General obstetrics

DOI: 10.1111/1471-0528.12234
www.bjog.org

Hidden acidosis: an explanation of acidbase and

lactate changes occurring in umbilical cord blood
after delayed sampling
P Mokarami,a N Wiberg,b P Olofssona
a

Institution of Clinical Sciences, Department of Obstetrics and Gynaecology, Sk

ane University Hospital, Lund University, Malm
o, Sweden
Institution of Clinical Sciences, Department of Obstetrics and Gynaecology, Sk

ane University Hospital, Lund University, Lund, Sweden
Correspondence: Dr P Mokarami, Department of Neurology, Sk

ane University Hospital, S20502 Malm
o, Sweden.
Email parisa.mokarami@med.lu.se
b

Accepted 25 December 2012. Published Online 10 April 2013.

Objective To explore the hidden acidosis phenomenon, in which

Results In both groups all arterial parameters, except for PCO2 in

there is a washout of acid metabolites from peripheral tissues

in both vaginal and abdominal deliveries, by investigating
temporal umbilical cord blood acidbase and lactate changes after
delayed blood sampling.

the group delivered by caesarean section, changed significantly

(pH decreased and the other variables increased). There were
corresponding changes in venous acidbase parameters. When
temporal arterial changes were compared between the two groups,
the decrease in pH and increase in PCO2 were more pronounced in
the group delivered vaginally. Neonates born vaginally had
significantly lower pH and higher lactate, Hct, and Hb
concentrations at T0 and T45 in both the artery and the vein. At
T45, arterial PCO2 and PO2 levels in the group delivered vaginally
were also significantly higher.

Design Prospective comparative study.

Setting University hospital.
Sample Umbilical cord blood from 124 newborns.
Methods Arterial and venous cord blood was sampled

immediately after birth (T0), and at 45 seconds (T45), from

unclamped cords with intact pulsations taken from 66 neonates
born vaginally and 58 neonates born via planned caesarean section
at 3642 weeks of gestation. Non-parametric tests were used for
statistical comparisons, with P < 0.05 considered significant.
Main outcome measures Temporal changes (T0T45) in

umbilical cord blood pH, the partial pressure of CO2 (PCO2) and
O2 (PO2), and in the concentrations of lactate, haematocrit (Hct),
and haemoglobin (Hb).

Conclusions Delayed umbilical cord sampling affected the acid

base balance and haematological parameters after both vaginal and

caesarean deliveries, although the effect was more marked in the
group delivered vaginally. The hidden acidosis phenomenon
explains this change towards acidaemia and lactaemia. Arterial
haemoconcentration was not the explanation of the acidbase
drift.
Keywords Blood gases, delayed sampling, hidden acidosis, lactate,
pH, umbilical cord blood.

Please cite this paper as: Mokarami P, Wiberg N, Olofsson P. Hidden acidosis: an explanation of acidbase and lactate changes occurring in umbilical cord
blood after delayed sampling. BJOG 2013;120:9961002.

Introduction
Delayed umbilical cord clamping at vaginal delivery results
in a decrease in pH and base excess (BE), and an increase
in the partial pressure of O2 (PO2), the partial pressure of
CO2 (PCO2), and lactate concentration in the umbilical
artery.13 These changes towards acidaemia and lactaemia
can be explained by the hidden acidosis phenomenon.
During uterine contractions, the fetal circulation is centralised at the expense of perfusion of low-priority organs and
peripheral tissues,4 with a build-up of acid metabolites

996

peripherally. When the newborn starts to breathe sufficiently the peripheral perfusion is restored and the
trapped metabolites surge into the central circulation and,
after some seconds, can be detected in umbilical cord
blood.3 The phenomenon has also been demonstrated in
animal studies at the restoration of the peripheral circulation after provoked hypovolaemic shock.5,6 Soon after volume expansion has started, a rapid drop in pH and
increase in lactate concentration are seen. In animal limb
tourniquet ischaemiareperfusion experiments, a similar
phenomenon is seen during reperfusion.7,8

