Fetal BiophysicalProfile:A CriticalAppraisalFRANK A. MANNING, MDDepartment of Obstetrics, Gynecology and Women’s Health, AlbertEinstein College of Medicine, Bronx, New York

The fetal biophysical profile score is anultrasound-based method that is used toevaluate the probability of a given fetus hav-ing or not having sufficient delivery of oxy-gen to select primary and secondary targetorgans, including the fetal brain, kidney, andto a lesser extent lung, so as to maintain nor-mal function. The testing method assumesthat the biophysical outputs of select organsystems, be they acute or chronic, reflect thefunctional integrity of that system, and con-versely that the absence of the select outputvariable be considered as evidence of dys-function until proven otherwise. Underlyingthis operating principle is the concept thattissue hypoxia, of whatever diverse origin,will result in suppression or loss of normalfunction. The physiological basis to supportthis testing concept is well defined in experi-mental models. In the fetal lamb, hypox-emia, induced by maternal hypoxia, placen-tal ischemia, or both, produces profound andreproducible changes in organ system func-tion.1 There are at least two functional path-ways that mediate these responses (Fig. 1).

The first pathway is a direct one: that is,cell function alters in the presence of dimin-ished oxygen delivery. This effect is ex-pressed most dramatically in neuronal tis-sue, and in particular in the collection ofneurons that form the regulatory centerscontrolling biophysical activities. In theseregulatory centers tissue hypoxia that fallsbelow a functional threshold results in animmediate and complete cessation of thebiophysical activity regulated by that spe-cific center. The evaluation of the acute bio-physical output of these discrete centers pro-vides three critical and unique interpreta-tions regarding immediate fetal condition.

Firstly, the observation of a normal vari-able, both in frequency and pattern, is the ex-pression of the regulatory center output, andimplies that the center is functional andtherefore not subject to immediate tissuehypoxemia. This becomes an important piv-otal point in the use of antepartum testing,setting the principle that a normal variableimplies absence of threshold acidemia atthat instance in time. As always there are ex-ceptions, and this is certainly true in regardsto acute biophysical variables in the pres-ence of extreme and near-lethal degrees of

Correspondence: Frank A. Manning, MD, 5 RutlandRoad, Scarsdale, NY 10583.E-mail: fmanningob@aol.com

PROD. # GRF20407

CLINICAL OBSTETRICS AND GYNECOLOGYVolume 45, Number 4, 975–985© 2002, Lippincott Williams & Wilkins, Inc.

CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 45 / NUMBER 4 / DECEMBER 2002

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hypoxemia and acidemia (asphyxia). In fetallife, as in extrauterine life, deregulation oraberrant output from regulatory centers canresult in the presence of an abnormal type ofbiophysical activity. The extrauterine ex-amples are well-known: Cheyne-Stokesbreathing, generalized seizures, and athetoidrigidity. In the fetus extreme deregulationresults in abnormal breathing movements,manifest as monotonous “picket-fence”breathing, continuous breathing, and gasp-ing,2–4 and abnormal muscle movements,manifest as intrauterine seizures.5 There-fore, the occurrence of a variable per se can-not be taken as certain evidence of tissuenormoxia, but rather it is the presence of thevariable in its normal state. Further, it is im-portant to recognize that regulatory centerscan adapt to degrees of central hypoxemia.6

This adaptation involves several mecha-nisms designed to increase tissue oxygen de-

livery and include increased oxygen-carrying capacity, improved oxygen releasebinding and release, and increased bloodflow to the tissues.7 Thus, the observation ofacute normal variable, while always a reli-able indication of normal tissue oxygen-ation, may not be as reliable an indicator ofnormal central PO2. It follows that the ob-servation of a normal acute biophysical vari-able offers little if any insight into the re-serve of the given fetus.

