Biophysical profile test for antepartum fetal assessment

INTRODUCTION — The fetal biophysical profile (BPP) is a noninvasive, easily learned and performed antepartum test for evaluating fetal well-being. Ultrasound is used to assess four discrete biophysical parameters: fetal movement, fetal tone, fetal breathing, and amniotic fluid volume. A separate nonstress test of the fetal heart rate can also be performed as a component of the BPP. Each of the four ultrasound parameters and the nonstress test are assigned a score of either 0 or 2 points (there is no 1 point), depending upon whether specific criteria are met (table 1). A total score ≥8 is a strong indicator that fetal oxygen levels and acid-base status are normal and the fetal brain is well perfused and oxygenated, whereas a score ≤4 can be a sign of fetal compromise. Ideally, identification of a compromised fetus will make it possible for the provider to perform interventions that prevent adverse fetal/neonatal sequelae.

The five biophysical parameters were chosen based upon their ease of measurement and the ability to evaluate them objectively using universally available equipment. Other fetal biophysical activities (eg, sucking, eye movements, swallowing, micturition) might serve equally well as markers of fetal health but are not included in the BPP because measurement is more difficult and may be subjective.

This topic will review issues related to the BPP. An overview of antenatal fetal surveillance and detailed information on the nonstress test and the contraction stress test are available separately. (See "Overview of antepartum fetal assessment" and "Nonstress test and contraction stress test".)

INDICATIONS — Antepartum fetal surveillance with tests such as the biophysical profile for pregnancies is indicated in pregnancies at increased risk of antepartum fetal demise. Specific conditions and clinical settings that may be indications for antenatal fetal assessment are discussed separately, but the decision is ultimately based on the clinical judgment of the provider. (See "Overview of antepartum fetal assessment", section on 'Indications for fetal assessment'.)

Although the BPP is typically used for antepartum fetal assessment, it can also be performed intrapartum; however, its clinical utility in the intrapartum setting is unclear [1,2].

PHYSIOLOGIC BASIS OF THE BIOPHYSICAL PROFILE

●All fetal biophysical activities are regulated by discrete centers in the brain that are sensitive to both local factors and feedback from peripheral sensors. The degree of fall in oxygen concentration necessary to abolish a given central nervous system regulatory center output and thereby reduce fetal oxygen requirements varies by center.

The two most oxygen-sensitive centers are (1) the cardioregulatory neurons, which control the coupling of fetal movement and heart rate acceleration, and (2) the fetal breathing center neurons, which control fetal breathing movements. The centers regulating fetal breathing and fetal heart rate (FHR) accelerations can be affected by mild hypoxemia, fetal movement has a higher threshold before being affected by hypoxemia, and the fetal tone center has the highest threshold. Thus, these fetal biophysical activities respond to hypoxemia in a predictable, physiologically based cascade: loss of fetal breathing movements and FHR accelerations, followed by decreased fetal movement, and finally loss of fetal tone. This sequence is informative clinically since it allows for estimation of both the presence and severity of hypoxemia.

●The BPP with a nonstress test assesses five discrete biophysical parameters (table 1) that reflect central nervous system regulatory output and thus indirectly reflect the integrity of the regulatory center. Four of these parameters reflect acute fetal status: fetal breathing movements, generalized fetal movements, fetal tone, and FHR accelerations in response to fetal movements (nonstress test).

•When most of the acute parameters are present, the brain’s regulatory center is likely to be intact, and pathologic conditions, such as hypoxemia leading to acidemia, can be reliably excluded.

•When most of the acute parameters are absent, the reason for the absent biophysical activity needs to be assessed.

-A deep stage of normal quiet sleep is a benign etiology, although it is unusual to observe the absence of two or more acute parameters as a consequence of quiet sleep alone. Transplacental passage of drugs that cause general suppression of the brain, such as sedatives and opiates, is another benign etiology.

