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In the early 1960s, 2 clinical investigative teams, one headedby Hon in Yale and the other by Caldero-Barcia in Uruguay,reported methods for continuous recording of the fetal heartrate.1,2 This innovation ushered in the contemporary era offetal evaluation based on dynamic biophysical monitoring.Although designed for the intrapartum period, the applica-tion of heart rate monitoring in the antepartum period wasquickly realized, and a generation of tests based on heart rateresponses to contractions (the contraction stress test), fetalmovements (the nonstress test [NST]), or both came intovogue3 and quickly supplanted the biochemical tests. In thelate 1960s, 2 groups, those of Dawes in Oxford andTchobroutsky in Paris, reported fetal breathing movementsas a normal characteristic of intrauterine life.3,4 Dawes et al ina series of elegant experiments in the chronic fetal lambpreparation were able to demonstrate an exquisite sensitivityof the fetal respiratory center to experimental hypoxemia,5

thereby creating interest in the potential of this measure-ment in predicting human fetal compromise. The clinicalapplication of these observations was thwarted by the inabil-ity to record human fetal breathing accurately.

In the mid-1970s a revolutionary clinical tool,dynamic real-time B-mode ultrasound, became available.Through this method observation of a broad range ofdynamic fetal biophysical activities became clinically facile.From the outset of clinical testing it was evident thatobservation of the presence or absence of breathing move-ments in the human fetus was as predictive as the NST6

was useful in the differentiation of true-positive and false-positive contraction stress test results7 and, when com-bined with heart rate test, yielded a better prediction thanany single test.8 Further, it became evident that objectiverecording of gross body movements was predictive of fetalhealth and disease9 and that, when combined with otherbiophysical variables, predictive accuracy was improved.The preliminary observations provided a first insight intoa fundamental tenet of antepartum risk assessment: thepredictive accuracy of fetal testing methods improves asmore fetal variables are considered. Even from what wouldbe crude ultrasound images by today’s standards, it waspatently evident that the wealth of fetal information thatcould be assessed was vast and included a wide spectrum ofacutely dynamic biophysical activities, ranging from grossbody movements to fine finger control, an objective meansof determining the presence (or lack of) and distribution of

705Chapter 23 Fetal Biophysical Profile Score: Theoretical Considerations and Practical Application

Frank A. Manning

Chapter 23

FETAL BIOPHYSICAL PROFILE SCORE:THEORETICAL CONSIDERATIONS ANDPRACTICAL APPLICATION

Definitions

1. Antepartum fetal testing: a compilation of methodsdevised to differentiate normal from compromisedfetuses prior to the onset of labor. These methodsmay be based on endocrine markers in maternalserum, Doppler-ultrasound-based continuous fetalheart rate monitoring, and real-time ultrasound eval-uation of fetal biophysical variables and amnioticfluid volume.

2. Fetal biophysical profile score: a score derived fromobservation of 4 discrete dynamic fetal biophysicalvariables (heart rate acceleration in response to fetalmovement [nonstress test or NST], fetal breathing,gross body movement, tone) and one static variable(amniotic fluid volume). The score can range from10/10 (all variables normal) to 0/10 (all variablesabnormal). The method is highly accurate in differen-tiating healthy from compromised fetuses.

3. Perinatal asphyxia: a collective term describing thefetus, who in response to exposure to either hypoxiaor ischemia, exhibits hypoxemia and a metabolic aca-demia (abnormal base deficit). Perinatal asphyxiamay be acute or chronic. The fetal adaptive responseto perinatal asphyxia forms the basis for the evalua-tion of fetal dynamic biophysical variables and amni-otic fluid volume. Perinatal asphyxia is a recognizedcause of perinatal death and morbidities such ascerebral palsy among affected surviving perinates.

INTRODUCTION

The development of objective clinical methods for the detec-tion of the fetus at risk for death or damage in utero began inearnest only in the past few decades. The initial forays werein the measurement of endocrine products released by theplacenta into the maternal circulation. A wide range of com-pounds, including placental enzymes (alkaline phosphatase,leucine amino-peptidase), placental-specific hormones (pla-cental lactogen), and placental conversion products (estriols,estetrol) were studied. For most there was a relation to fetaloutcome, but none of these measures had the necessaryaccuracy to become a useful adjunct to clinical management.

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amniotic fluid, a detailed measurement of fetal structures(morphometrics), and an evaluation of the organ system’sstructural and functional integrity (morphology). Fromthese observations arose the now entrenched concept ofcomposite fetal assessment. The fetal biophysical profilescoring method emerged from this rich clinical milieu as ameans of integration of dynamic biophysical activities intoa workable clinical format.10 As from its inception, itremains critical today to interpret the results of the biophys-ical profile score (BPS) within the context of all the informa-tion concurrently rendered accessible by dynamic ultra-sound fetal imaging.

It is the intent of this chapter to review the clinical roleof the fetal BPS in the prediction and prevention of perina-tal mortality, perinatal morbidity as reflected by antenatalacidosis, immediate neonatal compromise, and long-termsequelae, and to review application of the testing methodto discrete at-risk pregnancy categories.