Secondly, regulatory center tissue hypox-emia will invariably abolish its biophysicalvariable. For example, fetal breathing move-ments, a normal biophysical event in fetallife and arising from signals generated bythe respiratory center located in the region ofthe low midbrain, cease abruptly when thetissue P02 falls by about 8 to 10 torr.8 Thus,it may be said with certainty that a fetus withtissue hypoxemia will never exhibit normal

FIG. 1. Fetal biophysical effect of hypoxemia on the fetus. Conditions inparentheses refer to neonatal sequels of fetal asphyxia. CNS = central ner-vous system, IUGR = intrauterine growth retardation, IVH = intraventricularhemorrhage, RDS = respiratory distress syndrome. (From Manning FA. Fe-tal biophysical profile scoring. In: Fetal Medicine, Principles and Practice.Norwalk, CT: Appleton Lange, 1995, with permission.)

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breathing movements, and hence the axiom“normal variables, normal oxygen.” How-ever, the control of the central nervous sys-tem (CNS) regulatory centers is in itselfcomplex, and it is certain that factors otherthan hypoxemia not only can abolish an ac-tivity but in fact are the most likely explana-tion for variable absence. The regulatorycenters are bombarded with signals arisingfrom a variety of sources both within andoutside the brain, and these signals modulatethe output of the regulatory center. Suppres-sive signals from the reticular activatingcenter and other higher CNS centers associ-ated with sleep–wake cycles and in particu-lar quiet sleep are by far the most commoncause of absence of a given variable in a de-fined time interval. From this observationflows two important corollaries: the clinicalsignificance of an absent biophysical vari-able is a direct function of the duration ofobservation, and that to define a variable asabnormally absent, the observation periodmust at a minimum exceed the normal dura-tion proportionate to the average period of agiven sleep state (about 20 minutes) and ide-ally should be at least half again as long (30minutes).

Thirdly, it is evident that the functionalthreshold of regulatory neurons is not uni-form but rather varies between individualcenters.9 This variation may be a result ofvariation in intracellular neuronal metabo-lism and therefore oxygen demand, the re-sult of adaptation of blood flow to increasetotal oxygen delivery, or both. In any event,the stepwise variation in regulatory centerhypoxemia threshold provides an importantclinical insight to the presence and severityof the hypoxia. It is this threshold sensitivityof acute biophysical variables that providesthe unique discriminatory power and reli-ability of the fetal biophysical profile scoremethod.

The reflex redistribution of cardiac out-put in response to central hypoxemia/aca-demia is critical to fetal survival. This reflexis mediated by aortic arch and carotid arterychemoreceptors responding primarily to

hypoxemia.2 These chemoreceptors have anextraordinarily high metabolic rate and toremain stable and silent require constantperfusion with the highest oxygenated bloodin the fetal circulation (hence their location).In the presence of central hypoxemia and inparticular with central acidemia and tissueacidity, these receptors begin to dischargeand send afferent traffic via the vagal nerveto the cardioregulatory center. The efferenttraffic from this center in conjunction with arise in circulating catecholamines results inincreased blood pressure, pulse rate, andcardiac output in the presence of selectiveorgan vasoconstriction. As a result bloodflow to the heart, brain, thymus, and pla-centa increases, whereas blood flow to al-most all other organs declines, often to a pre-cipitous degree. Reflex vasoconstrictiveischemia is manifest by abnormal organfunction and in particular by abnormal pro-duction. From a fetal testing perspective thecritical organs in this sequence are the kid-neys and the lungs, the principal sources ofamniotic fluid. Fetal urine production fallsin the presence of hypoxemia/acidemia, andat near-lethal degrees of asphyxia urine pro-duction ceases.10,11 In contrast, swallowing,the mechanism for elimination of amnioticfluid, is initiated and controlled by a rela-tively hypoxemia-resistant hindbrain regu-latory center. Fetal swallowing is a com-monly observed even among severely as-phyxiated fetuses and newborns,12 and thecoincidence of diminished fetal urine (amni-otic fluid) production and normal elimina-tion invariably results in a decline in amni-otic fluid volume. The rate of decline of am-niotic fluid volume is regulated primarily bythe decline in fetal urine production, andeven with intense vasoconstriction of the re-nal vessels some urine production persists. Itis therefore exceedingly uncommon to seean acute decline in amniotic fluid volume inthe presence of hypoxemia, although thishas been reported.13 The average time for afetus to progress from normal to barely ab-normal fluid is about 15 days; the averagetime to reach severe oligohydramnios is about

