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etal Growth Restriction due to Placentalisease

hmet A. Baschat* and Kurt Hecher†

ormal fetal growth depends on the genetically predetermined growth potential and its modulationy the health of the fetus, placenta and the mother. Fetuses that are small because of intrauterinerowth restriction (IUGR) are at higher risk for poor perinatal and long-term outcome than those whore appropriately grown. Of the many potential underlying processes that may result in IUGR,lacental disease is clinically the most relevant. Fetal cardiovascular and behavioral responses tolacental insufficiency and the metabolic status are interrelated. The concurrent evaluation of fetaliometry, amniotic fluid volume, heart rate patterns, arterial and venous Doppler, and biophysicalariables therefore allow the most comprehensive fetal evaluation in IUGR. In the absence ofuccessful intrauterine therapy, the timing of delivery is perhaps the most critical aspect of thentenatal management. A discussion of the fetal responses to placental insufficiency and a manage-ent protocol that accounts for multiple Doppler and biophysical parameters as well as gestational

ge is provided in this review.2004 Elsevier Inc. All rights reserved.

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ince the landmark observations of Lub-chenco et al in 1963, it is becoming increas-

ngly apparent that neonates who fail to fulfillheir growth potential in fetal life are at in-reased risk for adverse health events through-ut life.1-5 It is the aim of modern perinatologyo identify fetuses with intrauterine growth re-triction (IUGR) early enough to institute ap-ropriate intervention and hopefully prevent

urther damage. This process requires knowl-dge about the etiology, pathophysiology, natu-al history, prognostic factors, and effects of in-ervention. Because our knowledge is expandingn all aspects of this disease, ongoing reappraisals necessary to incorporate new information intohe clinical management.

Neonatal weight, size and condition at birthre dependent on 4 principle variables. The ge-etically predetermined growth potential mod-lated by the health of the fetus, placenta, and

he mother. Successful implantation of a genet-cally normal fetus and placenta in a healthy

other is most likely to produce a healthy baby.n the other hand, if any of these factors iseficient, adverse pregnancy outcome and/or

etal growth restriction may be the consequence.herefore, IUGR is a not a specific disease per

e, because it may be the manifestation of aariety of conditions. Because outcome is oftenependent on the etiology an attempt at identi-cation of the underlying disease is an essential

Seminars in Perinatology, Vol 28, No

rst step to direct appropriate management in aatient in whom fetal growth failure is sus-ected.

The many causes of IUGR have traditionallyeen subdivided into fetal, placental and mater-al. From a clinicians standpoint fetal abnormal-

ties (both chromosomal and/or anatomic) andbnormal placental vascular development in theetal and/or maternal compartments are re-ponsible for the vast majority of IUGR in sin-leton pregnancies.6-10 Maternal causes such ashronic renal disease, hypertension, collagenascular disease, thrombophilia, and aggravatingircumstances such as smoking, malnutrition,nd drug use are either readily apparenthrough the maternal history or can be deter-

ined with relatively minor effort. Prenatal ul-rasound evaluation and invasive fetal testingffer the opportunity to investigate fetal causes.his review focuses on the pathophysiology, di-

rom the *Department of Obstetrics, Gynecology & Reproductiveciences, Center for Advanced Fetal Care, University of Maryland,altimore, MD; and †Department of Fetal Diagnosis and Therapy,llgemeines Krankenhaus Barmbek, Hamburg, Germany.ddress reprint requests to Ahmet A. Baschat, MD, Department ofbstetrics, Gynecology & Reproductive Sciences, Center for Ad-anced Fetal Care, 405 W. Redwood St, 4th Floor, University ofaryland, Baltimore, MD 21201.2004 Elsevier Inc. All rights reserved.