-The more acute parameters that are absent (ie, the lower the BPP score), the less likely the change is due to a sleep state.

-The longer the absence of acute parameters, the more likely the cause is pathologic. Extending the observation period to encompass the usual duration of sleep state cycles (20 to 40 minutes) minimizes the possibility of misdiagnosis of pathologic versus physiologic fetal conditions.

•Amniotic fluid volume is a nonacute parameter since decreases in amniotic fluid volume in response to chronic uteroplacental vascular insufficiency generally occur gradually. Fetal urine is the predominant source of amniotic fluid after approximately 16 weeks of gestation. Fetal urine production is primarily dependent upon renal perfusion, which in turn reflects selective distribution of cardiac output. The fetus responds to sustained hypoxemia by selective redistribution of its cardiac output, with preferential flow directed to the brain, heart, adrenals, and placenta at the expense of all other organ systems [3]. This protective mechanism is initiated by specialized chemoreceptors in the aortic arch and carotid arteries. (See "Physiology of amniotic fluid volume regulation".)

Hypoxemia-induced reflex redistribution of cardiac output away from the kidneys results in diminished fetal urine production, ultimately leading to oligohydramnios and then anhydramnios [4]. Theoretically, a decrease in fetal swallowing, which removes amniotic fluid, could compensate for the decrease in urine production, but fetal swallowing is a vegetative reflex that is very resistant to the effects of hypoxemia.

The time for development of oligohydramnios is usually relatively long. On average, it takes approximately 15 days for a fetus to progress from normal to reduced amniotic fluid volume (in the absence of membrane rupture) and 23 days to develop severe oligohydramnios [4]. However, acute changes in amniotic fluid volume and rapid deterioration of the BPP score have been reported [5].

DETERMINING THE BIOPHYSICAL PROFILE SCORE

Assigning points — The composite BPP score is derived from five fetal parameters: four acute parameters (heart rate accelerations in response to movement [nonstress test], breathing movement, body and limb movement, tone) and one chronic parameter (amniotic fluid volume), as discussed above (see 'Physiologic basis of the biophysical profile' above). Each of these five parameters has been evaluated independently and the normal characteristic defined (table 1) [6]. The scoring method used for each parameter is binary (ie, the parameter is either normal or abnormal; gradations of abnormality are not used). A normal parameter is assigned a score of 2 and an abnormal parameter is assigned a score of 0. The maximum score is 10/10 and the minimum score is 0/10.

Pathologic conditions that should not be confused with normal fetal activity include the following [7-9]:

•Monotonous picket-fence breathing or gasping should not be considered normal breathing movements

•Seizures should not be counted as normal fetal limb movements

•Sinusoidal fetal heart rate (FHR) on the nonstress test should not be confused with normal long-term variability

Duration of fetal observation — A parameter may be assigned a normal score (2) as soon as it is observed. Because the acute parameters are subject to fetal sleep-wake cycles, the fetus should be observed continuously for at least 30 minutes before assigning 0 points for any acute parameter. This time is based on ultrasound studies of fetuses from uncomplicated pregnancies. In one such study at 36 to 42 weeks of gestation, the mean duration of a fetal sleep (no somatic movements) was approximately 20 minutes, with an upper range of approximately 40 minutes [10].

The average time to obtain a normal BPP score (BPP 10/10, 8/8) is 5.3 minutes, and the test can be stopped at that point. When all tests are considered (normal, equivocal, abnormal) the average testing time is approximately 18 minutes [11]. Fetal acoustic stimulation may be used to try to shorten testing time [12].

Can the nonstress test be omitted?

●A nonstress test should always be performed if any ultrasound-monitored parameter is 0 (ie, BPP ≤6/8).

●The nonstress test can be omitted when the BPP is 8/8 as it does not enhance test performance. The predictive value of the four ultrasound biophysical parameters (movement, tone, breathing, amniotic fluid volume) is equivalent to that of the four ultrasound parameters plus a nonstress test when the four ultrasound parameters are normal (2 points for each).

