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Doppler Vascular Changes
in Intrauterine Growth RestrictionGiancarlo Mari, MD, and Jason Picconi, MD, PhD
Intrauterine growth restriction (IUGR) secondary to placental insufficiency is a major cause
of perinatal morbidity and mortality in the United States. Historically, Doppler changes
occurring in IUGR fetuses play an important role in the diagnosis and management of these
fetuses, and now, based on these changes, we have proposed a staging system for IUGR
fetuses that demonstrates prognostic value. This manuscript also summarizes a practical
classification for IUGR fetuses. We believe that future studies should differentiate among
the different types of IUGR fetuses.
Semin Perinatol 32:182-189 © 2008 Elsevier Inc. All rights reserved.
KEYWORDS IUGR, Doppler, IUGR stages, IUGR classification
Doppler ultrasound plays a fundamental role in the diag-nosis of intrauterine growth-restricted (IUGR) fetuses
and also has the potential to play an important role in timingthe delivery of some IUGR fetuses. Doppler ultrasonographyof the umbilical and middle cerebral artery, in combinationwith biometry, provides the best tool to identify small fetusesat risk foran adverse outcome.1,2 In addition,Doppler studiesof the fetal cardiovascular system allow assessment of theblood flow redistribution observed in IUGR.1 This process is
mainly characterized by an increased umbilical artery and adecreased middle cerebral artery pulsatility index (MCA-PI),which suggests increased vascular resistance of the umbilicalartery and cerebral vasodilatation.
Approximately 10,000 papers on IUGR fetuses havebeen published in the literature (http://www.pubmed.com). Despite this large number of studies, there is stillconfusion on the definition and management of IUGR fe-tuses, because of the failure to differentiate between con-stitutionally and pathologically small fetuses. Addition-ally, studies on the pathogenesis of IUGR have beenlimited by the concept that IUGR fetuses represent a ho-
mogeneous group. This has created confusion and ham-pered our understanding of the mechanisms that consti-tute the basis of IUGR. The result of this is that an IUGR can be defined differently in New York, London, or Paris.Therefore, it would be important to establish an interna-tional classification of IUGR fetuses.
Several studies have determined longitudinal Doppler
changes occurring in IUGR fetuses and, based on these
changes, the authors of these studies have provided recom-
mendations regarding the timing of delivery for IUGR fe-
tuses. Loss of the “brain-sparing effect” was initially con-
sidered a parameter to guide timing for the delivery of a
growth-restricted fetus.3 Arduini and coworkers reported
that there is a Doppler temporal sequence that precedes
the onset of late decelerations.4 Hecher and coworkers5
evaluated 93 IUGR fetuses with at least 3 Doppler studies
following the diagnosis of IUGR, the last measurements
being taken within 24 hours of delivery or intrauterine
death. The amniotic fluid index and umbilical artery pul-
satility index were the first variables to become abnormal,
followed by changes in short-term variability of the fetal
heart rate, middle cerebral artery pulsatility index, aortic
pulsatility index, and ductus venosus S/a ratio. In fetuses
delivered before 32 weeks, the perinatal mortality was
higher if both short-term variability and ductus venosus
pulsatility index were abnormal (39%) compared with
only 1 or neither being abnormal (7%). The median time
interval between the occurrence of the first persistently
abnormal finding and delivery was 3 days (range, 0-19
days) if short-term variability was the first abnormal sign
and 7 days (range, 0-43 days) if the ductus venosus pul-
satility index was the first variable to become abnormal.
The authors did not perform biophysical profiles (BPPs) in
their population.
Baschat and coworkers6 studied growth-restricted fe-
tuses with an umbilical artery pulsatility index 2 SD
above the mean for gestational age, and serially assessed
Department of Obstetricsand Gynecology,Wayne StateUniversity, Detroit,MI.
