The development of objective clinical methods for the detection of the fetus at risk for death or damage in utero began in earnest only in the past few decades. The initial forays were in the measurement of endocrine products released by the placenta into the maternal circulation. A wide range of compounds, including placental enzymes (alkaline phosphatase, leucine amino-peptidase), placental-specific hormones (placental lactogen), and placental conversion products (estriols, estetrol) were studied. For most there was a relation to fetal outcome, but none of these measures had the necessary accuracy to become a useful adjunct to clinical management. In the early 1960s, 2 clinical investigative teams, one headed by Hon in Yale and the other by Caldero-Barcia in Uruguay, reported methods for continuous recording of the fetal heart rate.^1,2 This innovation ushered in the contemporary era of fetal evaluation based on dynamic biophysical monitoring. Although designed for the intrapartum period, the application of heart rate monitoring in the antepartum period was quickly realized, and a generation of tests based on heart rate responses to contractions (the contraction stress test), fetal movements (the nonstress test [NST]), or both came into vogue³ and quickly supplanted the biochemical tests. In the late 1960s, 2 groups, those of Dawes in Oxford and Tchobroutsky in Paris, reported fetal breathing movements as a normal characteristic of intrauterine life.^3,4 Dawes et al in a series of elegant experiments in the chronic fetal lamb preparation were able to demonstrate an exquisite sensitivity of the fetal respiratory center to experimental hypoxemia,⁵ thereby creating interest in the potential of this measurement in predicting human fetal compromise. The clinical application of these observations was thwarted by the inability 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 of dynamic fetal biophysical activities became clinically facile. From the outset of clinical testing it was evident that observation of the presence or absence of breathing movements in the human fetus was as predictive as the NST,⁶ was useful in the differentiation of true-positive and false-positive contraction stress test results⁷ and, when combined with heart rate test, yielded a better prediction than any single test.⁸ Further, it became evident that objective recording of gross body movements was predictive of fetal health and disease⁹ and that, when combined with other biophysical variables, predictive accuracy was improved. The preliminary observations provided a first insight into a fundamental tenet of antepartum risk assessment: the predictive accuracy of fetal testing methods improves as more fetal variables are considered. Even from what would be crude ultrasound images by today’s standards, it was patently evident that the wealth of fetal information that could be assessed was vast and included a wide spectrum of acutely dynamic biophysical activities, ranging from gross body movements to fine finger control, an objective means of determining the presence (or lack of) and distribution of amniotic fluid, a detailed measurement of fetal structures (morphometrics), and an evaluation of the organ system’s structural and functional integrity (morphology). From these observations arose the now entrenched concept of composite fetal assessment. The fetal biophysical profile scoring method emerged from this rich clinical milieu as a means of integration of dynamic biophysical activities into a workable clinical format.¹⁰ As from its inception, it remains critical today to interpret the results of the biophysical profile score (BPS) within the context of all the information concurrently rendered accessible by dynamic ultrasound fetal imaging.

It is the intent of this chapter to review the clinical role of the fetal BPS in the prediction and prevention of perinatal mortality, perinatal morbidity as reflected by antenatal acidosis, immediate neonatal compromise, and long-term sequelae, and to review application of the testing method to discrete at-risk pregnancy categories.

Whereas in the majority of high-risk pregnancies there are either no or minimal noxious fetal consequences, in a small percentage, 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 even lethal interruptions in placental respiratory function. Unable to extricate itself from this hostile environment the mammalian fetus has evolved remarkable protective compensatory mechanisms. It is these adaptations to hypoxemia and acidemia (asphyxia) that result in the deviation from normal of the components of the BPS. In response to acute hypoxemia, for example, as may occur with fulminant preeclampsia or abruption, the fetus ceases all acute biophysical activities nonessential to immediate survival: the fetus will stop moving and breathing and will lose flexor tone. In the fetal lamb, abolition of all skeletal muscle activity, as induced by pharmacologic footplate blockade (eg, gallamine), produces an immediate reduction in oxygen consumption by up to 17% and yields a rise in fetal Po₂.¹¹ In the human fetus, we have observed a similar effect: In alloimmune anemic fetuses undergoing intravascular transfusion, the measured Po₂ in venous blood increases after pancuronium blockade.¹² This adaptive response is mediated by acute tissue hypoxia in central nervous system neurons that initiate the discrete biophysical activities (Figure 26-1). Evidence of this adaptive response in high-risk human fetuses is demonstrated by antenatal venous cord blood analysis. For each of the individual acute biophysical variables, the mean pH was always significantly higher when the activity was observed than when the activity was absent (Figure 26-2).¹³ Further, there appears to be a differential sensitivity between these acute variables: The NST and fetal breathing movements were absent with the least decline in pH, whereas larger falls were observed before fetal body movement and tone became abnormal. The animal fetus with mild to moderate sustained stable nonacidemic hypoxemia may exhibit the return of acute biophysical activities, albeit at a lower frequency.¹⁴ The physiologic basis for this partial recovery is complex and involves such factors as increased oxygen-carrying capacity, improved oxygen extraction, resetting of receptor thresholds, and increased cerebral blood flow. Thus, the BPS is a reflection of tissue hypoxemia but may not predict circulating Po₂. The statistically significant but clinically poor correlation between the fetal BPS and antenatal venous Po₂ confirms this explanation.¹⁴ It is of clinical importance to note that progressive hypoxemia, acidemic hypoxemia (asphyxia), or both have not been associated with reemergence of acute biophysical variables in either animal or human fetuses.