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23 days.10 Whereas amniotic fluid volumemay be the most obvious fetal sign of chronichypoxemia/acidemia, it is not the only one.Diminished and disproportionate fetal growthis a classic finding with chronic hypox-emia/acidemia, and indeed most of the new-born signs of birth asphyxia can be traced backto the reflex redistribution of blood flow.

Fetal biophysical profile scoring differsfrom all other antepartum fetal testing mo-dalities in that it combines measures of theacute biophysical variables, fetal breathing,heart rate accelerations, gross body move-ments, and fetal tone (variables that reflectthe immediate fetal condition) with amnioticfluid volume (a variable that reflects thechronic fetal condition). In a sense, then,were one able to converse with the fetus, thequestion put by the fetal biophysical profilescore would be: How are you now, and howhave you been in the past 1 to 2 weeks? Itwould appear from the data provided by thebiophysical variables sampled that thisquestion can be answered with considerableaccuracy.

What Does the FetalBiophysical Profile ScoreMeasure Directly?The fetal biophysical profile score, whennormal (�8/10), is a direct, reliable, and ex-ceedingly accurate measure of normal tissueoxygenation and, by inference, absent cen-tral acidemia. When abnormal (6/10 or less),the fetal biophysical profile score is a mea-sure of the probability of tissue hypoxia andcentral acidemia and secondarily a measureof the likely degree or severity of existingcentral hypoxemia/acidemia (asphyxia). In-terestingly, whereas the relationship be-tween individual acute biophysical variablesand changes in P02 and pH are well definedin animal models,3,6,8 the relationship be-tween composite variables (ie, the total bio-physical profile score) is not reported in ani-mal experiments but is clearly defined in thehuman. In the human the correlation be-

tween the fetal biophysical profile score andfetal pH can be defined with precision usingcordocentesis data. In these observations theinterval between measurement of the fetalbiophysical profile score and measurementof antepartum fetal pH (usually venous) isusually very short, often only a few minutes.To date, 698 paired observations of a fetalbiophysical profile score and antenatalblood gas/pH have been reported,9,14–17 andthere are at least 600 more pairings that havebeen compiled but not yet reported in detail.This database of almost 1,300 paired obser-vations confirms with uniformity that a nor-mal profile score is never associated with anabnormal fetal pH. Conversely, there is lessconformity regarding the predictive accu-racy of the abnormal profile score. How-ever, the largest such series, involving some493 paired observations, suggests that thiscorrelation is relatively precise9 (Fig. 2).These relationships persist when the intervalbetween testing and cord blood analysis in-creases and may persist even with immedi-ate postnatal cord blood,18 although both ac-curacy and reliability are diminished.

What Does the FetalBiophysical Profile ScoreMeasure Indirectly?

RISK OF PERINATAL DEATHAt least until recently, the primary reason forand purpose of antepartum fetal testing wasto identify that fetus at risk for death in uteroand effect delivery by the safest and mostexpeditious route and in so doing avert thetragic outcome. Clinical analysis of stillborninfants and of pregnancies ending in still-birth indicate that at least 70% of these still-born fetuses have evidence of intrauterinegrowth retardation (IUGR)19 and that 90%or more have clinical signs of either chronicor acute on chronic compromise.20 Theseobservations imply that in many and indeedmost instances there will be signs of im-pending trouble and that these signs will be