In a prospective study in which the nonstress test was only performed if the ultrasound score was <8, nonstress tests were performed in 2.7 percent of patients without reducing the predictive value of the test, which significantly reduced the average testing time per patient [13]. In a retrospective study (985 women and 3981 BPPs), the positive screen rate for the BPP using the four ultrasound parameters alone was 0.4 percent and the false negative rate 0.3 percent, which was comparable to the false negative rates of the nonstress test (0.19 percent) and the full BPP (0.08 percent) [14]. Three antepartum fetal demises occurred; two were growth-restricted, and the third pregnancy was complicated by preexisting diabetes. The interval from normal ultrasonographic BPP to fetal demise was seven, seven, and six days, respectively.

ALTERNATIVES

Modified biophysical profile — The modified BPP was developed to simplify the examination and reduce the time necessary to complete testing by focusing on those components of the BPP that are most predictive of outcome: nonstress test and amniotic fluid volume. Assessment of both the nonstress test and amniotic fluid volume appears to be as reliable a predictor of long-term fetal well-being as the full BPP [15,16]. The rate of stillbirth within one week of a normal modified BPP is the same as with the full BPP: 0.8 per 1000 women tested [16].

Approximately 90 percent of pregnancies that undergo a modified BPP will have a normal result, the remainder will need to proceed to a full biophysical evaluation.

INTERPRETATION — Interpretation of the BPP is based on the author's extensive published and unpublished experience [11,17-26].

10/10, 8/8, or 8/10 with normal amniotic fluid — 10/10, 8/8 (nonstress test omitted), or 8/10 (-2 points for either fetal movement, tone, or breathing but not amniotic fluid) is a normal test result: The risk of fetal death within one week if the fetus is not delivered is low (0.4 to 0.6/1000 births) [17]. A BPP score of 8/10 by any combination of parameters is as reliable as a score of 10/10 for the prediction of fetal well-being, as long as no points are deducted for amniotic fluid volume.

A normal score is predictive of the absence of fetal compromise in the setting of high-risk factors, such as diabetes mellitus, hypertension, or fetal growth restriction. Before term, a normal score provides reassurance that the benefits of continued intrauterine maturation far outweigh the very small risk of fetal demise. Fetal death after a normal BPP is often due to an acute and unpredictable insult such as sudden cord prolapse, large fetomaternal hemorrhage, or abruption.

However, a change in maternal condition affects this balance. For example, the decision to intervene in a patient with worsening preeclampsia or unstable lie and prelabor rupture of membranes may depend less on the BPP score and more on maternal and fetal risk from continuing the pregnancy. Similarly, the presence of a favorable cervix may prompt delivery despite a normal BPP score when the fetus is at term.

6/10 with normal amniotic fluid — 6/10 (-4 points for two of fetal movement, tone, breathing, but +2 points for amniotic fluid) is an equivocal test result because a significant possibility of developing fetal asphyxia cannot be excluded. The test is repeated within 24 hours to see if one of the absent acute variables returns to normal or, if the patient is at or near term, delivery is a reasonable option.

6/10 or 8/10 with oligohydramnios — 6/10 or 8/10 with 0 points for amniotic fluid is an abnormal test, as the risk of fetal asphyxia within one week is 89/1000 with expectant management.

These scores should be interpreted within the context of gestational age (eg, neonatal morbidity and mortality if the fetus is delivered) and maternal and obstetric factors (eg, risk of fetal death related to maternal, fetal, or obstetric disorder if the fetus is not delivered; whether cervix is favorable; maternal risks from continuing the pregnancy). As an example, a low BPP score in a high-risk patient requires the provider to consider the fetal and neonatal risks of expectant management versus delivery, and deliver when the balance shifts to greater fetal risk (figure 1).

