cerebroplacental ratio in fetal well being assessment in SGA and AGA fetus

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OBSTETRICS

The importance of the cerebroplacental ratio in theevaluation of fetal well-being in SGA and AGA fetusesGreggory R. DeVore, MD

he cerebroplacental ratio (CPR) is

The cerebroplacental ratio (CPR) is emerging as an important predictor of adversepregnancy outcome, and this has implications for the assessment of fetal well-being infetuses diagnosed as small for gestational age (SGA) and those appropriate for gesta-tional age close to term. Interest in this assessment tool has been rekindled because ofrecent reports associating an abnormal ratio with adverse perinatal events and asso-ciated postnatal neurological outcome. Fetuses with an abnormal CPR that are appro-priate for gestational age or have late-onset SGA (>34 weeks of gestation) have a higherincidence of fetal distress in labor requiring emergency cesarean delivery, a lower cordpH, and an increased admission rate to the newborn intensive care unit when comparedwith fetuses with a normal CPR. Fetuses with early-onset SGA (<34 weeks of gestation)with an abnormal CPR have a higher incidence of the following when compared withfetuses with a normal CPR: (1) lower gestational age at birth, (2) lower mean birthweight,(3) lower birthweight centile, (4) birthweight less than the 10th centile, (5) higher rate ofcesarean delivery for fetal distress in labor, (6) higher rate of Apgar scores less than 7 at5 minutes, (7) an increased rate of neonatal acidosis, (8) an increased rate of newbornintensive care unit admissions, (9) higher rate of adverse neonatal outcome, and (10) agreater incidence of perinatal death. The CPR is also an earlier predictor of adverseoutcome than the biophysical profile, umbilical artery, or middle cerebral artery. Inconclusion, the CPR should be considered as an assessment tool in fetuses undergoingthird-trimester ultrasound examination, irrespective of the findings of the individualumbilical artery and middle cerebral artery measurements.

Key words: biophysical profile, Doppler, fetal distress, intrauterine growth restriction,middle cerebral artery, perinatal morbidity, umbilical artery

T emerging as an important predic-tor of adverse pregnancy outcome, andthis has implications for the assessmentof well-being in fetuses diagnosed assmall for gestational age (SGA) and thoseappropriate for gestational age (AGA)close to term. The CPR is calculatedby dividing the Doppler indices ofthe middle cerebral artery (MCA) bythe umbilical artery (UA) (Table 1 andFigure 1).1-12

The CPR represents the interactionof alterations in blood flow to the brainas manifest by increased diastolic flowas the result of cerebrovascular dilationresulting from hypoxia and increasedplacental resistance, resulting in decrea-sed diastolic flow of the umbilical ar-tery.1-12 When these alterations occur,the increased diastolic flow of the MCAis manifest by a decrease in the systolic/diastolic ratio (S/D), resistance index(RI); [(systolic peak velocity/diastolicpeak velocity)/systolic peak velocity],and the pulsatility index (PI); [(systolicpeak velocity/diastolic peak velocity)/velocity time integral], whereas thesemeasurements are increased in the um-bilical artery as the result of increasedresistance to blood flow as the result

From the Department of Obstetrics andGynecology, David Geffen School of Medicineat University of California, Los Angeles,Los Angeles, CA.

Received April 7, 2015; revised April 29, 2015;accepted May 13, 2015.

The author reports no conflict of interest.