Address reprint requests to Giancarlo Mari, MD, Department of Obstetrics
andGynecology, Wayne State University, 3990 John R. Box163,Detroit,
MI 48201. E-mail: [email protected]
182 0146-0005/08/$-see front matter © 2008 Elsevier Inc. All rights reserved.doi:10.1053/j.semperi.2008.02.011
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fetal well-being using BPP scoring and additional Dopplerstudies. In 34 fetuses, Doppler studies revealed deteriora-tion of the umbilical artery and ductus venosus parametersat a median of 4 days before delivery, whereas 2 to 3 daysbefore delivery, fetal breathing movement began to de-cline, followed by a drop in amniotic fluid volume the nextday. Delivery occurred between 24 and 37 weeks’ gesta-
tion and was prompted by an abnormal BPP and abnormalDoppler. Computerized cardiotocography was not em-ployed in this study.
Ferrazzi and coworkers7 conducted a longitudinal studyof 26 growth-restricted fetuses that had abnormal uterineand umbilical artery Doppler velocimetry, and based thedecision to deliver the fetus on a nonreactive nonstress test(NST) defined as the absence of accelerations of at least 10beats per min for10 seconds, with a short-term variation2.2 seconds for a period of greater than 120 minute. Theauthors reported that an abnormal ductus venosus as wellas decreased aortic and pulmonary outflow tract velocities
were associated with perinatal death and occurred in 50%of patients 4 to 5 days before delivery. Interestingly, theauthors observed that more than 50% of fetuses that weredelivered because of an abnormal fetal heart rate did nothave venous Doppler abnormalities. The authors likewisedid not perform BPPs in their population.
Cosmi and coworkers were the first to perform a longitu-dinal study on IUGR fetuses in which no cause for the IUGR with placental insufficiency was detected(idiopathic IUGR).8
The authors reported that 54% of the fetuses had a normalvenous Doppler at the time of delivery.
We reported a longitudinal study in 10 IUGR fetuses fol-
lowed from the time the diagnosis of IUGR was made up todelivery of IUGR fetuses.9 The data are summarized inFigure 1. The data suggest that the last changes occurring inthe cardiovascular system of severe IUGR fetuses are rightcardiac failure followed by left cardiac failure.
Limitations ofPrevious LongitudinalStudies on IUGR Fetuses
Although previously cited studies suggest that there might be
a commonsequence of biophysical changes that indicate pro-
gressive fetal compromise in IUGR, a careful review revealsthat there are some differences among the studies. For exam-
ple, the involvement of the fetal brain and heart, as detected
by an abnormal fetal heart rate/BPP,or DV Doppler indices, is
highly variable among fetuses and does not follow a predict-
able pattern. Amniotic fluid volume was among the first pa-
rameters to become abnormal in the study of Hecher and
coworkers,5 but was among the last in the study of Baschat
and coworkers.6 Whereas Ferrazzi and coworkers7 and
Hecher and coworkers5 based their interventionson comput-
erized cardiotocography, which is not used in the US, Bas-
chat and coworkers6 used Doppler abnormality and the ab-
normal BPP, which is not used in Europe. Moreover, ourstudy on the longitudinal cardiovascular changes, as well as
the above-cited studies, considered IUGR fetuses as a homo-
geneous group and did not distinguish between IUGR with
and without maternal disease.
It is likely that the differences found amongtheabovestudies
can be attributed to differences in the growth-restricted fetuses
studied. We believe that more useful information could be
provided if authors differentiated between idiopathic IUGR
and IUGR secondary to maternal diseases.
A recent preliminary study has reported that IUGR fetuses
undergo a series of cardiovascular changes which are differ-
ent between idiopathic IUGR fetuses and IUGR diagnosed inpatients with preeclampsia.10 In idiopathic IUGR fetuses,
Doppler changes can be predicted on almost a day-by-day
basis, and if no abrupt adverse event occurs, such as a pla-
cental abruption, these fetuses can be followed until fetal
cardiac failure occurs. This is not the case in patients with
preeclampsia or other maternal pathology in which the
changes occurring in IUGR fetuses are unpredictable.10
Therefore, IUGR fetuses should be differentiated on the basis
of associated maternal or fetal pathology.