146-0005/04/2801-0008$30.00/0oi:10.1053/j.semperi.2003.10.014

671 (February), 2004: pp 67-80

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Baschat and Hecher68

gnosis, and management of IUGR caused bylacental vascular disturbance.

etal Consequences of Placental Vascularnsufficiency

dequate fetal growth depends on the efficientelivery of nutrients from the mother to the

etus and therefore requires normal uterine per-usion, normal transplacental exchange of nutri-nts and waste and normal umbilical perfusion.lucose and essential aminoacids are actively

ransported across the placenta and metabolizederobically by the fetus.11,12 The glucose/insu-in/insulin-like growth factor (ILF) axis plays aentral role in tissue-specific growth regulationuring critical periods of development and over-ll regulation of fetal growth.13 Because approx-mately 70% of glucose and 45% of oxygen aresed by the placenta itself, adequate fetal deliv-ry of nutrients and oxygen is dependent onterine perfusion, fetoplacental exchange areand high oxygen affinity of fetal hemoglo-in.14,15 Drastic changes in maternal and fetallacental blood flow dynamics are necessary toccommodate accelerating fetal growth with ad-ancing gestation. With successful trophoblastnvasion and increased compliance of the spiralrteries a low impedance high capacitance pla-ental vascular bed is established. As a result, anncreasing proportion of maternal cardiac out-ut is distributed to placental cotyledons as ges-

ation advances and blood flow volumes reach00 to 600 mL/minute at term.16-18 In the fetalascular compartment of the placenta, this pro-ess is paralleled by increases in villous and cap-llary surface areas resulting in marked decreasen umbilical vascular resistance and an increasen the exchange area.19 Concurrently fetal car-iac function increases exponentially permittingn almost 5- to 10-fold rise in umbilical arterynd venous volume flow with advancing gesta-ion.20-23 This increase is necessary to maintain aelatively constant blood flow volume/Kg fetalody weight throughout gestation.21,22

Once nutrients have entered the fetal circu-ation through the umbilical vein their distribu-ion to vital organs such as the liver, heart, brain,nd kidney is insured by the unique dynamics ofhe fetal circulation. Venous shunting at theevel of the ductus venosus modifies the propor-ion of nutrient rich blood that is distributed to

he liver and heart.24 At the level of the righttrium differential directionality of the incom-ng bloodstreams ensures that nutrient richlood is distributed to the heart and brain whileenous return is distributed to the placenta fore-oxygenation and nutrient and waste ex-hange.25,26 In addition to this overall distribu-ion of left- and right-sided cardiac output, sev-ral organs are able to modify local blood flow toeet oxygen and nutrient demands by the pro-

ess of autoregulation.23 The consequences ofteroplacental insufficiency are complex sinceetoplacental respiratory function is affected at

ultiple levels. Nutrient delivery, placental up-ake, and distribution within the fetus as well aselivery of waste to the placenta are deficient.he combination of these factors is responsible

or the multisystem disorder that constitutesUGR.

In IUGR fetuses, transplacental transfer ofxygen, glucose, and aminoacids is impairednd pancreatic insulin responses to glucose arelunted.28-31 The relative hypoinsulinemia mayecrease placental glucose transfer even fur-her.32,33 This places the fetus into a situationhere supply of oxygen and substrate and there-

ore the ability for aerobic metabolism and tissuerowth become limited. Enhanced erythropoie-is may improve oxygen carrying and bufferingapacity through increases in red cell mass andemoglobin concentration.34 Other nutrient de-ands are harder to accommodate. Hepatic gly-

ogen stores may initially provide a limitedupply of glucose. Eventually gluconeogenicminoacids from endogenous tissue catabolismay serve as an alternative nutrient sources.35-39

ith these limitations, lactate productionhrough anaerobic metabolism increases. Al-hough glucose is the primary fuel for the brainnd heart, lactate and ketones become substi-utes during prolonged hypoglycemia.40 Underuch circumstances cardiac metabolism may re-ove up to 80% of the circulating lactate.41,42

oncurrently increases in vessel caliber in vari-us oxygen sensitive vascular beds optimize per-usion in vital organs while perfusion to less vitalarts of the body may be compromised. Sequen-ial decline in fetal dynamic variables such aseart rate variation, movement, and tone help toonserve energy.43

Fetal adaptations are therefore made at manyevels and if compensatory mechanisms are suc-