FETAL ADAPTIVE RESPONSES TO ACUTE ANDCHRONIC HYPOXEMIA OR ACIDEMIA

Whereas in the majority of high-risk pregnancies there areeither no or minimal noxious fetal consequences, in a smallpercentage, estimated to be in the range of 2% to 3% based

on our large clinical trials of more than 82,000 referrals,the fetus will be exposed to potentially damaging or evenlethal interruptions in placental respiratory function.Unable to extricate itself from this hostile environment themammalian fetus has evolved remarkable protective com-pensatory mechanisms. It is these adaptations to hypox-emia and acidemia (asphyxia) that result in the deviationfrom normal of the components of the BPS. In response toacute hypoxemia, for example, as may occur with fulmi-nant preeclampsia or abruption, the fetus ceases all acutebiophysical activities nonessential to immediate survival:the fetus will stop moving and breathing and will loseflexor tone. In the fetal lamb, abolition of all skeletal mus-cle activity, as induced by pharmacologic footplate block-ade (eg, gallamine), produces an immediate reduction inoxygen consumption by up to 17% and yields a rise in fetalPo

2.11 In the human fetus, we have observed a similar

effect: In alloimmune anemic fetuses undergoing intravas-cular transfusion, the measured Po

2in venous blood

increases after pancuronium blockade.12 This adaptiveresponse is mediated by acute tissue hypoxia in centralnervous system neurons that initiate the discrete biophys-ical activities (Figure 23-1). Evidence of this adaptiveresponse in high-risk human fetuses is demonstrated byantenatal venous cord blood analysis. For each of the indi-vidual acute biophysical variables, the mean pH was always

706 Part 3 RISK ASSESSMENT AND THERAPY

Suppressor effect of CNSrhythm generators

CNS regulatorycenter

Suppressed orabsent signal

output

Exogenous pharmoactiveagents Tranquilizers Nicotine Alcohol Narcotics

Abnormal metabolicproducts Hydrogen ion excess (acidosis) Lactic acid accumulation Prostaglandins Interleukin II

Normal signal output

SubstrateDeficiencyHypoglycemia

Abnormal oxygen deliveryHypoxemiaAnemiaIschemia

Normal biophysicalvariable

Normal oxygen deliveryNormal metabolism

Abnormal biophysicalvariable

Abnormal

Normal

Figure 23-1. A schematic of the factors, both normal and pathologic and both intrinsic and extrinsic, that modulate dynamic fetal bio-physical activities. The observation of a normal given biophysical activity is strong presumptive evidence that the central nervous sys-tem (CNS) regulatory neurons are not hypoxic. In contrast, the failure to observe a variable necessitates a differential diagnosis.(Reproduced with permission from Manning FA, ed. Fetal Medicine: Principles and Practice. Norwalk, CT: Appleton & Lange, 1995.)


significantly higher when the activity was observed thanwhen the activity was absent (Figure 23-2).13 Further, thereappears to be a differential sensitivity between these acutevariables: The NST and fetal breathing movements wereabsent with the least decline in pH, whereas larger fallswere observed before fetal body movement and tonebecame abnormal. The animal fetus with mild to moderatesustained stable nonacidemic hypoxemia may exhibit thereturn of acute biophysical activities, albeit at a lowerfrequency.14 The physiologic basis for this partial recoveryis complex and involves such factors as increased oxygen-carrying capacity, improved oxygen extraction, resetting ofreceptor thresholds, and increased cerebral blood flow.Thus, the BPS is a reflection of tissue hypoxemia but maynot predict circulating Po

2. The statistically significant but

clinically poor correlation between the fetal BPS andantenatal venous Po

2confirms this explanation.14 It is of

clinical importance to note that progressive hypoxemia,acidemic hypoxemia (asphyxia), or both have not beenassociated with reemergence of acute biophysical variablesin either animal or human fetuses.

The fetus has a second adaptive response to hypox-emia, which is the aortic arch chemoreceptor reflex redis-tribution of cardiac output. This reflex, which probablyrequires either more severe hypoxemia or acidemia to betriggered, results in preferential shunting of blood flowaway from all nonessential organs to essential organs (theheart, brain, placenta, and adrenals).15 The measurable clin-ical effect manifest over days is oliguric oligohydramnios

and over weeks is intrauterine growth restriction (IUGR).This reflex accounts for an important principle of fetalassessment by the BPS, which is that in the presence ofintact membranes and a functional genitourinary tractoligohydramnios is near certain presumptive evidence offetal compromise. Although exceptions to this clinical dic-tum may occur, they must be exceedingly rare because ourgroup has yet to identify one in more than 160,000 tests.

The time differential between the immediate adaptiveresponse to hypoxemia, acidemia (loss of acute biophysicalvariables), or both, and the delayed reflex response (olig-uric oligohydramnios) permits an assessment of thechronicity of the insult. The differential sensitivity of theregulatory centers provides some insight into the severityof the insult. These 2 components are critical to the testingfrequency and interpretation in specific risk categories.Thus, for example, in clinical circumstances in which fetalcompromise is apt to be sudden (eg, insulin-dependentdiabetes), testing is frequent (twice weekly) with anemphasis on acute biophysical variables. In other condi-tions where fetal compromise is rapidly progressive, as, forexample, with severe alloimmune anemia, testing mayoccur very frequently (daily or twice daily), with emphasison the acute variables, and continue until treatment(intravascular transfusion) restores normal oxygen-carryingcapacity. With indolent progressive placental failure, asmay occur in the postdate pregnancy, the focus of biophys-ical scoring is to detect evidence of chronic adaptation(oligohydramnios), the superimposition of acute onchronic hypoxemia (loss of some or all acute variables), orboth. Because the rate of deterioration in these circum-stances may be rapid, the testing interval is shortened to atleast twice weekly. It is likely that, as our understanding ofthe pathophysiology of other abnormal fetal conditionsimproves, the frequency and emphasis of fetal biophysicalprofile scoring will be altered.