2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2013 RCOG

Acidbase changes after delayed umbilical cord sampling

Our hypothesis was that hidden acidosis occurs in the

newborn (Figure 1). As newborns after planned caesarean
delivery (caesarean section) seldom show acrocyanosis, we
hypothesized that hidden acidosis would be most pronounced after vaginal delivery. The opening of peripheral
vascular beds might result in changes in haemoconcentration in the cord blood, and therefore we investigated temporal changes not only in blood gases and lactate
concentration, but also in haematocrit (Hct) and total haemoglobin (ctHb) concentration.

Methods
Arterial and venous umbilical cord blood were sampled from
124 newborn singletons immediately after birth (T0), and
again at 45 seconds (T45), from unclamped umbilical cords
with intact pulsations. The womens length of gestation was
determined at an early second trimester ultrasound, and all
were found to be at 3642 weeks of gestation. Of the 124
neonates, 66 were born vaginally in cephalic presentation
and 58 were delivered by planned caesarean section. The
newborns included in the study were expected to have no
need of immediate rescue procedures that would interfere
with the delayed cord clamping. The women who delivered
vaginally were included in a previously published study.3
Women in the group delivering vaginally were recruited
to the study at admission to the labour and delivery ward,
and women in the group delivering by caesarean section
were asked to participate a few hours before the operation.

Lactate
pH

First few minutes

after birth

All caesarean sections were planned and the indications

were breech presentation or maternal request. Women
undergoing spinal anaesthesia were placed in supine position, tilted 15 to the left, and received prehydration. Bupivacaine and fentanyl were used for spinal anaesthesia.
Simultaneously, an intravenous infusion of ephedrine
(50 mg in 500 ml of sodium chloride solution) was started
and adjusted with the aim to maintain a mean arterial
pressure within 25% of its initial value. Women undergoing general anaesthesia also received prehydration. Drugs
administered at general anaesthesia were thiopental, suxamethonium, and sevoflorane. After cord clamping, all
women received oxytocin.
During cord blood sampling, babies delivered vaginally
were placed on the abdomen of the mother, whereas babies
born by caesarean section were placed between the
mothers legs and kept warm under a towel. The procedure
was meticulously prepared, and the samples were taken and
analysed by one of the authors (N.W.), who was not
involved in the obstetric care of the women. Blood was
drawn first from the cord artery and then, within a few
seconds, and at the same location on the cord, from the
vein. The next pair of samples were taken 45 seconds later,
and the needle punctures were made a few millimetres closer to the placenta. A 0.6- or 0.9-mm needle was used, and
the samples were collected in 2ml pre-heparinised plastic
syringes. A minimum of 0.5 ml of blood from each vessel
was used for analysis in the blood gas analyser (ABL735;
Radiometer A/S, Copenhagen, Denmark). All samples were
analysed within 15 min, in chronological order. The radiometer analyser works by measuring pH and PCO2 by
potentiometry, PO2 and lactate by amperometry, and ctHb
by spectrophotometry. ctHb includes deoxy-, oxy-,
carboxy-, and methemoglobin. Hct is available as a derived
parameter, calculated according to the formula: Hct =
0.0485 9 ctHb + 8.3 9 10 3. The analyser was operated
in an accredited laboratory (Laboratory Medicine Sk

ane,
Clinical Chemistry, Lund and Malm
o).
All women in labour were monitored with cardiotocography during the second stage of labour. Small for gestational age (SGA) was defined as a birthweight below 2
SD from the gestational age-adjusted mean value, appropriate for gestational age (AGA) was defined as a birthweight
within the mean  2 SD range, and large for gestational
age (LGA) was defined as a birthweight above the
mean + 2 SD.9

Statistical analyses
Labour

Birth

Postpartum

Figure 1. Schematic illustration of the hidden acidosis phenomenon.

