American Journal of Obstetrics and Gynecology

Founded in 1920
volume 187 number 1 JULY 2002

CLINICAL OPINION

Use of umbilical artery base excess: Algorithm for the

timing of hypoxic injury
Michael G. Ross, MD, and Rageev Gala, MD
Torrance, Calif

Intrapartum asphyxia is responsible for only a small proportion of cerebral palsy cases, although
obstetricians are often held accountable. Umbilical cord pH and blood gas values provide valuable
information regarding the status of the infant at birth; base excess determination quantifies the magnitude of
metabolic acidosis, the putative risk factor for central neurologic injury. Human and animals studies have
confirmed normal values of base excess before labor, and consistent rates of base excess change in relation
to the degree of fetal hypoxemia or heart rate patterns. Thus, the combination of assumed base excess
values before labor and measured values after birth, together with an assessment of degrees of fetal
hypoxemia during labor, permits an interpolation of fetal base excess values throughout the course of labor.
Because threshold levels of base excess (eg, –12 mmol/L) have been associated with an increased risk of
neonatal neurologic injury, this approach provides a framework for the assessment of fetal heart rate tracings
during labor and, potentially, the timing of hypoxic/ischemic injury. (Am J Obstet Gynecol 2002;187:1-9.)

Key words: Cerebral palsy, fetus, brain damage

Cerebral palsy is a chronic nonprogressive neuromuscu-
lar condition that results in muscular spasticity or paralysis
and may have associated mental retardation. It was previ-
ously believed that intrapartum hypoxemia and asphyxia
was a primary cause for the 1 to 2 cases of cerebral palsy per
1000 live births. Earlier studies concluded that up to 50% of
cerebral palsy was attributable to perinatal asphyxia. More
recently, it has been recognized that intrapartum asphyxia
is accountable for only 10% of cases. Just as the cause for
most cases of cerebral palsy are unknown, most asphyxiated
newborns do not have cerebral palsy. Nevertheless, obste-
tricians are often held responsible for this adverse out-
come; the cause frequently is attributed to intrapartum
From the Department of Obstetrics and Gynecology, Harbor–University of
California Los Angeles Medical Center.
Received for publication September 19, 2001; revised December 21,
2001; accepted January 17, 2002.
Reprint requests: Michael G. Ross, MD, MPH, Harbor–UCLA -
Medical Center, 1000 W Carson St, Box 3, Torrance, CA 90509.
E-mail: mikeross@ucla.edu
© 2002, Mosby, Inc. All rights reserved.
0002-9378/2002 $35.00 + 0 6/1/123204
doi:10.1067/mob.2002.123204
asphyxia, as evidenced by fetal heart rate abnormalities,
meconium staining, low Apgar scores, neonatal en-
cephalopathy, nucleated red blood cells, and/or umbilical
cord acidosis. However, many of these surrogate markers
may occur in infants with preexisting antenatal neurologic
damage and may be unrelated to acute asphyxial injury.
Consequently, the timing of perinatal neurologic injury
has been a frequent controversy in the determination of
medicolegal causation, preventability, and liability. Perhaps
more importantly, the lack of consensus on the timing of in-
trapartum hypoxic injury has limited advancements in fetal
heart rate monitoring interpretation and the development
of accepted protocols for treatment of heart rate abnor-
malities.
The modalities that are available to time neurologic in-
sults (eg, biochemical markers, electroencephalogram,
magnetic resonance and computer tomography imaging,
clinical course) may be valuable in the determination of
antenatal versus intrapartum events. However, for those
cases thought to result from intrapartum asphyxia, these
modalities are generally unable to differentiate time peri-
ods of minutes to hours in which potential interventions

1
2 Ross and Gala
may be alleged to have or have not occurred. Yet, timing
to this precision is often essential, both for a deter-
mination of the opportunity and/or responsibility for
prevention and to learn the margin of safety and possible
outcomes of future clinical practice.
Although fetal umbilical artery or vein pH has
been historically used as a primary marker of hypoxic/
ischemic injury, “base excess” is currently often reported.
To provide the clinician with a full understanding of new-
born acid base assessments, we sought to present a review
of the derivation of base excess. Further, we provide a
schema in which base excess may be used, in conjunction
with the fetal heart monitor patterns, to provide a frame-
work for the timing of hypoxic/ischemic injury.
Basics of acid and base balance
The concentration of hydrogen ions is expressed as
pH, which is calculated as the negative log of the hydro-
gen ion concentration; thus, the pH falls as the hydrogen
ion concentration exponentially increases. The normal
pH of arterial blood in the adult is 7.4; the normal pH of
venous blood is 7.35. Deviation in the pH above or below
the normal values constitutes alkalosis and acidosis, re-
spectively.
