PROD.
# GRF20407
Fetal Biophysical
Profile:A Critical
Appraisal
FRANK A. MANNING, MD
Department of Obstetrics, Gynecology and Women’s Health, Albert
Einstein College of Medicine, Bronx, New York
The fetal biophysical profile score is an
ultrasound-based method that is used to
evaluate the probability of a given fetus hav-
ing or not having sufficient delivery of oxy-
gen to select primary and secondary target
organs, including the fetal brain, kidney, and
to a lesser extent lung, so as to maintain nor-
mal function. The testing method assumes
that the biophysical outputs of select organ
systems, be they acute or chronic, reflect the
functional integrity of that system, and con-
versely that the absence of the select output
variable be considered as evidence of dys-
function until proven otherwise. Underlying
this operating principle is the concept that
tissue hypoxia, of whatever diverse origin,
will result in suppression or loss of normal
function. The physiological basis to support
this 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 and
reproducible changes in organ system func-
tion.1 There are at least two functional path-
ways that mediate these responses (Fig. 1).
Correspondence: Frank A. Manning, MD, 5 Rutland
Road, Scarsdale, NY 10583.E-mail: fmanningob@aol.
com
CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 45
CLINICAL OBSTETRICS AND GYNECOLOGY
Volume 45, Number 4, 975–985
© 2002, Lippincott Williams & Wilkins, Inc.
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 of
neurons that form the regulatory centers
controlling biophysical activities. In these
regulatory centers tissue hypoxia that falls
below a functional threshold results in an
immediate and complete cessation of the
biophysical 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, and
implies that the center is functional and
therefore not subject to immediate tissue
hypoxemia. This becomes an important piv-
otal point in the use of antepartum testing,
setting the principle that a normal variable
implies absence of threshold acidemia at
that instance in time. As always there are ex-
ceptions, and this is certainly true in regards
to acute biophysical variables in the pres-
ence of extreme and near-lethal degrees of
/ NUMBER 4 / DECEMBER 2002
975
976 MANNING

FIG. 1. Fetal biophysical effect of hypoxemia on the fetus. Conditions in

parentheses refer to neonatal sequels of fetal asphyxia. CNS = central ner-
vous system, IUGR = intrauterine growth retardation, IVH = intraventricular
hemorrhage, 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.)

hypoxemia and acidemia (asphyxia). In fetal
life, as in extrauterine life, deregulation or
aberrant output from regulatory centers can
result in the presence of an abnormal type of
biophysical activity. The extrauterine ex-
amples are well-known: Cheyne-Stokes
breathing, generalized seizures, and athetoid
rigidity. In the fetus extreme deregulation
results 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 tissue
normoxia, but rather it is the presence of the
variable in its normal state. Further, it is im-
portant to recognize that regulatory centers
can 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 release
binding and release, and increased blood
flow to the tissues.7 Thus, the observation of
acute normal variable, while always a reli-
able indication of normal tissue oxygen-
ation, may not be as reliable an indicator of
normal 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 biophysical
variable. For example, fetal breathing move-
ments, a normal biophysical event in fetal
life and arising from signals generated by
the respiratory center located in the region of
the low midbrain, cease abruptly when the
tissue P02 falls by about 8 to 10 torr.8 Thus,
it may be said with certainty that a fetus with
tissue hypoxemia will never exhibit normal

