flow, and E, reversed end-diastolic flow.igueras and Gardosi. Intrauterine growth restriction. Am J Obstet Gynecol 2010.

nimal106 and mathematical107 models

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f chronic placental embolization, thebliteration of more than 50% of the pla-ental vessels is required before absent oreversed end-diastolic velocities appear.here is good evidence that umbilicaloppler ultrasound use in these preg-ancies improves a number of obstetricare outcomes and reduces perinataleaths.108

Whereas abnormal umbilical arteryoppler is associated with adverse peri-atal and neurodevelopmental out-ome,109-112 small fetuses with normalmbilical artery Doppler are considered

o represent one end of the normal-sizepectrum, and the importance of manag-ng them as completely differently fromrue IUGR babies has been stressed.113,114

his may not be true for late-onset cases, inhich a substantial proportion of casesith a normal umbilical artery may have

rue growth restriction, and are at risk ofdverse perinatal outcome.109,110,115,116

ther Doppler parametersecause the identification of late-onsetGA fetuses with mild forms of growthestriction cannot only be relied on bymbilical artery Doppler, other vascular

erritories have been proposed. Abnor-al uterine artery Doppler is compara-

le with umbilical artery Doppler as aredictor of adverse outcome in growth-estricted fetuses.116-118 Up to 20% ofGA fetuses have reduced resistance inhe middle cerebral artery (MCA), andhis sign is also associated with poorererinatal outcome116-119 and subopti-al neurodevelopmental development

t 2 years of age.120 Umbilical and cere-ral Doppler can be combined in the ce-ebroplacental ratio. This ratio has beenemonstrated in animal121 and clini-al122 models to be more sensitive toypoxia than its individual componentsnd correlates better with adverseutcome.123

ssessment of the IUGR fetusecause no treatment has been demon-

trated to be of benefit for FGR,124-127

he assessment of fetal well-being andimely delivery remains as the maintrategy for management. Fetal well-be-ng tests could be classified as chronic or
cute. Whereas, the former becomes o
rogressively abnormal because of in-reasing hypoxemia and/or hypoxia, theatter correlates with acute changes oc-urring in advanced stages of fetal com-romise, characterized by severe hyp-xia and metabolic acidosis, and usuallyrecedes fetal death by a few days. Be-ause a fixed sequence of fetal deteriora-ion does not exist, integration of severalell-being tests into comprehensiveanagement protocols is required.

hronic testsmbilical artery. Absent or reversed

nd-diastolic velocities are mostly foundn early-onset IUGR, and these patternsave been reported to be present onverage 1 week before the acute deterio-ation.128 Up to 40% of fetuses withcidosis show this umbilical flow pat-ern.128 Despite the fact that an associa-ion exists between the presence ofeversed end-diastolic flow in the umbil-cal artery and adverse perinatal out-ome (with a sensitivity and specificity ofbout 60%), it is not clear whether thisssociation is confounded by prematu-ity. More recent series129 of severelyompromised IUGR fetuses suggest thatuch a finding has value independentlyf gestational age in the prediction oferinatal morbidity and mortality.

iddle cerebral artery. Longitudinaltudies on deteriorating early-onsetUGR fetuses have reported that the pul-atility index in the MCA progressivelyecomes abnormal.130 Figure 5 showshe progression of this parameter. Up to0% of fetuses have vasodilatation 2eeks before the acute deterioration,128

lthough other series have found this fig-re to be less than 50%.129 Preliminaryndings of an acute loss of the MCA va-odilatation in advanced stages of fetalompromise have not been confirmed inore recent series,128-131 and therefore

his sign does not seems to be clinicallyelevant for management purposes inarly-onset cases. In late-onset IUGR,here is observational evidence116,119

hat MCA vasodilatation is associatedith adverse outcome independently of

he umbilical artery. This suggests a role
f MCA Doppler for fetal monitoring in f
MONTH 2010 A

ate-onset IUGR cases, which needs fur-her investigation in randomized trials.

mniotic fluid. A metaanalysis132 of 18andomized studies demonstrated thatn amniotic fluid index of less than 5 isssociated with abnormal 5 minute Ap-ar score but failed to demonstrate anssociation with acidosis.

