IUGR New Concepts - AJOG Review

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Review www.AJOG.orgorigin on the principle that one size doesnot fit all.8 The stepwise improvement ofprediction through this method is illus-trated in Figure 1.Second, pathological factors such as

smoking, hypertension, diabetes, and

Thenew standardhas been applied to theresearch of birthweight as well as fetalweight and has helped to improve ourunderstanding of the association be-tween smallness and outcome.In studies of birthweight databases,

prints: Jason Gardosi, MD, FRCOG,ector, West Midlands Perinatal Institute,ingham B6 5RQ, UK.

[email protected].

2-9378/$36.00010 Mosby, Inc. All rights reserved.BSTETRICS

trauterine growth rerveillance, diagnosi

ncesc Figueras, MD, PhD; Jason Gardos

ntrauterine growth restriction (IUGR)is associated with stillbirth, neonatalth, and perinatal morbidity as well asayed effects including cerebral palsyP) and adult diseases.1-3 In most cases,GR is due to placental insufficiency buty also be due to a number of other con-ions such as congenital anomalies, in-tions, or drug and substance misuse.owever, the study of the natural his-

y of IUGR or fetal growth restrictionR) has particular challenges. First,wth failure is often not detected ante-tally, and in routine clinical practice,many as three-quarters of babies atk of IUGR are not recognized as suchfore delivery.4 In low-risk pregnancy,th a lower threshold of suspicion, thetection rate is even lower, about 15%.5

ond, when IUGR is recognized, thegnancy is likely to be interrupted if thewth failure is considered severe and ifbabies are mature enough to have ater chance ex utero. Therefore, mostalitative and quantitative evidence forsignificance of IUGR comes from therospective assessment of the birth-ight of live or stillborn babies.tudies have been hampered by thedespread practice of using the termsall for gestational age (SGA) andGR synonymously. SGA simply refersa weight for gestation below a given

m the Department ofMaternal-Fetaldicine, University of Barcelona, Hospitalnic, Barcelona, Spain (Dr Figueras); andstMidlands Perinatal Institute,mingham, UK (Dr Gardosi).pre: 10.1016/j.ajog.2010.08.055triction: new concep, and managementD, FRCOG

eshold, but a significant proportionofallness is due to constitutional orysiological causes, which means thatassociation between pathological

allness and adverse outcome isrred. However, such factors can nowadjusted for by the use of the custom-d growth potential, which improvesassociation between low birthweight

d pathology, as explained in the nexttion.

sociation betweenR and outcomew tools andnew insightsmodern epidemiological research, thendard for birthweight for gestations been refined to be able to assessthweight not against the average ofpopulation but against an individualwth potential calculated for eachby in each pregnancy.his is based on 3 principles.6,7 First,standard is adjusted or customized

Intrauterine growth restriction (IUGR) remains oImprovements have to start from a better defifetal growth potential. Customized standards fdetection of IUGR by better distinction betweeand have led to internationally applicable norminsights in the assessment of risk and surveillameasurement plotted on customized chartsbiometry and Doppler flow are the mainstayAppropriate protocols based on available evidsessment are essential to ensure good manag

Key words: birthweight, customized charts, fterm delivery are excluded to predict SG

MONTH 2010 Ams in antenatal

optimum weight that a baby canch at the end of a normal pregnancy.hird, the term optimal weight andociated normal range is projectedckward for all gestational age points,ng an ultrasound growth based pro-rtionality curve; this avoids basing thendard on preterm neonatal weights,ich by definition are derived fromgnancies with a pathological (pre-m) outcome and hence do not repre-t the growth potential.6,7

ecent studies have shown that thisnciple is also internationally applica-, with striking similarities of the pre-ted birthweight of a baby born to andardEuropeanmother in theUnitedgdom, Australasia, and the Unitedtes.9,10 In practice, the fetal growthtential, and the individually adjustedcustomized normal limits (eg, theth and 90th centile), are calculated byputer software11 because of the infi-

e number of possible variations.

of themain challenges inmaternity care.on of IUGR, applying the concept of theetal growth and birthweight improve thehysiological and pathological smallnessuch developments have resulted in newe during pregnancy. Serial fundal heighta useful screening tool, whereas fetalr investigation and diagnosis of IUGR.ce as well as individualized clinical as-ent and timely delivery.

