American Journal of Obstetrics and Gynecology (2006) 195, 16516

www.ajog.org

Base deficit estimation in umbilical cord blood is

influenced by gestational age, choice of fetal fluid
compartment, and algorithm for calculation
Nana Wiberg, MD,a,b,* Karin Kallen, PhD,a,c Per Olofsson, MD, PhDa,b
Perinatal Revision South Register,a,y Lund, Sweden; Department of Obstetrics and Gynecology, Malmo University
Hospital,b University of Lund, Malmo, Sweden; Tornblad Institute,c University of Lund, Lund, Sweden
Received for publication November 7, 2005; revised May 31, 2006; accepted May 31, 2006

KEY WORDS
Acidosis
Base decit
Base excess
Blood gas
Fetal uid
compartment
Gestational age
Pregnancy
Umbilical cord

Objective: The purpose of this study was to explore the influences of gestational age, the choice
of fetal fluid compartment, and the algorithm for calculation on the estimation of the base deficit
in umbilical cord arterial blood at birth.
Study design: From 1995 to 2002, cord arterial blood gases and obstetric data were available for
43,551 newborn infants at 37C weeks of gestation (cohort I). The mean base deficit in blood and
the base deficit in extracellular fluid were estimated from pH and PCO2 values in 28,213 newborn
infants with a 5-minute Apgar score of R9 (cohort II) with the use of 3 different calculation
algorithms (base deficit in blood, base deficit in extracellular fluid [A], and base deficit in extracellular fluid [B]).
Results: In cohort II, the base deficit in blood, the base deficit in extracellular fluid (A), and the
base deficit in extracellular fluid (B) increased with advancing gestational age (linear regression;
P ! .0001). The curves run almost parallel, with the base deficit in blood being higher than the base
deficit in extracellular fluid (A) and (B). With the use of receiver operating characteristic curves in
cohort I, the area under curve to indicate a 5-minute Apgar score of !7 and !4 showed the area
under curvepH to be greater than the area under curvebase deficit in extracellular fluid (A) and
(B), the area under curvebase deficit in blood to be greater than the area under curvebase deficit
in extracellular fluid (A) and (B) for a 5-minute Apgar score of !7, and the area under curvebase
deficit in blood to be greater than the area under curvebase deficit in extracellular fluid (A) and (B)
for an Apgar score of !4. The cutoffs with highest sensitivity and lowest false-positive rate for a
5-minute Apgar score of !7 and !4 were, for both scores, a pH value of 7.15, a base deficit in blood
of 10 mmol/L, a base deficit in extracellular fluid (A) of 8 mmol/L, and a base deficit in extracellular
fluid (B) of 6 mmol/L.

Supported by grants from the Medical Faculty at the University of Lund, Region Skane, and the Wallenberg Foundation.
* Reprint requests: Nana Wiberg, MD, Department of Obstetrics and Gynecology, Malmo University Hospital, S-205 02 Malmo, Sweden.
y
The Perinatal Revision South Register comprises data from Obstetric and Neonatal units at the University Hospitals in Lund and Malmo,
the Central Hospitals in Halmstad, Helsingborg, Karlskrona, Kristianstad and Vaxjo, and the County Hospitals in Ljungby and Ystad.
E-mail: nana.wiberg@med.lu.se
0002-9378/$ - see front matter 2006 Mosby, Inc. All rights reserved.
doi:10.1016/j.ajog.2006.05.043

Wiberg, Kallen, and Olofsson

1652

Conclusion: The calculated values of the base deficit in umbilical cord arterial blood are influenced decisively by gestational age, the choice of fetal fluid compartment, and the calculation
algorithms that are used. The power of the base deficit to indicate neonatal distress depends
on the choices of fluid compartment and the algorithm that is used to calculate the base deficit.
2006 Mosby, Inc. All rights reserved.