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manifest long before stillbirth occurs. Thefetal biophysical profile score result allowsfor fetuses to be classified as either havingnormal blood gases and pH (normal acutevariables, normal amniotic fluid), normalblood gases and pH secondary to compensa-tion for hypoxemia (normal acute variable,abnormal amniotic fluid volume), or abnor-mal blood gases and pH of either an acute(abnormal acute variables, normal amnioticfluid volume) or chronic (abnormal acutevariables, decreased amniotic fluid volume)duration. Since asphyxia is the commonmechanism for stillbirth, detection of thepresence, severity, and duration of asphyxia,a product of fetal biophysical profile scoretesting, should by inference result in a de-crease in the frequency of stillbirth. As peri-natal asphyxia is also a contributor to neona-tal death, both immediate and remote, it fol-lows that antenatal recognition of perinatalasphyxia and delivery before extremis couldreduce the neonatal death rate. The cumula-tive data indeed support the conclusion thatmanagement based on fetal biophysical pro-file scoring has a major and highly signifi-cant impact on the stillbirth rate and a lessdramatic but nonetheless apparent effect onneonatal death rates, and collectively pro-duces a significant reduction in the perinatalmortality rate within a tested popula-tion5,21,22 (Table 1). There are no prospec-tive blinded clinical studies to determine ifmanagement according to the fetal biophysi-cal profile score will reduce perinatal mor-

FIG. 2. Mean umbilical vein pH (±2 SD) val-ues in fetal blood obtained by cordocentesis ob-served for each possible fetal biophysical profile(BPP) score. The mean pH did not vary betweenscores of 10/10 and 8/10 and way always normal.A progressive and highly significant direct linearrelationship was observed between abnormalBPP scores (BPP � 6/10) and umbilical vein pH(R2 = 0.912, p < .01). Asterisks denote a signifi-cantly lower mean pH compared with value re-corded for the immediately higher BPP score(student’s t-test, p <.1) (From Manning FA, Sni-jders RJM, Harman CR. Fetal biophysical pro-file scoring. VI. Correlation with antepartumumbilical venous pH. Am J Obstet Gynecol.1993;169:755, with permission.)

TABLE 1. Perinatal Mortality and BPS: Manitoba Experience, 1979–1989

Variable Tested High Risk Nontested % Change

No. fetuses 55,661 104,337 —Mean age at test 33.8 weeks — —PNM (gross) 6.71 9.87 ↓32PNM (corrected) 1.86 7.69 ↓76SB (gross) 3.31 5.20 ↓36SB (corrected) 1.23 4.57 ↓73NND (gross) 3.40 4.67 ↓27NND (corrected) 0.63 3.08 ↓80

From reference 5.

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tality, and any such beneficial effect must bedrawn from comparison with nontested butnot randomly selected low-risk controls orwith historical controls. Recognizing that ei-ther comparison introduces error that mightnot occur in a randomized trial, nonethelesssuch comparisons strongly suggest a signifi-cant reduction in perinatal mortality.Among two large comparative studies(>9,000 cases each) the reduction in cor-rected perinatal mortality (excluding deathsdue to anomaly) in the tested populations ascompared with historical controls rangedfrom 61% to 76%.5

Certain aspects of antepartum fetal riskevaluation by multiple variable assessment,as in the fetal biophysical profile score, suchas the test score distribution, are in stark con-trast to that observed with any single vari-able. Thus, for example, the probability ofthe fetal biophysical profile score in a givenhigh-risk fetus being normal (at least 8/10,normal amniotic fluid) exceeds 97%,21

whereas the probability of a normal (reac-tive) nonstress test is in the range of 85%.23