Corresponding author: Greggory R. DeVore,MD. [email protected]

0002-9378/$36.00ª 2015 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.ajog.2015.05.024

Click Supplemental Materials underthe article title in the online Table ofContents

of placental pathology.1-12 Although theS/D ratio, RI, and PI have been report-ed when computing the CPR, morerecently the PI is the computation ofchoice.1,5,6,8-12

An abnormal CPR may result from3 types of Doppler measurement pat-terns. The first is when the UA andMCAPI are in the upper and lower rangeof the distribution curve, resulting inan abnormally low CPR (Figure 2). Thesecond is when the UA PI is normalbut the MCA PI is decreased, resultingin an abnormally low CPR (Figure 3).13

The third pattern consists of an abnor-mally elevated UA PI and an abnormallydecreased MCA PI, resulting in an ab-normally low CPR (Figure 4).Whereas the CPR was first described

in the 1980s, interest in this assessmenttool has been rekindled because of

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recent reports associating an abnormalratio with adverse perinatal outcome andpostnatal neurological deficit.14-18 Thepurpose of this article was to review thedata from studies in which the CPRhas been evaluated in fetuses that wereAGA and those with SGA to determinewhether this test should be consideredfor integration into clinical practice.

Appropriate-for-gestational-agefetuses: the role of CPR in thedetection of fetuses at risk foradverse outcomePrior et al19 prospectively evaluated 400AGA fetuses at term and reported anabnormal CPR in 11%. Of those whounderwent cesarean delivery for fetaldistress, 36.4% had an abnormal CPRcompared with 10.1% (P < .001) thathad a normal CPR (Table 2).19 An

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TABLE 1Studies reporting the value for an abnormal cerebroplacental ratioStudy Year Study type Doppler indices Computation of ratio Abnormal criteria

Arbeille et al1 1988 Cross-sectional S-D/S MCA/UA Ratio <1

Arias6 1994 Cross-sectional RI MCA/UA Ratio <1

Gramellini et al5 1992 Cross-sectional PI MCA/UA Ratio <1.08

Bahado-Singh et al8 1999 Cross-sectional PI MCA/UA MoM Ratio <0.05 MoM

Baschat and Gembruch9 2003 Cross-sectional PI MCA/UA Less than fifth centile

Odibo et al10 2005 Cross-sectional PI MCA/UA Ratio <1.08

Ebbing et al11 2007 Longitudinal PI MCA/UA <2.5th centile

Morales et al12 2014 Cross-sectional PI MCA/UA Less than fifth centile or MoM <0.6765

MCA, middle cerebral artery; MoM, multiple of the median; PI, pulsatility index; RI, resistance index; S/D, systolic/diastolic ratio; UA, umbilical artery.

DeVore. Cerebroplacental ratio in fetal well-being in SGA and AGA fetuses. Am J Obstet Gynecol 2015.

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abnormal CPR was a better predictor foran emergency cesarean delivery thanan abnormal UA or MCA (Table 2). Nofetuses with a CPR greater than the90th centile required cesarean deliveryfor fetal distress in labor.19 Therefore,the assessment of the CPR in term AGAfetuses before active labor predictedintrapartum fetal compromise and theneed for emergency cesarean delivery.19

In a study reported by Morales-Rosello et al,20 who evaluated the CPRin AGA fetuses between 37 and 41.9weeks of gestation, they found that theUA and venous pH were significantlylower in AGA newborns who had anabnormal CPR than AGA fetuses with anormal CPR (Table 2). These data sug-gest that the CPR could be used to assessthe risk of intrapartum fetal distressrequiring cesarean delivery, or acidemiaat birth, in AGA fetuses.

This poses a larger question as towhether a screening test at the timeof admission to labor and delivery forinduction of labor, or in early sponta-neous labor, should be considered. Ibelieve that this question will requirefurther studies, but the data appear tosupport that the CPR is a candidate forsuch assessment.