The grey box represents the first few minutes after birth, when a steep
decrease in pH and an increase in lactate concentration are first seen,
according to the hypothesis.

The MannWhitney U test was used for comparison of

continuous parameters between groups, and the Wilcoxon
signed-ranks matched-pairs test was used for longitudinal
comparisons. Values are reported as median and range or
mean with 95% confidence interval (95% CI), as appropri-

2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2013 RCOG

997

Mokarami et al.

ate. A two-tailed P < 0.05 was considered to be statistically

significant. Statistical analyses were performed with the aid
of STATVIEW (SAS Institute, Cary, NC, USA). As umbilical
cord blood gas and lactate values are dependent on gestational age,1012 comparisons between groups delivered vaginally and by caesarean section were also performed using
cord arterial pH adjusted to a gestational age of 280 days,
according to the regression coefficient 0.00096 per day of
gestational age.10

Results
The characteristics of the study population are shown in
Table 1. Gestational age at delivery was significantly lower,
and Apgar score (AS) at 1 minute was significantly higher,

Table 1. Characteristics of the study population (n = 124)

Vaginal delivery
(n = 66)
Maternal characteristics
Duration of second
41
stage of labour (min)
Duration of
24
pushing (min)
Induction of labour
5
Instrumental birth
9
Drugs administered
Pethidin
6
Oxytocin
31
Nitrous oxide
50
Anaesthesia
Epidural
15
Spinal
General
Newborn characteristics
Gestational age
40+0
(weeks)*
Birthweight (g)
3595
SGA
3
AGA
62
LGA
1
Apgar score
1 minute*
9
5 minute
10
10 minute
10
Cardiotocography
Intermediate
13
Pathological
3

Caesarean
delivery (n = 58)

(5234)

(490)

(7.6%)
(13.6%)

(9.1%)
(47.0%)
(75.8%)

(22.7%)

52 (90.0%)
6 (10.0%)

(36+0 42+0)

38+4 (36+4 40+3)

(25604405)
(4.5%)
(93.9%)
(1.5%)

3535 (25165320)
0
47 (81.0%)
11 (19.0%)

(410)
(810)
(910)
(19.7%)
(4.5%)

9 (810)
10 (710)
10 (910)

Longitudinal changes between T0 and T45

Longitudinal changes in arterial blood gases, and in lactate,
Hct, and ctHb concentrations are illustrated in Figure 2.
With the exception of PCO2 in the group delivered by caesarean section (P = 0.4), all blood gas and lactate parameters changed significantly. Acidbase changes in venous
blood were in the same directions as in arterial blood,
although in the group delivered vaginally only the increase
in lactate was significant (P = 0.001), and in the group
delivered by caesarean section only the decrease in pH
(P = 0.03) and increase in lactate (P < 0.0001) were significant (not shown in Figure 2). Hct and ctHb increased significantly in the artery in both groups, whereas venous
values decreased significantly in the group delivered vaginally (P  0.04), and remained unchanged in the group
delivered by caesarean section (P  0.2).

Vaginal versus caesarean delivery

When longitudinal arterial pH, lactate, and PCO2 changes
were compared between groups, the decrease in pH and
increase in PCO2 were found to be significantly greater in
the group delivered vaginally (P  0.04), but there was no
statistically significant difference between the groups
regarding the increase in lactate concentration from T0 to
T45 (P = 0.9). Adjusting pH for the difference in gestational age between the groups did not change the results.
Neonates born by vaginal delivery had significantly lower
pH values and higher lactate, Hct, and ctHb concentrations
at T0 and T45, in both the artery and the vein, compared with
neonates delivered by caesarean section (Tables 1 and 2). At
T45, PCO2 and PO2 in the artery in the group delivered vaginally were also significantly higher.

Spinal versus general anaesthesia

*The difference in gestational age and Apgar score at 1 minute was

statistically significant (MannWhitney U test; P  0.03) between
the two groups.
Values are median (range) or number of cases (%).