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2tential is more strongly associatedth abnormal antenatal Doppler find-s, fetal distress, cesarean section,mission, and prolonged stay in neo-tal intensive care as well as stillbirthsd neonatal deaths than centilessed on population standards.12-16 Int, SGA by population centiles butrmal size by customized growth po-tial can be termed physiologicalallness because it is not associatedth adverse outcome. Importantly,

IGURE 1ccuracy of birthweight prediction aharacteristics (n 313,285)

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edish births with gestational age-controlled residinst variables added. R2 was best in the middleonly, to 0.73 with all variables included. Upper

roduced, with permission, from Francis and Gardosi.152

eras and Gardosi. Intrauterine growth restriction. Am J Obscustomized standard also detects a on

American Journal of Obstetrics& Gynecology MONTbstantial number of additional, sig-cantly at-risk cases that were notgged up as SGA by the populationrm.12,13,16 This dual effect of identi-ng normal-small cases not at risk,d pathologically small cases that arerisk, is illustrated in Figure 2. Suchdings lead to the useful conclusiont SGA by customized growth po-tial represents pathological small-ss and can be used interchangeablyth IUGR for retrospective research

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H 2010stimated fetal weight also varies withividual characteristics in low- as wellhigh-risk pregnancies.17,18 An adjust-le standard improves the associationth pathology, while reducing false-sitive assessments by adjusting forstitutional smallness.19 This can have

nical relevancewhen seeking to reducese-positive diagnoses of IUGRandun-cessary intervention.20

ecent work has shown that the lengthgrowth deficit is linked with perinatalrbidity,21 in that morbidity is worselonger the slow growth has occurred

utero. A similar principle could be in-red from the findings of a case controldy of birthweight and CP,2 in whichGR at term was highly associated withincreased risk of CP, whereas it didt increase the risk in early and late pre-m gestations.

llbirth and IUGRch validation of the principles of thewth potential have allowed IUGR orR to be introduced as an additionalegory when classifying stillbirth andnd that after excluding congenitalomalies, more than 50% of stillbirthsdpreceding IUGR(10th customizedtile). As a result, the proportion ofexplained stillbirths drops from-70% using the Wigglesworth classifi-ion to 15%.22 This has since been con-ed in an independent comparative

dy.23While IUGR is usually the resultunderlying placental pathology andt in itself the cause of the demise,24 it islinically relevant condition. Aware-ss of this strong link allows a renewedus of attention on the antenatal iden-cation of IUGR as a first step towardvention. Antenatal awareness that theus is not growing well is an essentialality indicator of maternity care.

rpose of detectionst, detection informs the clinician andnce the mother that the pregnancy isincreased risk, allowing consider-ons on the optimal timing for delivery.pending on severity, babies that aret fulfilling their growth potential have- to 10-fold risk of dying in utero.12

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www.AJOG.org Obstetrics Reviewbilical artery Doppler, which hasen shown to reduce stillbirth and in-ase preterm delivery without increas-neonatal mortality.25 In a large sin--center retrospective study, Lindqvistd Molin26 found that antenatal detec-n of SGA led to significantly improvedtcome.

reening for the at-risk fetusstoryvious history of growth restriction orlbirth. Women with a previouswth-restricted baby have a 50% in-ased risk of severe growth restrictionthe current pregnancy,27 and serialrd-trimester assessment for this indi-ion is common practice. A history oflbirth is also an accepted indicationintensive antepartum surveillance

cause more than half of normallymed stillbirths are associated withGR.22 Stillbirths before 32 weeks ges-ion have a particularly strong associa-n with IUGR.28 Previous stillbirthuld appear to be a significant risk fac-, especially when associated with a di-osis of hypertension or clinicalGR.29

abetes. Women with diabetes are atreased risk of having a babywithmac-omia as well as FGR, with increasedk of perinatal morbidity and mortal-.30 Preeclampsia is observed in-20% of pregnancies complicated bye 1 diabetes mellitus without ne-ropathy and approximately 50% inpresence of nephropathy.31 Pre-

ampsia is also more likely in womenthhypertension andpoor glucose con-l.32 When assessed by customizedndards, 15%of womenwith type 2 di-etes are found to have an SGA baby.33

egular monitoring of fetal growth isommended in diabetic pregnancies.34

bilical artery Doppler seems to bere effective than biophysical profilecardiotocography,35-37 but its useuld be limited to women with addi-nal risk factors for placental insuffi-ncy, such as SGA or preeclampsia.