Late-onset SGA fetuses: the role ofCPR in the detection of fetuses at riskfor adverse outcomeLate-onset SGA is diagnosed after 34weeks of gestation and is characterizedby abnormal Doppler indices involving

6 American Journal of Obstetrics & Gynecology JU

theMCA, with a normal resistance of theUA.3,21-23 Identifying and monitoringthe fetus with late-onset SGA is prob-lematic because of the paucity of studiessuggesting perinatal identification andmanagement protocols.2,3,24,25

Cruz-Martinez et al26 evaluated the210 fetuses at greater than 37 weeks ofgestation suspected of having late-onsetSGA and reported an abnormal CPRwas associated with a significantly higherrate of emergency cesarean delivery forfetal distress in labor (37.8% vs 20.4%;P < .001) and was a better predictorthan an isolated MCA measurement(Table 2).Figueras et al27 evaluated 509 fetuses

with late-onset SGA and found 39.3%to have an abnormal CPR. When anabnormal CPR was present, there was asignificantly higher rate of fetal distress(79.1% vs 10.7%; P < .001) in laborrequiring emergent delivery. In addition,fetuses with an abnormal CPR also hada lower umbilical cord pH (7.17 vs 7.25;P < .001) and a higher rate of newbornintensive care unit (NICU) admissions(11.25% vs 5.6%; P ¼ .03) (Table 2).27

They found the best predictors foridentifying fetuses at risk for emergencycesarean delivery in labor were thefollowing: (1) an abnormally low CPR,(2) an estimated fetal weight less thanthe third centile, and (3) an elevated PIof the uterine arteries (Table 2).27

These data suggest that an abnormalCPR appears to identify late-onset SGAfetuses at increased risk for adverse

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intrapartum and neonatal complica-tions. Because the majority of these fe-tuses have a normal Doppler resistance(PI, RI, or S/D ratio) of the UA, thephysician may falsely conclude that thereis no increased risk for adverse outcome,even though an abnormal CPR may bepresent but not measured. Therefore,it is imperative that Doppler assessmentof the MCA occurs and the CPRcomputed in late-onset SGA fetusesto identify those at risk for perinatalcomplications.

Newborns classified as SGA: the roleof CPR in the detection of fetuses atrisk for adverse outcomeRecently Khalil et al17 examined 2485patients who underwent third-trimesterscreening ultrasound between 34 and36 weeks of gestation, with deliveryoccurring after 37 weeks of gestation.Using multivariate logistic regressionanalysis, they found a significant associ-ation between SGA and an abnormalCPR as indicators for admission to theNICU (Table 2).17

In a subsequent study, Khalil et al18

examined 8382 patients who under-went ultrasound examination after 37weeks of gestation. In fetuses requiringan emergency cesarean delivery for fetaldistress, an abnormal CPR was signifi-cantly more frequent (13.1% vs 9.4%;P < .001) than those not requiringoperative delivery. Multivariate logis-tic regression identified an abnormalCPR and birthweight centile to be

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FIGURE 1Recordings from a fetus whose mother was a late registrant for prenatalcare

These recordings are from a fetus whose mother was a late registrant for prenatal care. There was

a 14 day difference between the menstrual age and the mean ultrasound gestational age. The

abnormal cerebroplacental ratio suggested that fetal growth restriction was the correct diagnosis. How

to acquire the images and make the measurements is illustrated in the Video available at ajog.org.


ajog.org Obstetrics Expert Reviews

independently associated with the riskfor emergency operative delivery in boththe SGA and AGA birthweight groups.Fetuses with an abnormal CPR had ahigher rate of NICU admissions (14.3%)compared with those with a normalCPR (9.7%; P < .004) (Table 2).18 Inthis group, however, birthweight centilewas not independently associated withNICU admissions.

When the newborns were dividedinto groups based on whether SGA waspresent or absent and the CPR wasnormal or abnormal, those with anabnormal CPR had a higher cesareandelivery rate (11% vs 8.7%; P ¼ .043)and higher instrumental delivery rate(11.2% vs 7.8%; P ¼ .003).

These data underscore that an ab-normal CPR was a better predictor thanlow birthweight for identifying thosefetuses requiring emergent operativedelivery for fetal distress in labor andNICU admission associated with neo-natal complications. Therefore, when afetus with late-onset SGA is identified,the examiner should strongly considercomputing the CPR to stratify risk forintrapartum fetal distress and adverseneonatal outcome prior to the onset oflabor.