We have reported that if IUGR fetuses are delivered before
25 weeks, they invariably die, whereas if they are delivered
after 29 weeks, such fetuses usually survive.11
Based on ges-tational age at diagnosis, we have divided IUGR fetuses into
(1) very early IUGR (25 weeks), (2) early IUGR (between
25 and 30 weeks), and (3) late IUGR fetuses (30 weeks).
MCA-PSV:A New Parameter in theAssessment of IUGR Fetuses
Recently, we have performed a cross-sectional and a longitu-
dinal assessment of the MCA-PI and MCA-PSV in growth-
restricted fetuses.12
Our data show that, although the MCAwaveforms change in growth-restricted fetuses, the MCA-
Figure 1 The bars indicate the time interval (median time in days)between occurrence of pathologic findings and delivery IUGR
fetuses. MV, mitral valve; TV, tricuspid valve; AoA, aortic arch; RF,
reversed flow; UV umbilical vein; P, pulsation; DV, ductus venosusreversed flow; AoI, aortic isthmus; PI, pulsatility index; UA, umbil-
ical artery;MCA, middlecerebral artery; PSV, peak systolic velocity,
HA, hepatic artery; SA, splenic artery, IVC, inferior vena cava.(Color version of figure is available online.)
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PSV predicts perinatal mortality more accurately than theMCA-PI. This finding can be explained in the following way:initially, the MCA-PI is abnormal in most of the fetuses, but
subsequently the MCA-PI increases and a tendency towardnormalization occurred before delivery or fetal death. The
MCA-PSV, conversely, progressively increased with advanc-ing gestation in all fetuses, with a tendency to slightly de-crease just before fetal biophysical deterioration or theoccur-
rence of fetal demise. However, despite this decrease, theMCA-PSV value remains above the upper limit of normal (ie,
Figure 2 Individual longitudinal values for the middle cerebral artery peak systolic velocity in 10 IUGR fetuses plotted
over thereference range. IUFD, intrauterine-fetaldemise; ND,neonatal death;g, grams. (Reprinted with permission.12)
184 G. Mari and J. Picconi
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Figure 3 Linear regressions with the 95% confidence interval of the middle cerebral artery peak systolic velocity
(MCA-PSV) multiples of the mean (MoM), with: (A) the hemoglobin MoM values, (B) the pO2 MoM values, (C) thepCO2 MoM values, and (D) the pH MoM values in fetuses at risk of anemia. (Reprinted with permission.13)
Figure 4 Linear regressions with the 95% confidence interval of the of the middle cerebral artery peak systolic velocity
(MCA-PSV) multiples of the mean (MoM) with: (A) the hemoglobin MoM values, (B) the pO2 MoM values, (C) the
pCO2 MoMvalues, and (D) thepH MoMvalues in fetuseswith intrauterine growthrestriction (IUGR). (Reprinted withpermission.13)
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abnormal) until a few hours before delivery or fetal demise(Fig. 2).
Why Is the MCA-PSVIncreased in IUGR Fetuses?
Although the MCA-PSV is increased in anemic fetuses, IUGR fetuses are not anemic. Therefore the question that arises is:
What is the mechanism of increased MCA-PSV in anemic andnonanemic fetuses? To answer this question, Hanif and co-workers performed a new study which demonstrated themechanisms thatdetermine increased MCA-PSV are differentin anemic appropriate- for-gestational-age (AGA) comparedwith nonanemic IUGR fetuses.13 In anemic fetuses, the highMCA-PSV is related to a decreased fetal hemoglobin thatmight decrease blood viscosity, and consequently there is an
increased cardiac output. On the other hand, in IUGR fe-tuses, theMCA-PSV increase is significantlyrelated tohypox-emia and hypercapnia, and thus to brain auto-regulation.Figures 3 and 4 report thecorrelation between MCAPSVandfetal blood gas analysis.