998

in the group delivered by caesarean section. One newborn

had an AS of 4 at 1 minute, but otherwise all scores at
1 minute were  8 and at 5 and 10 minutes were  9.
Serial blood samples were taken in all 124 cases, but four
analyses at T0 (one vaginal delivery and three caesarean
sections) and ten analyses at T45 (six vaginal deliveries and
four caesarean sections) failed because of instrument failure
or blood clotting. For each parameter, only cases with valid
measurements obtained at both T0 and T45 were included
in the statistical analyses. Data for arterial and venous
acidbase and haematological measurements are shown in
Tables 2 and 3.

Neonates in the group delivered by caesarean section with

spinal anaesthesia (n = 52) had lower pH values, and
higher PCO2 and lactate concentration at T0, compared with
neonates in the general anaesthesia group (n = 6), but only
the difference in lactate concentration was statistically significant (P = 0.03).

2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2013 RCOG

Acidbase changes after delayed umbilical cord sampling

Table 2. Arterial blood gas, lactate, haematocrit (Hct), and total haemoglobin (ctHb) concentration median (range) values obtained immediately
after birth (time T0), and again 45 seconds later (T45), in unclamped umbilical cords with intact pulsations after vaginal delivery and caesarean
delivery
Vaginal

pH
PCO2 (kPa)
PO2 (kPa)
Lactate
(mmol/l)
Hct
ctHb
(g/l)

T0

Caesarean

T45

Vaginal versus
caesarean

Vaginal

Caesarean

Vaginal

Caesarean

Median (range)

Median (range)

Median (range)

Median (range)

58
58
57
56

39
39
39
37

7.235
7.55
2.31
4.8

57
57

38
38

0.507 (0.0510.625)
167 (134205)

(7.0087.379)
(5.2411.6)
(0.627.93)
(2.013.3)

7.305
7.30
1.99
1.8

(7.1627.397)
(5.869.56)
(1.183.72)
(1.14.8)

0.452 (0.4090.585)
148 (133191)

7.207
7.87
2.66
5.5

(7.0057.384)
(5.9411.8)
(1.094.94)
(2.313.3)

0.514 (0.4230.635)
168 (138208)

Significance of
difference (P)
T0

T45

(7.1167.424)
(5.5610.4)
(1.183.25)
(1.56.2)

<0.0001
0.3
0.1
<0.0001

<0.0001
0.03
0.02
<0.0001

0.460 (0.3720.583)
151 (121191)

<0.0001
<0.0001

<0.0001
<0.0001

7.296
7.57
2.28
2.2

The MannWhitney U test was used for group comparisons.

Table 3. Venous blood gas, lactate, haematocrit (Hct), and total haemoglobin (ctHb) concentration median (range) values obtained immediately
after birth (time T0), and again 45 seconds later (T45), in unclamped umbilical cords with intact pulsations after vaginal delivery and caesarean
delivery
Vaginal

pH
PCO2 (kPa)
PO2 (kPa)
Lactate
(mmol/l)
Hct
ctHb
(g/l)

T0

Caesarean

T45

Vaginal versus
caesarean

Vaginal

Caesarean

Vaginal

Caesarean

Median (range)

Median (range)

Median (range)

Median (range)

64
64
63
60

41
41
41
40

7.331
5.49
3.57
4.6

63
64

38
39

0.515 (0.4010.648)
168 (131212)

(7.0687.471)
(3.919.70)
(1.4615.70)
(1.910.9)

7.371
5.78
3.46
1.5

(7.3207.479)
(4.377.46)
(1.877.45)
(1.12.7)

0.455 (0.4100.585)
148 (133191)

7.329
5.42
3.68
4.7

(7.4707.474)
(4.059.54)
(1.527.38)
(2.110.8)

0.513 (0.0580.633)
168 (126208)

Significance of
difference (P)
T0

T45

(7.3187.469)
(4.697.54)
(1.406.43)
(1.23.0)

<0.0001
0.2
0.6
<0.0001

<0.0001
0.1
0.9
<0.0001

0.456 (0.3890.590)
149 (127193)

<0.0001
<0.0001

<0.0001
<0.0001

7.367
5.77
3.46
1.6

The MannWhitney U test was used for group comparisons.