Early onset SGA fetuses: the role ofCPR in the detection of fetuses at riskfor adverse outcomeEarly-onset SGA is characterized by theonset of abnormal growth prior to 34weeks of gestation with concomitantabnormal Doppler indices of the UA andMCA.3,21-23 Table 3 summarizes findingsfrom 6 studies in which the CPR wasevaluated in fetuses with early-onsetSGA. In this group of fetuses, an ab-normal CPR was associated with ahigher incidence of the following whencompared with fetuses with a normalCPR: (1) lower gestational age at birth,(2) lower mean birthweight, (3) lowerbirthweight centile, (4) birthweight lessthan the 10th centile, (5) higher rate ofcesarean delivery for fetal distress in la-bor, (6) higher rate of Apgar scores lessthan 7 at 5 minutes, (7) an increased rateof neonatal acidosis, (8) an increasedrate of NICU admissions, (9) higher rateof adverse neonatal outcome, and (10)

a greater incidence of perinatal death(Table 3).5,6,8,13,28-30

In addition to predicting adverse fetaland neonatal outcome, an abnormalCPR was a better predictor of adverse

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outcome than the biophysical profile,suggesting that CPR changes may occurbefore the deterioration of this test.28,29

Although early-onset SGA fetuses areat highest risk for adverse outcome,

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FIGURE 2Fetus with several abnormalities

=


8 American Journal of Obstetrics & Gynecology JULY 2015

classification by birthweight has failedas a discriminator within this groupfor fetal and neonatal complications.It would appear from the studiesreviewed in this paper that an abnormalCPR might be a powerful identifier foradverse pre- and postnatal outcomes infetuses with early-onset SGA and shouldbe included as part of the prenatal ul-trasound evaluation.

Which CPR measurement is the bestpredictor of adverse outcome?In 2014, Flood et al30 reported resultsfrom 881 fetuses with early-onset SGAthat were examined for a composite ofadverse outcomes that included intra-ventricular hemorrhage, periventricularleukomalacia, hypoxic ischemic ence-phalopathy, necrotizing enterocolitis,bronchopulmonary dysplasia, sepsis,and death. They computed the sensi-tivity and specificity for adverse outcomeusing the following thresholds for anabnormal CPR: PI less than 1, RI lessthan 1, PI less than 1.085,6,10,29 and thefifth centile from 1 cross-sectional9 and1 longitudinal study (Table 1).11 Theydetermined that the ratios had lowersensitivities but higher specificities,whereas values less than the fifth centileshad higher sensitivities but lower speci-ficities (Table 4).

The clinical application of CPRevaluation during the third trimesterof pregnancyGiven the data reviewed in this paper,there are several questions that cliniciansmight consider.

This is an example of a fetus with A, a high but

normal PI of the umbilical artery, B, low but

normal PI of the middle cerebral artery, and C,

an abnormal cerebroplacental ratio below the

fifth centile (red ). Each graph illustrates the raw

data for the mean (dots ) and 95th and fifth

centiles (solid lines ). The dotted line is the mean

of the regression line. The reference ranges are

from a study by Baschat and Gembruch.9

CPR, abnormal cerebroplacental ratio.

DeVore. Cerebroplacental ratio in fetal well-being in SGAand AGA fetuses. Am J Obstet Gynecol 2015.

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FIGURE 3Fetus with other abnormalities


1. Which CPR reference should be usedto determine an abnormal value?

Table 1 lists the studies and cutoffvalues to identify an abnormal CPR. Inthe earlier studies, investigators deter-mined the threshold for an abnormalCPR from their respective controlgroups.5,6,8 After the publication byBashat and Gembruch9 in 2003, whichprovided the mean and SD for the UA,MCA, and CPR, Figueras et al,27 Floodet al,30 and Cruz-Martinez et al,26 usedthis dataset to determine abnormalvalues for their studies. Flood et al30

compared the sensitivity and specificityof ratios and gestational age-related fifthcentile cutoffs to determine the abnor-mality of the CPR (Table 4).