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 itself
complex, and it is certain that factors other
than hypoxemia not only can abolish an ac-
tivity but in fact are the most likely explana-
tion for variable absence. The regulatory
centers are bombarded with signals arising
from a variety of sources both within and
outside the brain, and these signals modulate
the output of the regulatory center. Suppres-
sive signals from the reticular activating
center and other higher CNS centers associ-
ated with sleep–wake cycles and in particu-
lar quiet sleep are by far the most common
cause of absence of a given variable in a de-
fined time interval. From this observation
flows two important corollaries: the clinical
significance of an absent biophysical vari-
able is a direct function of the duration of
observation, and that to define a variable as
abnormally absent, the observation period
must at a minimum exceed the normal dura-
tion proportionate to the average period of a
given sleep state (about 20 minutes) and ide-
ally should be at least half again as long (30
minutes).
Thirdly, it is evident that the functional
threshold of regulatory neurons is not uni-
form but rather varies between individual
centers.9 This variation may be a result of
variation in intracellular neuronal metabo-
lism and therefore oxygen demand, the re-
sult of adaptation of blood flow to increase
total oxygen delivery, or both. In any event,
the stepwise variation in regulatory center
hypoxemia threshold provides an important
clinical insight to the presence and severity
of the hypoxia. It is this threshold sensitivity
of acute biophysical variables that provides
the unique discriminatory power and reli-
ability of the fetal biophysical profile score
method.
The reflex redistribution of cardiac out-
put in response to central hypoxemia/aca-
demia is critical to fetal survival. This reflex
is mediated by aortic arch and carotid artery
chemoreceptors responding primarily to
Fetal Biophysical Profile 977
hypoxemia.2 These chemoreceptors have an
extraordinarily high metabolic rate and to
remain stable and silent require constant
perfusion with the highest oxygenated blood
in the fetal circulation (hence their location).
In the presence of central hypoxemia and in
particular with central acidemia and tissue
acidity, these receptors begin to discharge
and send afferent traffic via the vagal nerve
to the cardioregulatory center. The efferent
traffic from this center in conjunction with a
rise in circulating catecholamines results in
increased blood pressure, pulse rate, and
cardiac output in the presence of selective
organ vasoconstriction. As a result blood
flow 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 vasoconstrictive
ischemia is manifest by abnormal organ
function and in particular by abnormal pro-
duction. From a fetal testing perspective the
critical organs in this sequence are the kid-
neys and the lungs, the principal sources of
amniotic fluid. Fetal urine production falls
in the presence of hypoxemia/acidemia, and
at near-lethal degrees of asphyxia urine pro-
duction ceases.10,11 In contrast, swallowing,
the mechanism for elimination of amniotic
fluid, 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 the
coincidence 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 by
the decline in fetal urine production, and
even with intense vasoconstriction of the re-
nal vessels some urine production persists. It
is therefore exceedingly uncommon to see
an acute decline in amniotic fluid volume in
the presence of hypoxemia, although this
has been reported.13 The average time for a
fetus to progress from normal to barely ab-
normal fluid is about 15 days; the average
time to reach severe oligohydramnios is about
978 MANNING
23 days.10 Whereas amniotic fluid volume
may be the most obvious fetal sign of chronic
hypoxemia/acidemia, it is not the only one.
Diminished and disproportionate fetal growth
is a classic finding with chronic hypox-
emia/acidemia, and indeed most of the new-
born signs of birth asphyxia can be traced back
to the reflex redistribution of blood flow.
Fetal biophysical profile scoring differs
from all other antepartum fetal testing mo-
dalities in that it combines measures of the
acute biophysical variables, fetal breathing,
heart rate accelerations, gross body move-
ments, and fetal tone (variables that reflect
the immediate fetal condition) with amniotic
fluid volume (a variable that reflects the
chronic fetal condition). In a sense, then,
were one able to converse with the fetus, the
question put by the fetal biophysical profile
score would be: How are you now, and how
have you been in the past 1 to 2 weeks? It
would appear from the data provided by the
biophysical variables sampled that this
question can be answered with considerable
accuracy.
What Does the Fetal
Biophysical Profile Score
Measure Directly?
The fetal biophysical profile score, when
normal (ⱖ8/10), is a direct, reliable, and ex-
ceedingly accurate measure of normal tissue
oxygenation 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 and
central acidemia and secondarily a measure
of the likely degree or severity of existing
central hypoxemia/acidemia (asphyxia). In-
terestingly, whereas the relationship be-
tween individual acute biophysical variables
and changes in P02 and pH are well defined
in 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 the
human. In the human the correlation be-
tween the fetal biophysical profile score and
fetal pH can be defined with precision using
cordocentesis data. In these observations the
interval between measurement of the fetal
biophysical profile score and measurement
of antepartum fetal pH (usually venous) is
usually very short, often only a few minutes.
To date, 698 paired observations of a fetal
biophysical profile score and antenatal
blood gas/pH have been reported,9,14–17 and
there are at least 600 more pairings that have
been 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 an
abnormal fetal pH. Conversely, there is less
conformity regarding the predictive accu-
racy of the abnormal profile score. How-
ever, the largest such series, involving some
493 paired observations, suggests that this
correlation is relatively precise9 (Fig. 2).
These relationships persist when the interval
between 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 Fetal
Biophysical Profile Score
Measure Indirectly?
RISK OF PERINATAL DEATH
At least until recently, the primary reason for
and purpose of antepartum fetal testing was
to identify that fetus at risk for death in utero
and effect delivery by the safest and most
expeditious route and in so doing avert the
tragic outcome. Clinical analysis of stillborn
infants and of pregnancies ending in still-
birth indicate that at least 70% of these still-
born fetuses have evidence of intrauterine
growth retardation (IUGR)19 and that 90%
or more have clinical signs of either chronic
or acute on chronic compromise.20 These
observations imply that in many and indeed
most instances there will be signs of im-
pending trouble and that these signs will be
 Fetal Biophysical Profile 979