Longitudinal studies in early-onsetUGR fetuses have shown that the am-iotic fluid index progressively de-reases.129,130 Amniotic fluid volume iselieved to be a chronic parameter. Inact, among the components of biophys-cal profile, it is the only one that is notonsidered acute. One week before acuteeterioration, 20-30% of cases haveligohydramnios.129,130

cute markersuctus venosus (DV). Early studies on

UGR fetuses demonstrated a good cor-elation of abnormal DV waveform withcidemia at cordocentesis,133 and thisoppler sign is considered a surrogatearameter of the fetal base-acid status.he progression of this parameter is

hown in Figure 6. Absent-reversed ve-ocities during atrial contraction are asso-iated with perinatal mortality indepen-ently of the gestational age at delivery,134

ith a risk ranging from 60% to 100% inetuses with early-onset IUGR.135 How-ver, its sensitivity for perinatal death is still0-70%.134,136,137

Longitudinal studies have demon-trated that DV flow waveforms becomebnormal only in advanced stages of fetalompromise.128-131 Whereas in about0% of cases abnormal DV precedes theoss of short-term variability in the fetaleart rate,130 in about 90% of cases it be-omes abnormal only 48-72 hours be-ore the biophysical profile.131 Debatexists regarding the advantages of DVoppler investigation over biophysicalrofile. However, observational stud-

es138 suggest the integration of both DVoppler investigation and biophysicalrofile in the management of pretermUGR because these strategies seem totratify IUGR fetuses into risk categories

ore effectively. An ongoing random-zed clinical trial (Trial of umbilical and
etal flow in Europe, TRUFFLE) is aimed

aoce

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t evaluating the role of DV assessmentver standard management based onardiotocography for timely delivering

FIGURE 5Color Doppler assessment of the m

A

B

C

, Color Doppler assessment of the MCA at thehigh diastolic velocities and decreased pulsatilitCA, anterior cerebral artery; MCA, middle cerebral artery; PCA,


arly-onset IUGR cases. c


etal heart rate (FHR) analysis. Earlytudies on high-risk pregnancies showedhat, although highly sensitive, cardioto-

le cerebral artery

l of the circle of Willis. B, Normal and abnormaldex) C, waveforms are shown.rior cerebral artery.

t Gynecol 2010.

ography has a 50% rate of false positives r

NTH 2010

or the prediction of adverse outcome.139

n addition, a metaanalysis140 of its ap-lication in high-risk pregnancies failedo demonstrate any beneficial effect in

FIGURE 6Insonation of the ductusvenosus with color Doppler

A

B

C

D

E

, Site of insonation of the DV with color Doppler.rogressive waveform patterns with advancingeverity are shown: B, normal DV waveform, C,ncreased impedance to flow, D, absent end-iastolic flow, and E, reversed end-diastolic flow., descendent aorta; DV, ductus venosus; H, heart; UV, umbilicalein.

igueras and Gardosi. Intrauterine growth restriction. Am Jbstet Gynecol 2010.

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here is no evidence to support the use ofraditional fetal heart rate monitoring oronstress tests in IUGR fetuses. How-ver, these studies were conducted in thearly 1980s, and the control group hado fetal well-being assessment or out-ated techniques such as biochemicalests.