Several authors have also reportedusing the multiple of the median(MoM) (Table 1).8,12,31 Other than us-ing the ratios of less than 1 and lessthan 1.08, computation of gestationalage-related centiles and MoM requiresoff-line computing unless the equa-tions are part of an online softwareprogram incorporated into the ultra-sound machine.

Depending on the clinical setting, theclinician may use the PI , RI, or the S/DCPR ratios of less than 1 or the PI CPRratio of less than 1.08 because these areeasy computations (Table 1). If serialexaminations of the CPR are performedto track the trends, the longitudinalstudy reported by Ebbing et al11 shouldbe considered. For those desiring toevaluate all options, an Excel spreadsheetof the computations listed in Table 1 that

This is an example of a fetus with A, a normal PI

of the umbilical artery, B, abnormal low PI of the

middle cerebral artery, and C, an abnormal CPR

below the fifth centile (red ). Each graph illus-

trates the raw data for the mean (dots ) and 95th

and fifth centiles (solid lines ). The dotted line is

the mean of the regression line. The reference

ranges are from a study by Baschat and

Gembruch.9

CPR, cerebroplacental ratio; SGA, small for gestational age; PI,pulsatility index.


<

JULY 2015 American Journal of Obstetrics & Gynecology 9

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FIGURE 4Fetus with an elevated PI of the UA, low PI of the MCA, and an abnormalCPR

=



includes the ratios and computation ofgestational age-related centiles is pro-vided for the reader at ajog.org.

2. Should the CPR be used to detectfetuses with early-onset and late-onset SGA?

When the clinician assesses the fetalweight and gestational age using diag-nostic ultrasound, fetuses are classifiedas early-onset SGA, late-onset SGA, orAGA. Once SGA is detected, the ques-tion is whether there is an increasedrisk for adverse outcome. Using pulsedDoppler to measure the UA and MCAand computing the CPR, fetuses athigher risk for adverse outcomes maybe detected. This is particularly usefulif the sonologist is confronted withpatients who have entered the healthcare system in the third trimester andhave a discrepancy between the gesta-tional age by last menstrual periodand the ultrasound gestational age(Figure 1). If the CPR ratio is ab-normal, the sonologist has to stronglyconsider SGA and incorrect gestationalage assignment using the last menstrualperiod.

3. Is there a role for late third-trimesterevaluation of all fetuses, given theability to detect AGA fetuses whoseweights are greater than the 10thcentile but are at risk for adverseoutcome because of an abnormalCPR?

Studies summarized in this paperhave demonstrated that AGA fetuseshave a higher incidence of adverse

This is an example of a fetus with A, an elevatedPI of the umbilical artery, B, low PI of the middle

cerebral artery, and C, an abnormal CPR below

the fifth centile (red ). Each graph illustrates the

raw data for the mean (dots ) and 95th and fifth

centiles (solid lines ). The dotted line is the mean

of the regression line. The reference ranges are

from a study by Baschat and Gembruch.9

CPR, cerebroplacental ratio; MCA, middle cerebral artery; PI,pulsatility index; SGA, small for gestational age; UA, umbilicalartery.


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TABLE 2Comparison of findings at birth and adverse neonatal outcomes in term fetuses with normal vs CPRs

VariableCruz-Martinez et al(2011)26

Prior et al(2013)19

Figueras et al(2014)27

Morales-Rosello et al(2015)20

Khalil et al(2015)17

Khalil et al (Part I)(2015)18

Type of study Prospective Prospective Prospective Retrospective Retrospective Retrospective

Purpose of study Evaluate CPR to predictemergency cesareandelivery for fetal distressin term fetuses with late-onset SGA

Evaluate CPRobtained before laborto detect fetuses atrisk for emergencycesarean delivery forfetal distress