manifest long before stillbirth occurs. The

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 between
scores of 10/10 and 8/10 and way always normal.
A progressive and highly significant direct linear
relationship was observed between abnormal
BPP scores (BPP ⱕ 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 antepartum
umbilical venous pH. Am J Obstet Gynecol.
1993;169:755, with permission.)
fetal biophysical profile score result allows
for fetuses to be classified as either having
normal blood gases and pH (normal acute
variables, normal amniotic fluid), normal
blood 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 amniotic
fluid volume) or chronic (abnormal acute
variables, decreased amniotic fluid volume)
duration. Since asphyxia is the common
mechanism for stillbirth, detection of the
presence, severity, and duration of asphyxia,
a product of fetal biophysical profile score
testing, 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 perinatal
asphyxia and delivery before extremis could
reduce the neonatal death rate. The cumula-
tive data indeed support the conclusion that
management based on fetal biophysical pro-
file scoring has a major and highly signifi-
cant impact on the stillbirth rate and a less
dramatic but nonetheless apparent effect on
neonatal death rates, and collectively pro-
duces a significant reduction in the perinatal
mortality rate within a tested popula-
tion5,21,22 (Table 1). There are no prospec-
tive blinded clinical studies to determine if
management according to the fetal biophysi-
cal profile score will reduce perinatal mor-

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 ↓32
PNM (corrected) 1.86 7.69 ↓76
SB (gross) 3.31 5.20 ↓36
SB (corrected) 1.23 4.57 ↓73
NND (gross) 3.40 4.67 ↓27
NND (corrected) 0.63 3.08 ↓80
From reference 5.
980 MANNING
tality, and any such beneficial effect must be
drawn from comparison with nontested but
not randomly selected low-risk controls or
with historical controls. Recognizing that ei-
ther comparison introduces error that might
not occur in a randomized trial, nonetheless
such 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 deaths
due to anomaly) in the tested populations as
compared with historical controls ranged
from 61% to 76%.5
Certain aspects of antepartum fetal risk
evaluation by multiple variable assessment,
as in the fetal biophysical profile score, such
as the test score distribution, are in stark con-
trast to that observed with any single vari-
able. Thus, for example, the probability of
the fetal biophysical profile score in a given
high-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 results
raises two critical issues. Firstly, if the test
were 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 percentage
of normal test results would occur. There are
two powerful arguments against this sce-
nario: a normal biophysical profile score is
never associated with concurrent acidemia,
and the fetal death rate within a week of a
normal test result is in the range of 0.4 to 0.6
per 1,000 live births (a rate that is about 10%
of the observed perinatal mortality in any
high-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 cord
compression, fetomaternal hemorrhage, or
maternal abruption). Serendipitous clinical
observations support this contention. In a re-
cent study of fetal deaths after a normal fetal
biophysical profile score, Dayal et al25 noted
that the shortest interval between a normal
score was in the range of 30 minutes. This
fetus developed an apparent acute cardiac
arrhythmia during the testing, recovered,
and then developed a second episode and
died.
The positive predictive accuracy of the
fetal biophysical profile, as expected, varies
directly with the test score result. A false-
positive rate of at least 75% is observed with
the equivocal score of 6/10, whereas the
most abnormal score (0/10) is almost always
indicative 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 testing
method. In the original blind study of fetal
biophysical profile scoring, perinatal death
was observed in association with abnormal
test results, but even under these circum-
stances most fetuses survived to delivery
and 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 sleep
state 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 fetuses
who adapt can and do survive, often for ex-
tended periods, and that concurrent with the
biophysical adaptation to asphyxia there is
most likely an endocrine response that,
through mechanisms not clearly defined,
initiates parturition and egress of the fetus
from the hostile environment. Thus, it might
be that if the fetus can live long enough after
the insult, it can escape death. The fetal bio-
physical profile measures that phase of fetal
adaptation. The perinatal mortality rate is
the ultimate measure of the success of the
adaptation.
RISK OF PERINATAL MORBIDITY
Immediate perinatal morbidity parameters
such as fetal distress in labor, delivery by ce-
sarean section for fetal distress, Apgar
 Fetal Biophysical Profile 981