Staging andClassification of IUGR Fetuses
Categorization of IUGR fetuses into three stages of severity
using nonstress testing and umbilical artery Doppler ve-locimetry has previously been performed by Pardi andcoworkers.14 This study showed that, if the nonstress testand umbilical artery Doppler studies were normal (group
I fetuses), there was no fetal acidosis or hypoxemia. Incontrast, group II fetuses with a normal nonstress test andabnormal umbilical artery Doppler study (pulsatility in-
dex 2 SD below the mean) showed a 5% rate of hypoxia/ acidemia, and group III fetuses with an abnormal non-stress test and umbilical artery Doppler studies showed a
60% rate of hypoxia/acidemia. Although the study byPardi and coworkers is informative, greater clinical utility
may be achieved by the use of fetal Doppler in additionalvessels. We have recently proposed a staging for IUGR fetuses based on fetal biometry, Doppler cardiovascularchanges, amniotic fluid, and clinical parameters.15 Asummary of this staging system is reported in Table 1.
Figure 5 (A) An abnormal umbilical artery Doppler (the arrows point to the low diastole indicating a high placentalresistance).(B) Abnormal middlecerebral artery Doppler at 27 weeks’gestation (the vertical arrows point to thediastole
that is increased, indicating “brain sparing effect”; the horizontal arrows indicate the peak systolic velocity that appears
normal). Anabnormal pulsatility index of either theumbilicalor middlecerebral arterycharacterizes stage I. (Reprintedwith permission.15) (Color version of figure is available online.)
Table 1 IUGR Staging
Stage
Umbilical a.
Middle
Cerebral a. Ductus v. Umbilical v.
TV
TR
aPI ARF aPI aPSV aPI RF P RF E/A
I*
II†
III‡
The presence of any one abnormal parameter in a stage would place the fetus in that stage.
*Stage I: Abnormal (a) umbilical artery pulsatility index (PI) or middle cerebral artery PI.
†Stage II: Umbilical artery absent/reversed flow (ARF), elevated middle cerebral artery peak systolic velocity, abnormal ductus venosus
pulsatility index (absent ductus venosus is included in this stage), and pulsation (P) of the umbilical vein.
‡Stage III: Ductus venosus reversed flow, umbilical vein reversed flow, tricuspid valve (TV) E/A ratio >1, tricuspid valve regurgitation (TR).
Reprinted with permission.15
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The Doppler waveforms used for staging are shown inFigures 5-7.
Stage I IUGR fetuses are considered mild IUGR, and suchpatients are usually managed as outpatients, whereas stage IIand III patients need to be admitted to the hospital when thefetuses are considered viable. Stage II patients are admittedfor observation, whereas stage III patients are at high risk forfetal demise. The major advantage for selecting the parame-
ters included in this staging system is the ability to clearlytrack the progression of abnormal parameters that start at theumbilical and middle cerebral arteries, and later progres-sively extend to the other parameters, up to the time of fetaldemise if the fetuses remain undelivered.9,10 Another advan-tage is the simplicity of the system. Only four fetal vessels andonecardiac valve need tobe investigated with Doppler.Further-more, it isnot necessary todeterminetheparametersreportedin
Figure 6 (A) Flow velocity waveforms of the middle cerebral artery. These waveforms were obtained in an IUGR fetus
at 27 weeks’ gestation. The transverse arrows point to the MCA peak systolic velocity that is abnormal (76 cm/s).(B, C) Two sets of umbilical artery absent and reversed flow, respectively. (D) An abnormal ductus venosus Doppler
(the arrows point to the “a” wave recorded at the atrial contraction; when there is a low “a” wave, the pulsatility indexis abnormal). Thepresence of oneof these findings characterizes stage II. (Reprinted with permission.15) (Colorversion
of figure is available online.)