The PCO2 is inversely related to pH. When gaseous car-
bon dioxide (CO2) is allowed to come into equilibrium
with dissolved CO2, the partial pressures of both are
equal. The presence of the enzyme carbonic anhydrase in
red blood cells allows for the rapid formation of carbonic
acid from CO2:
CO2 + H2O ←→ H2CO3 (1)
Because of the lack of carbonic anhydrase in the
plasma, this equation is displaced far to the left, and for
all practical purposes, the concentration of carbonic acid
in plasma is negligible.
Need for normal plasma and cellular pH
Hydrogen ion concentration is a fundamental factor in
the maintenance of body homeostasis. Even slight devia-
tions of hydrogen ion concentration from normal values
can cause marked changes in the rates of chemical reac-
tions throughout the body. Hydrogen ion concentration
also affects and is affected by the exchange of gasses and
cellular metabolism. Severe acidosis can lead to death
through coma, although severe alkalosis may result in
tetany and convulsions. Because hydrogen ion concentra-
tion plays such a vital role in homeostasis, our physiologic
features provide for defenses against its variation in the
form of buffers, stimulation of the respiratory center, and
alteration of urine production.
Buffers
An acid-base buffer is a solution that contains 2 or more
chemical compounds that prevents marked changes in hy-
July 2002
Am J Obstet Gynecol
drogen ion concentration when either an acid or a base is
added to the solution. Hydrogen ions are constantly being
produced throughout the body, and the presence of
buffers allows the body to maintain a relatively constant pH,
and thus free hydrogen ion concentration, under normal
and some abnormal circumstances. The buffers can be di-
vided into bicarbonate buffers and nonbicarbonate buffers,
which account for 53% and 47% of the total buffering ca-
pacity, respectively. Bicarbonate buffers, which are primar-
ily in red blood cells that contain carbonic anhydrase,
buffer hydrogen ions in the following manner:
H+ + HCO3– ←→ H2CO3 ←→ CO2 + H2O (2)
Importantly, carbonic acid is highly volatile; therefore,
the bicarbonate buffering system is subject to physiologic
regulation. As a result, pH may be influenced by the con-
centration of the various components in the equation.
Nonbicarbonate buffers consist of hemoglobin, organic
phosphates, inorganic phosphates, and plasma proteins.
Among these, hemoglobin is responsible for most of the
buffering in the following reaction:
H+ + HbO2 ←→ HHb + O2 (3)
Respiratory and metabolic acidosis
Respiratory acidosis occurs in response to excess carbon
dioxide levels, which leads to an increase in dissolved car-
bon dioxide that is converted into H2CO3 and ultimately
H+ and HCO3–, thus giving rise to acidosis (equation 2).
Metabolic acidosis refers to acidosis that is not caused by
carbon dioxide of respiratory origin. Causes of metabolic
acidosis include failure of the kidneys to excrete acids (eg,
uremia), excessive formation of metabolic acids in the
body (eg, hypoxemia, diabetes mellitus), oral and intrave-
nous administration of metabolic acids, and loss of base
from the body fluids, as in diarrhea and severe vomiting. In
regard to the timing of hypoxic injury, measures of meta-
bolic acidosis are of greater value than measures of respi-
ratory acidosis. Although hypoxemia may occur
concomitantly with hypercarbia, and thus respiratory aci-
dosis, it is the cellular production of metabolic acids that
reflects the degree of insult or injury.
Fetal asphyxia can be defined as a condition of impaired
blood gas exchange that leads to progressive hypoxemia
and hypercapnia, with a significant metabolic acidosis.1
The process by which fetal asphyxia leads to metabolic aci-
dosis is as follows: fetal asphyxia → Tissue oxygen debt →
Hyperlactemia with increased lactate/pyruvate ratio →
metabolic acidosis with decreased buffer base → decrease
of pH. Although many acids may contribute to the acido-
sis, the principal fixed acid is lactic acid.
Base excess
As noted earlier, pH may be influenced by both respi-
ratory and metabolic alterations. Because pH represents
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Am J Obstet Gynecol
the inverse log of the hydrogen ion concentration, it does
not change linearly with hydrogen ion concentration or
with the use of base. For example, the amount of acid that
is necessary to effect a 0.1 unit reduction in pH from 7.4
to 7.3 is markedly less than the acid needed to reduce pH
from 7.0 to 6.9. If one assumes that organ and cellular re-
sponses to hypoxia/ischemia result in the accumulation
of acid in a relatively linear proportion to the degree and
duration of the insult, the exponential function pH has
limited usefulness in the prediction of hypoxia timing.