Computerized FHR has provided newnsight into the pathophysiology ofUGR. Short-term variability closelyorrelates with acidosis and severe hyp-xia as demonstrated by cord bloodampling at the time of a cesarean sec-ion.141 Whereas Bracero et al142 demon-trated no significant differences in peri-atal outcome between visual andomputerized FHR, more recent longi-udinal series have pointed to a potentialole as an acute marker.130 Short-termariability becomes abnormal, coincid-ng with the DV: whereas in about half ofhe cases, abnormal DV precedes the lossf short-term FHR variability, the latter

s the first to become abnormal in thether cases.130 Both parameters are con-idered acute responses to fetal acidosis.

iophysical profile. Some observationaltudies show an association between ab-ormal biophysical profile (BPP) anderinatal mortality and cerebral palsy,143

hereas others fail to demonstrate thisssociation.129 In IUGR infants, BBP wasot predictive of cognitive function at 2ears.144 Similarly, whereas some studiesith cordocentesis demonstrated a cor-

elation with acidosis,145 with fetal tonend gross motor movements the bestorrelated components, others have notound this correlation.146

As with FHR , a high false-positive rate50%) limits the clinical usefulness of theiophysical profile.147 A recent study148

as shown that BPP alone in fetuseseighting more than 1000 g is not a reli-

ble test in the treatment of pretermUGR fetuses because of high false-posi-ive and -negative results. A metaanaly-is149 showed no significant benefit of aiophysical profile in high-risk pregnan-ies, although more recent series150,151

n IUGR have suggested that bothoppler and biophysical profile effec-

ively stratify IUGR fetuses into risk cat-
gories. Because fetal deterioration ap- c
ears to be independently reflected byoth tests, further studies are required torove the usefulness of combining bothesting modalities.

Longitudinal series131 have demon-trated that except for amniotic fluid vol-me and the fetal heart rate, the otheromponents (tone, breathing, and bodyovements) of the biophysical profile

ecome abnormal only in advancedtages of fetal compromise. In fact, inbout 90% of cases, the biophysical pro-le becomes abnormal only 48-72 hoursfter the ductus venosus.131

iming of deliveryUGR is one of the most common preg-ancy complications and substantially

ncreases the prospective risk of adverseutcome. Yet according to pregnancyudits, most instances of IUGR are notetected as such antenatally. Modernbstetric care needs to raise the level ofwareness of the importance of this con-ition, and establish evidence-basedrotocols for improved surveillance.Because the only current treatment for

UGR is delivery, the main considerationeeds to be appropriate timing, balanc-

ng the risk of potential iatrogenic mor-idity and continued exposure to annfavorable intrauterine environment.tudies are now in progress with regardo late-onset IUGR to evaluate whetherlective induction beyond 36 weeks’ ges-ation is of benefit. To date, prospectiverials have not been able to throw muchight and are often underpowered orawed.Regarding early-onset IUGR, the mul-

icentre Growth Restriction Interven-ion Trial153 compared outcome afterandomization with early or delayed de-ivery and concluded that it was safe toait, especially at preterm gestations.owever, the study design has been crit-

cized because it did not account for theases that were not randomized andhich were estimated to represent theajority of all eligible cases:154 clinical

election bias may have preferentially in-luded the less severe cases, in which itould be safe to wait anyway. Therefore,

uch results cannot be extrapolated to all
ases with IUGR. c
MONTH 2010 A

Improved definition of the intrauter-ne standard for IUGR by the use of theetal growth potential allows a more dis-erning assessment. A baby with an EFWelow the 10th customized centile has aignificantly elevated risk of morbidity,ven in the absence of an abnormal um-ilical artery Doppler.110 Added into thequation is the awareness that leavingregnancies with IUGR to deliver at termay also lead to perinatal morbidity and

elayed effects such as cerebral palsy.2

Therefore, current best practice wouldndicate that from the time fetal pulmo-ary maturity can be inferred, there is

ittle to be gained by allowing a preg-ancy to continue if good fetal growthannot be demonstrated. However, eachase needs to be carefully assessed andndividually considered, in consultationith the parents. f

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ONTH 2010

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MONTH 2010 Am

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http://www.rcog.org.uk/files/rcog-corp/uploadedfiles/GT31SmallGestationalAgeFetus.pdf



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