FETAL BIOPHYSICAL PROFILE SCORE:METHOD AND MODIFICATION

The original method of fetal biophysical profile scoring wasbased on a composite assessment of 5 variables: fetalbreathing, gross body movements, tone, heart rate acceler-ation with fetal movement (NST), and semiquantitativeamniotic fluid volume as measured by the ventricle diame-ter of the largest pocket. Each of these variables, with theexception of fetal tone, has been evaluated in separate stud-ies, and the norms and predictive accuracies deter-mined.6,16,17 Based on cumulative experience we introducedmodification of the original criteria; the definition of oligo-hydramnios was increased from a pocket of 1 cm to apocket of 2 cm,18 and the definition of fetal tone wasadvanced to include the dynamics of opening and closing ofthe fetal hand and sustained closure in the absence of activemovement.19 The contemporary criteria for interpretationof the BPS variable are given in Table 23-1. In a subsequentmodification, based on a prospective study, we excluded theresult of the NST in those fetuses in whom the otherdynamic ultrasound-monitored variables were normal.20

This modification yielded a new score category of 8/8.


NST

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Biophysical variable

AFV

Figure 23-2. The mean pH + 2 SD observed in antenatal cord blood(cordocentesis) for each of the components of the biophysical profilescore when normal (open circles) or abnormal (closed circles). A differen-tial effect is observed with the nonstress test (NST), requiring the leastperturbation in pH to become abnormal, and fetal movement requiringthe greatest. (AFV, amniotic fluid volume; FBM, fetal breathing move-ment; FM, fetal movement; FT, fetal tone.) (Reproduced with permissionfrom Manning FA, Snijders RL, Harman CR, et al: Fetal biophysical pro-file score. VI. Correlation with antepartum umbilical venous fetal pH. AmJ Obstet Gynecol 1993;165:755 Oct 169(4):755-763.)

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Additional modifications have been proposed by otherinvestigators. Phelan et al modified the determination ofamniotic fluid volume by summing the vertical diametersof the largest pocket in each uterine quadrant (amnioticfluid index [AFI]).21 Because this method appears equiva-lent in predictive accuracy to the single pocket method,22

the substantiation of the AFI for the single pocket meas-urement seems reasonable. To date, however, there are noprospective clinical trials of sufficient size to establish thevalidity of this substantiation. Vintzileos et al modified theoriginal method by introducing graduated scoring of eachof the original 5 variables and by inclusion of a sixth vari-able, placental grade.23 This modification has not beenshown to confer any clinical advantage. The value ofincluding static placental morphology to an acute assess-ment method is unclear, particularly because the clinicalvalue of placental grade is controversial.24,25

Eden et al have proposed a “modified biophysical pro-file” by which a reactive (normal) NST alone is used to con-firm the immediate well-being of the fetus, and a normalamniotic fluid index is used to exclude the absence ofchronic hypoxemia, ischemia, or both.25 This method hasclinical practicalities because the NST data can beobtained in a setting that does not require constant super-vision by a technician, the hard copy can be interpreted ata later time (ie, offline), and the time needed to determinethe amniotic fluid index daily is minimal. Further, the NSTcomponent is often done on a more frequent schedule thatamniotic fluid volume determination. The “modified bio-physical profile” has been evaluated in a well-designed,randomized, large clinical study26: the cumulative dataamong the 2774 randomized high-risk patients assessedconfirms that the predictive accuracy of a normal modifiedbiophysical profile score (reactive NST/normal AFI) is

comparable to the classic method utilizing all 5 variables(ie, both have exceedingly low false-negative rates). Theinterpretation of the abnormal modified biophysical pro-file score is more problematic. First, there is no clinical evi-dence that a modified biophysical profile composed of anonreactive NST/normal AFI is predictive of fetal compro-mise. Second, since determination of the amniotic fluidindex is a statistical continuum derived from a compositemeasurement of vertical pockets of amniotic fluid columnsand gestational age (both variables are known to have sig-nificant intrinsic measurement error) the relationship ofdegrees of abnormality to fetal hypoxemia is imprecise andinterpretive. Only when the amniotic fluid index criteriaare sufficiently reduced to meet the criteria for an abnor-mal single pocket assessment (<2 cm vertical pocket) is itlikely to be of equal (and high) predictive accuracy of fetalcompromise as the classic biophysical profile score. Thesepotential errors in interpretation of the abnormal modifiedbiophysical profile scoring method are easily resolved by aprotocol that uses the modified biophysical profile methodfor screening and the classic method for confirmation andrefinement of the significance of an abnormal modifiedbiophysical profile result. The alternate method is to useeither the classic complete biophysical profile scoringmethod or an alternate modification using the ultrasoundcomponents (fetal breathing, movement, tone, and amni-otic fluid by largest pocket), and when all are normal deferfrom using the NST, but when not all are normal incorpo-rate the NST. The predictive accuracy of this method hasbeen clearly documented.25

Other modifications, such as including acousticstimulation26 and umbilical artery flow velocity waveformassessments, although intriguing, have not been sufficientlyevaluated.