scores, and birth weight centile are often

cited as measures of the accuracy of a given
testing 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, in
mimicking 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 of
adaptation to asphyxia, and since the imme-
diate neonatal adaptive reflex and direct re-
sponses are identical to those of the fetus, the
highly significant direct linear correlation
between the biophysical profile score and
Apgar score is predictable (Fig. 3). True
dysmature IUGR is a manifestation of
chronic fetal asphyxia and therefore must
and does correlate with the fetal biophysical
profile score. In essence, the fetal biophysi-
cal profile score reflects fetal adaptation to FIG. 3. Relationship between last BPS result,
asphyxia, and the immediate postnatal mor- incidence of intrauterine growth retardation
bidity measures reflect the consequences of (IUGR) and frequency of admission to a neona-
such adaptation. Accordingly, these two tal intensive care unit (NICU) for perinatal as-
variable sets ought to bear a direct linear re- phyxia. (From Manning FA. Fetal biophysical
lationship, and clinical observations con- profile scoring. In: Fetal Medicine, Principles
firm this fact. and Practice. Norwalk, CT: Appleton Lange,
The more important emerging issue cen- 1995:237, with permission.)
ters on the relationship between fetal as-
phyxia, adaptation, survival, and long-term
sequelae. If failed adaptation can result in fe- tainly yields a significant fall in perinatal
tal death, an undisputed fact, then there must mortality.
be degrees of failed adaptation to potentially Cerebral palsy, a nonprogressive neuro-
lethal asphyxia that bring the fetus near logic abnormality of varying severity, while
death. The critical clinical issue is whether of diverse etiology28 can be a consequence
such fetuses experience irreversible tissue of perinatal asphyxia. This condition may be
damage and whether this damage might be an ideal marker to examine the relationship
later expressed in the surviving infant. The between successful adaptation and insult
perhaps even more important corollary is and the impact of recognition and interven-
whether the recognition of fetuses with po- tion on disease prevalence. Because it is pos-
tentially damaging degrees of asphyxia and sible in Manitoba to access antepartum test-
timed intervention (usually delivery) can ing, obstetric, and long-term infant and
prevent some or all of the damage. The fetal childhood data by a common identity num-
biophysical profile score is undoubtedly ac- ber and generate a single comprehensive da-
curate in identifying fetuses with asphyxia at tabase for the entire population, it is also
the time of the test, and application of this possible to identify all cases of cerebral
test to a high-risk population almost cer- palsy (prevalence), stratify cases by timing
982 MANNING

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 or
older has been reported among the offspring
of 26,288 high-risk mothers subjected to se-
rial antepartum testing by fetal biophysical
profile 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). The
similarities between last biophysical profile
score and mortality, acidemia, and cerebral
palsy are remarkably similar: all are expo-
nential, inverse, and highly significant, and
the 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 the
fetal biophysical profile reflects the pres-
ence and degree of acidemia, acidemia is a
manifestation of asphyxia, and asphyxia is
the cause of either death or damage.
The relationship between last fetal bio-
physical profile score and adverse long-term
outcome is not restricted to the gross and
more 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, and
poor first-grade school performance,30 and a
similar relationship has been observed for
attention deficit disorder in children 8 years
of age or older.31 There is now increasing
tangential 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 fetuses
subjected to serial BPP testing, an inverse exponential and highly significant
relationship between BPP and cerebral palsy was observed. (From Manning
FA, Harman CR, Menticoglou S, et al. Fetal assessment by fetal biophysical
profile score. VI. The incidence of cerebral palsy among tested and non-
tested perinates. Am J Obstet Gynecol. 1998;178:696, with permission.)