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Fetal Growth Restriction in Placental Disease 69

essful fetal survival and even growth are possi-le. Fetal decompensation sets in when adapta-ion cannot maintain organ function and isharacterized by concurrent failure of forwardardiac function, metabolic acidemia and loss oformal fetal behavior and finally stillbirth.44-46

mpairment of placental transport mechanismannot be directly measured but may be inferredy the degree of vascular insufficiency. A num-er of cardiovascular and central nervous systemCNS) responses in IUGR fetuses have been de-cribed.

irculatory Findings in Uteroplacentalnsufficiency

levation of the uterine artery Doppler indexnd/or persistence of an early diastolic notcheyond the mid-trimester is evidence of abnor-al trophoblast invasion, placental bed infarcts

nd enhanced apoptosis47,48 (Fig 1). Decrease,bsence, or reversal of umbilical artery end-dia-tolic velocity indicate progressive increases inlood flow resistance due to loss of tertiary vil-

ous vessels49 (Fig 2). Disturbed feto-placentalerfusion also effects venous return and a de-rease in umbilical venous volume flow is ob-erved and precedes the onset of overt growthelay.50 Abnormal flow patterns in the uterinerteries identify patients at risk for pre eclamp-ia, placental abruption, and IUGR,51 while ab-ormal umbilical flow patterns indicate in-reased risk for hypoxemia and acidemiaroportional to the severity of Doppler abnor-ality.49

Several fetal arterial blood flow characteristicsay accompany elevated placental blood flow

esistance. There may be elevation of thoracicnd descending aortic blood flow imped-nce,52-54 reflecting the elevated blood flow re-istance in the placenta and/or the lower limb“hind limb reflex”).55 Through the parallel ar-angement of the fetal circulation elevated feto-lacental blood flow resistance favors redistribu-

ion of cardiac output towards the left ventriclend therefore cardiac and cerebral circulations.his redistribution can be verified by direct mea-

urement of cardiac output or by demonstratingnd-diastolic flow reversal in the aortic isth-us.56-58 Enhanced cerebral perfusion can be

ocumented in two principal ways. Doppler ex-mination of the middle cerebral artery wave-

orm may indicate decreased blood flow imped-nce (“brain sparing”)59 (Fig 3). Alternatively,he ratio between cerebral and descending tho-acic aorta or placental Doppler indices (cere-roplacental ratio) enhances the detection ofentralization of cardiac output toward the cere-ral circulation particularly in fetuses with moreubtle Doppler findings.60-64 Enhanced perfu-ion of the myocardium on the other hand isvident through examination of the coronaryirculation.65 Examination of multiple arterialeds suggests that blood flow in the adrenallands,66 spleen,67 and liver68 is enhanced whileerfusion of the lungs,69 bowel,70 and kidneys71

s decreased with further compromise. Althoughrterial Doppler can provide information onownstream distribution of cardiac output this

nformation is incomplete without the evalua-

igure 1. Flow velocity waveforms obtained from theterine artery beyond 24 weeks gestation. In the firstatient (A) high volume diastolic flow is established

ndicating successful trophoblast invasion. (B) Ele-ated placental vascular resistance is associated with aecline in diastolic velocities and a subsequent rise inhe Doppler index. Persistence of an early diastolicotch in the uterine artery flow velocity waveform isvidence of increased spiral artery blood flow resis-ance. (C) Frequently “notching” is more subtle be-ond 32 weeks (C) than in the (D) late second or earlyhird trimesters.

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ion of cardiac function. Failure of forward car-iac function is the hallmark of cardiovasculareterioration in IUGR72 and can be associatedith deregulation of cardiovascular homeostasisnormalization of cerebral Doppler indices,73,74

hich in turn could affect reliability of arterialoppler analysis. Under such circumstances ex-mination of the venous system provides docu-entation of cardiac status and therefore im-

roves detection of further compromise.Forward blood flow in the venous system is

etermined by cardiac compliance, contractilitynd afterload. A decline in forward velocitiesuring atrial systole (a-wave) results in increasedenous Doppler indices and suggests impairedreload handling75-77 (Fig 4 and 5). Evidence of