Biophysical Variable Normal (Score = 2) Abnormal (Score = 0)

FBM At least one episode of FBM of at least 30 s duration Absent FBM or no episode of >30 s in 30 min

in 30 min observation

Gross body movement At least three discrete body/limb movements in 30 min Two or fewer episodes of body/limb in 30 min

(episodes of active continuous movement considered

movements as single movement)

Fetal tone At least one episode of active extension with return to Either slow extension with return to partial

flexion of fetal limb(s) or trunk; opening and closing of flexion or movement of limb in full extension;

hand considered normal tone absent fetal movement

Reactive FHR At least two episodes of FHR acceleration of >15 beats/min Less than two episodes of acceleration

and of at least 15 s duration associated with fetal movement of FHR or acceleration of <15 beats/min

in 30 min in 30 min

Qualitative AFV At least one pocket of AF that measures at least 2 cm Either no AF pockets or a pocket

in two perpendicular planes <2 cm in two perpendicular planes

FBM, fetal breathing movement; FHR, fetal heart rate; AFV, amniotic fluid volume; AF, amniotic fluid.

BIOPHYSICAL PROFILE SCORING: TECHNIQUE AND INTERPRETATION Table 23-1


FETAL BIOPHYSICAL PROFILE SCORING:CLINICAL APPLICATION, PREDICTIVEACCURACY, AND IMPACT ON OUTCOME

Clinical Application

Fetal biophysical profile scoring is used to predict the pres-ence or absence of fetal asphyxia. Both the gestational ageat which testing is begun and the testing frequency will dif-fer depending on both the maternal and fetal risk factors.In general, testing is not begun at a gestational age beforewhich intervention for fetal reasons is contemplated. Thisage will differ across centers; in our facility, testing is notstarted before 26 weeks except in clinical circumstanceswhere fetal therapy is possible (eg, alloimmune anemia). Inmost cases, testing is not instituted until there is demon-strable clinical evidence of maternal (eg, preeclampsia) orfetal (eg, IUGR) disease. The exception is the diabetic preg-nancy: Testing is begun at 28 weeks in class 1 diabetics andat 32 weeks in gestational diabetics, even if there is noother evidence of pregnancy complications.

The distribution of BPS test results across all high-riskpregnancies studied (n = 155,000 tests) is quite remarkablein that most test results are normal (~98%), equivocalresults (BPS 6/10) are uncommon (~1.5%), most (66%)revert to normal on repeat testing, and abnormal tests(BPS ≤4/10) are decidedly rare (0.5%).27 This distributionof test results mirrors the incidence of perinatal compro-mise in the untested population, implying that the test isselecting those fetuses at risk. Given the high probability ofa normal test result even in the pregnancy considered atrisk, the false-negative rate (defined as stillbirth within aweek of a normal test result) is of critical importance. In aninitial study we observed a false-negative rate of 0.645 per

1000 among 19,221 referred high-risk pregnancies,27 andthis rate has remained at or below this value over the past10 years in 82,000 patients).

Management has been based on the BPS result asinterpreted within the overall clinical context includinggestational age, maternal condition, and obstetric factors.The management criteria based on BPS results are given inTable 23-2. The gestational age at which intervention willoccur varies by BPS result (Figure 23-3).

Perinatal Outcome: Mortality and Morbidity

The relation between the last BPS result and perinatalmortality has been confirmed in several large studiesinvolving 3000 or more high-risk patients.27–31 All of thesestudies have demonstrated a significant increase in grossand corrected perinatal death among fetuses with anabnormal (low) score. In our studies a highly significantinverse exponential correlation between the last test scoreand perinatal mortality was observed.32 There have beenno randomized controlled trials contrasting perinatal mor-tality between patients managed by BPS results andpatients who were not subjected to any antepartum test-ing; however, comparison of observed perinatal mortalitybetween tested patients and concurrent untested (histori-cal) controls has yielded encouraging results. Chamberlainreported a corrected perinatal mortality of 4.16 among3202 tested high-risk pregnancies as compared with a rateof 10.7 among 5814 untested historical controls (netdecrease 61%).30 Our group observed a corrected perinatalmortality of 1.86 per 1000 among tested and managed55,661 high-risk pregnancies as compared with a rate of7.69 per 1000 in 104,337 untested historical controls (netdecrease 76%): these differences were highly significant.31


PNM1 Within 1 wk Test Score Result Interpretation Without Intervention Management

10 of 10 Risk of fetal asphyxia extremely rare 1 per 1000 Intervention only for obstetric and

8 of 10 (normal fluid), maternal factors; no indication for

8 of 8 (NST not done) intervention for fetal disease

8 of 10 (abnormal fluid) Probable chronic fetal compromise 89 per 10001 Determine that there is functioning

renal tissue and intact membranes;

if so, deliver for fetal indications

6 of 10 (normal fluid) Equivocal test, possible fetal asphyxia Variable If the fetus is mature, deliver; in the

immature fetus, repeat test within

24 h; if <6/10, deliver

6 of 10 (abnormal fluid) Probable fetal asphyxia 89 per 100011 Deliver for fetal indications

4 of 10 High probability of fetal asphyxia 91 per 10001 Deliver for fetal indications

2 of 10 Fetal asphyxia almost certain 125 per 10001 Deliver for fetal indications

0 of 10 Fetal asphyxia certain 600 per 10001 Deliver for fetal indications

1PNM, perinatal mortality; NST, nonstress test.