Develop an integratedmodel to predictadverse outcome infetuses with late-onset SGA

Determine whether SGAand appropriate-for-gestational-age termfetuses with a CPR haveworse neonatal acidebasestatus than those with anormal CPR

Compare CPR andEFW at term todetect NICUadmission whenCPR obtainedduring midthirdtrimester

Evaluate CPR andbirthweight models interm fetuses to predictoperative delivery forfetal compromise andadmission to the NICU

Gestational weeks ultrasoundstudies were obtained

>37 37e42 34e40 37e41.9 34þ0 to 35þ6 >37

Classification and number offetuses studied, n, %

Control (n ¼ 210),suspected SGA (n¼ 210)

Low-risk patients(n ¼ 400)

No control SGA(n ¼ 509)

All patients (n ¼ 2927),SGA (n ¼ 640, 25.8%)

All patients(n ¼ 2485) SGA(n ¼ 640, 25.8%)

All patients (n ¼ 8382)SGA (n ¼ 1282, 15.3%)

Interval from ultrasoundto delivery

Induction after 37 wks Examined within 72 hof delivery

Not stated Up to 2 wks Up to 6 wks 2 wks

Type of CPR measurement(abnormal Value)

PI less than fifth centile9 PI <10th centile(<1.24)

PI (<10th centile)9 PI MoM <0.6765 PI MoM <0.6765 PI MoM <0.6765

Did CPR perform better thanother tests?

Yes (MCA) Yes (UA, MCA) No (CPR combinedwith UtA PI >95thcentile and EFW lessthan third centile)

Yes (birthweight) Yes (EFW,birthweightcentile)

Yes (birthweight centile)

Findings at birth: classificationby abnormal vs normal CPR

Weeks of gestation at delivery — 40þ5 vs 40þ3

(P < .004)38.1 vs 38.5 (notsignificant)

— — —

Mean birthweight, g — Not significant 2280 vs 2466(P < .001)

— — —

Birthweight centile, n,% — 48 vs 55 (P ¼ .04) — — — —

Abnormal fetal heart ratemonitoring during labor

— 86% vs 31%(P < .001)

— — — —

Operative delivery for fetaldistress (cesarean delivery,instrumental delivery)

CPR less than fifth:37.8% (14/37) CPR morethan fifth: 20.4% (29/142) (P < .001)

36.4% vs 10.1%(P < .001)

79.1% vs 10.7%(P < .001)

— — 13.1% vs 9.4% (P < .01)

DeVore. Cerebroplacental ratio in fetal well-being in SGA and AGA fetuses. Am J Obstet Gynecol 2015. (continued)

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TABLE

2Com

parisonof

findings

atbirthandadverseneonataloutcom

esin

term

fetuseswithnorm

alvs

CPRs(continued)

Variable

Cruz-Martinezet

al(2011)

26

Prior

etal

(2013)

19

Figu

eras

etal

(2014)

27

Morales-Roselloet

al(2015)

20

Khalilet

al(2015)

17

Khalilet

al(PartI)

(2015)

18

Neonatalfindings:classification

byabnorm

alvs

norm

alCPR

Meconiumstainedliquor

—22.7%

vs9%

(P¼

.02)

——

—

Apgar

<7at5minutes

—Notsignificant

0.7%

vs1.3%

(not

significant)

——

—

Abnormalcord

pH—

Notsignificant

UA7.17

vs7.25

(P<

.001)

UAandUV

——

New

born

intensivecare

unitadmission

—Notsignificant

Allpatients12.6%

vs6.1%

(P<

.001)SGA22.5%

vs8.4%

(P<

.001)AGA9.8%

vs5.5%

Not

significant

14.3%

vs9.7%

(P¼

.004)

Neonatalcom

plications

—Notsignificant

11.25%

vs5.6%

(P¼

.03)

——

—

AGA,appropriateforgestationalage;CPR,abnormalcerebroplacentalratio;EFW,ultrasound

estim

ated

fetalw

eight;MCA,middlecerebralartery;MoM

,multipleofthemedian;NICU,newborn

intensivecareunit;PI,pulsatilityindex;SG

A,late-onsetsm

allfor

gestationalage;UA,um

bilicalartery;UV,um

bilicalvein.