Base excess can be most easily explained as an excess or
deficit of buffer base as compared with the normal values
of buffer base in the system:
Base excess =
Observed buffer base – Normal buffer base (4)
Base excess represents a linear correlate and thus a po-
tentially valuable index of the degree and duration of
metabolic acidosis.
Base excess can be calculated with the alignment
nomogram of Siggaard-Andersen (Figure). With this
nomogram, if 2 factors of the Henderson-Hasselbalch
equation (pH = pK + log10 [HCO3–]/.03 [PaCO2]) are
known, they can be plotted to determine the third factor.
The base excess can be derived from the point at which
the line cuts the curved grid of the nomogram. Blood
base excess is defined as the titratable base of blood and
may be experimentally determined by titration with
strong acid or base to a plasma pH of 7.40 with PCO2 = 40
mm Hg at 37°C. Alternatively, automated acid base ana-
lyzers use the following formulas:
Bicarbonate concentration:
log10 [HCO3–] = pH + log10 PCO2 – 7.604 (5)
Base excess (blood) = (1 – 0.014[Hb])
([HCO3–] – 24 + [1.43(Hb) + 7.7][pH – 7.4]) (6)
Base excess of the extra cellular fluid or standard base
excess is a measure of the metabolic component of the
acid-base interbalance in a patient. As with the titratable
base of blood, the base excess of extra cellular fluid may
be experimentally determined by the titration of a model
of extra cellular fluid. Acid base analyzers calculate base
excess of extra cellular fluid as follows:
Base excess (extracellular fluid) =
(HCO3–) – 25 + 16.2(pH – 7.400) (7)
From the formulas for base excess (blood) and base ex-
cess (extracellular fluid), it is apparent that the values will
be similar, although statistically different. Considering a
hypothetic example, assuming that HCO3– = 15, Hb = 18,
and pH = 7.2, the calculated base excess will be –12.56
mmol/L in blood and –13.24 mmol/L in extracellular
fluid. The base excess of the extracellular fluid better rep-
resents the organism’s ability to prevent a fall in pH. There-
Ross and Gala 3
fore, unless otherwise specified, the term base excess in this
article refers to the base excess of the extracellular fluid.
Abnormal base excess values during labor
There have been several studies that examined the in-
cidence of abnormal base excess values.1,2 Low et al2 ini-
tially used a measure of buffer base (<36.1 mEq/L) as an
indicator of acidosis and in subsequent studies reverted
to the use of a (nearly equivalent) base excess <–12
mmol/L. For consistency, we will refer to both buffer
base and base excess measurement in terms of millimoles
per liter. Among high-risk patients in the early 1970s, the
incidence of asphyxia (buffer base, <36.1 mmol/L) was
reported as high as 20%,2 although this rate has likely de-
creased at present. Among a normal obstetric popula-
tion, the incidence of base excess of <–12 mmol/L was
2%, although only 0.5% had values of <–16 mmol/L.1 A
base excess of –12 mmol/L is approximately 2 SDs below
the mean.3,4
Effects of base excess values on fetal outcome
Fetal and intrapartum asphyxia that leads to newborn
acidosis are recognized as serious threats to fetal and new-
born survival and quality of life. Among term infants with
neonatal acidosis, respiratory acidosis alone is generally
not associated with newborn complications.5 In a study
that matched 59 term fetuses with metabolic acidosis, 59
control fetuses, and 51 fetuses with respiratory acidosis,
the complication rate was higher in the metabolic acido-
sis group (78%) than in the control group (27%), and
there was no significant difference between the respira-
tory acidosis and control groups.5 Among those infants
with multiorgan complications, 23 of 27 complications
were from the metabolic acidosis group. The frequency
and severity of the complications in the metabolic acido-
sis group increased as the severity and duration of the aci-
dosis increased. In a similar study of preterm infants,6
fetal asphyxia contributed significantly to neonatal com-
plications among newborns who were delivered at 32 to
36 weeks, although not in newborns who were delivered
at <32 weeks. Seven of the 8 deaths in the study popula-
tion occurred among neonates with asphyxia. These stud-
ies may suggest that the term newborn is less vulnerable
to complications of metabolic acidosis than the 32 to 36
week newborn, but more vulnerable than the extremely
premature newborn (<32 weeks). Alternatively, the pre-
term fetus may compensate for a longer period of time,
before decompensating in a more profound manner
compared with the term infant.