mpaired cardiac forward function has been doc-mented in the precordial veins (ductus veno-us,77 inferior vena cava,78 superior vena cava79),he hepatic veins (right, middle and left he-atic80,81) and head and neck veins (jugulareins82 and cerebral transverse sinus83). If failureo accommodate preload is progressive umbili-al venous pulsations may be observed as theltimate reflection of increased central venousressure84 (Fig 6). In the final stages of compro-ise cardiac dilatation with holosystolic tricus-

igure 2. (A) The normal umbilical artery flow velocincreases in proportion to systole toward term. (B) Mohe blood flow resistance and are associated with aroportion of the villous vascular tree is abnormal (50%D) reversed. Depending on the magnitude of placeeversal of end-diastolic velocities may be (D) minimalenous flows were universally abnormal.

id insufficiency may be observed preceding in-rauterine demise.85

etal Biophysical Responses interoplacental Insufficiency

ormal development of fetal behavior involvesncorporation of isolated movements into pat-erns and finally behavioral states. Once orga-ized behavioral states are established diurnalnd responsive cyclicity (eg, fetal movement cou-ling with heart rate variables) are generallychieved by 28 weeks of gestation.86 In IUGRetuses with chronic hypoxemia all aspects ofhis process may be delayed. This includes thestablishment of organized behavior and transi-ion between behavioral states as well as de-reases in overall unstimulated and stimulatedie, vibroacoustic stimulation) behavior. Theseehavioral alterations are particularly evidentetween 28 to 32 week’s gestation.87-91 The de-rease in all behavioral variables and probablylso delayed maturation in the central integra-ion of fetal heart rate control results in higherasal heart rates and lower short- and long-termariation on computerized analysis.92,93 Progres-ive hypoxemia is associated with gradual de-

veform has marked positive end-diastolic velocity thatte abnormalities in the villous vascular structure raiseline in end-diastolic velocities. When a significant

%), end-diastolic velocities may be (C) absent or evenblood flow resistance and the fetal cardiac functionmoderate, or (F) severe. In the latter case, precordial

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line in amniotic fluid volume, fetal breathing,ross body movements, tone and computerizedeart rate variables.94-96 While this developmentay be associated with abnormal Doppler find-

ngs in the placental, arterial, and venous circu-ations, the decline of biophysical variables isetermined by effects of hypoxemia/acidemian the central regulation of fetal behavior ratherhan vascular status.43,46,97,98-100 With the devel-pment of acidemia fetal movement and tonere lost and overtly abnormal heart rate pat-erns may be observed.97,101 These may includevert late decelerations and/or a decrease of thehort term variation on computerized analy-is.46,74,83,102,103,104 (Fig 7).

igure 3. (A) The normal middle cerebral arteryow pattern has relatively little diastolic flow. Withlevation of placental blood flow resistance thehanges in the middle cerebral artery waveform maye subtle, although the cerebroplacental ratio mayecome abnormal as in fetus B. With progressive pla-ental dysfunction there may be increase in the dia-tolic velocity resulting in a decrease in the Dopplerndex (Brain sparing, C). With marked brain sparinghe systolic down slope of the waveform becomesmoother so that the waveform almost resembles thatf the umbilical artery (D). The associated rise in theean velocity results in a marked decline in theoppler index.

The biophysical profile score is a compositecore that applies categorical cut-offs for dy-amic variables such as fetal tone, breathingovement, gross body movement, and the am-

iotic fluid volume as well as traditional fetaleart rate analysis. Although a gradual decline

n all of these parameters precedes an overtlybnormal BPS analysis of percentage changes inhese variables offers no advantage in the pre-iction of acidemia.95 The BPS shows a reliablend reproducible relationship with the fetal pHrrespective of the underlying pathology and ges-ational age.105,106

dentification of the Small Fetus at Riskor Adverse Outcome

he first step in the management of IUGR fe-uses is to identify those fetuses that are truly atisk for adverse outcome. This requires exclu-ion of small fetuses that are normally grown and

igure 4. The venous flow velocity waveform reflectstrial pressure changes during the cardiac cycle andherefore has a triphasic flow pattern. In the inferiorena cava blood flow may be antegrade toward theeart throughout the whole cardiac cycle (A) or briefeversal of blood flow during atrial systole (B) is nor-al. However a relative decrease of diastolic forward

elocity (*) and marked reversal of the a-wave (�) isbnormal and in this fetus (C) was associated withardiac dilatation, tricuspid insufficiency and subse-uent stillbirth.