INTERPRETATION OF FETAL BIOPHYSICAL PROFILE SCORE RESULTS AND RECOMMENDED CLINICAL MANAGEMENTTable 23-2


The relation between last BPS result and perinatal mor-bidity has been studied extensively by our group and oth-ers.28,29,32 Unlike perinatal mortality the incidence of immediateperinatal morbidity, as reflected by fetal distress in labor (withor without lower-segment cesarean section), low Apgar score(≤7 at 5 minutes), cord vein acidosis (≤7.20), and admission toan intensive care unit for reasons other than immaturity alone,showed a direct inverse relation to the last BPS. These differ-ences are predicted because mortality must reflect a failure ofcompensation (hence, the exponential curve), whereas imme-diate morbidity (a linear curve) is a reflection of either compen-sation per se (eg, low Apgar) or failure of compensation withadded stress (fetal distress in labor). A highly significant inverselinear correlation between cumulative (any) immediate mor-bidity and the last BPS is observed (Figure 23-4). It is of interestto note that no correlation between meconium staining ofamniotic fluid and the last BPS result is observed.

BIOPHYSICAL PROFILE SCORE AND FETALCORD BLOOD ACID–BASE AND pH VALUES

The relation between the BPS result and fetal blood gas andpH has been studied in several clinical settings. A highly sig-nificant direct linear correlation between the BPS result andcord blood obtained at delivery has been reported.32

Vintzileos et al compared cord blood gas and pH values withthe BPS result in samples collected at cesarean section beforethe onset of labor in 124 cases and reported a highly signifi-cant direct linear correlation with both arterial and venouspH.33 The mean pH in 102 fetuses with a last normal score(Vintzileos method) was 7.28, and 2 (1.9%) were mildly

acidotic; in 13 fetuses with an equivocal BPS, the mean pHwas 7.19, and 9 (69%) were acidotic; and in 9 fetuses with anabnormal score, the mean pH was 6.99 and all (100%) wereacidotic.33 Our group studied 557 fetuses delivered by electivecesarean section and noted a similar relation.27 Extrapolationof cord blood obtained26 at delivery is less precise, tending tosignificantly underestimate antenatal values.34 The adventof ultrasound-guided cordocentesis now permits direct com-parison of immediate BPS results and antenatal venous pH.At the time of this writing there are at least 4 reported studiesof this comparison. Ribbert et al compared BPS and venousblood gas and pH values in 14 severely nonanomalous IUGRfetuses15: A highly significant direct correlation between BPSand venous pH (SD below normal) was reported, but no rela-tion between BPS and Po

2, Pco

2, oxygen saturation, or content

was identified. Manning et al reported comparative results in493 structurally normal fetuses, of which 104 were severelygrowth retarded and 393 had alloimmune anemia.13 A highlysignificant linear correlation between BPS and mean pH wasobserved (Figure 23–5). The mean pH with a normal scorewas 7.37 ± + 0.06 (±2 SD), and the lowest observed pH was7.26. In contrast, with a very abnormal score (BPS = 0), themean pH was 7.07 ± 0.15 and ranged from 7.17 to 6.86. Thedistribution of abnormal results defined as a pH below an


220

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24 26 28 30 32

Gestational age

BPS 0/10

BPS 2/10

BPS 4/10BPS 6/10

36 38 4034

Figure 23-3. A schematic of the interaction of gestational age, the pre-dictor of neonatal death, and the biophysical profile score (BPS), the pre-dictor of fetal death, in the management of the high-risk fetus. Timing ofintervention depends on these relative risks. The fetal mortality predic-tion by BPS should be uniform and accurate across centers, but theneonatal survival curves may differ by center. (Reproduced with permis-sion from Manning FA, Harman CR, Morrison I, et al. Am J ObstetGynecol 1990;162:703.)

100

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GAR

≤ 7

pH ≤ 7.2040

% 50

60

70

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6 4 2

Normal Equivocal Abnormal Very abnormal

Last BPS before delivery

0

Figure 23-4. The relation between the incidence (percentage of occur-rence) of indices of perinatal morbidity and the last fetal biophysical pro-file score (BPS). Note the inverse linear correlation. (FD, fetal distress;LSCS, lower-segment cesarean section.) (Reproduced with permissionfrom Manning FA, ed. Fetal Medicine: Principles and Practice. Norwalk,CT: Appleton & Lange, 1995.)


arbitrary threshold differed by the selected threshold andassumed a curvilinear distribution at a pH cutoff of 7.20.Serial sampling in some patients confirmed that the BPSresult mirrored the change in fetal venous pH. Salversen et alcompared the BPS and antenatal cord pH in 41 diabetic preg-nancies.35 A significant correlation between BPS and pH wasreported. In this study 1 fetus had a normal score and avenous pH of 7.228. Because, by comparison with establishednormal pH distribution for gestational age, the mean pHamong these diabetics was significantly reduced, interpreta-tion of the relation of BPS to pH in these diabetics is difficult.A fourth study by Okamura et al of 150 fetuses, including 79anomalous fetuses, failed to demonstrate any correlationbetween the BPS (Vintzileos method) and antenatal venouspH.36 Because values for structurally normal fetuses are notgiven in this study, direct comparison with studies havingconflicting results is difficult.

FETAL BIOPHYSICAL PROFILE SCORING:OUTCOME IN SELECTED HIGH-RISK SUBGROUPS

As the experience with the fetal biophysical profile scoringmethod has accumulated, it has become possible to assessits impact, if any, on perinatal outcome in relatively largenumbers of patients in specific high-risk subgroups.