DeVore.Cerebroplacentalratioin

fetalw

ell-beingin

SGAandAGAfetuses.Am

JObstetGynecol2015.



outcome when they have an abnormalCPR. Because these fetuses may not beidentified using traditional clinical toolssuch as fundal height measurements,evaluation of the amniotic fluid, orantepartum testing, the question has tobe asked whether it would be prudent toconsider routine late third-trimesterevaluation of growth as well as mea-surement of the CPR? Although routinethird-trimester ultrasound is morecommon in European and other coun-tries, it is not routine practice in NorthAmerica.

Given the findings of the studies citedin this paper, the data would suggestthat third-trimester routine ultrasoundmight be of value for identifying thosefetuses at risk for adverse outcome dur-ing labor and subsequent neonatalcomplications.

For some clinicians, the data reportedin this paper may be sufficient to inte-grate this approach into clinical practice.For others, further studies may berequired before this becomes the stan-dard practice. Although third-partypayers do not reimburse the clinicianfor evaluation for the MCA unless fetalanemia is suspected, acquiring theDoppler waveform takes less than a fewminutes and may be advantageous whendetecting fetuses at increased risk foradverse outcome.

4. Should CPR be a component part ofantepartum testing?

In studies reported by Makhseedet al28 and Ebrashy et al,29 they foundthat CPR identified more fetuses withadverse outcome than did the bio-physical profile. Because the cost ofultrasound equipment is decreasing,portable ultrasound machines can bepurchased for less than $15,000, andthese machines allow the clinician touse color Doppler to identify the UAand MCA and acquire pulsed Dopplerwaveforms in which the UA and MCAPI and are automatically measured andthe CPR computed as described inTable 1. Although further studies maybe considered before this becomesaccepted protocol, clinicians mightconsider this as an option to refine thepredictability of adverse outcome in

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TABLE 3Studies evaluating the CPR as a diagnostic tool in fetuses with predominantly early-onset fetal growth restriction (SGA)

Variable Gramellini et al (1992)5 Arias et al (1994)6Bahado-Singh et al(1999)8

Makhseed et al(2000)28 Ebrashy et al (2005)29 Flood et al (2014)30

Type of study Retrospective Prospective Prospective Prospective Prospective Retrospective

Purpose of the study Compare CPR, UA, andMCA to predict adverseoutcome in SGA

Evaluate CPR topredict adverseoutcome in SGA

Evaluate CPR topredict adverseoutcome in SGA

Compare CPR and UAto predict adverseoutcome in SGA

Evaluate CPR to predictadverse outcome inwomen with preeclampsia

Evaluate CPR to predictadverse outcome in SGA

Gestational weeks ultrasoundstudies were obtained

30e41 24e38 <34 29e42 >28 29e36

Classification and number offetuses studied (n)

Control (n ¼ 45),SGA (n ¼ 45)

Control (n ¼ 25), riskSGA (n ¼ 61)

Control (n ¼ 82), riskSGA (n ¼ 125)

No control, SGA(n ¼ 70)

Control (n ¼ 30), SGA(n ¼ 38)

No control, SGA (n ¼ 881)

Interval from ultrasoundto delivery

Not stated <2 <3 3.8e8.6 Not stated 32e42

Type of CPR measurement(abnormal value)

PI (<1.08) RI (<1.0) MoM (<0.5) RI (<1.05) RI (<1.0) RI (<1); PI (<1, <1.08); PI(less than fifth centile9) PI(less than fifth centile11)

Did CPR perform better thanother tests?