FIG. 5. Relationship between the last bio-
physical profile and select end points including
perinatal morbidity (cumulative), antepartum fe-
tal umbilical vein acidemia (pH ⱕ 7.20), perina-
tal mortality (PNM), and cerebral palsy at age 5
years. The relationship is inverse and linear,
whereas the relationship for acidemia, death, and
cerebral palsy is inverse and exponential. The
similarity in relationships for the latter three end
points implies that each represents failed fetal
compensation and that the clinical line between
acidemia-related death and damage is likely to
be fine. (From Manning FA. Fetal biophysical
profile scoring. In: Fetal Medicine, Principles
and Practice. Norwalk, CT: Appleton Lange,
1995, with permission.)
that term infants born with severe (<3d cen-
tile) dysmature IUGR (a fetal adaptation to
asphyxia) are as young adults significantly
more likely to either fail or not take the tests
of higher education.32
The question of whether recognition of
fetal asphyxia and intervention can prevent
sequelae is at the heart of all antepartum test-
ing strategies. Using perinatal death as the
endpoint, it appears evident that manage-
ment based on fetal biophysical profile scor-
ing can achieve this goal. Recent data sug-
Fetal Biophysical Profile 983
gest that same benefit might be achieved for
cerebral palsy and other long-term end-
points. In a comparative study between
58,659 low-risk obstetric patients managed
by conventional means and without using
fetal biophysical profile scores and 26,288
high-risk patients whose management in-
cluded fetal biophysical profile score testing
and intervention for abnormal test scores,
the incidence of cerebral palsy at age 5 years
was significantly lower in the tested high-
risk group than in the nontested low-risk
group (1.33/1,000 vs. 4.74/1,000, P <
0.0001)29 (Fig. 6). These observations are in
opposition to the conventional thought that
cerebral palsy cannot be prevented or
avoided. In similar comparative studies the
incidence of mental retardation, language
development delay, cortical blindness and
deafness, and attention deficit disorders was
significantly lower in tested high-risk fe-
tuses than in nontested low-risk controls.
Collectively these data imply that the clini-
FIG. 6. Incidence of cerebral palsy (CP) at age
5 years among 26,288 high-risk fetuses sub-
jected to serial biophysical profile (BPP) testing
and among 58,659 contemporaneous nontested
predominantly low-risk patients. In the tested
group /in whom intervention occurred for a per-
sistent BPP of 6/10 or less, the CP rate was 1.33
per 1000, compared with an observed rate of
7.74 per 1000 in the nontested patients. These
differences were highly significant. (From
Manning FA. Fetal biophysical profile scoring.
In: Fetal Medicine, Principles and Practice.
Norwalk, CT: Appleton Lange, 1995, with
permission.)
984 MANNING
cal benefits of antepartum testing by the fe-
tal biophysical profile scoring method will
extend beyond prevention of perinatal death
and immediate morbidity and extend to in-
fant and childhood health.
At the other extreme of age, Barker et al33
reported that low birthweight is associated
with a significantly increased risk of late
adult-onset hypertension and cardiovascu-
lar-related morbidity and mortality. The
alpha–omega theory encompasses these col-
lective observations and suggests that prena-
tal adaptation to fetal asphyxial is manifest
as a spectrum of disease across the span of
postnatal life.34 A key question is whether
prenatal 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 on
immediate endpoints (perinatal mortality)
and infant and childhood diseases seems
evident, there is as of yet insufficient obser-
vation time to measure the impact, if any, in
late adult life. Fortunately the data bases are
now secured that will allow such future
evaluations. It seems a reasonable and safe
prediction that the same beneficial effect of
asphyxia recognition and intervention will
accrue to the individual at risk for cardiovas-
cular disease in late life. What an odd and
complete full circle it would be if antepar-
tum testing were the first step in securing
sustained extrauterine health! The evidence
to date suggests this will in fact be the case.
References
1. Cohn HE, Sacks GT, et al. Cardiovascular
responses to hypoxemia and acidemia in fe-
tal lambs. Am J Obstet Gynecol. 1974;120:
817.
2. Patrick JE, Dalton KJ, Dawes GS. Breathing
patterns before death in fetal lambs. Am J
Obstet Gynecol. 1976;125:73.
3. Manning FA, Martin CVB Jr, Murata Y, et
al. Breathing movements before death in the
primate fetus. Am J Obstet Gynecol. 1979;
135:71.
4. Manning FA, Harman CR, Boyce D, et al.
Intrauterine fetal tachypnea. Am J Obstet
Gynecol. 1982;144:356.
5. Manning FA. Fetal biophysical profile scor-
ing. In: Fetal Medicine, Principles and Prac-
tice. Norwalk, CT: Appleton Lange,
1995:237.
6. Bocking AD, Gagnon R, Milne KM, White
SE. Behavioral activity during prolonged
hypoxemia in fetal sheep. J Appl Physiol.
1988;65:2420.
7. Harman CR, Menticoglou S, Manning FA,
Morrison I. Fetal biophysical variables and
fetal status. In: Asphyxia and Fetal Brain
Damage. New York: Wiley-Liss, 279.
8. Boddy K, Dawes GS, Fisher R, et al. Fetal
respiratory movements, electrocortical and
cardiovascular responses to hypoxemia and
hypercapnia in sheep. J Physiol (London).
1974;243:599.
9. Manning FA, Snijders RJM, Harman CR.
Fetal biophysical profile scoring. VI. Corre-
lation with antepartum umbilical venous
pH. Am J Obstet Gynecol. 1993;169:755.
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 renal
failure associated with intrauterine growth
retardation. 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 2000
14. 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, et
al. Prediction of fetal acidemia in pregnan-
cies complicated by maternal diabetes by fe-
tal biophysical profile scoring and fetal
heart rate monitoring. Br J Obstet Gynecol.
1993;100:227.
16. Ribbert LSM, Snijders RJM, Nicolaides
KH. Relationship of fetal biophysical pro-
file and blood gas values at cordocentesis in
severely 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 blood
gas levels obtained by cordocentesis. Acta
Obstet Gynecol Japan. 1991;43:1573.