esity. Obesity has been considered atective factor for growth restric-n,38,39 but such findings are likely to

artifactual because of the use of unad- meted population standards. When SGAefined by customized centiles, obesityreases the risk of SGA by 50%.15 Suchative smallness is pathological: a largepulation-based study40 reported thatobese women, higher perinatal mor-ity is associated with higher rates ofA but only when SGA is defined bystomized growth potential (Figure 3).hough obesity affects the accuracy ofrasound biometry, it makes palpationd fundal height measurement evenre difficult. A small series includingobese women showed that ultrasoundimation of fetal weight was more ac-rate than abdominal palpation in pre-ting birthweight.41

ltiple pregnancy. Compared withgletons, twin pregnancies have in-ased risk of mortality and morbid-.42 Because growth restriction andight discordance are responsible for age part of this higher risk of mortalityd morbidity,43 optimal monitoring ofal growth is essential. Clinical assess-

IGURE 2tillbirth and SGA status by customiz

all for gestational age was defined according toA by customized centiles (all SGA by Cust) (bluemp and Cust SGA), by the population method only (st only SGA) (red markers) are shown. Odds rati, small for gestational age.roduced, with permission, from Gardosi and Francis.15

eras and Gardosi. Intrauterine growth restriction. Am J Obsnt does not allow individual fetal com

MONTH 2010 Amluation, and therefore, serial fetalight estimation by ultrasound fromweeks is considered best practice.owth standards for multiple pregnan-s have been published,44 but singletonmograms are more commonly usedth good accuracy.45

ustomized charts for estimated fetalight (EFW) can also be used for twinscause the growth potential up to 37eks is similar to that in singleton preg-ncy.46 There is no consensus on thest definition of weight discordanced its correlation to clinical events,43

t discordance greater than 20-25% istainly considered significant.n addition, the clinical meaning ofwth discordance may differ greatlytween monochorionic and dichori-ic pregnancies.42 Although it maym reasonable to incorporate umbili-artery Doppler for an earlier detec-n of growth restriction, there is insuf-ient evidence to support its use inhorionic multiple pregnancies not

and population-based centiles

pulation-based centiles (Popn only SGA) anders). Subgroups that are SGA by bothmethodsPop only), or by the customized method onlynd 95% confidence intervals are shown.

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4eening in early pregnancychemical markers. In the first trimes-, an unexplained low pregnancy-asso-ted plasma protein A or human cho-nic gonadotropin (hCG) is associatedth an increased risk of placental-re-ed diseases such as IUGR or pre-ampsia.49,50 In the second trimester,unexplained elevation of serum al-a-fetoprotein, hCG, or inhibin-Aalso associated with these adversetcomes.51-54

n general, the association is morerked for early-onset IUGR or pre-ampsia.55 Despite these associations,performance in terms of sensitivity/cificity and predictive values of theserkers individually or combined doest support their use.Moreover, no clearnefit of intensive surveillance56 or pro-

IGURE 3erinatal mortality rate and SGA by cnd population-based centiles

inatal mortality rate (PMR) and SGA by customApop), according to maternal body mass indexR vs SGAcust: P .753; PMR vs SGApop: P, small for gestational age.roduced, with permission, from Gardosi et al.40

eras and Gardosi. Intrauterine growth restriction. Am J Obsylactic strategies57 in women with ab- na

American Journal of Obstetrics& Gynecology MONTrmal biochemical markers has beenmonstrated.

rly growth restriction. Low first-tri-ster measurement of crown-rumpgth in pregnancies dated by the lastnstrual period is also linked withR.58,59 However, practical applicabil-is limited in spontaneously conceivedgnancies because the exact date ofception is usually not known, and awn-rump length measurement can-t be used simultaneously for establish-gestational age and for assessing fetale for gestation.ore recently, it has been demon-

ated that slow growth between thest and second trimester is able tontify a subgroup of slow-growingbies that are at increased risk of peri-