Figure 7 The presence of one of the following findings characterizes stage III ductus venosus reversed flow
(A), umbilicalvein reversed flow(B), abnormal tricuspidvalve waveform (E/A 1) (C). (Reprintedwithpermission.15)(Color version of figure is available online.)
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a certainstage if the parametersof the previousstageare normal.For example, if the UA PI and the MCA PI are normal, it is not
necessary to determine the parameters of the next stage. Thismakes the staging system more easily applicable.
The staging system is applicable both in pregnancies at agestational age30 weeks and30 weeks, which makes thestaging system applicable across all gestational. ages. Thedata also indicate that stage III fetuses have a lower birthweight than both stage II and stage I fetuses at similar gesta-tional ages (Fig. 8). Moreover, the data suggest that stage IIand III IUGR fetuses are delivered earlier than fetuses of stageI (Fig. 9). No deaths occurred in stage I fetuses. At the otherextreme, the mortality for stage III fetuses was high (50% if there was DVRF; 85% when DVRF was present in combina-tion with one of the other parameters that characterize stageIII), whereas the mortality in stage II IUGR fetuses was inter-mediate between the two other stages (Fig. 10).
In this study, we also noticed that fetuses could survive fordays or weeks when ductus venosus reversed flow (RF) waspresent. It has been suggested that, when DVRF is present,the fetus may be acidemic. A recent preliminary study hasreported that fetuses with DVRF are not necessarily acidemicat birth.16 Based on the information obtained from our stag-ing system, we have proposed the following steps to classifyIUGR fetuses: (1) In the presence of a fetus with an estimated
weight below the 10th percentile, the first step would be todetermine the stage and amount of amniotic fluid; (2) Mater-nal or fetal pathology/anomalies should be identified, if any;and (3) the gestational age should be reported. For example,if a fetus with an estimated weight below the 10th percentilehas an abnormal umbilical and/or middle cerebral arterypul-satility index, the amniotic fluid index (AFI) is 5.0 cm,there is no maternal or fetal pathology, and the gestationalage is 28 weeks, the IUGR fetus should be classified as IUGR stage IA, 28 weeks, idiopathic. We use the term “idiopathic”for those IUGR fetuses in which no cause for placental insuf-ficiency is found.17 If a fetus with an estimated weight belowthe10th percentile hasreversed umbilical arteryDoppler, the
AFI is 7 cm, the mother has diabetes and chronic hyperten-sion, and the gestational age is 26 weeks, then the IUGR should be classified as IUGR stage IIB, 26 weeks, diabetes–chronic hypertension. If, in the previous case, instead of di-abetes and chronic hypertension, a diagnosis is made of cy-tomegalovirus (CMV) infection, theIUGR would be classifiedas IUGR stage IIB, 26 weeks, CMV infection. If, instead of CMV infection, a diagnosis of Down syndrome is made, theIUGR would be classified as IUGR stage IIB, 26 weeks, Downsyndrome.
Conclusion
In conclusion, we believe that IUGR fetuses with and with-out placenta insufficiency should be differentiated. In ad-dition, we should also divide the different types of IUGR with placenta insufficiency based on the fetal and maternalpathology.
The above-mentioned concepts are important and mighthave great implications for the future of IUGR studies. Frominformation presented in this chapter, it is clear that not allIUGR fetuses are the same and they must be categorized intoappropriate groups of severity and etiology, which has not
been uniformly done in the past publications. This is useful,not just formanagement purposes,butalso for theconduct of
Figure 10 The bars represent the median mortality values (mortality
occurringbetween 20 weeks’ gestationand28 days after birth) forthe fetuses in the three stages. The number in parentheses indicates
the number of total deaths/total number of fetuses. The mortalitywas 50% when there was DVRF only; it was 85% when DVRF was
present in combination with one of the other parameters. (Re-printed with permission.15)
Figure 8 The bars represent the median gestational age values atdelivery for the fetuses in the three stages. The numbers in paren-
theses indicate the number of fetuses. (Reprinted with permis-sion.15)
Figure 9 The bars represent the median birth weight values for the
fetuses in the three stages. The numbers in parentheses indicate thenumber of fetuses. (Reprinted with permission.15)
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any clinical trials that aim to test the hypothesis that IUGR fetuses behave in different ways.