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hose in whom IUGR is due to an underlyingondition where management will not alterutcome (eg, aneuploidy, nonaneuploid syn-romes, viral infection). The initial focus there-ore lies on a complete maternal history andhysical examination and a thorough ultra-ound evaluation of fetal anatomy, size, symme-ry, and amniotic fluid volume.

Identification of small fetal size is initiallyased on combined measurements of head sizebiparietal diameter and head circumferenceHC)], abdominal circumference (AC) andone length [femur (FL) and humerus length].UGR may be defined as an estimated fetaleight (calculated through algorisms using theC, AC and FL) below the 10th percentile or anC below the 5th, 3rd, or 2nd percentiles. TheC offers superior sensitivity that may be furthernhanced by serial measurements at least 14ays apart.107,108 Fetal asymmetry of the HC/ACatio suggests altered growth dynamics, whileymmetrically small growth may simply indicateeduced genetic potential.109-111 However, al-hough biometry provides important clues to theresence of IUGR the liability of preterm deliv-ry and iatrogenic complications is great if theiagnosis is based solely on biometry.112 Theombination of biometry with umbilical andiddle cerebral artery Doppler provides the best

ool to identify small fetuses at risk for adverseutcome. This applies both to small fetuses with

tegrade throughout the cardiac cycle under normalatterns obtained at the inlet (A) versus the outlet (B).n forward flow during atrial systole (C). If progressivest fetus with this severely abnormal waveform pattern

culatory insufficiency, necrotising enterocolitis, grade.

igure 5. In the ductus venosus, blood flow is always anircumstances. Pulsatility is less pronounced in waveform pith impaired cardiac forward function there is a decline i

trial forward flow may be lost (D) or reversed (E). In the lat 28 weeks (F), the neonatal course was complicated by cirV intraventricular hemorrhage and finally neonatal death

igure 6. In the umbilical vein the normally constantaveform pattern may show subtle pulsations withlevated placental blood flow resistance (A). Withrogressive increase in precordial venous indicesonophasic, biphasic and even triphasic pulsationsay be observed (B,C,D).

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levated umbilical artery, and those with evi-ence of brain sparing and normal umbilicalrtery Doppler.63,107,111,113,114 Randomized trialsnd meta-analyses confirm that the use of um-ilical artery Doppler in this setting results in aignificant reduction in perinatal mortality.114-116

Once the suspicion of IUGR is confirmedetal karyotyping should be offered and furtherpecialized tests such as maternal serologyTORCH), thrombophilia studies, or amnioticuid viral DNA testing, may be indicated. Onceontreatable underlying fetal conditions andhromosome abnormalities have been ruled outurther antenatal surveillance should be insti-uted based on the severity of the maternalnd/or fetal condition.

ntenatal Surveillance of the High-risketus

ntenatal surveillance should provide longitudi-al assessment that is tailored to the severity of

he fetal condition and directs appropriate in-

igure 7. A progressive deterioration in fetal cardiecline of metabolic status. In the majority of IUGR fe

he venous side of the circulation. While cardiac adaay be operational for a variable period, overt abno

nhanced coronary blood flow is generally not obiophysical variables shows a reproducible relationshtillbirth ensues. UA, umbilical artery; EDV, end-diastoH, fetal heart rate; BPS, biophysical profile score.

ervention to improve outcomes of critical im-ortance. Although assessment should be de-ailed, antenatal tests also need be practicable toacilitate application on a large scale as is neces-ary for a global problem such as IUGR.