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d (SGAcust) and population-based centilesI). Comparison test for difference of slopes:7.

ynecol 2010.tal death before 34 weeks gestation, firs

H 2010most cases with growth restriction.60

early indication of an increased riskuld allow more intensive fetal as-sment and surveillance. Therefore,ial ultrasound evaluation of fetalwth in the third trimester seemstified in these cases.

erine artery. Uterine Doppler evalua-n in the second or first trimester hasen proposed as a screening tool forly-onset IUGR,withdetection rates ofout 75% and 25%, respectively, for ase-positive rate of 5-10%.61,62 Thesesitivities are higher for predictingly IUGRassociatedwith preeclampsiad lower for late IUGR. Different strat-es combining maternal risk factors,od pressure, and biochemical mark-have been published with detectiones greater than 90% for early-onseteclampsia,63,64 and associated IUGR.metaanalysis65 of 5 randomized

dies including 1052 women with ab-rmal uterine Doppler in the secondmester treated with aspirin showed a% reduction in the incidence of pre-ampsia, without reaching statisticalnificance (relative risk, 0.8; 95% con-ence interval, 0.611.06). Only 2 ran-mized studies (n 225) have evalu-d the efficacy of aspirin in womenth abnormal uterine Doppler in thet trimester,66,67 showing a pooled% reduction in the incidence of pre-ampsia. The limited number of casesluded a high incidence of preeclamp-in the control group, and there is un-tainty whether the standard of careld be extrapolated between countriesdraw reliable conclusions.hus, so far, there is no evidence inor of any prophylactic strategy ines of abnormal uterine artery Dopp-. However, it could be useful in de-ing the standard of prenatal care byessing the womans risk at the be-ning of the pregnancy. This is ineement with the recommendationsde by the UK National Institute oninical Excellence for risk-adjustedenatal care.68

eening in the third trimesterial fundal height measurement. Thenode

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www.AJOG.org Obstetrics Reviewl assessment as well as the baseline forsequentmeasurements, which are in-preted on the basis of the slope or ve-ity of growth. Indications for referralfurther investigations include cases inich the first fundal height measure-nt is below the 10th centile or consec-ve measurements suggest static orw growth, meaning that the serialasurements do not follow the ex-cted slope of the growth curve. An au-on the population in the catchmenta of a referral hospital in the Westdlands (UK) showed that the detec-n rates for SGA fetuses are improved iferral recommendations are fully ad-red to, highlighting the need for a con-uous program of education andining.69

ot all pregnancies are suitable formary surveillance by fundal heightasurement and require ultrasoundbi-etry instead. In most instances, thesegnancies fall into the following cate-ries: (1) fundal height measurementsuitable (eg, due to fibroids, high ma-nal body mass index) or (2) preg-ncy considered high risk (eg, due tovious history of SGA).undal heightmeasurement ismore ofurveillance than a screening tool be-se its strength lies in serial assess-nt. However, most clinicians are notmally taught how to measure fundalight and use a variety of differentthods. This reduces accuracy and in-ases interobserver variation. Not sur-singly, the evidence on fundal heightessment is mixed, with some studiesorting that it is a good predictor forGR,70-73 whereas others fail to findch benefit.74-78

recent review has summarized theorts being made to standardize thisl to improve its reliability and effec-eness.79 The name symphysis-fundusght is in factmisleadingbecause thepre-red direction of measurement is fromvariable (the fundus) to the fixed pointe top of the symphysis). The measure-nt shouldbealong the fetal axis,withnorectionof the fundus to themidline,us-a nonelastic tape.ne of the main problems has beenassumption that has crept into com-

n clinical practice, without any good 69dence, that 1 cm fundal height shouldal 1 week of gestation and the defini-n of normal as fundal height 2 ormof gestational age. But aswith birth-ight and ultrasound growth, one sizees not fit all, and different-sizedmoth-have different normal fundal heightwth curves.80 As a serial assessment,emphasis with fundal height mea-ement is on the slope of the curve. Re-ral guidelines for further investigationultrasound biometry and Doppler in-de a single fundal height measurementich plots below the 10th customizedtile, and serial measurements whichss centiles (ie, are slower than the pre-ted growth velocity).79