References1. Mari G, Deter RL: Middle cerebral artery flow velocity waveforms in
normal and small-for-gestational-age fetuses. Am J Obstet Gynecol
166:1262-1270, 1992
2. Trudinger BJ, Giles WB, Cook CM, et al: Fetal umbilical artery flowvelocity waveforms and placental resistance: clinical significance. Br J
Obstet Gynaecol 92:23-30, 1985
3. Mari G, Wasserstrum N: Flow velocity waveforms of the fetal circula-
tion preceding fetal death in a case of lupus anticoagulant. Am J Obstet
Gynecol 164:776-778, 1991
4. Arduini D, Rizzo G, Romanini C: Changes of pulsatility index fromfetal
vessels preceding the onset of late decelerations in growth-retarded
fetuses. Obstet Gynecol 79:605-610, 1992
5. Hecher K, Bilardo CM, Stigter RH, et al: Monitoring of fetuses with
intrauterine growth restriction: a longitudinal study. Ultrasound Ob-
stet Gynecol 18:564-570, 2001
6. Baschat AA, Gembruch U, Harman CR: The sequence of changes in
Doppler and biophysical parameters as severe fetal growth restriction
worsens. Ultrasound Obstet Gynecol 18:571-577, 2001
7. Ferrazzi E, Bozzo M, Rigano S, et al: Temporal sequence of abnormalDoppler changes in the peripheral and central circulatory systems of
the severely growth-restricted fetus. Ultrasound Obstet Gynecol 19:
140-146, 2002
8. Cosmi E, Ambrosini G, D’Antona D, et al: Doppler, cardiotocography,
and biopgysical profile changes in growth restricted fetuses. Obstet
Gynecol 106:1240-1245, 2005
9. Mari G, Deter RL, Hanif F, et al: Sequence of cardiovascular changes
occurring in severe IUGR fetuses: part II. Ultrasound Obstet Gynecol
28:390, 2006
10. Mari G, Hanif F, Kruger M: Sequence of cardiovascular changes in
IUGR in pregnancies with and without preeclampsia. Prenatal Diagno-
sis 28:377-383, 200811. Mari G, Hanif F, Treadwell MC, et al: Gestational age at delivery and
Doppler waveforms in very preterm IUGR fetuses as predictors of peri-
natal mortality. J Ultrasound Med 26:555-559, 2007
12. Mari G, Hanif F, Kruger M, et al: Middle cerebral artery peak systolic
velocity: a new Doppler parameter in the assessment of growth-
restricted fetuses. Ultrasound Obstet Gynecol 29:310-316, 2007
13. Hanif F, Drennan K, Mari G: Variables affecting the middle cerebral
arterypeak systolic velocity in anemicand IUGR fetuses. Am J Perinatol
24:501-505, 2007
14. Pardi G, Cetin I, Marconi AM, et al: Diagnostic value of blood sampling
in fetuses with growth retardation. N Engl J Med 238:692-696, 1993
15. Mari G, Hanif F, Drennan F, et al: Staging of intrauterine growth-
restricted fetuses. J Ultrasound Med 26:1469-1477, 2007
16. Picconi J, Hanif F, Mari G: Ductus venosus reversed flow in IUGR
fetuses: Is it an indication for delivery? Am J Perinatol 25:199-204,2008
17. Mari G, Hanif F: Intrauterine growth restriction: how to manage and
when to deliver. Clin Obstet Gynecol 50:497-509, 2007
Doppler changes in IUGR fetuses 189