The high incidence of normal test resultsraises two critical issues. Firstly, if the testwere insensitive (that is, even in the pres-ence of existing life-threatening conditions,fetuses were still to manifest normal bio-physical activities), then a high percentageof normal test results would occur. There aretwo powerful arguments against this sce-nario: a normal biophysical profile score isnever associated with concurrent acidemia,and the fetal death rate within a week of anormal test result is in the range of 0.4 to 0.6per 1,000 live births (a rate that is about 10%of the observed perinatal mortality in anyhigh-risk study population).24,25 Therefore,it is highly likely that the residual fetal popu-lation at risk despite a normal fetal biophysi-cal profile score do not have pre-existing as-phyxial disease but rather are exposed to ei-ther an acute insult (eg, accidental cordcompression, fetomaternal hemorrhage, ormaternal abruption). Serendipitous clinicalobservations support this contention. In a re-cent study of fetal deaths after a normal fetal

biophysical profile score, Dayal et al25 notedthat the shortest interval between a normalscore was in the range of 30 minutes. Thisfetus developed an apparent acute cardiacarrhythmia during the testing, recovered,and then developed a second episode anddied.

The positive predictive accuracy of thefetal biophysical profile, as expected, variesdirectly with the test score result. A false-positive rate of at least 75% is observed withthe equivocal score of 6/10, whereas themost abnormal score (0/10) is almost alwaysindicative of fetal compromise.26 The ques-tion arises as to whether this range of predic-tive accuracy is sufficiently broad to pre-clude clinical application of the testingmethod. In the original blind study of fetalbiophysical profile scoring, perinatal deathwas observed in association with abnormaltest results, but even under these circum-stances most fetuses survived to deliveryand made a successful adaptation to extra-uterine life. While some of these false-positive results must truly represent an over-interpretation of fetal biophysical observa-tions (eg, confusion of an extended sleepstate with an asphyxial response), in most in-stances the abnormal test result likely re-flects fetal adaptation to an asphyxial insult.The essence of the argument is that fetuseswho adapt can and do survive, often for ex-tended periods, and that concurrent with thebiophysical adaptation to asphyxia there ismost likely an endocrine response that,through mechanisms not clearly defined,initiates parturition and egress of the fetusfrom the hostile environment. Thus, it mightbe that if the fetus can live long enough afterthe insult, it can escape death. The fetal bio-physical profile measures that phase of fetaladaptation. The perinatal mortality rate isthe ultimate measure of the success of theadaptation.

RISK OF PERINATAL MORBIDITYImmediate perinatal morbidity parameterssuch as fetal distress in labor, delivery by ce-sarean section for fetal distress, Apgar

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scores, and birth weight centile are oftencited as measures of the accuracy of a giventesting method. Using these endpoints to un-derscore test accuracy is a circular argu-ment. An abnormal heart rate test, for ex-ample a positive contraction stress test, inmimicking labor, must have a higher inci-dence of intrapartum heart rate abnormali-ties (fetal distress), and indeed this is re-ported27 (although remarkably in some stud-ies the false-positive rate is as high as 50%).The Apgar score is the neonatal measure ofadaptation to asphyxia, and since the imme-diate neonatal adaptive reflex and direct re-sponses are identical to those of the fetus, thehighly significant direct linear correlationbetween the biophysical profile score andApgar score is predictable (Fig. 3). Truedysmature IUGR is a manifestation ofchronic fetal asphyxia and therefore mustand does correlate with the fetal biophysicalprofile score. In essence, the fetal biophysi-cal profile score reflects fetal adaptation toasphyxia, and the immediate postnatal mor-bidity measures reflect the consequences ofsuch adaptation. Accordingly, these twovariable sets ought to bear a direct linear re-lationship, and clinical observations con-firm this fact.

The more important emerging issue cen-ters on the relationship between fetal as-phyxia, adaptation, survival, and long-termsequelae. If failed adaptation can result in fe-tal death, an undisputed fact, then there mustbe degrees of failed adaptation to potentiallylethal asphyxia that bring the fetus neardeath. The critical clinical issue is whethersuch fetuses experience irreversible tissuedamage and whether this damage might belater expressed in the surviving infant. Theperhaps even more important corollary iswhether the recognition of fetuses with po-tentially damaging degrees of asphyxia andtimed intervention (usually delivery) canprevent some or all of the damage. The fetalbiophysical profile score is undoubtedly ac-curate in identifying fetuses with asphyxia atthe time of the test, and application of thistest to a high-risk population almost cer-

tainly yields a significant fall in perinatalmortality.