controlled study of 1200 patientspared measurement and plotting ofdal height on customized growtharts against routine clinical assessmentpalpation and found that it resulted inignificant increase in antenatal detec-n of SGA babies from 29% to 54%.81

rthermore, there was a significant re-ction of false-positive rates (ie, small-rmal babies being referred unneces-ily for investigation). The study wast powered to assess the effect on peri-tal mortality, and there is a paucity ofspective trials large enough to be ableassess the effect on hard outcomeasures. However, the antenatal iden-cation of IUGR is already of provennefit in itself and allows further inves-ations and interventions that areown to improve outcome. Serial mea-ement of fundal height and plottingcustomized growth charts are recom-nded by the Royal College of Obste-cians andGynaecologists guidelines.82

utine/intermittent third-trimester ul-sound biometry. The effectiveness ofrd-trimester ultrasound biometrythe diagnosis of growth restriction

d its impact on perinatal outcome iscertain. Sensitivity of abdominalcumference for detecting a birth-ight less than the 10th centile rangesm 48% to 87%, with specificity from% to 85%.83-88 For estimated fetalight, sensitivities of 25-100% haveen reported, with a specificity of

-97%.84,87-89 cie

MONTH 2010 Amhe high heterogeneity between stud-does not allow the calculation of

oled values. The largest study,88 fromUnited Kingdom, included 3616-risk women on whom a third-tri-ster (28-36 weeks) ultrasound wasrformed with abdominal circumfer-ce measurement. Sensitivity for birth-ight less than the 10th centile was%, with a false-positive rate of 7%.dqvist andMolin26 introduced a pol-of a routine scan at 32 weeks and ob-ved a detection rate of 54% for SGAfined as birthweight deviation of atst 22% from the mean, equivalent tothird centile).Hedriana andMoore89

pared serial vs single scan in low-riskmen between 28 and 42 weeks andnd that multiple ultrasonographicminations provided little improve-nt in the prediction of birthweightpared with a single observation.Kenna et al90 tested randomly a pol-of 2 scans at 30 and 36 weeks and

served that fewer babies were bornA as a result of increased interventionthe study group, although no datare given on actual detection rates.he impact of routine third-trimesterrasound on perinatal outcome is alsoclear. Seven trials83,85,86,91-94 haveen included in a recently updatedtaanalysis95 that showed that routinee pregnancy ultrasound in low-risk orselected populations does not confernefit onmother or baby. Furthermore,ay be associatedwith a small increase

cesarean section rates.owever, it could be argued that the

ults of this metaanalysis have limitedidity for contemporary practice be-se it included studies that used out-ted surrogates of fetal growth suchbiparietal diameter measurement83

protocols in which the diagnosis ofGR was not followed by a change innagement. A Swedish population-sed study96 compared the perinataltcome of 56,371 unselected women inom routine third-trimester ultra-nd was performed with the outcome153,355 women with no such screen-. No differences in perinatalmortalityearly neonatal morbidity were found.here is currently therefore insuffi-

nt evidence to support routine third-


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6 American Journal of Obstetrics& Gynecology MONTH 2010mester ultrasound in all pregnancies.management trial to investigate thepact of third-trimester ultrasounduld be feasible in terms of maternalllingness to participate97 but will re-ire a large sample size to test effect onrd outcomes such as perinatal mortal-. Further trials will also need to in-de growth scans in the late third tri-ster because most cases of IUGRliver at term.98

ial ultrasound biometry. For preg-ncies at risk, serial assessment of esti-ted fetal weight or abdominal cir-mference is the best predictor of FGRassessed by neonatal morphometry.99

erefore, serial biometry is the recom-nded gold standard for assessinggnancies that are high risk,82 eitherthe basis of past history or because ofplications that arose during the cur-t pregnancy. In the absence of cleardence and consensus about the fre-ency and timing of scans, protocolsd individual management plans areen limited by the resources available.wever, more than fortnightly scansnot indicated because the scan errorikely to exceed the increment in sizecause of growth during the interval.82