18. Vintzileos AM, Fleming AD, Scorza WE, et
al. Relationship between fetal biophysical
profile activities and cord gas values. Am J
Obstet 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 J
Med Sci. 1991;160:251.
21. Manning FA, Morrison I, Lange I, et al. Fe-
tal assessment based on fetal biophysical
profile scoring: Experience in 12,620 re-
ferred high-risk pregnancies. Am J Obstet
Gynecol. 1985;151:343.
22. Baskett TF, Allen AC, Gray JH, et al. Fetal
biophysical 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 19,921
referred high-risk pregnancies. II. The false-
negative rate by frequency and etiology. Am
J Obstet Gynecol. 1987;157:880.
25. Dayal A, Manning FA, Harman CR, Berck
D. 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 biophysical
profile scoring. IV. Positive predictive accu-
Fetal Biophysical Profile 985
racy of the abnormal test. Am J Obstet Gy-
necol. 1990;162:703.
27. Freeman RK, Anderson G, Dorchester W. A
prospective multi-institutional study of an-
tepartum fetal heart rate monitoring. I. Risk
of perinatal mortality and morbidity accord-
ing to antepartum fetal heart rate results. Am
J Obstet Gynecol. 1982;143:771.
28. Manning FA, Bondagji N, Harman CR, et al.
The relationship of the fetal biophysical to
the incidence of cerebral palsy. Eur J Obstet
Gynecol Reprod Sci. 1981;138:675.
29. Manning FA, Harman CR, Menticoglou S,
et al. Fetal assessment by fetal biophysical
profile score. VI. The incidence of cerebral
palsy among tested and non-tested peri-
nates. Am J Obstet Gynecol. 1998;178:696.
30. Manning FA. Unpublished data 2002
31. Manning FA. The fetal biophysical profile
score. Obstet Gynecol Clin North Am.
1999;26:557.
32. Larroque B, Bertrais S, Czernichow P,
Leger J. School difficulties in 20-year-olds
who were born small for gestational age at
term in a regional cohort study. Pediatrics.
2001;108:111–115.
33. Barker DPJ, Osmond C, Golding J, et al.
Growth in utero, blood pressure in child-
hood and adult life, and mortality from car-
diovascular disease. Br Med J. 1989;298:
564.
34. Manning FA. The alpha-omega theory: The
prenatal origins of postnatal disease. OB
Management 2000, p. 30.