The adjunctive value of BPS in the management of thepostdate pregnancy has been studied by several groups. It isimportant to stress that in these studies BPS testing isreserved for those patients in whom the cervix is unfavorable

for induction or unresponsive to attempts at cervical ripen-ing by local prostaglandin. In an initial study, Johnson et alused BPS to guide management in 243 postdate patients withan unfavorable cervix.37 These patients were tested twiceweekly, and intervention was delayed until either the cervixbecame favorable or the score became equivocal or abnor-mal (13.2% of cases). There were no perinatal deaths in thisseries. The incidence of cesarean section was 17.7%, of which5.3% were performed for fetal distress. In contrast, in a con-trol group of 50 patients induced electively at 42 weeksregardless of cervical findings, although there were no fetaldeaths, the overall cesarean section rate was 42%, of which14% were for fetal distress. There were no significant differ-ences in perinatal morbidity between the conservative (BPS)and actively managed patients; however, in patients with anabnormal BPS (32 of 243 fetuses) perinatal morbidity wassignificantly increased. Our experience with selected post-date pregnancies managed conservatively by BPS exceeds1400 cases, yielding a perinatal mortality of 0.7 per 1000.

Outcome among diabetic pregnancies managed by serialBPS testing has been reported by our group and others.Johnson et al studied 235 diabetics (50 class 1) and reportedan intervention rate of 3.3% for an abnormal BPS and no peri-natal deaths.38 Dicker et al studied 98 insulin-dependent dia-betics, with no perinatal deaths: the intervention rate for anabnormal BPS result was 2.9%.39 Manning et al reportedoutcomes in 1153 diabetics (252 class 1) and observed anintervention rate for abnormal BPS of 3.1% and a correctedperinatal mortality rate of 1.73 per 1000.28 In our extendedexperience, we have used BPS in the management of 4973diabetics (1087 class 1). The intervention rate for an abnormalBPS was 3.2%, the corrected stillbirth rate was 1.2 per 1000,and the corrected perinatal mortality was 2.01 per 1000.27

The use of BPS in the management of the IUGR fetushas reduced perinatal mortality, but the relative rate remainshigh.27 In our experience of 2218 IUGR fetuses (below thethird percentile for age and sex) we have observed a grossperinatal mortality of 31 per 1000 (versus 6.69 per 1000 in53,443 appropriate for gestational age [AGA] tested controls)and a corrected perinatal mortality of 7.42 per 1000 versus1.86 per 1000 in AGA tested controls. Although high, theperinatal mortality results observed in test IUGR fetusescompares favorably with 1765 untested historical IUGR con-trols in whom the gross perinatal mortality was 56 per 1000and the corrected perinatal mortality was 37 per 1000.27

Recently, we reported outcomes in 731 structurally normalIUGR fetuses delivered at or beyond 34 weeks; there were noperinatal deaths among these mature IUGR fetuses.40

Biophysical profile scoring plays a valuable clinicalrole in the management of the alloimmune anemic fetus.In these fetuses, the assessment of fetal condition by BPS isused as a secondary adjunct to determine the timing andurgency of fetal transfusion, both initial and subsequent.There is a highly significant relation between diseaseseverity, as assessed by ultrasound pathomorphology or byfetal blood indices, and the BPS result.41 Specific determi-nation of the positive contribution of BPS for such patientsis difficult to ascertain because fetal treatment by transfu-sion yields such excellent results.42 The observation of adeteriorating BPS despite fetal intravascular transfusionhas been lifesaving in some cases, prompting repeat invasive


10

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um

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enou

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7.30

7.35

7.40

8 6 4

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2 0

∗

∗

∗

∗

Figure 23-5. The relation between mean umbilical vein pH (±2 SD) andthe fetal biophysical profile score. The correlation is direct, linear, and highlysignificant (R2 0.912; P < .01). The asterisks denote a pH value significantlyless than the immediate. (Reproduced with permission from Manning FA,Snijders RL, Harman CR, et al: Fetal biophysical profile score. VI. Correlationwith antepartum umbilical venous fetal pH. Am J Obstet Gynecol 1993;165:755 Oct 169(4):755-763.)

Fleischer_Ch23.qxd 8/23/10 8:31 PM 11

testing (cordocentesis) and repeat transfusion for unrecog-nized bleeding from the puncture site.

The role of BPS testing in other high-risk subgroups,such as the hypertensive patient, the patient reportingdecreased fetal movement, and the anomalous fetus, hasyet to be systematically analyzed; however, given the lowcorrected perinatal mortality rate in the high-risk group atlarge (1.86 per 1000), such analysis holds promise.

BIOPHYSICAL PROFILE SCORE: RELATION TONEUROLOGIC CONDITIONS OF CHILDHOOD

The association of the fetal BPS to childhood diseasesknown or suspected to be a consequence of perinatalasphyxia or infection has been an area of active research.Because the BPS is an accurate proxy for the presence andextent of fetal academia, and because intervention for fetalindication is based on the BPS results, it follows that somerelation between the fetal condition, as reflected by theBPS, and postnatal outcome may exist. Recently, we exam-ined these relations for 4 childhood diseases, namely cere-bral palsy, attention deficit disorders, cortical blindness,and mental retardation.43 Among 19,660 high-risk patientssubjected to serial testing by BPS and managed according tothe last BPS result, there was a highly significant inverseexponential relation between last test score and incidenceof each of these conditions. In contrasting the prevalence ofthese disorders between the 19,660 tested high-risk fetusesand 63,540 contemporaneous nontested control patients,we noted a highly significant lowering of disease prevalencefor each end point in the tested population. Interestingly,for conditions not suspected to be associated with fetalasphyxia (eg, emotional disorders of childhood, brachialplexus injury), we noted no relation between prevalenceand last BPS result, and the incidence of these disorders didnot differ significantly between tested and nontested popu-lations. These data imply that intervention for the abnor-mal BPS result not only can reduce perinatal mortality andimmediate neonatal morbidity, but also may prevent someof the devastating asphyxia-related diseases of childhood.