gnosis of IUGRrrent thinking on the natural his-y of growth restriction differentiatestween early-onset and late-onsetms,100 which have different biochem-l, histological, and clinical features.101

hereas the former is usually diagnosedth an abnormal umbilical arteryppler and is frequently associated witheclampsia, the latter is more prevalent,ws less change in umbilical flow pat-n, and has a weaker association witheclampsia.101

bilical arteryDopplerst instances of growth restriction cor-pond with cases of placental insuffi-ncy.102 Evaluation of placental func-n by umbilical artery Doppler is anical standard to distinguish betweenA and IUGR.103-105 The pathophysio-ical progression of this parameter isstrated in Figure 4. As suggested byIGURE 4nsonation of the umbilical artery Doppler

Site of insonation of the umbilical artery Doppler. Progressive waveform patterns with advancingerity were: B, normal umbilical artery waveform, C, increased impedance to flow, D, absent-diastolic flow, and E, reversed end-diastolic flow.eras and Gardosi. Intrauterine growth restriction. Am J Obstet Gynecol 2010.imal106 and mathematical107 models

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www.AJOG.org Obstetrics Reviewchronic placental embolization, theliteration ofmore than 50%of the pla-tal vessels is required before absent orersed end-diastolic velocities appear.ere is good evidence that umbilicalppler ultrasound use in these preg-ncies improves a number of obstetrice outcomes and reduces perinatalaths.108

hereas abnormal umbilical arteryppler is associated with adverse peri-tal and neurodevelopmental out-e,109-112 small fetuses with normalbilical artery Doppler are consideredrepresent one end of the normal-sizectrum, and the importance of manag-them as completely differently frome IUGR babies has been stressed.113,114

ismaynotbe true for late-onset cases, inich a substantial proportion of casesh a normal umbilical artery may havee growth restriction, and are at risk oferse perinatal outcome.109,110,115,116

herDoppler parameterscause the identification of late-onsetA fetuses with mild forms of growthtriction cannot only be relied on bybilical artery Doppler, other vascularritories have been proposed. Abnor-l uterine artery Doppler is compara-with umbilical artery Doppler as adictor of adverse outcome in growth-tricted fetuses.116-118 Up to 20% ofA fetuses have reduced resistance inmiddle cerebral artery (MCA), and

s sign is also associated with poorerrinatal outcome116-119 and subopti-l neurodevelopmental development2 years of age.120 Umbilical and cere-l Doppler can be combined in the ce-roplacental ratio. This ratio has beenmonstrated in animal121 and clini-122 models to be more sensitive topoxia than its individual componentsd correlates better with adversetcome.123

sessment of the IUGR fetuscause no treatment has been demon-ated to be of benefit for FGR,124-127

assessment of fetal well-being andely delivery remains as the mainategy for management. Fetal well-be-tests could be classified as chronic or

te. Whereas, the former becomes ofgressively abnormal because of in-asing hypoxemia and/or hypoxia, theter correlates with acute changes oc-rring in advanced stages of fetal com-mise, characterized by severe hyp-ia and metabolic acidosis, and usuallycedes fetal death by a few days. Be-se a fixed sequence of fetal deteriora-n does not exist, integration of severalll-being tests into comprehensivenagement protocols is required.

ronic testsbilical artery. Absent or reversed

d-diastolic velocities are mostly foundearly-onset IUGR, and these patternsve been reported to be present onrage 1 week before the acute deterio-ion.128 Up to 40% of fetuses withdosis show this umbilical flow pat-n.128 Despite the fact that an associa-n exists between the presence ofersed end-diastolic flow in the umbil-l artery and adverse perinatal out-e (with a sensitivity and specificity of

out 60%), it is not clear whether thisociation is confounded by prematu-y. More recent series129 of severelypromised IUGR fetuses suggest thath a finding has value independentlygestational age in the prediction ofrinatal morbidity and mortality.

ddle cerebral artery. Longitudinaldies on deteriorating early-onsetGR fetuses have reported that the pul-ility index in the MCA progressivelycomes abnormal.130 Figure 5 showsprogression of this parameter. Up to