Sustained fetal hypoxia and the development of

metabolic acidosis implies an increased risk of manifest
motor and cognitive defects.1,2 Umbilical cord blood
gases at birth therefore are used comparatively to quantify the degree of acidosis and retrospectively to estimate
the extent of fetal exposure and response to hypoxia.
Determinations of cord arterial blood pH and base deficit (BD) are key elements. However, both pH and BD
measurements are liable to considerable methodologic
confounding, which may inuence the settlement of an
acidosis diagnosis.
pH and BD and other cord blood gases change with
progression of pregnancy. pH, bicarbonate and PO2
decrease, and PCO2 and BD increase.3-8 The traditionally
used stationary cutos for dening abnormal values
may then result in false-positive or -negative diagnoses.7
Moreover, blood gas analyzers measure pH and PCO2
by electrodes, whereas BD is calculated from algorithms
that are based on these parameters. Dierent brands of
blood gas analyzers use dierent calculation algorithms,
which may result in dierent BD values. Finally, calculation of the BD in blood (BDblood) and extracellular
uid (BDecf) may result in dierent values.
The aim of the present study was to explore the
inuence on cord arterial BD calculations from 3 dierent methodologic confounders: the physiologic increment of BD with advancing gestational age,8 the choice
of fetal uid compartment, and the dierence between
algorithms to calculate BD. In addition, the power of
dierent BD calculations and of pH to indicate neonatal
distress was estimated.

Material and methods

Data about pregnancy course, delivery, and the neonatal period were collected from the Perinatal Revision
South Register (PRSR) database between 1995 and
2002. The PRSR comprises all 9 delivery units in the
southern Swedish region, with a population of 1.6 million
and approximately 17,000 annual deliveries. The main
purpose of the PRSR is quality assurance of perinatal
care.9 Registry-based scientic research, without identication of individual cases, and rules for publication
have been approved by the Research Ethics Committee
at the Lund University Medical Faculty and by the South
Swedish Regional Board of Chairmen, which represent
the involved delivery units.

Inclusion criteria were appropriate information in

the database about obstetric and neonatal courses,
umbilical cord arterial pH and PCO2 (only arterial blood
gases are reported to the PRSR), year of birth, delivery
unit, maternal age and parity, and singleton pregnancy
R37 C 0 completed weeks C days (conrmed by an
early second-trimester ultrasound fetometry) aimed for
vaginal delivery. Two cohorts were compiled from the
PRSR: Cohort I comprised all 43,551 newborn infants
who fullled the inclusion criteria, and cohort II 28,213
comprised newborn infants with a 5-minute Apgar score
of R9. Cohort I data were retrieved from all 9 hospitals,
but cohort II data were retrieved only from the 2 university clinics, because the Malmo and Lund university
clinics perform cord blood gases determinations routinely. The other 7 hospitals perform these determinations only on indication. Cohort I thus contained
cohort II.
Immediately after delivery and before spontaneous
breathing, umbilical cord arterial blood was sampled in
preheparinized syringes and analyzed within 5 minutes
in automatic blood gas analyzers (ABL 520; Radiometer, Copenhagen, Denmark). The analyzers work by
measuring pH and PCO2 at a temperature of 37(C,
whereas the concentrations of bicarbonate (HCO3),
BDblood, and BDecf are calculated from equations and
algorithms. From the determinations of pH and PCO2,
the following parameters were calculated post hoc:
Bicarbonate (HCO3) in plasma according to the
algorithm given in the Radiometer ABL 520 manual10:
HCO3 = 0.23 ! PCO2 ! 10(pH  6.1).
BDblood according to the algorithm given in the
Radiometer ABL 520 manual10: BDblood 0:5 
8  0:00404 0:000425  9:3087  0:919=0:00404
0:000425  9:3087 0:5  0:919  8  0:00404
0:000425  9:3087=0:00404 0:000425  9:30872
 4  24:47  cHCO3  5:33=0:00404 0:000425 
9:30871=2 , where 9.3087 represents the calculated total
hemoglobin concentration (in millimoles per liter),
which corresponded to a value of 150 g/L.
BDecfA according to the algorithm given in the Radiometer ABL 520 manual10: BDecf = BDblood at a ctHb = 3
mmol/L, where ctHb represents the calculated concentration of total hemoglobin in blood (deoxy-, oxy-, carboxy-,
met-, and sulfhemoglobin).
BDecfB according to the algorithm derived from the
Siggaard-Andersen Acid Base Chart11: BDecf = 0.9149
(0.23 ! PCO2 ! 10[pH  6.1]  24.1 C 16.21 ! [pH  7.4]).