Sequelae of asphyxia and metabolic acidosis
During the first few days of newborn life, the conse-
quences of asphyxia with metabolic acidosis vary from no
ill effects to multiorgan complications and death. This
huge diversity in outcome is a result of the severity and
4 Ross and Gala
Figure. Siggaard-Andersen alignment nomogram.
duration of the asphyxia and the occurrence of asphyxia-
induced cardiovascular decompensation and hypo-
tension. As one would assume, the severity of the
complication is directly related to the severity and dura-
tion of the asphyxial insult and the time to recovery.
Although cardiovascular, renal, and respiratory complica-
tions occur in association with asphyxia, early-onset en-
cephalopathy is the best single predictor of long-term
outcome.1 Low1 has proposed 3 levels of newborn en-
cephalopathy: minor encephalopathy that consists of
newborn jitteriness and irritability, moderate en-
cephalopathy that consists of lethargy or abnormal
July 2002
Am J Obstet Gynecol
neonatal tone, and severe encephalopathy that consists of
coma or both abnormal tone and seizures. However, the
threshold for newborn central nervous system injury may
be at the severe end of the spectrum of intrapartum as-
phyxia.7 Compared with a matched cohort of control ma-
ture newborns, infants with intrapartum asphyxia (buffer
base, <34 mmol/L) demonstrated no differences in be-
havioral assessments at 2 days and 3 weeks. Notably, only
6% of newborns with intrapartum asphyxia exhibited en-
cephalopathy during the neonatal period.7
Risk factors may aid in the prediction of both the cause
and outcome of neonatal encephalopathy. Among 303
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high-risk preterm and term newborns, 72% of infants
with mild-moderate encephalopathy had no identifiable
risk factors. However, severe encephalopathy was attrib-
uted to fetal hypoxemia in 22% of cases.8 Alternatively,
Volpe9 followed 100 consecutive mature newborns with
hypoxic-ischemic encephalopathy and attributed 90% of
the cases to definite or probably intrauterine fetal as-
phyxia and only 10% to postnatal asphyxia. The differ-
ence between these studies may be due to the increased
number of risk factors and the inclusion of preterm new-
borns,8 which resulted in more numerous and severe
episodes of postnatal asphyxia.
Newborn complications and the incidence of cerebral
palsy are dependent on the degree and severity of hypox-
emia and metabolic acidosis. Among term infants who
were born with metabolic acidosis, the incidence of major
or minor motor and/or cognitive deficits at 1 year of age
increased from 20% in infants with an umbilical artery
buffer base of 30 to 34 mmol/L to 80% among infants with
buffer base of <22 mmol/L. In proposing a base excess
level of <–12 mmol/L as a threshold of metabolic acidosis
that is associated with newborn complications, Low et al10
examined the newborn course of 174 term newborns with
a range of umbilical artery base excess. Among infants with
a base excess of –12 to –16 mmol/L, moderate and severe
newborn encephalopathy and respiratory complications
occurred in 10%. Similarly, after intrapartum asphyxia
(buffer base, <34 mmol/L), the incidence of major or
minor deficits was 20%, which increased to 80% among in-
fants with the most severe metabolic acidosis (buffer base,
<22 mmol/L).11 A subsequent study confirmed a 14% in-
cidence of major deficits and a 27% incidence of minor
deficits at 1 year of age among infants with a newborn
buffer base of <34 mmol/L.12
Prelabor base excess in the human fetus
As a result of gestational physiologic features, human
fetal arterial pH and PO2 are lower, and PCO2 is higher
than maternal values.13 As pregnancy advances, fetal PO2
and pH decrease and PCO2 increases.13 Fetal arterial PO2
falls as a result of increased placental and fetal consump-
tion, although the total oxygen content in fetal blood
remains relatively stable because of fetal physiologic
adaptive mechanisms (eg, increased hemoglobin). The
metabolic increase in oxygen consumption contributes to
a rise in fetal PCO2.
Data on normal human fetal base excess values are lim-
ited. However, normal respiratory gas and acid base val-
ues were reported by Lazarevic et al13 after cordocentesis
on 70 uncomplicated pregnant patients between 18 to 38
weeks of gestation. Mean values for base excess and pH
were –2.3 ± 0.6 mmol/L and 7.39 ± 0.05 mmol/L, respec-
tively. The authors confirmed a negative correlation be-
tween gestational age and pH and PO2 and a positive
correlation with the PCO2. Base excess values did not
Ross and Gala 5
change with gestation. Similar results have been obtained
from other studies. Thus, the normal fetus may be ex-
pected to enter labor with a base excess of approximately
–2 mmol/L, although there may be individual variation.