% of fetuses have vasodilatation 2eks before the acute deterioration,128

hough other series have found this fig-to be less than 50%.129 Preliminary

dings of an acute loss of the MCA va-ilatation in advanced stages of fetalpromise have not been confirmed inre recent series,128-131 and therefores sign does not seems to be clinicallyevant for management purposes inly-onset cases. In late-onset IUGR,re is observational evidence116,119

t MCA vasodilatation is associatedth adverse outcome independently ofumbilical artery. This suggests a role

MCA Doppler for fetal monitoring in fet

MONTH 2010 Ame-onset IUGR cases, which needs fur-r investigation in randomized trials.

niotic fluid. A metaanalysis132 of 18domized studies demonstrated thatamniotic fluid index of less than 5 isociated with abnormal 5 minute Ap-score but failed to demonstrate an

ociation with acidosis.ongitudinal studies in early-onsetGR fetuses have shown that the am-tic fluid index progressively de-ases.129,130 Amniotic fluid volume islieved to be a chronic parameter. Int, among the components of biophys-l profile, it is the only one that is notsidered acute. One week before acute

terioration, 20-30% of cases havegohydramnios.129,130

utemarkersctus venosus (DV). Early studies onGR fetuses demonstrated a good cor-ation of abnormal DV waveform withdemia at cordocentesis,133 and thisppler sign is considered a surrogaterameter of the fetal base-acid status.e progression of this parameter iswn in Figure 6. Absent-reversed ve-ities during atrial contraction are asso-ted with perinatal mortality indepen-tly of the gestational age at delivery,134

h a risk ranging from 60% to 100% inuses with early-onset IUGR.135 How-r, its sensitivity forperinataldeath is still70%.134,136,137

ongitudinal studies have demon-ated that DV flow waveforms becomenormal only in advanced stages of fetalpromise.128-131 Whereas in about

% of cases abnormal DV precedes thes of short-term variability in the fetalart rate,130 in about 90% of cases it be-es abnormal only 48-72 hours be-

e the biophysical profile.131 Debatests regarding the advantages of DVppler investigation over biophysicalfile. However, observational stud-

138 suggest the integration of both DVppler investigation and biophysicalfile in the management of pretermGR because these strategies seem toatify IUGR fetuses into risk categoriesre effectively. An ongoing random-d clinical trial (Trial of umbilical and

al flow in Europe, TRUFFLE) is aimed


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eras and Gardosi. Intrauterine growth restriction. Am J Obsly-onset IUGR cases. cog

American Journal of Obstetrics& Gynecology MONTal heart rate (FHR) analysis. Earlydies on high-risk pregnancies showedt, although highly sensitive, cardioto-

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H 2010the predictionof adverse outcome.139

addition, a metaanalysis140 of its ap-cation in high-risk pregnancies faileddemonstrate any beneficial effect in

IGURE 6nsonation of the ductusenosus with color Doppler

ite of insonation of the DV with color Doppler.gressive waveform patterns with advancingerity are shown: B, normal DV waveform, C,reased impedance to flow, D, absent end-stolic flow, and E, reversed end-diastolic flow.escendent aorta; DV, ductus venosus; H, heart; UV, umbilical.

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www.AJOG.org Obstetrics Reviewre is no evidence to support the use ofditional fetal heart rate monitoring ornstress tests in IUGR fetuses. How-r, these studies were conducted in thely 1980s, and the control group hadfetal well-being assessment or out-

ted techniques such as biochemicalts.omputerized FHR has provided newight into the pathophysiology ofGR. Short-term variability closelyrelates with acidosis and severe hyp-ia as demonstrated by cord bloodpling at the time of a cesarean sec-

n.141Whereas Bracero et al142 demon-ated no significant differences in peri-tal outcome between visual andputerized FHR, more recent longi-inal series have pointed to a potentiale as an acute marker.130 Short-termiability becomes abnormal, coincid-with theDV: whereas in about half ofcases, abnormal DV precedes the lossshort-term FHR variability, the latterthe first to become abnormal in theer cases.130 Both parameters are con-ered acute responses to fetal acidosis.