Wiberg, Kallen, and Olofsson

Simple linear regression analysis was used to determine the relationship between gestational age and blood
gases and Pearsons rho between dierent BD calculations. For each neonate, the dierences between the BD
estimates with the various algorithms were calculated,
and the signicance of the over-all dierences was tested
by paired t-test. Receiver operating characteristic (ROC)
curves were created to estimate the optimal cuto points
(highest sensitivity with lowest false-positive rate) of pH
(steps by 0.05 units from 6.8 to 7.5) and BD (steps by
2.0 mmol/L from 6.0 to 22.0 mmol/L), respectively,
for a 5-minute Apgar score of !7 and !4. For each cuto
step, the sensitivity, specicity, positive predictive value,
negative predictive value, height over the line, and
distance to the optimal point in the ROC curve (100%
sensitivity, 100% specicity) were estimated. The distance
P
to the optimal point was calculated through
([1sensitivity]2 C [1-specicity]2). The height over the line
(sensitivity = 1-specicity) was estimated with the following expression: height = sensitivity  (1-specicity).
The area under the ROC curve (AUC) was used to
estimate the overall ability of pH and BD to indicate
a low Apgar score. The variance of each AUC and the
variance with 95% CI of the dierence between 2
dependent AUCs were computed according to DeLong
et al.12

Results
In cohort II, BD increased linearly with advancing
gestational age (Figure 1; Table I). The calculation of
BD in dierent compartments and with dierent algorithms showed not only signicant dierences (linear
regression; P ! .0001) over the whole period but also
compared week by week (Table I). The curves for mean
values ran almost parallel, with the BDblood curve indicating higher values and the BDecf curve that was based
on the Siggaard-Andersen Acid-Base Chart algorithm
(BDecfB) showing the lowest values. The dierence between BDblood and BDecfA,B was 1.2 to 2.0 mmol/L.
The correlation coecient (Pearsons rho) between
BDblood and BDecfA,B was 0.97 and between BDecfA and
BDecfB was 1.0.
Table II shows how the ROC curves and AUC calculations were performed for BDblood with a 5-minute Apgar score of !7. Similar calculations were done for pH
and BDecfA,B with 5-minute Apgar scores of !7 and !4
(Figures 2 and 3). The predictive values of pH and BD
on a 5-minute Apgar score of !7 are shown in Figure 2,
and the predictive values on a 5-minute Apgar score of
!4 are shown in Figure 3. In Figure 2, the ROC curve
for pH described a larger AUC (0.728) than those for
BDblood (0.721), BDecfA (0.700), and BDecfB (0.697).
For AUC-pH, the dierence was signicant compared
with AUC-BDecfA and AUC-BDecfB (variance with

1653

Figure 1 Gestational age-related changes of umbilical cord

arterial blood BD in 28,213 vigorous newborn infants. BD
was calculated in blood (BDblood) and in the extracellular uid
(BDecf) with dierent calculation algorithms. Mean values with
95% CIs are indicated. Simple linear regression show signicant relationships (P ! .0001) for all 3 calculations.

95% CI, 0.0042-0.0534 and 0.0062-0.0569, respectively),

but not compared with AUC-BDblood. Moreover, AUCBDblood was signicantly larger than AUC-BDecfA
(0.0133-0.0301), but the dierence between AUC-BDecfA
and AUC-BDecfB was not signicant.
For Apgar scores of !4 (Figure 3), the dierences
between AUC-pH (0.759), AUC-BDblood (0.736), AUCBDecfA (0.712), and AUC-BDecfB (0.709) were signicant
only for AUC-BDblood versus AUC-BDecfA (variance
with 95% CI, 0.0033-0.0465).
For both Apgar scores of !7 and !4, the cuto
points with highest sensitivity and lowest false positive
rate were a pH of 7.15, BDblood of 10.0 mmol/L, BDecfA
of 8.0 mmol/L, and BDecfB of 6.0 mmol/L (Figures 2
and 3).

Comment
Studies on the inuence of gestational age on cord artery
BD are conicting.4,6,8,13 In the present study, cord artery blood samples from a large series of vigorous newborn infants at term showed that BD in fetal blood
increases linearly in the last weeks of gestation. This
indicates a gradual development of a physiologic fetal
metabolic acidemia with advancing gestational age,
because BD merely reects the inuence of the nonrespiratory component on the umbilical artery pH. However, because the arterial PCO2 increases because of an
increasing carbon dioxide load from the growing fetus,
a respiratory component is also involved.8 This indicates
the development of a mixed metabolic and respiratory
acidemia with gestational age.