Base excess during normal labor: First and
second stage
The process of normal labor and vaginal delivery
stresses the fetus such that there is the development of
mild acidosis in almost all labors. To assess the base excess
values of nonasphyxiated newborns, Helwig et al3 exam-
ined the records of 15,703 newborns with a 5-minute
Apgar of >7. The mean umbilical artery and umbilical
vein base excess values were –4 ± 3 mmol/L and –3 ± 3
mmol/L, respectively. Notably, the 2.5 percentile of the
umbilical artery base excess was –11. Similarly, Arikan et
al4 reported mean umbilical artery and umbilical vein
base excess values of –4.8 and –3.9 mmol/L, respectively,
in more than 1500 live-born neonates. Postterm infants
had values approximately 1 mmol/L lower. Acidosis, de-
fined as 2 SDs below the mean, was a base excess of –10.5
mmol/L. This was in agreement with the results of Hel-
wig et al.3Assuming that the normal fetus enters labor
with a base excess of –2 mmol/L, one may therefore ex-
pect uncomplicated labor to reduce the base excess by an
additional 3 mmol/L.
Hagelin and Leyon14 developed regression equations
that correlate umbilical artery blood with the duration of
first- and second-stage labor among 1255 singleton term
infants with vertex presentation and nonoperative vaginal
deliveries. Although there was no statistical correlation
with the duration of the first stage of labor, fetuses were
predicted to enter the second stage with base excess val-
ues of –2 to –4 mmol/L. Assuming a normal 6-hour active
phase of labor, these studies suggest that the stress of nor-
mal (active phase) labor may decrease fetal base excess by
–1 mmol/L per 3 to 6 hours. The correlation analysis of
Hagelin and Leyon suggested that additional fetal stress
occurs in the second stage because base excess decreased
by 0.7 and 1.3 times the duration (hours) of the second
stage of labor in nulliparous and multiparous women, re-
spectively. Thus, on average, the normal stress of second-
stage labor may decrease base excess by approximately 1
mmol/L per hour in the normal fetus.
Base excess during human fetal compromise
As noted earlier, the average fetus enters labor with a
base excess of –2 mmol/L. In normal active phase labor,
base excess may decrease by 1 mmol/L per 3 to 6 hours,
with a further decrease of approximately 1 mmol/L per
hour of second stage. These values assume the normal
stresses of active phase labor and the commonly occur-
ring variable heart rate decelerations in the second stage.
Because base excess decreases in proportion to the de-
gree of fetal compromise, quantification of total and late
6 Ross and Gala
fetal heart rate decelerations can predict the probability
of fetal asphyxia. More recently, Dellinger et al15 demon-
strated a progressive decline in base excess at delivery
with a classification of heart rate patterns from normal to
fetal stress to fetal distress.
Importantly, there has been little examination of the
rate of base excess loss in comparison with fetal heart rate
patterns, because of, in part, limitations of repeated fetal
scalp blood sampling and the obvious interventions that
are prompted with the recognition of fetal compromise.
Nevertheless, several studies provide an index for rates of
base excess changes in relation to intrapartum asphyxia.
Among fetuses that exhibit repetitive fetal heart rate de-
celerations for periods of hours, buffer base decreased by
approximately 4 mmol/L during the 2 hours before de-
livery (ie, 1 mmol/L per 30 minutes).16 Although the
fetal heart rate patterns were not quantified, fetuses with
intrapartum hypoxemia that result in asphyxia demon-
strated a decrease in buffer base of 8 to 11 mmol/L dur-
ing the last 60 minutes of labor (ie, 1 mmol/L per 6
minutes).11 Conversely, among fetuses with terminal as-
phyxia, buffer base decreased an average of 7 mmol/L in
the 15 minutes before delivery (ie, 1 mmol/L per 2 min-
utes).16 Studies of acute uterine rupture provide an
assessment of human fetal base excess loss under condi-
tions of severe hypoxemia. The mean base excess was
–10.4 mmol/L among 82 neonates who were delivered
after acute uterine rupture, without any apparent nursery
morbidity.17 Because 73% of patients received oxytocin
for an average duration of ≥10 hours,17 one may reason-
ably assume a base excess before acute uterine rupture of
–2 to –4 mmol/L. The mean time from onset of pro-
longed deceleration to delivery was 13 to 14 minutes
among those infants who experienced only a prolonged
deceleration or among all infants with “no complica-
tion.”17 The estimated base excess loss of approximately 6
to 7 mmol/L during the prolonged deceleration (13 to
14 minutes) is consistent with a loss of 1 mmol/L per 2
minutes of severe compromise.