0 to 4/10 — 0 to 4/10 is abnormal; the risk of fetal asphyxia within one week is 91 to 600/1000 if there is no intervention. Delivery is usually indicated. (See 'Route of delivery after a low biophysical profile score' below.)

FACTORS POTENTIALLY AFFECTING THE SCORE

●Antenatal corticosteroids – Administration of antenatal corticosteroids can be associated with transient fetal heart rate (FHR) and behavioral changes, but these changes typically return to baseline by day 4 after treatment [27]. The most consistent change is a decrease in FHR variability on days 2 and 3 after administration [28-32]. Fetal breathing and body movements are also commonly reduced, which may result in a lower BPP score or nonreactive nonstress test [32-35]. These findings should be considered within the total clinical scenario when considering delivery because of a nonreassuring fetal evaluation (nonstress test or BPP) after corticosteroid administration.

The behavioral changes may reflect a physiologic response of the brain to glucocorticoids. Alternatively, they may be a consequence of a transient increase in fetal vascular resistance and blood pressure, which has been demonstrated in animal studies. Fetal blood flow velocity waveform patterns in the umbilical artery, middle cerebral artery, and ductus venosus do not appear to be affected [34,36,37].

●Subclinical infection – The effect of subclinical infection on test results is controversial. Although intraamniotic infection in a patient with preterm prelabor rupture of membranes may be associated with a low BPP score in the absence of hypoxemia [38], most studies have found that the BPP score is an insensitive method for detecting subclinical infection [39-42]. (See "Preterm prelabor rupture of membranes: Management and outcome", section on 'Fetal monitoring'.)

●Preterm labor – Preterm labor may be associated with absence of fetal breathing movements, but absence of fetal breathing movements is not a good predictor of preterm delivery within 48 hours or seven days [43].

●Fasting – There are sparse data on the effect of fasting on fetal biophysical activities. A study that performed a BPP one hour after a meal and 10 to 12 hours after abstaining from food and drink in 30 patients with uncomplicated pregnancies reported scores were ≥8/10 for all postprandial BPPs, but two fasting BPPs were 4/10 and 6/10; both increased to 10/10 after the mother ate a meal [44]. Point reductions during fasting were primarily due to nonreactive nonstress tests and inadequate fetal breathing movements.

It is difficult to draw any conclusion about the effect of fasting on the BPP score in the clinical setting, given the small size of this study and the absence of indications for antepartum fetal assessment. Some clinicians give the patient juice or another type of food/drink if a BPP shows inadequate breathing or the nonstress test is nonreactive. However, a meta-analysis found that maternal glucose administration did not significantly decrease the incidence of nonreactive test results related to quiet fetal sleep [45].

●Mild maternal anemia does not appear to affect fetal biophysical activities [46].

TESTING SCHEDULE

Initiation — Testing should begin as soon as an increased risk of fetal demise is identified and delivery for perinatal benefit would be considered if test results are abnormal. This may be as early as 24 weeks of gestation. (See "Periviable birth (limit of viability)".)

In the general obstetric population, observational data show that rate of stillbirth in non-growth-restricted fetuses significantly rises between approximately 32 to 34 weeks and term [47]. Based on these data and data from large series of high-risk pregnancies [48-50], 32 weeks of gestation has become a common threshold for initiation of fetal surveillance when an indication for fetal surveillance is present and the pregnancy is not complicated by multiple high-risk conditions or a condition strongly associated with early fetal demise (eg, severe growth restriction).

Frequency — A normal BPP score (10/10 or 8/10 without oligohydramnios) is repeated weekly or twice weekly until delivery when the high-risk condition persists and appears stable. Some authorities recommend more frequent testing intervals, with individualization based on the high-risk clinical setting [51]. For example, severe growth restriction caused by uteroplacental insufficiency requires very close fetal monitoring. In one study, 48 growth-restricted fetuses <32 weeks of gestation with umbilical artery Doppler pulsatility index <95^th percentile underwent BPP daily and nonstress testing three times daily [52]. Ten of 27 fetuses with BPP scores of 8 developed nonreassuring fetal heart rate (FHR) tracings 3.5 to 24 hours after the BPP, and the repeat BPP score was 2 in all of these fetuses; three died in utero, seven were delivered promptly, and six of these neonates had acidemic umbilical artery blood gases at birth.