Cerebral palsy, a nonprogressive neuro-logic abnormality of varying severity, whileof diverse etiology28 can be a consequenceof perinatal asphyxia. This condition may bean ideal marker to examine the relationshipbetween successful adaptation and insultand the impact of recognition and interven-tion on disease prevalence. Because it is pos-sible in Manitoba to access antepartum test-ing, obstetric, and long-term infant andchildhood data by a common identity num-ber and generate a single comprehensive da-tabase for the entire population, it is alsopossible to identify all cases of cerebralpalsy (prevalence), stratify cases by timing

FIG. 3. Relationship between last BPS result,incidence of intrauterine growth retardation(IUGR) and frequency of admission to a neona-tal intensive care unit (NICU) for perinatal as-phyxia. (From Manning FA. Fetal biophysicalprofile scoring. In: Fetal Medicine, Principlesand Practice. Norwalk, CT: Appleton Lange,1995:237, with permission.)

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of insult and presumed etiology, and com-pare these parameters between tested high-risk and nontested low-risk patients. The in-cidence of cerebral palsy at age 5 years orolder has been reported among the offspringof 26,288 high-risk mothers subjected to se-rial antepartum testing by fetal biophysicalprofile scoring and managed in part accord-ing to these test results.29 A highly signifi-cant inverse exponential relationship be-tween last test score and the incidence of ce-rebral palsy is observed (Fig. 4). Thesimilarities between last biophysical profilescore and mortality, acidemia, and cerebralpalsy are remarkably similar: all are expo-nential, inverse, and highly significant, andthe curves overlap almost exactly (Fig. 5).While there are always alternate explana-tions for any data set, the one that seems

most logical for these endpoints is that thefetal biophysical profile reflects the pres-ence and degree of acidemia, acidemia is amanifestation of asphyxia, and asphyxia isthe cause of either death or damage.

The relationship between last fetal bio-physical profile score and adverse long-termoutcome is not restricted to the gross andmore localized injury of cerebral palsy.Similar highly significant inverse exponen-tial relationships are observed between men-tal retardation, language development delay,cortical blindness, cortical deafness, andpoor first-grade school performance,30 and asimilar relationship has been observed forattention deficit disorder in children 8 yearsof age or older.31 There is now increasingtangential evidence to support this concept.For example, recently it has been reported

FIG. 4. Relationship between the last biophysical score (BPS) and cere-bral palsy (CP) at age 5 years. In these 26,288 referred high-risk fetusessubjected to serial BPP testing, an inverse exponential and highly significantrelationship between BPP and cerebral palsy was observed. (From ManningFA, Harman CR, Menticoglou S, et al. Fetal assessment by fetal biophysicalprofile score. VI. The incidence of cerebral palsy among tested and non-tested perinates. Am J Obstet Gynecol. 1998;178:696, with permission.)

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that term infants born with severe (<3d cen-tile) dysmature IUGR (a fetal adaptation toasphyxia) are as young adults significantlymore likely to either fail or not take the testsof higher education.32

The question of whether recognition offetal asphyxia and intervention can preventsequelae is at the heart of all antepartum test-ing strategies. Using perinatal death as theendpoint, it appears evident that manage-ment based on fetal biophysical profile scor-ing can achieve this goal. Recent data sug-

gest that same benefit might be achieved forcerebral palsy and other long-term end-points. In a comparative study between58,659 low-risk obstetric patients managedby conventional means and without usingfetal biophysical profile scores and 26,288high-risk patients whose management in-cluded fetal biophysical profile score testingand intervention for abnormal test scores,the incidence of cerebral palsy at age 5 yearswas significantly lower in the tested high-risk group than in the nontested low-riskgroup (1.33/1,000 vs. 4.74/1,000, P <0.0001)29 (Fig. 6). These observations are inopposition to the conventional thought thatcerebral palsy cannot be prevented oravoided. In similar comparative studies theincidence of mental retardation, languagedevelopment delay, cortical blindness anddeafness, and attention deficit disorders wassignificantly lower in tested high-risk fe-tuses than in nontested low-risk controls.Collectively these data imply that the clini-