EMERGING CONCEPTS

Detecting fetal asphyxia and appropriately intervening cer-tainly can reduce perinatal mortality. The benefits may extendbeyond better immediate perinatal outcome and mightinclude either preventing or ameliorating conditions such asspastic quadriplegia (cerebral palsy) and mental retardation.

CLINICAL CORRELATE

A 19-year-old primigravid patient presents at 28 weekswith a history of antepartum bleeding (now subsided) anda 2-day history of decreased fetal movement. Fetal ultra-sound reveals a normal anatomy scan, estimated fetalweight of 2150 g, and a biophysical score of 2/10 (absentfetal breathing, movement, tone, and a nonreactive NST—amniotic fluid is normal). A repeat biophysical profilescore done 1 hour later reveals the same 2/10 score.

What are the key management variables in this caseand what is the recommended management?

Answer

1. The options are intervention (delivery) versus con-tinued observation. At 31 weeks, delivery is associ-ated with a significant risk of prematurity-relatedmorbidities.

2. The probability of a false-positive abnormal bio-physical profile score is directly related to the score.Repeating the test immediately can reduce thefalse-positive rate to almost zero.

3. The risk of fetal death and serious perinatal mor-bidity with a persistent fetal biophysical profilescore of 2/10 is greater than the risks associatedwith premature delivery

4. The risk of serious maternal morbidity withcesarean section is greater than the risk with vagi-nal delivery.

5. Delivery is the appropriate management in thiscase. The mode of delivery is determined by obstet-ric factors (eg, cervical findings) and, if labor induc-tion is the delivery method selected, by continuousmonitoring of fetal tolerance to labor.


1. Fetal in utero adaptation to acute or chronic hypoxemiaproduces manifest fetal signs that can be detected byreal-time ultrasound.

2. Amniotic fluid volume can be assessed by either a sin-gle largest pocket method or a combined measure-ment of largest pocket in 4 quadrants (amniotic fluidindex). The methods are at least comparable, and thesingle pocket method is likely more predictive of fetalcompromise.

3. A normal modified biophysical profile result has thesame exceedingly low false-negative rate as the classicbiophysical profile score.

4. An abnormal modified biophysical profile score requires further fetal evaluation, which is most effectively achieved by obtaining a classic fetal biophysical profile score.

5. Clinical management based on the fetal biophysicalprofile score can reduce perinatal mortality and short-term morbidity, and likely also reduce long-term morbidity.

6. It is imperative to interpret any and all fetal biophysicalprofile score results within the clinical context of eachcase (ie, treat the patient not the test).

KKEEYY PPOOIINNTTSS

REFERENCES1. Hon EH. The electronic evaluation of the fetal heart rate. Am J

Obstet Gynecol 1980;75:1215.2. Caldero-Barcia R, Poseiro JJ, Pantle G, et al. Effects of uterine contrac-

tion on the heart rate of the human fetus. Proceedings of the FourthInternational Conference on Medical Electronics. New York, 1961.


3. Dawes GS, Fox HE, Leduc BM, et al. Respiratory movements andparadoxical sleep in foetal lambs. J Physiol (Lond) 1970;210:77.

4. Merlet C, Hoertner J, Devilleneuve C, et al. Mise en evidence demovements respiratories chez la foetus d’argeau in utero au cours dudernier mois de la gestation. Can R Acad Sci 1970;270:2462.

5. Boddy K, Dawes GS, Fisher R, et al. Foetal respiratory movements,electrocortical and cardiovascular responses to hypoxemia andhypercapnia in sheep. J Physiol (Lond) 1974;243:599.

6. Platt LD, Manning FA, LeMay M. Human fetal breathing: relation-ship to fetal condition. Am J Obstet Gynecol 1978;132:514.

7. Manning FA, Platt LD. Fetal breathing movements and the abnor-mal contraction stress test. Am J Obstet Gynecol 1979;133:590.

8. Manning FA, Platt LD, Sipos L, et al. Fetal breathing movements andthe non-stress test in high risk pregnancies. Am J Obstet Gynecol1979;135:511.

9. Manning FA, Platt LD, Sipos L. Fetal movements in human preg-nancy in the third trimester. Obstet Gynecol 1979;54:699.

10. Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: devel-opment of a fetal biophysical profile score. Am J Obstet Gynecol1980;136:787.

11. Rurak DW, Gruber NC. Effect of neuromuscular blockade on oxy-gen consumption and blood gases. Am J Obstet Gynecol1983;145:258.

12. Harman CR, Manning FA. Unpublished observations, 1994.13. Manning FA, Snijders RL, Harman CR, et al. Fetal biophysical pro-

file score. VI: Correlation with antepartum umbilical venous pH.Am J Obstet Gynecol 1993;165:755.

14. Bocking AD, Gagnon R, Milne KM, et al. Behavioural activity duringprolonged hypoxemia in fetal sheep. J Appl Physiol 1988;65:2420.

15. Ribbert LSM, Snijders RJM, Nicolaides KH, et al. Relationship offetal biophysical profile score and blood gas values at cordocentesisin severely growth-retarded fetuses. Am J Obstet Gynecol1990;163:569.

16. Cohn HE, Sacks GT, Heyman M, et al. Cardiovascular responses tohypoxemia and acidemia in fetal lambs. Am J Obstet Gynecol1974;120:817.