These results suggest that fetal stress (eg, repetitive typ-
ical severe variable decelerations that may or may not
prompt physician intervention) may reduce the buffer
base by approximately 1 mmol/L per 30 minutes, that
subacute fetal compromise may reduce the buffer base by
1 mmol/L per 6 to 15 minutes, and that acute, severe
compromise (eg, terminal bradycardia) may reduce the
buffer base by as much as 1 mmol/L per 2 to 3 minutes.
Umbilical artery versus umbilical vein
base excess
There are typically marked differences in umbilical
artery and vein gas partial pressures (ie, PO2 and PCO2.).
In contrast, fetal cord blood artery and vein base excess
values generally are similar because of the limited trans-
fer of bicarbonate across the placenta. However, there are
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Am J Obstet Gynecol
occasions in which marked differences are observed. Low
et al6 postulated that long-duration asphyxia results in an
umbilical artery–to–vein buffer base difference of <6
mmol/L; short duration asphyxia results in an artery-to-
vein buffer base difference of >6 mmol/L. However, we
believe it is more likely that the greater buffer base differ-
ences are due to markedly restricted placental blood flow
that is associated with severe umbilical cord compression,
such that umbilical vein values reflect the fetal acid-base
condition at the time of initiation of cord compression
(ie, similar to cord clamping at birth). As such, the hy-
pothesis of Low et al would be consistent with a large base
excess difference that occurs in acute asphyxia that is as-
sociated with umbilical cord compression or prolapse, al-
though not with abruptio placentae or uterine rupture.
Because this article6 was published before the increased
use of vaginal birth after cesarean delivery, it is likely that
their case mix included few patients with acute uterine
rupture.
Changes in base excess after birth
Often umbilical artery values are not available for the
assessment of fetal status at birth, and the assessment is
limited to postnatal arterial or venous determinations. Al-
though base excess values were not presented, Casey et
al18 demonstrated that the direction of pH change from
birth in the immediate neonatal period was related to
morbidity and death. Buffer base loss is unlikely to occur
in the neonatal period, unless continued neonatal severe
hypoxemia, hypotension, or sepsis is evident. Therefore,
if no sodium bicarbonate (alkali) is administered, one
may assume minimal acute changes in the buffer base
among infants who are appropriately resuscitated and
oxygenated in the immediate newborn period. Con-
versely, continued severe hypoxemia (eg, inadequate ven-
tilation) during the neonatal period may be expected to
result in base excess losses similar to severe intrapartum
asphyxia (ie, 1 mmol/L per 2 minutes).
Fetal base excess: Animal studies
Because of the limited information from human stud-
ies, animal studies (particularly fetal sheep) have pro-
vided important information regarding fetal loss of
buffer base in response to hypoxemia. Fetal responses
differ markedly, depending on the model of hypoxemia,
because fetal cardiac output may increase (eg, maternal
hypoxemia) or decrease (eg, umbilical cord occlusion) in
conjunction with the model of hypoxemia.
Maternal hypoxemia. Perhaps the most widely used
fetal hypoxemia model has been the reduction in mater-
nal inspired oxygen. With this model, mild fetal hy-
poxemia to a fetal arterial saturation of 40% (ie, 20%
decrease in fetal PO2) does not result in loss of fetal buffer
base, even when continued for 24 hours.19 However, a de-
crease in fetal arterial oxygen saturation to <30% (ie,
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Am J Obstet Gynecol
35% decrease in fetal PO2) begins to evoke a decrease in
the fetal buffer base.20 Maternal hypoxemia that evoked a
35% reduction in fetal PO2 decreased fetal base excess to
–4 mmol/L at 1.4 hour and –12 at 2.8 hours.21 A similar
reduction in fetal PO2 (18 to 10 mm Hg) resulted in a re-
duction in base excess of 3 mmol/L per hour.22 Notably,
with stable fetal hypoxemia, the linear reduction in base
excess continued from l.4 to 7.4 hours. Thus, fetal base
excess is not appreciably affected until oxygen saturation
is reduced to <30%, after which chronic reductions near
this saturation level result in a linear reduction in buffer
base at approximately 3 mmol/L per hour. Notably, the
preterm ovine fetus may be somewhat resistant to the
metabolic effects of hypoxemia because a similar de-
crease in maternal hypoxemia–induced fetal hypoxemia
to an oxygen saturation level of <30% (45% decrease in
fetal PO2) decreases base excess only 1 to 2 mmol/L per
hour.23
Umbilical cord occlusion. Umbilical cord occlusion in
ovine fetuses may be used to simulate human fetal cord
occlusion (eg, acute bradycardia, prolapsed cord), which
evokes compensatory cardiovascular responses different