physical profile. Some observationaldies show an association between ab-rmal biophysical profile (BPP) andrinatalmortality and cerebral palsy,143

ereas others fail to demonstrate thisociation.129 In IUGR infants, BBPwast predictive of cognitive function at 2rs.144 Similarly, whereas some studiesth cordocentesis demonstrated a cor-ation with acidosis,145 with fetal toned gross motor movements the bestrelated components, others have notnd this correlation.146

s with FHR , a high false-positive rate%) limits the clinical usefulness of thephysical profile.147 A recent study148

s shown that BPP alone in fetusesighting more than 1000 g is not a reli-le test in the treatment of pretermGR fetuses because of high false-posi-e and -negative results. A metaanaly-149 showed no significant benefit of aphysical profile in high-risk pregnan-s, although more recent series150,151

IUGR have suggested that bothppler and biophysical profile effec-ely stratify IUGR fetuses into risk cat-

ries. Because fetal deterioration ap- casars to be independently reflected byth tests, further studies are required tove the usefulness of combining bothting modalities.ongitudinal series131 have demon-ated that except for amniotic fluid vol-e and the fetal heart rate, the otherponents (tone, breathing, and bodyvements) of the biophysical profilecome abnormal only in advancedges of fetal compromise. In fact, inout 90% of cases, the biophysical pro-becomes abnormal only 48-72 hourser the ductus venosus.131

ing of deliveryGR is one of the most common preg-ncy complications and substantiallyreases the prospective risk of adversetcome. Yet according to pregnancydits, most instances of IUGR are nottected as such antenatally. Modernstetric care needs to raise the level ofareness of the importance of this con-ion, and establish evidence-basedtocols for improved surveillance.ecause the only current treatment forGR is delivery, themain considerationeds to be appropriate timing, balanc-the risk of potential iatrogenic mor-ity and continued exposure to anfavorable intrauterine environment.dies are now in progress with regardlate-onset IUGR to evaluate whetherctive induction beyond 36 weeks ges-ion is of benefit. To date, prospectiveals have not been able to throw muchht and are often underpowered orwed.egarding early-onset IUGR, themul-

entre Growth Restriction Interven-n Trial153 compared outcome afterdomization with early or delayed de-ery and concluded that it was safe toit, especially at preterm gestations.wever, the study design has been crit-zed because it did not account for thees that were not randomized andich were estimated to represent thejority of all eligible cases:154 clinicalection biasmay have preferentially in-ded the less severe cases, in which ituld be safe to wait anyway. Therefore,h results cannot be extrapolated to all

es with IUGR.

woces

MONTH 2010 Ammproved definition of the intrauter-standard for IUGR by the use of the

al growth potential allows a more dis-ning assessment. A baby with an EFWlow the 10th customized centile has anificantly elevated risk of morbidity,n in the absence of an abnormal um-ical artery Doppler.110 Added into theation is the awareness that leavinggnancieswith IUGR todeliver at termy also lead to perinatal morbidity andlayed effects such as cerebral palsy.2

herefore, current best practice wouldicate that from the time fetal pulmo-ry maturity can be inferred, there isle to be gained by allowing a preg-ncy to continue if good fetal growthnot be demonstrated. However, eache needs to be carefully assessed andividually considered, in consultationth the parents. f

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www.AJOG.org Obstetrics ReviewMONTH 2010 American Journal of Obstetrics& Gynecology 13

Intrauterine growth restriction: new concepts in antenatal surveillance, diagnosis, and managementAssociation between IUGR and outcomeNew tools and new insightsValidation

Stillbirth and IUGRPurpose of detectionScreening for the at-risk fetusHistoryPrevious history of growth restriction or stillbirthDiabetesObesityMultiple pregnancy

Screening in early pregnancyBiochemical markersEarly growth restrictionUterine artery

Screening in the third trimesterSerial fundal height measurementRoutine/intermittent third-trimester ul-trasound biometrySerial ultrasound biometry

Diagnosis of IUGRUmbilical artery DopplerOther Doppler parametersAssessment of the IUGR fetusChronic testsUmbilical arteryMiddle cerebral arteryAmniotic fluid

Acute markersDuctus venosus (DV)Fetal heart rate (FHR) analysisBiophysical profile

Timing of deliveryREFERENCES

Documents

IUGR New Concepts - AJOG Review