FIG. 5. Relationship between the last bio-physical profile and select end points includingperinatal morbidity (cumulative), antepartum fe-tal umbilical vein acidemia (pH � 7.20), perina-tal mortality (PNM), and cerebral palsy at age 5years. The relationship is inverse and linear,whereas the relationship for acidemia, death, andcerebral palsy is inverse and exponential. Thesimilarity in relationships for the latter three endpoints implies that each represents failed fetalcompensation and that the clinical line betweenacidemia-related death and damage is likely tobe fine. (From Manning FA. Fetal biophysicalprofile scoring. In: Fetal Medicine, Principlesand Practice. Norwalk, CT: Appleton Lange,1995, with permission.)

FIG. 6. Incidence of cerebral palsy (CP) at age5 years among 26,288 high-risk fetuses sub-jected to serial biophysical profile (BPP) testingand among 58,659 contemporaneous nontestedpredominantly low-risk patients. In the testedgroup /in whom intervention occurred for a per-sistent BPP of 6/10 or less, the CP rate was 1.33per 1000, compared with an observed rate of7.74 per 1000 in the nontested patients. Thesedifferences were highly significant. (FromManning FA. Fetal biophysical profile scoring.In: Fetal Medicine, Principles and Practice.Norwalk, CT: Appleton Lange, 1995, withpermission.)

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cal benefits of antepartum testing by the fe-tal biophysical profile scoring method willextend beyond prevention of perinatal deathand immediate morbidity and extend to in-fant and childhood health.

At the other extreme of age, Barker et al33

reported that low birthweight is associatedwith a significantly increased risk of lateadult-onset hypertension and cardiovascu-lar-related morbidity and mortality. Thealpha–omega theory encompasses these col-lective observations and suggests that prena-tal adaptation to fetal asphyxial is manifestas a spectrum of disease across the span ofpostnatal life.34 A key question is whetherprenatal recognition and intervention for as-phyxial disease can prevent or at least ame-liorate all of these sequelae. While the im-pact of testing and timed intervention onimmediate endpoints (perinatal mortality)and infant and childhood diseases seemsevident, there is as of yet insufficient obser-vation time to measure the impact, if any, inlate adult life. Fortunately the data bases arenow secured that will allow such futureevaluations. It seems a reasonable and safeprediction that the same beneficial effect ofasphyxia recognition and intervention willaccrue to the individual at risk for cardiovas-cular disease in late life. What an odd andcomplete full circle it would be if antepar-tum testing were the first step in securingsustained extrauterine health! The evidenceto date suggests this will in fact be the case.

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responses to hypoxemia and acidemia in fe-tal lambs. Am J Obstet Gynecol. 1974;120:817.

2. Patrick JE, Dalton KJ, Dawes GS. Breathingpatterns before death in fetal lambs. Am JObstet Gynecol. 1976;125:73.

3. Manning FA, Martin CVB Jr, Murata Y, etal. Breathing movements before death in theprimate fetus. Am J Obstet Gynecol. 1979;135:71.

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Intrauterine fetal tachypnea. Am J ObstetGynecol. 1982;144:356.

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6. Bocking AD, Gagnon R, Milne KM, WhiteSE. Behavioral activity during prolongedhypoxemia in fetal sheep. J Appl Physiol.1988;65:2420.

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8. Boddy K, Dawes GS, Fisher R, et al. Fetalrespiratory movements, electrocortical andcardiovascular responses to hypoxemia andhypercapnia in sheep. J Physiol (London).1974;243:599.