Yes (UA and MCA) Yes (UA and MCA) Yes (UA) Yes (BP, AEDV of UA) Yes (BP, UA, MCA) Equal (UA)

Findings at birth: classificationby abnormal vs normal CPR

Weeks of gestation at delivery 34.9 vs 39.4 (P < .001) — 31.6 vs 35.7(P < .0001)

35.4 vs 37.3 (P< .05) — 34.6 vs 38.3 (P < .001)

Mean birthweight, g 1659 vs 3031 (P < .001) — 1138 vs 2098(P < .0001)

1835 vs 2351(P < .0001)

— 1763 vs 2611 (P < .0001)

Birthweight <10th centile 100% (P < .001) 45.4% vs 7.6%(P < .001)

94.4% vs 57.5%(P < .001)

— — —

Cesarean delivery forfetal distress

88.8% vs 12.5% (P < .05) 86.3% vs 51.2%(P ¼.01)

41.7% vs 13.8%(P < .01)

65.7% vs 42.9%(P < .05)

— —

Neonatal findings: classificationby abnormal vs normal CPR

Apgar <7 at 5 min 16.6% vs 2.7% (P < .001) — Not significant Not significant Relative risk 1.4 (P < .05) —

Abnormal cord pH UV 7.25 vs 7.33 (P < .001) — — — — —

Newborn intensive careunit admission

77.7% vs 11.1% (P < .001) 26 d vs 14.5 d(P ¼ .03)

77.8% vs 41.4%(P < .001)

74.3% vs 31.4%(P < .001)

Relative risk 1.4(P < .05)

64% vs 22% (P < .0001)

Neonatal complications 33.3% vs 1.38% (P < .001) Relative risk 1.4 (P < .05) 18% vs 2% (P < .001)

DeVore. Cerebroplacental ratio in fetal well-being in SGA and AGA fetuses. Am J Obstet Gynecol 2015. (continued)

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TABLE

3Studies

evaluating

theCPRas

adiagnostictoolin

fetuseswithpredom

inantlyearly-onsetfetalg

rowth

restriction(SGA)(continued)

Variable

Gramellinietal(1992)

5Arias

etal(1994)

6Bahado-Singh

etal

(1999)

8Makhseedet

al(2000)

28

Ebrashyet

al(2005)

29

Floodet

al(2014)

30

Brochopulmonarydysplasia

——

1.7%

vs1.1%

(P<

.01)

——

—

Necrotizingenterocolitis

——

Notsignificant

——

—

Perinataldeath

—18%

vs0%

(P<

.05)

8.3%

vs0%

(P<.05)

——

2%vs

0%(P<

.0001)

AEDV,absentend-diastolicflow;BP,biophysicalprofile;CPR,abnormalcerebroplacentalratio;EFW

,ultrasound

estim

ateoffetalweight;MCA,m

iddlecerebralartery;M

oM,m

ultipleofthemedian;PI,pulsatility

index;RI,resistance

index;SG

A,smallforgestational

age;UA,um

bilicalartery;UtA,uterineartery.

DeVore.Cerebroplacentalratioin

fetalw

ell-beingin

SGAandAGAfetuses.Am

JObstetGynecol2015.

TABLE 4Sensitivities, specificities, and odds ratio for CPR computations fordetecting adverse perinatal outcomea30

Cerebroplacental ratioMeasurementstandard Sensitivity Specificity Odds ratio

<1 Pulsatility index 66% 85% 11.7

<1 Resistance index 66% 84% 11.8

Less than fifth centile(cross-sectional study)9

Centile 80% 60% 6.2

Less than fifth centile(longitudinal study)11

Centile 85% 41% 4.1

CPR, abnormal cerebroplacental ratio.

a Intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis,bronchopulmonary dysplasia, sepsis, and death.



14 American Journal of Obstetrics & Gynecology

high-risk fetuses undergoing antepart-um testing. -

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