Wiberg, Kallen, and Olofsson

1654
Table I

Gestational age-related changes of BD in 28,213 vigorous newborn infants

Gestational age (wk C d)

BDblood (mmol/L)

BDecfA (mmol/L)

BDecfB (mmol/L)

37
38
38
39
39
40
40
41
41
42

1656
1266
2501
2713
4844
3866
4750
2624
2220
1774

5.39
5.61
5.70
5.71
5.92
6.13
6.24
6.49
6.69
6.81

4.22
4.41
4.48
4.49
4.64
4.79
4.88
5.08
5.22
5.29

3.76
3.95
4.02
4.03
4.16
4.32
4.40
4.59
4.72
4.78

C
C
C
C
C
C
C
C
C
C

0-37
0-38
3-38
0-39
3-39
0-40
3-40
0-41
3-41

C
C
C
C
C
C
C
C
C

6
2
6
2
6
2
6
2
6

G
G
G
G
G
G
G
G
G
G

3.59
3.57
3.63
3.61
3.64
3.73
3.76
3.73
3.82
3.84

G
G
G
G
G
G
G
G
G
G

3.38
3.38
3.38
3.38
3.38
3.46
3.52
3.45
3.58
3.56

G
G
G
G
G
G
G
G
G
G

3.30
3.29
3.30
3.31
3.30
3.38
3.43
3.37
3.48
3.48

Data are given as mean G SD. Significant differences (P ! .0001) for BDblood vs BDecfA and BDecfB, respectively, and for BDecfA vs BDecfB for all gestational
weeks.

Table II

ROC curve for BDblood relative to the 5-minute Apgar score

Numbers above cutoff

Cutoff
(mmol/L)

Apgar
score !7

Apgar
score R7

Sensitivity

Specificity

Positive
predictive value

Negative
predictive value

Distance to line
through 0.1

Height

22.0
20.0
18.0
16.0
14.0
12.0
10.0
8.0
6.0
4.0
2.0
0.0
2.0
4.0
6.0

12
19
28
41
66
102
149
186
217
254
281
287
289
289
289

59
153
338
762
1,632
3,484
7,016
12,702
21,192
31,003
39,071
42,593
43,193
43,237
43,262

0.042
0.066
0.097
0.142
0.228
0.353
0.516
0.644
0.751
0.879
0.972
0.993
1
1
1

0.001
0.004
0.008
0.018
0.038
0.081
0.162
0.294
0.490
0.717
0.903
0.985
0.998
0.999
1

0.169
0.110
0.077
0.051
0.039
0.028
0.021
0.014
0.010
0.008
0.007
0.007
0.007
0.007
0.007

0.994
0.994
0.994
0.994
0.995
0.995
0.996
0.997
0.997
0.997
0.998
0.997
1
1
0

0.958
0.934
0.903
0.858
0.773
0.652
0.511
0.462
0.550
0.727
0.904
0.985
0.998
0.999
1

0.040
0.062
0.089
0.124
0.191
0.272
0.353
0.350
0.261
0.162
0.069
0.009
0.002
0.001
0

For each step (2.0 mmol/L), the values were estimated. The optimal cutoff was 10.0 mmol/L (height over the 0.1 line, 0.353). AUC: 0.721 (95% CI,
0.688-0.754).

The respiratory component of the mixed acidemia

apparently is explained, but the nature of the metabolic
component is complex and open for speculation. Various
buering systems in the body act to maintain the acidbased homeostasis, including the bicarbonate-carbonic
acid buer system, hemoglobin, and proteins. The hemoglobin buering capacity may change gradually towards
term, because the fetal type of hemoglobin is exchanged
with the adult type. Moreover, the erythrocyte content of
carbon anhydrase, which enhances the homeostasis between bicarbonate and carbon dioxide through carbonic
acid, and the activity of the enzyme 2,3-diphosphoglycerate, which stabilizes the deoxygenated form of hemoglobin, may be of importance also.
The fetus buering capacity is merely outside the
vascular compartment because of low plasma protein
concentrations and, in comparison with adults, a

relatively large extravascular uid compartment. BDecf,

rather than BDblood, has been advocated therefore to
reect fetal acid-base status, especially at a high PCO2.14
In case of hypercapnia, the equilibrium HC C HCO3
5 H2CO3 5 H2O C CO2 is displaced to the left, with
an excess of HCO3 (bicarbonate) in the blood. Bicarbonate escapes rapidly from plasma to the interstitial uid
compartment, which results in higher calculated values
of BD in the blood, with an overestimation of the metabolic component theoretically.14,15 The distinction between blood and the extracellular uid is demonstrated
by the dierent BD curves that run 1 to 2 mmol/L apart
and almost parallel to each other in relation to gestational age. To assess the impact of this displacement,
we created ROC curves on how BD indicates neonatal distress (ie, a low 5-minute Apgar score). This procedure
demonstrated that the power of BD to indicate neonatal

Wiberg, Kallen, and Olofsson

1655

Figure 2 ROC curve for the prediction of pH and BD values

on an Apgar score of !7 at 5 minutes. For statistical comparisons between areas under the curve, see the text and Table II.
Optimal cuto points were pH = 7.15 (analyzed in steps by
0.05), BDblood = 10.0 mmol/L, BDecfA = 8.0 mmol/L, and
BDecfB = 6.0 mmol/L (analyzed in steps by 2.0 mmol/L).