Discussion
This study showed significant changes in acidbase and
haematological parameters in umbilical cord blood when
sampling was delayed by 45 seconds, with these changes
being more marked for pH and PCO2 in the group delivered
vaginally. The similar increases in lactate concentration in
the two groups indicate that considerable hidden acidosis was also present in the group delivered by caesarean
section.

The lack of change in venous PCO2 indicates that placental perfusion and gas exchange were maintained during the
first 45 seconds, after both vaginal and abdominal deliveries. Thus, the temporal increase in arterial PCO2 must be a
result of CO2 inflow from the newborn, and not from the
placenta, or of an accumulation of CO2 in the blood circuit. Moreover, the significant increase in PO2 indicates the
rapid establishment of functional pulmonary ventilation,
which would result in the escape of CO2 and in a lowering
of PCO2 unless there was a considerable continuing fetal

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999

Mokarami et al.

Vaginal delivery

Caesarean delivery

7,32

8,6

8,2

PCO2 (kPa)

7,28

pH

7,26

****

7,24
7,22

8,0

NS

7,8
7,6
7,4

7,20

7,2

7,18

7,0

2,9

2,6

2,5
2,4
2,3
2,2

Lactate (mmol/L)

6,0

2,7

5,5
5,0
4,5
4,0
3,5
2,5

2,0

2,0

1,9

1,5

54

175

****

****

3,0

2,1

53

****

6,5

***

2,8

PO2 (kPa)

***

8,4

7,30

****

170

52

Hct (%)

50

49
48
47

ctHb (g/L)

165

51

**

160
155
150

46
45

T0

T45

145

T0

T45

Figure 2. Measurements of arterial umbilical cord blood gases, and concentrations of lactate, haematocrit (Hct), and total haemoglobin (ctHb)
obtained immediately after birth (T0), and then again 45 seconds later (T45), in unclamped umbilical cords with intact pulsations after vaginal and
caesarean deliveries. The figure shows mean values and 95% confidence intervals. The Wilcoxon signed-ranks test was used to compare values at
T0 and T45: *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; NS, not significant.

contribution. As it is unlikely that the CO2 contribution

was a result of a sudden rise in neonatal metabolism, a
washout of CO2 from peripheral tissues is the most plausible explanation for this finding.
After 45 seconds, arterial blood showed a small but significant haemoconcentration and venous blood showed a
haemodilution in the group delivered vaginally. A relevant
question is, then, whether these concentration changes
could have influenced the temporal acidbase and lactate
changes. According to Stewarts physicochemical concept, a
change towards alkalosis should occur during haemoconcentration, as dehydration results in a higher [OH ].13 In
the present study, the changes in haemoconcentration paralleled changes towards acidosis in the artery, indicating

1000

that the temporal acetous change was not a result of the

haemoconcentration.
The study was performed in cases in which minimal
neonatal assistance was expected to be required, and only
two newborns in the group delivered vaginally and none
in the group delivered by caesarean section had an umbilical artery pH <7.10 in the first samples. Both these newborns had a pathological cardiotocogram. One newborn
was vigorous immediately, with 1-, 5-, and 10-minute AS
scores of 8, 9, and 10, respectively, whereas the other was
initially moderately depressed, and had corresponding AS
scores of 4, 8, and 10. Interestingly, in the newborn with
a 1-minute AS score of 8, the blood gas and lactate values
deteriorated further by 45 seconds of age: pH changed

2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2013 RCOG

Acidbase changes after delayed umbilical cord sampling

from 7.06 to 7.02; PCO2 changed from 10.0 to 10.5 kPa;