The fetus has a second adaptive response to hypoxemia, which is the aortic arch chemoreceptor reflex redistribution of cardiac output. This reflex, which probably requires either more severe hypoxemia or acidemia to be triggered, results in preferential shunting of blood flow away from all nonessential organs to essential organs (the heart, brain, placenta, and adrenals).¹⁵ The measurable clinical effect manifest over days is oliguric oligohydramnios and over weeks is intrauterine growth restriction (IUGR). This reflex accounts for an important principle of fetal assessment by the BPS, which is that in the presence of intact membranes and a functional genitourinary tract, oligohydramnios is near certain presumptive evidence of fetal compromise. Although exceptions to this clinical dictum may occur, they must be exceedingly rare because our group has yet to identify one in more than 160,000 tests.

The time differential between the immediate adaptive response to hypoxemia, acidemia (loss of acute biophysical variables), or both, and the delayed reflex response (oliguric oligohydramnios) permits an assessment of the chronicity of the insult. The differential sensitivity of the regulatory centers provides some insight into the severity of the insult. These 2 components are critical to the testing frequency and interpretation in specific risk categories. Thus, for example, in clinical circumstances in which fetal compromise is apt to be sudden (eg, insulin-dependent diabetes), testing is frequent (twice weekly) with an emphasis on acute biophysical variables. In other conditions where fetal compromise is rapidly progressive, as, for example, with severe alloimmune anemia, testing may occur very frequently (daily or twice daily), with emphasis on the acute variables, and continue until treatment (intravascular transfusion) restores normal oxygen-carrying capacity. With indolent progressive placental failure, as may occur in the postdate pregnancy, the focus of biophysical scoring is to detect evidence of chronic adaptation (oligohydramnios), the superimposition of acute on chronic hypoxemia (loss of some or all acute variables), or both. Because the rate of deterioration in these circumstances may be rapid, the testing interval is shortened to at least twice weekly. It is likely that, as our understanding of the pathophysiology of other abnormal fetal conditions improves, the frequency and emphasis of fetal biophysical profile scoring will be altered.

Doppler waveforms can be measured in all visible fetal arteries and veins but of clinical importance are the waveforms of the umbilical artery, the middle cerebral artery and the ductus venosus. Placental resistance determines the shape and character of the umbilical artery Doppler waveform. In general as fetal placental vascular resistance increases umbilical artery peak systolic blood flow velocity increases and the diastolic velocity waveform decreases. This observation has lead to the development of the S/D ratio. Clinical conditions that reduce placental size and effective vasculature (e.g. maternal hypertension, chronic abruption, idiopathic IUGR) result in an increase in systolic to diastolic waveform velocities (S/D ratio) that progresses to an absence of diastolic flow velocities (AEDF) and finally at end stage to reverse diastolic flow velocity waveforms (REDF). The relationship between abnormal umbilical artery flow velocities (increased S/D ratio, AEDF and REDF), a measure of placental blood flow resistance and fetal condition, a measure of placental function is indirect and except in most severe forms (AEDF) is of limited to no value in immediate fetal assessment. Absent end diastolic flow velocities waveform may persist weeks of even months without any adverse fetal effects. In contrast reverse end diastolic flow velocity waveform indicates severe placental vascular resistance and is associated with a sharply increased risk of fetal asphyxia and death. An increasing S/D ratio or AEDF are indications for increased fetal surveillance but are not an indication for intervention. Reverse end diastolic flow velocity waveform is an indication for immediate fetal assessment and in the mature fetus may be an indication for intervention.

Blood flow redistribution from non-essential to essential organ systems is a critical component of fetal adaptation and compensation to hypoxemia/academia. Blood flow to the brain is increased during chronic hypoxia and this effect can be measured in the Doppler flow velocities of the middle cerebral artery. A rising MCA velocity waveform suggests the clinical possibility of fetal hypoxia but the correlation is poor and is nowhere near the predictive accuracy of the fetal biophysical profile score. However MCA velocity waveforms can be used to estimate fetal hemoglobin concentration and are a good means to assess and monitor fetal anemia.