Fetal heart rate analysis (both traditional andomputerized), Doppler ultrasound, measure-ent of amniotic fluid volume, assessment of

etal breathing, movement, and tone are pri-ary fetal assessment tools. Traditional heart

ate analysis has the advantage of widespreadamiliarity but carries the disadvantage of poornter- and intraobserver agreement even in thenterpretation of key factors such as accelera-ions, reactivity and decelerations.117 While a re-ctive CTG even by criteria graded for gesta-ional age virtually excludes hypoxemia, aonreactive CTG has a poor correlation with

etal status unless overtly abnormal patterns arebserved.46,74,118 The computerized analysis cir-umvents some of these problems as it providesn objective and reproducible means of longitu-inal analysis of fetal heart rate characteristics.

ular and behavioral variables that is observed with, Doppler abnormalities progress from the arterial tons and alterations in coronary blood flow dynamics

lities of cardiac function and evidence of markedlyd until the late stages of disease. The decline inith acid base status. If adaptation mechanisms fail,locity; UV, umbilical vein; AV, atrioventricular valves;

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Doppler analysis is an invaluable tool to gradehe severity of the fetal disease. Although multi-le vessels have been investigated in IUGR aombination of arterial and venous vessels is theost practicable to demonstrate 1) degree of

lacental disease, 2) level of redistribution, and) degree of cardiac compromise. The umbilicalrtery, middle cerebral artery, descending tho-acic aorta, ductus venosus, inferior vena cavand free umbilical vein provide comprehensivevaluation of these aspects. Since the longitudi-al progression of Doppler abnormalities ad-ances from arterial to the venous side in theajority of cases46,73,74,102,104 multivessel Doppler

s indispensable in planning the frequency ofetal testing.119

Although the combination of nonstress test-ng and amniotic fluid index (modified biophys-cal profile score)120 works well in a low-riskontext assessment of many aspects of IUGRemains incomplete. The biophysical profile us-ng the full five component score evaluates fetalesponses to metabolic disturbance and providesccurate reflection of current metabolic statusnd can provide reasonable assurance of fetalell being.121 As a single assessment tool in

UGR, it has several disadvantages. Fetal heartate scoring is based on visual assessment ofeactivity and therefore has the same drawbackss the traditional nonstress test. In the absencef oligohydramnios the biophysical profile scorerovides insufficient information on the severityf the fetal cardiovascular compromise to plan

ongitudinal assessment.46,118,119

Even more comprehensive fetal assessmentan be provided through concurrent evaluationf arterial and venous Doppler waveforms andiophysical parameters (integrated fetal test-

ng).118 In general, the most comprehensive pre-iction of critical perinatal variables is achievedhen multiple testing modalities are com-ined.122 This can take the form of arterial andenous Doppler, the combination of Dopplernd computerized CTG,104 5 component bio-hysical profile scoring or a combination ofoppler and biophysical profile scoring.123 The

ccurate guidance of intervention is of particu-ar importance in the preterm IUGR fetus inhom risks of adverse outcome due to prematu-ity are disproportionally high.3,112

iming of Intervention

ntervention may be preventative or therapeutic.recent Finnish prospective randomized study

n first trimester low-dose aspirin administrationn patients with abnormal uterine artery bloodow showed encouraging prevention of pre-clampsia.124 Although the rate of IUGR was notignificantly affected there are several argu-ents that support the use of low-dose Aspirin

n high-risk pregnancies that are identifiedhrough abnormal uterine artery Doppler. Theafety of Aspirin in pregnancy has been docu-ented in a large number of patients.125,126 The

everity of IUGR may be decreased127 and a de-line of maternal delivery indications for pre-clampsia is likely to decrease the preterm deliv-ry rate. Placental disease with severe IUGR maye the first manifestation of previously undiag-osed underlying thrombophilia.128

Numerous studies have evaluated other ther-peutic interventions such as maternal oxygenherapy,129 intravascular volume expansion,130

nd administration of aminoacids131 to alleviatehe fetal condition. The detailed appraisal ofhese approaches goes beyond the scope of thiseview. The universally available therapeutic op-ions that currently show any promise in affect-ng outcome are the antenatal administration ofteroids in preterm pregnancies and delivery atn institution with a neonatal care unit that isble to address the management complexities ofhe IUGR neonate. Antenatal steroids should bedministered to any IUGR fetus in whom deliv-ry is anticipated before 34 weeks’ gestation.he longheld belief that the “stress” of the in-

rauterine condition enhances maturation and isrotective against the effects of prematurity is ayth that is not supported by large population

tudies of IUGR neonates.3,132

The timing of delivery is of greatest relevanceo the managing physician. Unfortunately therere no randomized management trials that con-lusively adress the issue of delivery timingcross the whole clinical spectrum of IUGR.here are several difficulties in conducting suchtrial. The background morbidity and mortality

hat is not affected through intervention is un-nown. The critical perinatal variables that im-act on short and in particular long-term qualityf life are incompletely defined. Conclusive in-estigation of these issues requires large sample