17. Manning FA, Hill LM, Platt LD. Qualitative amniotic fluid volumedetermination by ultrasound: antepartum detection of intrauterinegrowth retardation. Am J Obstet Gynecol 1981;139:254.

18. Chamberlain PF, Manning FA, Morrison I, et al. Ultrasound evalua-tion of amniotic fluid volume. I: Relationship of marginal anddecreased amniotic fluid to perinatal outcome. Am J Obstet Gynecol1984;150:245.

19. Manning FA, Baskett TF, Morrison I, et al. Fetal biophysical profilescoring: a prospective study in 1184 high risk patients. Am J ObstetGynecol 1981;140:289.

20. Manning FA, Morrison I, Lange IR, et al. Fetal biophysical profilescoring: selective use of the non-stress test. Am J Obstet Gynecol1987;156:709.

21. Phelan JP, Ahn MO, Smith CV, et al. Amniotic fluid index measure-ments during pregnancy. J Reprod Med 1987;32:601.

22. Moore TR. Superiority of the four quadrant sum over the single-deepest-pocket technique in ultrasound identification of abnormalamniotic fluid volume. Am J Obstet Gynecol 1990;163:762.

23. Vintzileos AM, Campbell WA, Ingardia CT, et al. The fetal biophys-ical profile score and its predictive value. Obstet Gynecol1983;62:271.

24. Manning FA, Hohler C. Intrauterine growth retardation: diagnosis,prognostication, and management based on ultrasound methods. In:Fleischer AC, Romero R, Manning FA, et al, eds. The Principles andPractice of Ultrasonography in Obstetrics and Gynecology, 4th ed.Norwalk, CT: Appleton & Lange, 1991:331–47.

25. Eden RD, Gargely RZ, Schifrin BS, et al. Comparison of antepartumtesting methods for the management of the postdate pregnancy. AmJ Obstet Gynecol 1982;144:683.

26. Nageotte MP, Towers CV, Asrat T, Freeman RK. Perinatal outcomewith the modified biophysical profile. Am J Obstet Gynecol1994;170:1672-6.

27. Manning FA, ed. Fetal Medicine: Principles and Practice. Norwalk,CT: Appleton & Lange, 1995.

28. Manning FA, Morrison I, Harman CR, et al. Fetal assessment basedon fetal biophysical profile scoring: experience in 19,221 referredhigh risk pregnancies. II: An analysis of false negative fetal death.Am J Obstet Gynecol 1987;157:880.

29. Baskett TF, Allen AC, Gray JH, et al. Fetal biophysical profile andperinatal death. Obstet Gynecol 1987;70:357.

30. Chamberlain PF. Late fetal death—has ultrasound a role to play in itsprevention? Irish J Med Sci 1991;160:251.

31. Manning FA, Harman CR, Morrison I, et al. Fetal assessment basedon fetal biophysical profile scoring. IV: Positive predictive accuracyof the abnormal test. Am J Obstet Gynecol 1990;162:703.

32. Vintzileos AM, Fleming AD, Sconza WE, et al. Relationship betweenfetal biophysical activities and cord blood gas values. Am J ObstetGynecol 1991;165:707.

33. Vintzileos AM, Campbell WA, Rodis JF, et al. The relationshipbetween fetal biophysical profile score and cord pH in patientsundergoing elective cesarean section before the onset of labour.Obstet Gynecol 1987;70:196.

34. Khoury AD, Morehi ML, Barton JR, et al. Fetal blood sampling inpatients undergoing elective cesarean section: a correlation withcord blood gases obtained at delivery. Am J Obstet Gynecol1991;165:1026.

35. Salversen DR, Freeman J, Brudenell JM, et al. Prediction of foetal aci-daemia in pregnancies complicated by maternal diabetes mellitus bybiophysical profile scoring and fetal heart rate monitoring. Br JObstet Gynecol 1993;100:227.

36. Okamura K, Watanabe T, Endo H, et al. Biophysical profile and itsrelationship to fetal blood gases obtained by cordocentesis. ActaObstet Gynaecol Jpn 1991;43:1573.

37. Johnson JM, Harman CR, Lange IR, et al. Biophysical profile scoringin the management of the postdates pregnancy: an analysis of 307patients. Am J Obstet Gynecol 1986;154:269.

38. Johnson JM, Lange IR, Harman CR, et al. Biophysical profile scoringin the management of the diabetic pregnancy. Obstet Gynecol1988;72:841.

39. Dicker D, Feldberg D, Yeshaya A, et al. Fetal surveillance in insulindependent diabetics: predictive value of the fetal biophysical profilescore. Am J Obstet Gynecol 1988;159:800.

40. Morrison I, Manning FA, Harman CR, et al. Unpublished observa-tions, 1995.

41. Harman CR. Ultrasound in the management of the alloimmunizedpregnancy. In: Fleischer AC, Romero R, Manning FA, et al, eds. ThePrinciples and Practice of Ultrasonography in Obstetrics andGynecology, 4th ed. Norwalk, CT: Appleton & Lange, 1991:393–416.

42. Harman CR, Bowman JM, Manning FA, et al. Intrauterine transfu-sion: intraperitoneal versus intravascular approach: a case-controlcomparison. Am J Obstet Gynecol 1990;162:1053.

43. Manning FA. Fetal assessment: 1999 update. Clin Obstet Gynecol2000;26:557.

Highlighted Reference

1. Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation:development of a fetal biophysical profile score. Am J ObstetGynecol 1980;136:787.This is the original article describing the concept of a multiple vari-able assessment and the origination of the fetal biophysical profilescore.



fleischer

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