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10. Nicolaides KH, Peters MT, Vyas S, et al.Relation of rate of urine production to oxy-gen tension in small-for-gestational-age fe-tuses. Am J Obstet Gynecol. 1990;162:387.

11. Steele BT, Paes B, Towel ME. Fetal renalfailure associated with intrauterine growthretardation. Am J Obstet Gynecol. 1989;159:1200.

12. Ross MG, Sherman DJ, Darvin MG, et al.Stimuli for fetal swallowing: Systemic fac-tors. Am J Obstet Gynecol. 1989;161:1559.

13. Schifrin B. Personal communication 200014. Manning FA. Amniotic fluid volume. In:

Principles and Practice of Fetal Medicine.Norwalk, CT: Appleton Lange, 1995:202.

15. Salversen DR, Freeman J, Brudenell JM, etal. Prediction of fetal acidemia in pregnan-cies complicated by maternal diabetes by fe-tal biophysical profile scoring and fetalheart rate monitoring. Br J Obstet Gynecol.1993;100:227.

16. Ribbert LSM, Snijders RJM, NicolaidesKH. Relationship of fetal biophysical pro-file and blood gas values at cordocentesis inseverely growth-retarded fetuses. Am J Ob-stet Gynecol. 1990;163:569.

17. Okamura K, Watanabe T, Endo H, et al. Bio-physical profile and its relationship to bloodgas levels obtained by cordocentesis. ActaObstet Gynecol Japan. 1991;43:1573.

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18. Vintzileos AM, Fleming AD, Scorza WE, etal. Relationship between fetal biophysicalprofile activities and cord gas values. Am JObstet Gynecol. 1991;165:707.

19. Morrison I, Olsen J.20. Chamberlain PF. Later fetal death: has ultra-

sound a role to play in its prevention? Irish JMed Sci. 1991;160:251.

21. Manning FA, Morrison I, Lange I, et al. Fe-tal assessment based on fetal biophysicalprofile scoring: Experience in 12,620 re-ferred high-risk pregnancies. Am J ObstetGynecol. 1985;151:343.

22. Baskett TF, Allen AC, Gray JH, et al. Fetalbiophysical profile and perinatal death. Ob-stet Gynecol. 1987;70:357.

23. Nageotte MP, Towers CV, Asrat T, et al.The value of a negative antepartum test.Contraction stress test and modified bio-physical profile. Obstet Gynecol. 1994;84:231.

24. Manning FA, Morrison I, Harman CR, et al.Fetal assessment based on the fetal bio-physical profile score: Experience in 19,921referred high-risk pregnancies. II. The false-negative rate by frequency and etiology. AmJ Obstet Gynecol. 1987;157:880.

25. Dayal A, Manning FA, Harman CR, BerckD. Fetal biophysical profile score: An ap-praisal of the false-negative rate at two sepa-rate institutions. Am J Obstet Gynecol.1999.

26. Manning FA, Morrison I, Harman CR, et al.Fetal assessment based on fetal biophysicalprofile scoring. IV. Positive predictive accu-

racy of the abnormal test. Am J Obstet Gy-necol. 1990;162:703.

27. Freeman RK, Anderson G, Dorchester W. Aprospective multi-institutional study of an-tepartum fetal heart rate monitoring. I. Riskof perinatal mortality and morbidity accord-ing to antepartum fetal heart rate results. AmJ Obstet Gynecol. 1982;143:771.

28. Manning FA, Bondagji N, Harman CR, et al.The relationship of the fetal biophysical tothe incidence of cerebral palsy. Eur J ObstetGynecol Reprod Sci. 1981;138:675.

29. Manning FA, Harman CR, Menticoglou S,et al. Fetal assessment by fetal biophysicalprofile score. VI. The incidence of cerebralpalsy among tested and non-tested peri-nates. Am J Obstet Gynecol. 1998;178:696.

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