The ductus venosus is the primary vein of interest in applying Doppler venous waveform as a means of fetal assessment. The ductus venosus waveform is generated by the cardiac cycle with systole producing the a-wave. In the presence of increased afterload, especially as seen with the abnormal placentation accompanying dysmature intrauterine growth restriction, the ductus venosus a-wave becomes more pronounced and with extreme afterload and insipient cardiac failure the ominous finding of a retrograde a-wave be observed. The current clinical utility of ductus venosus Doppler waveform monitoring is primarily focused in the assessment of the IUGR fetus and broader application to detect and quantitate fetal hypoxia is less certain.

The original method of fetal biophysical profile scoring was based on a composite assessment of 5 variables: fetal breathing, gross body movements, tone, heart rate acceleration with fetal movement (NST), and semiquantitative amniotic fluid volume as measured by the ventricle diameter of the largest pocket. Each of these variables, with the exception of fetal tone, has been evaluated in separate studies, and the norms and predictive accuracies determined.^6,16,17 Based on cumulative experience, we introduced modification of the original criteria; the definition of oligohydramnios was increased from a pocket of 1 cm to a pocket of 2 cm,¹⁸ and the definition of fetal tone was advanced to include the dynamics of opening and closing of the fetal hand and sustained closure in the absence of active movement.¹⁹ The contemporary criteria for interpretation of the BPS variable are given in Table 26-1. In a subsequent modification, based on a prospective study, we excluded the result of the NST in those fetuses in whom the other dynamic ultrasound-monitored variables were normal.²⁰ This modification yielded a new score category of 8/8.

Additional modifications have been proposed by other investigators. Phelan et al modified the determination of amniotic fluid volume by summing the vertical diameters of the largest pocket in each uterine quadrant (amniotic fluid index [AFI]).²¹ Because this method appears equivalent in predictive accuracy to the single pocket method,²² the substantiation of the AFI for the single pocket measurement seems reasonable. To date, however, there are no prospective clinical trials of sufficient size to establish the validity of this substantiation. Vintzileos et al modified the original method by introducing graduated scoring of each of the original 5 variables and by inclusion of a sixth variable, placental grade.²³ This modification has not been shown to confer any clinical advantage. The value of including static placental morphology to an acute assessment method is unclear, particularly because the clinical value of placental grade is controversial.^24,25

Eden et al have proposed a “modified biophysical profile” by which a reactive (normal) NST alone is used to confirm the immediate well-being of the fetus, and a normal amniotic fluid index is used to exclude the absence of chronic hypoxemia, ischemia, or both.²⁵ This method has clinical practicalities because the NST data can be obtained in a setting that does not require constant supervision by a technician, the hard copy can be interpreted at a later time (ie, offline), and the time needed to determine the amniotic fluid index daily is minimal. Further, the NST component is often done on a more frequent schedule that amniotic fluid volume determination. The “modified biophysical profile” has been evaluated in a well-designed, randomized, large clinical study²⁶: the cumulative data among the 2774 randomized high-risk patients assessed confirms that the predictive accuracy of a normal modified biophysical profile score (reactive NST/normal AFI) is comparable to the classic method utilizing all 5 variables (ie, both have exceedingly low false-negative rates). The interpretation of the abnormal modified biophysical profile score is more problematic. First, there is no clinical evidence that a modified biophysical profile composed of a nonreactive NST/normal AFI is predictive of fetal compromise. Second, since determination of the amniotic fluid index is a statistical continuum derived from a composite measurement of vertical pockets of amniotic fluid columns and gestational age (both variables are known to have significant intrinsic measurement error) the relationship of degrees of abnormality to fetal hypoxemia is imprecise and interpretive. Only when the amniotic fluid index criteria are sufficiently reduced to meet the criteria for an abnormal single pocket assessment (<2 cm vertical pocket) is it likely to be of equal (and high) predictive accuracy of fetal compromise as the classic biophysical profile score. These potential errors in interpretation of the abnormal modified biophysical profile scoring method are easily resolved by a protocol that uses the modified biophysical profile method for screening and the classic method for confirmation and refinement of the significance of an abnormal modified biophysical profile result. The alternate method is to use either the classic complete biophysical profile scoring method or an alternate modification using the ultrasound components (fetal breathing, movement, tone, and amniotic fluid by largest pocket), and when all are normal defer from using the NST, but when not all are normal incorporate the NST. The predictive accuracy of this method has been clearly documented.²⁵