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izes that con only be accumulated throughulti-center collaboration. The efficiency of

hese collaborations is hampered by regionalifferences in primary fetal assessment tools, cri-

eria for definition of fetal status and standardsf care that govern intervention. In principleelivery timing is straightforward in the term

etus, when fetal lung maturity has been docu-ented, if there is fetal distress, or if the mater-al condition dictates delivery. Management isore complicated for pregnancies between 25

o 32 weeks’ gestation, where each day gained intero may improve survival by up to 1% to%.118 In recent years, several concepts havemerged that are likely to alter the standard ofanagement in these pre-term IUGR pregnan-

ies. Early delivery of IUGR fetuses with abnor-

igure 8. The management algorithm for pregnancibility to perform arterial and venous Doppler as webdominal circumference; AFV, amniotic fluid volumiophysical profile score; CPR, cerebroplacental ratiiddle cerebral artery; NST, nonstress test; NICU, ne

rtery.

al umbilical artery waveform (after completionf antenatal steroid course) offers the benefit ofhigher lifeborn rate and disadvantage of a higheonatal mortality. Delaying delivery until fetalistress evident may be associated with a highertillbirth rate but a lower neonatal mortality.

hile overall mortality is not affected, signifi-ant intrauterine time and weight gain can bexpected.133 Timing the delivery between thesewo points would be desirable. When a tempo-izing approach is elected assessment of fetaltatus needs to be accurate to avoid preventabledverse outcomes. The ultimate impact of ante-atal management protocols on outcomes is

ikely to be greatest if critical outcomes are ac-urately predicted prenatally. Such outcomes in-lude the risk for stillbirth and moderate to

mplicated by fetal growth restriction is based on thea full five component biophysical profile score. AC,/REDV, absent/reversed end-diastolic velocity; BPS,V, ductus venosus; HC, head circumference; MCA,l intensive care unit; tid, 3 times daily; UA, umbilical

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evere peripartum acidemia, which has been re-ated to poor neuro-development.134

We use a monitoring approach that combinesetal heart rate analysis with Doppler and bio-hysical assessment of the fetus that is initiatedt 24 weeks’ gestation. The management algo-ithm that is depicted in figure 8 requires thebility to perform arterial and venous Dopplertudies and is aimed at defining three key as-ects: 1) correct diagnosis of IUGR, 2) docu-entation of a fetal compensatory response 3)vidence of fetal decompensation. The interven-

ions are guided by severity of the fetal conditionnd gestational age at presentation.

Our knowledge about the pathophysiologynd clinical management impacts in IUGR aretill evolving. The potential for improved clinicalpplication of different fetal testing modalities isurrently being investigated in 2 multicentertudies. An IUGR registry has been created tobtain observational data in order to define theombination of Doppler and biophysical vari-bles that offer the most accurate prediction ofdverse outcomes. The TRUFFLE study group iseading an interventional trial randomizingUGR pregnancies before 32 weeks to deliveryased on computer CTG versus ductus venosusoppler.

eferences

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3. Bernstein IM, Horbar JD, Badger GJ, et al: Morbidityand mortality among very-low-birth-weight neonateswith intrauterine growth restriction. The VermontOxford Network. Am J Obstet Gynecol 182:198-206,2000

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11. Nicolini U, Hubinont C, Santolaya J, et al: Maternal-fetal glucose gradient in normal pregnancies and inpregnancies complicated by alloimmunization and fe-tal growth retardation. Am J Obstet Gynecol 161:924-927, 1989

12. Battaglia FC, Regnault TR: Placental transport and me-tabolism of amino acids. Placenta 22:145-161, 2001

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