BE changed from 12.7 to 15.3 mmol/l; and lactate changed from 12.2 to 12.9 mmol/l. In the depressed newborn,
the values remained mainly unchanged: pH was 7.01 at
both time points, PCO2 changed from 11.2 to 11.8 kPa, BE
changed from 14.9 to 14.4 mmol/l, and lactate concentration was 13.3 mmol/l at both time points. These observations further support the hypothesis that hidden acidosis
is a physiological phenomenon, occurring in newborns with
a rapidly established circulation.
It was not expected that the hidden acidosis phenomenon would occur so clearly in neonates born by caesarean
section, as these neonates were not exposed to hypoxic
stress by uterine labour contractions; however, it is well
known that fetal/neonatal effects occur during regional
anaesthesia for planned caesarean section. Despite precautions in terms of prehydration and vasopressor administration, spinal anaesthesia in particular is frequently associated
with maternal hypotension and lower umbilical cord arterial pH.1418 Vasopressor substances can cross the placenta,14,1922 and the maternal supine wedged position
during caesarean section frequently results in fetal heart
rate changes as a result of occult aortocaval compression.23
Doppler ultrasound has shown uteroplacental circulation to
be affected after spinal blockade.16,19,24,25 In concordance
with these findings, the present study showed higher lactate
values in the spinal anaesthesia group than in the general
anaesthesia group. It seems that, even with the most modern techniques for spinal anaesthesia, this side effect is difficult to avoid.26
An interesting finding was that at T0, PO2 was similar in
the groups delivered vaginally and by caesarean sections,
but at T45 it was significantly higher in the group delivered
vaginally, as a result of a steeper increase. This demonstrates the protective role of vaginal delivery, with the more
effective release of lung surfactant and alveolar expansion,
absorption of pulmonary fluid, and rapid circulatory transition to extra-uterine life. At 45 seconds, alveolar clearance
of fluid and alveolar expansion are the most important
processes.27

Strengths and weaknesses

Repeated blood sampling performed by an experienced
obstetrician and analyses within 15 minutes in chronological order minimised the sampling and measurement errors.
The inclusion of only newborns presumed to be vigorous
makes extrapolation to asphyxiated newborns problematic.

Interpretation
Even small blood gas changes can affect the interpretation
of a newborns status and lead to a false diagnosis of acidosis, as we have previously demonstrated.3 Hypoxic neonates
are expected to have a more pronounced circulatory cen-

tralisation and hidden acidosis, and, as they already have

lower pH levels, an additional decrease is more likely to tip
them below the lower limit of the reference interval. It
would be difficult to create reliable normal reference intervals taking late cord blood sampling into account, because,
as discussed above, vigorous newborns would show changes
towards acidaemia, lactaemia, and hypercapnia, whereas
depressed newborns would show small changes.

Conclusion
Delayed cord blood sampling with intact pulsations affected
umbilical acidbase values and haematological parameters
following both vaginal and caesarean deliveries. A change
towards acidaemia and lactaemia can be explained by the
hidden acidosis phenomenon. A small degree of haemoconcentration occurred in arterial blood, and haemodilution
occurred in venous blood, but these changes could not
explain the change in acidbase status.

Disclosure of interests
The authors state explicitly that there are no conflicts of
interest in connection with this article.

Contribution to authorship
PM was involved in the conception and planning of the
study, analysis of the data, and writing of the article; NW
was involved in the conception, planning, and carrying out
of the study, analysis of the data, and writing of the article.
PO was involved in the conception and planning of the
study, analysis of the data, and writing of the article.

Details of ethics approval

The study was approved on 24 February 2006 by the Central Ethical Review Board, Stockholm, Sweden (reference
50200), and all the women gave their informed
number O
oral and written consent to participate in the study.

Funding
This study was supported by grants from Region Sk

ane
and the Medical Faculty at Lund University (ALF). The
funding sources had no role in the writing of the article or
in the decision to submit it for publication.

Acknowledgement
None. &

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2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2013 RCOG