Figure 3 ROC curve for the prediction of pH and BD values

on an Apgar score of !4 at 5 minutes. For statistical comparisons between areas under the curve, see the text. Optimal cuto points were identical to cuto points for an Apgar score of
!7 (Figure 2).

distress decisively depends on the choice of uid compartment and the choice of algorithm to calculate BD. Because
BD might better than pH represent the fetal oxygen debt,
one would expect BD better than pH to predict neonatal
distress. This was not found in the study: The AUC-pH
was larger than AUC-BD and was signicant only for
BDecfA,B. This observation is in accordance with ndings
in a study by Gordon and Johnson,16 who found that
arterial pH better than BD correlated with 1-minute Apgar
scores; however, in a study by Victory et al,17 there was little dierence in pH and BD to predict a low 5-minute
Apgar score. Because in the present study cohort I was
not a population-based series, the study could not be conclusive about whether the blood or the extracellular compartment should be used to best reect fetal BD status
in relation to neonatal distress, or which cuto should be
used to indicate abnormal values. Future populationbased studies should address these issues. Development
of acidosis during labor has both a respiratory and a
metabolic component; therefore, both pH and BD determinations are needed to assess accurately the fetuss exposure and ability to resist hypoxia, ideally in both the
umbilical cord artery and vein.
It should be emphasized that BD is not a measured
parameter but is estimated by equations and algorithms
that are based on pH and PCO2 measurements, in some
blood gas analyzers also without considering the actual
hemoglobin concentration and oxygen saturation, which

may introduce methodologic confounding. BDblood is

dened as the estimated base or acid needed to titrate
blood to pH 7.40 at 37(C when PCO2 is held constant
at 5.3 kPa (40 mm Hg), whereas BDecf is a further mathematic adjustment of BDblood. The algorithms and equations are intended and adjusted for adults originally, but
the dierent fetal composition in uid distribution, hemoglobin type, oxygen saturation, temperature may inuence the calculated value of BD. Roemer18 estimated
BD by dierent algorithms in 7701 term singleton pregnancies and claims that the actual oxygen saturation and
concentration of the fetal type of hemoglobin must be
introduced in the BD algorithm to increase its accuracy.
Umbilical cord blood gases reect a course of events.
The progress of labor inuences the fetal acid-base
balance, with a decrease of pH and increase of PCO2
and BD.8 The BD increase is approximately 1 mmol/L
per hour in the second stage of labor, but healthy fetuses
are able to compensate for even severe reductions in oxygenation without experiencing signicant acidosis.19-21
Gestational age and the length of labor inuence umbilical cord blood gases at birth in the same directions, but
independently of each other, and labor is therefore not
the reason for gestational agedependent cord blood
gas changes.8
In summary, calculated values of fetal BD are inuenced decisively by gestational age and the choice
of fetal uid compartment and of the algorithms that

1656
are used. As demonstrated here and previously,7 stationary cuto points might give false-positive or -negative
diagnoses of cord blood acidemia and a false impression
of perinatal morbidity. Gestational ageadjusted cord
blood gas reference values are needed therefore, and a consensus on which uid compartment and which algorithm
should be used to calculate BD. Many physicians might
be unaware of the fundamental principle of uid compartment when assessing cord blood BD, but the present study
clearly demonstrates the need to consider it. The methodologic confounders and the lack of a true method to calculate BD cause denition problems of acidosis in clinical,
epidemiologic, and scientic situations: on the evaluation
of individual newborn infants and their subsequent neonatal treatment, in legal controversies, on comparative quality assurance of care at obstetric units, and when cord
blood gases are used as outcome measures in clinical
research.

Acknowledgments
We thank Professor Karel Mars al for initiating the
Perinatal Revision South Register and all those people
in the South Swedish Health Care Region who are
involved in delivering local data to the Register.

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