Any significant deterioration in the clinical status (eg, worsening preeclampsia, decreased fetal activity) requires reevaluation, regardless of the amount of time elapsed since the last test.

EVIDENCE OF EFFICACY — Although the use of biophysical testing schemes to monitor high-risk pregnancies has become routine, this practice pattern has evolved with limited high-quality scientific evidence to support its use [53]. Moreover, there are no randomized trials on which to base recommendations for the best initial testing approach for specific types of high-risk pregnancies, the optimal timing of test initiation, the frequency of testing based on test results, conditions that may affect test results, and the effect of gestational age.

●Meta-analysis of randomized trials – In a meta-analysis of randomized trials comparing BPP with conventional fetal heart rate (FHR) monitoring (five trials involving 2974 high risk pregnancies), use of the BPP did not reduce perinatal death (relative risk [RR] 1.33, 95% CI 0.60-2.98) or the frequency of low Apgar scores (RR 1.27, 95% CI 0.85-1.92) [54]. Three of the trials were of low quality; the two higher-quality studies were small (n = 280 high-risk pregnancies) and results did not exclude the possibility of a small or modest benefit.

●Observational studies – Observational studies have reported the BPP is accurate for predicting the absence of significant fetal acidemia [55] and comparable to the contraction stress test [56]. For example, in one observational study including almost 45,000 BPPs, the risk of fetal demise within one week of a normal test result was 0.8 per 1000 pregnant individuals tested (corrected for lethal congenital anomalies and unpredictable causes of demise) [17]. This result compares favorably with all other means of antepartum fetal assessment. In two observational studies including over 18,000 pregnant individuals, use of the BPP was associated with a 61 to 76 percent reduction in perinatal mortality (corrected) compared with historic controls [18].

In other observational studies, as the last BPP score fell (figure 2), perinatal mortality (gross and corrected) and serious perinatal morbidity (nonreassuring FHR pattern in labor, low Apgar scores, neonatal seizures, admission to an intensive care unit, hypoxemic-ischemic encephalopathy, intrauterine growth restriction) increased significantly [19,20]. In addition, the cord blood pH of newborns delivered either vaginally or by cesarean had a direct relationship to the last BPP score (figure 3) [57]. An inverse relationship between last BPP score and incidence of cerebral palsy has also been observed and may be related to antepartum asphyxia (figure 4). Long-term asphyxia leading to adverse neurologic outcomes such as cerebral palsy and intellectual disability appears to be significantly reduced in high-risk patients managed by fetal BPP scoring compared with untested low-risk patients [58].

●Physiologic data – The advent of ultrasound-guided intrauterine fetal blood sampling (cordocentesis) made it possible to measure the direct and immediate relationship between the BPP score, fetal PO₂, and fetal pH [21,59]. These studies, which include over 1000 paired observations, reported a direct relationship between the BPP score and mean umbilical venous pH and suggest that, in the individual fetus, the BPP score accurately predicts both the probability and severity of existing acidemia [60,61]. Thus, the score appears to be an accurate proxy for fetal acidosis. In contrast, the relationship between the BPP score and fetal PO₂ is less precise, which is expected since PO₂ varies according to fetal compensatory adaptive responses.

ROUTE OF DELIVERY AFTER A LOW BIOPHYSICAL PROFILE SCORE — The route of delivery is an obstetric decision based on multiple variables including presentation, cervical findings, and maternal and fetal condition. In the absence of an obstetric contraindication, induction of labor with continuous intrapartum fetal heart monitoring is a reasonable option for most patients, regardless of BPP score. The positive predictive value of a low BPP score for intrapartum fetal compromise (eg, a nonreassuring fetal heart tracing, neonatal acidemia, or other markers of neonatal morbidity at the time of delivery) is approximately 50 percent, with a negative predictive value greater than 99.9 percent.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Fetal surveillance".)