from those of maternal hypoxemia. Severe cord occlu-
sion that reduced fetal PO2 by 50% (28 to 15 mm Hg) re-
sulted in a fetal base excess of –10 mmol/L by 15 minutes
of occlusion.24 Intermittent total cord occlusion of 1
minute every 2.5 minutes, or 2 minutes every 5 minutes,
for a total of 48 to 54 minutes of occlusion induced a base
excess of –24 mmol/L, thus approximating a loss of 1
mmol/L per 2 minute of occlusion.25 Similarly, severe
cord occlusion for 60 minutes has produced a base excess
of –20 mmol/L at 60 minutes of occlusion. The compila-
tion of these studies suggests that repetitive intermittent
or continuous cord occlusion reduces the buffer base by
1 mmol/L per 1.5 to 3 minutes of occlusion. Conversely,
if cord occlusion is sufficiently spaced such that the fetus
can compensate (eg, partial cord occlusion for 1 minute
of every 3 or 5 minutes), then the base excess loss may
occur at a rate similar to that of moderate hypoxemia (eg,
2 mmol/L per hour).25
Reduced uterine blood flow. A model of reduced mater-
nal uterine blood flow perhaps best resembles the events
of abruptio placentae because it does not restrict fetal
cardiac output. Stepwise reduction in uterine blood flow
that was maintained for 60 minutes to reduce fetal PO2 by
40% induced a decrease in fetal base excess to –18
mmol.26 This rate (–1 mmol/L per 3 minute) approxi-
mates the loss of the buffer base that occurs with severe
cord occlusion. In models of reduced uterine blood flow,
the degree of fetal hypoxemia correlates with the loss of
the buffer base, similar to that noted in models of re-
duced uterine blood flow. A 25% reduction in fetal arte-
rial PO2 that is associated with a fetal oxygen saturation of
30% resulted in a base excess of –5 mmol/L at 1 hour.27
Notably, normalization of uterine blood flow for 30 min-
Ross and Gala 7
utes after the occlusion did not substantially change the
base excess, which indicates that in utero resuscitation
may correct oxygenation, but it does not rapidly alter
base excess values.26
Human and sheep correlation
Although there are marked variations in the models of
hypoxemia and the available human and ovine data
(human fetal heart rate monitors and scalp or cord blood
vs ovine fetal arterial blood pressure, heart rate, and
repetitive arterial blood samples), the compilation of
ovine and human studies demonstrate marked similari-
ties. Mild hypoxemia does not alter ovine fetal base ex-
cess until the oxygen saturation decreases to <30%. With
moderate hypoxemia (oxygen saturation, <30%), ovine
fetal base excess decreases by 2 to 3 mmol/L per hour,
which is similar to that observed in human fetuses who
have repetitive observed fetal heart rate decelerations. Se-
vere cord occlusion or marked reductions in uterine
blood flow (eg, ruptured uterus) may decrease ovine or
human fetal base excess by 1 mmol/L per 2 to 3 minutes.
Timing of irreversible human fetal asphyxial
injury
There are several principals that may be used to deter-
mine the timing of irreversible asphyxial human fetal in-
jury to a “more likely than not” (ie, >50%) probability.
First, we may assume that asphyxial injury does not occur
until fetal base excess is ≤–12 mmol/L. Notably, most
newborns with a base excess of <–12 mmol/L do not
demonstrate neurologic injury. Even at levels of severe
acidosis (base excess, <–16 mmol/L), most newborns ei-
ther die or survive normally, with only a small proportion
exhibiting cerebral palsy. Nevertheless, for an infant who
developed cerebral palsy, one may assume that the infant
was susceptible to asphyxial injury. Second, as discussed
earlier, the normal fetal base excess entering labor is –1
to –2 mmol/L. Third, one may use the umbilical artery
(or vein) base excess or an early newborn arterial blood
base excess value, before the administration of bicarbon-
ate, to reflect the level of acidosis at delivery. Thus, as-
suming beginning and ending base excess values, one
can extrapolate a rate of base excess decrease and a time
at which a threshold (eg, –12 mmol/L) level is reached.
However, this extrapolation is typically not linear
throughout the period of fetal monitoring. Rather, the
rate of base excess decrease is dependent on the stage of
labor and the evidence (ie, fetal heart rate pattern) of
severity of fetal hypoxemia. Thus, one can generally cate-
gorize the fetal heart monitor tracing into periods of nor-
mal labor stress, probable mild hypoxemia (eg, repetitive
moderate or severe typical variable decelerations), proba-
ble moderate hypoxemia (eg, repetitive late or severe
atypical variable heart rate decorations), or severe hypox-
emia (ie, bradycardia caused by cord compression,
8 Ross and Gala
abruptio placentae, uterine rupture). With the range of
base excess reductions for normal first- and second-stage
labor, mild-to-severe hypoxemia, and the duration of fetal
heart rate monitor patterns, one may interpolate the
probable base excess throughout labor.
Case 1. An otherwise normal fetus is monitored during
a trial of vaginal birth after cesarean delivery. After an un-
complicated first stage of spontaneous labor, the fetus
demonstrates repetitive moderate variable heart rate de-
celerations during the first 90 minutes of the second
stage. At this time, there is a sudden, irreversible brady-
cardia to 60 beats per minute that persists until operative
delivery 27 minutes later. Umbilical artery base excess is
–16 mmol/L. The newborn demonstrates encephalopa-
thy and ultimately exhibits cerebral palsy. Plaintiffs allege
that the cesarean delivery was delayed by 5 minutes be-
cause of difficulty in locating the anesthesiologist and
that the performance of cesarean delivery earlier would
have prevented cerebral palsy.
One may analyze the case as follows: Assume that the in-
fant entered labor with a base excess of –2 mmol/L, which
then decreased to –4 mmol/L after a normal active phase
of labor. Moderate hypoxemia (–2 mmol/L per hour) that
was associated with the 90-minute second stage may have
decreased the base excess to –7 mmol/L. The subsequent
27 minutes must then account for the decrease in the base
excess to the delivery value of –16 mmol/L. The assump-
tion of a change in base excess of 9 mmol/L over 27 min-
utes interpolates to a rate of 1 mmol/L per 3 minutes of
severe bradycardia, a rate that is consistent with human or
ovine severe fetal hypoxemia. To have prevented the fetus
from reaching a threshold value of –12 mmol/L, one
would have had to deliver the fetus approximately 15 min-
utes earlier, at which time an intervention may not have
been clinically possible.
Case 2. A patient has a term fetus and evidence of a
nonreactive fetal heart rate tracing with intermittent sus-
picious and atypical variable decelerations. The tracing is
observed for 1 hour by the nursing staff with unsuccessful
attempts to induce reactivity (maternal glucose, acoustic
stimulation). On notification of the obstetrician, a deci-
sion is made to induce labor with pitocin. With the occa-
sional induced contractions, further fetal heart rate
decelerations are observed. One hour later, an emer-
gency cesarean delivery is performed with the delivery of
a meconium-stained infant (Apgar scores 3 and 4 at 1 and
5 minutes, respectively). The umbilical artery base excess
is –17 mmol/L.
This case indicates evidence of preexisting hypoxemia
and acidosis, which occurred before admittance to the hos-
pital. In view of the limited uterine contractions, the fetus
was minimally affected by the 2-hour period of observa-
tion, perhaps experiencing a base excess loss of only 1 to 2
mmol/L. Thus, earlier intervention on admittance to the
hospital would not have altered the outcome substantially.
July 2002
Am J Obstet Gynecol
It is well accepted that a number of clinical and physio-
logic assumptions enter into the proposed model for the
calculation of fetal base excess. Furthermore, there are,
no doubt, differences in fetal responses to acute versus
chronic compromise, hypoxemia versus hypotension/hy-
poperfusion, and preterm versus near-term hypoxemia.
Anemic fetuses or fetuses with evidence of anatomic or
functional cardiac disease may be more susceptible to
hypoxia-induced acidosis. Nevertheless, the proposed
method of analysis provides a realistic analysis of fetal base
excess changes. The values and rates of base excess
change are in agreement with both human and animal
studies. Although there may be modest differences in the
actual-to-interpolated base excess values at any point in
time, the predicted values are likely close approximations.
Summary
Base excess values have a significantly greater usefulness
than umbilical cord pH values, because base excess does
not change significantly with respiratory acidosis and
demonstrates a linear, rather than logarithmic, correlation
to the degree of metabolic acidosis. The understanding and
use of umbilical cord or newborn arterial base excess values
may aid the obstetrician in the retrospective evaluation of
case treatment. When combined with a knowledge of nor-
mal fetal base excess values at the initiation of labor, addi-
tional insight may be derived regarding changes in base
excess with varying fetal heart rate patterns to ultimately aid
in prospective case treatment. The recent introduction of
fetal pulse oximetry may further permit a real-time estima-
tion of base excess changes in relation in scalp oxygen satu-
ration values and heart rate patterns. Although there have
been numerous proposed markers of fetal asphyxia (eg, nu-
cleated red blood cells, lymphocytes, creatine phosphoki-
nase), umbilical artery base excess is the most direct
measure of fetal metabolic acidosis. A continued under-
standing and use of this valuable laboratory parameter may
ultimately aid in the treatment and prevention of fetal hy-
poxic injury.
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