SUMMARY AND RECOMMENDATIONS

●Gestational age – The minimum gestational age for initiating biophysical testing should reflect the lower limit that intervention with delivery would be considered. (See 'Initiation' above.)

●Scoring – The five fetal parameters used for determining the biophysical profile (BPP) score are heart rate accelerations in response to movement (nonstress test), breathing movement, body and limb movement, tone, and amniotic fluid volume, as described in the table (table 1). (See 'Assigning points' above.)

A parameter may be assigned a normal score as soon as it is observed. The acute parameters (movement, tone, breathing) are subject to fetal sleep-wake cycles; therefore, the fetus should be observed continuously for at least 30 minutes before the parameter is assigned 0 points. A BPP cannot be scored as abnormal if the testing time is less than 30 minutes. (See 'Duration of fetal observation' above.)

The predictive value of the four ultrasound biophysical parameters (movement, tone, breathing, amniotic fluid volume) is equivalent to that of the four ultrasound parameters plus a nonstress test when the four ultrasound parameters are normal (2 points for each). A nonstress test can be omitted if the BPP score is 8/8 after ultrasound alone but should always be performed if any ultrasound monitored parameter is 0. (See 'Can the nonstress test be omitted?' above.)

The modified BPP simplifies the examination and reduces the time necessary to complete testing by focusing on those components of the BPP that are most predictive of outcome. Assessment of both amniotic fluid volume and the nonstress test appears to be as reliable a predictor of long-term fetal well-being as the full BPP. (See 'Modified biophysical profile' above.)

●Interpretation – A score of 10/10 or 8/10 without oligohydramnios is reassuring of fetal well-being; 6/10 without oligohydramnios is an equivocal test result and should be repeated within 24 hours if the patient is not delivered; and 0 to 4/10 suggests a high risk of fetal asphyxia within one week if the patient remains undelivered or no therapeutic intervention is undertaken. (See 'Interpretation' above.)

Scores of 6/10 or 8/10 with oligohydramnios (0 points for amniotic fluid) are abnormal tests, as the risk of fetal asphyxia within one week is 89/1000 with expectant management. These scores should be interpreted within the context of gestational age (eg, neonatal morbidity and mortality if the fetus is delivered) and maternal and obstetric factors (eg, risk of fetal death related to maternal, fetal, or obstetric disorder if the fetus is not delivered; whether cervix is favorable; maternal risks from continuing the pregnancy). A low BPP score in a high-risk patient requires the provider to consider the fetal and neonatal risks of expectant management versus delivery and deliver when the balance shifts to greater fetal risk (figure 1). (See 'Interpretation' above.)

The BPP score must be interpreted within the clinical context. The object is to treat the patient and not the test score. The selected mode of delivery for the fetus with an abnormal BPP score is an obstetric decision based on the clinician’s consideration of the entire clinical scenario. As a general rule, the more abnormal the score, the less likely vaginal delivery will be achieved and the more likely operative delivery will be required. (See 'Route of delivery after a low biophysical profile score' above.)

●Frequency of testing – We repeat a normal BPP score (10/10 or 8/10 without oligohydramnios) weekly or twice weekly until delivery when the high-risk condition persists and appears stable, and more frequently when there is significant deterioration in the clinical status (eg, worsening preeclampsia, decreased fetal activity) or in selected very high-risk settings (severe fetal growth restriction with abnormal Doppler velocimetry. (See 'Frequency' above.)

●Performance – In observational studies, use of the BPP score as part of the management of high-risk obstetric patients has been associated with a significant reduction in perinatal mortality. (See 'Evidence of efficacy' above.)