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

Hidden acidosis: an explanation of acid base and lactate changes occurring in umbilical cord blood after delayed sampling

P Mokarami, a N Wiberg, b P Olofsson a

a Institution of Clinical Sciences, Department of Obstetrics and Gynaecology, Sk ane University Hospital, Lund University, Malmo,Sweden

b 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, S 20502 Malm o,Sweden. Email parisa.mokarami@med.lu.se

Accepted 25 December 2012. Published Online 10 April 2013.

Objective To explore the ‘hidden acidosis’ phenomenon, in which there is a washout of acid metabolites from peripheral tissues in both vaginal and abdominal deliveries, by investigating temporal umbilical cord blood acid base and lactate changes after delayed blood sampling.

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 (T 0 ), and at 45 seconds (T 45 ), 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 (T 0 T 45 ) in umbilical cord blood pH, the partial pressure of CO 2 (P CO 2 ) and O 2 (P O 2 ), and in the concentrations of lactate, haematocrit (Hct), and haemoglobin (Hb).

Results In both groups all arterial parameters, except for P CO 2 in the group delivered by caesarean section, changed significantly (pH decreased and the other variables increased). There were corresponding changes in venous acid base parameters. When temporal arterial changes were compared between the two groups, the decrease in pH and increase in P CO 2 were more pronounced in the group delivered vaginally. Neonates born vaginally had significantly lower pH and higher lactate, Hct, and Hb concentrations at T 0 and T 45 in both the artery and the vein. At T 45 , arterial P CO 2 and P O 2 levels in the group delivered vaginally were also significantly higher.

Conclusions Delayed umbilical cord sampling affected the acidbase 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 acid base and lactate changes occurring in umbilical cord blood after delayed sampling. BJOG 2013;120:996 1002.

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 O 2 ( P O2 ), the partial pressure of CO 2 (P CO 2 ), and lactate concentration in the umbilical artery. 1 3 These changes towards acidaemia and lactaemia can be explained by the ‘hidden acidosis’ phenomenon. During uterine contractions, the fetal circulation is centra- lised at the expense of perfusion of low-priority organs and peripheral tissues, 4 with a build-up of acid metabolites

peripherally. When the newborn starts to breathe suffi- ciently 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 circula- tion after provoked hypovolaemic shock. 5,6 Soon after vol- ume expansion has started, a rapid drop in pH and increase in lactate concentration are seen. In animal limb tourniquet ischaemia reperfusion experiments, a similar phenomenon is seen during reperfusion. 7,8

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 pro- nounced after vaginal delivery. The opening of peripheral vascular beds might result in changes in haemoconcentra- tion in the cord blood, and therefore we investigated tem- poral changes not only in blood gases and lactate concentration, but also in haematocrit (Hct) and total hae- moglobin (ctHb) concentration.

Methods

Arterial and venous umbilical cord blood were sampled from 124 newborn singletons immediately after birth ( T 0 ), and again at 45 seconds ( T 45 ), from unclamped umbilical cords with intact pulsations. The women’s length of gestation was determined at an early second trimester ultrasound, and all were found to be at 36 42 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

to participate a few hours before the operation. Lactate pH First few minutes after birth Labour
to participate a few hours before the operation. Lactate pH First few minutes after birth Labour
to participate a few hours before the operation. Lactate pH First few minutes after birth Labour
to participate a few hours before the operation. Lactate pH First few minutes after birth Labour
First few minutes after birth Labour Postpartum Birth
First few minutes
after birth
Labour
Postpartum
Birth

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.

All caesarean sections were planned and the indications were breech presentation or maternal request. Women undergoing spinal anaesthesia were placed in supine posi- tion, tilted 15 º to the left, and received prehydration. Bupi- vacaine 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 undergo- ing general anaesthesia also received prehydration. Drugs administered at general anaesthesia were thiopental, sux- amethonium, 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 mother’s 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 clo- ser to the placenta. A 0.6- or 0.9-mm needle was used, and the samples were collected in 2 ml 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 radi- ometer analyser works by measuring pH and P CO 2 by potentiometry, P O2 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 cardiotocog- raphy during the second stage of labour. Small for gesta- tional age (SGA) was defined as a birthweight below 2 SD from the gestational age-adjusted mean value, appropri- ate 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

The Mann Whitney 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-

Mokarami et al.

ate. A two-tailed P < 0.05 was considered to be statistically significant. Statistical analyses were performed with the aid of STAT VIEW (SAS Institute, Cary, NC, USA). As umbilical cord blood gas and lactate values are dependent on gesta- tional age, 10 12 comparisons between groups delivered vagi- nally 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)

Caesarean delivery ( n = 58)

Maternal characteristics Duration of second

41

(5234)

stage of labour (min) Duration of

24

(490)

pushing (min) Induction of labour

5 (7.6%)

Instrumental birth

9 (13.6%)

Drugs administered Pethidin

6 (9.1%)

Oxytocin

31 (47.0%)

Nitrous oxide

50 (75.8%)

Anaesthesia Epidural

15 (22.7%)

Spinal

 

52 (90.0%)

General

6 (10.0%)

Newborn characteristics Gestational age

40 +0 (36+0 42+0) 38 +4 (36+4 40 +3)

(weeks)* Birthweight (g)

3595 (25604405)

3535 (25165320)

SGA

3 (4.5%)

0

AGA

62 (93.9%)

47 (81.0%)

LGA Apgar score

1 (1.5%)

11 (19.0%)

1

minute*

9 (410)

9 (810)

5

minute

10 (810)

10 (710)

10 minute

10 (910)

10 (910)

Cardiotocography

 

Intermediate

13 (19.7%)

Pathological

3 (4.5%)

*The difference in gestational age and Apgar score at 1 minute was statistically significant (Mann Whitney U test; P 0.03) between the two groups. Values are median (range) or number of cases (%).

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 T 0 (one vaginal delivery and three caesarean sections) and ten analyses at T 45 (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 T 0 and T 45 were included in the statistical analyses. Data for arterial and venous acidbase and haematological measurements are shown in Tables 2 and 3.

Longitudinal changes between T 0 and T 45

Longitudinal changes in arterial blood gases, and in lactate, Hct, and ctHb concentrations are illustrated in Figure 2. With the exception of P CO 2 in the group delivered by cae- sarean section ( P = 0.4), all blood gas and lactate parame- ters changed significantly. Acid base 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 signifi-

cant (not shown in Figure 2). Hct and ctHb increased sig-

nificantly in the artery in both groups, whereas venous values decreased significantly in the group delivered vagi- nally ( 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 P CO 2 changes were compared between groups, the decrease in pH and increase in P CO 2 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 T 0 to T 45 (P = 0.9). Adjusting pH for the difference in gesta- tional 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 T 0 and T 45 , in both the artery and the vein, compared with neonates delivered by caesarean section (Tables 1 and 2). At T 45 , P CO 2 and P O 2 in the artery in the group delivered vagi- nally were also significantly higher.

Spinal versus general anaesthesia

Neonates in the group delivered by caesarean section with spinal anaesthesia (n = 52) had lower pH values, and higher P CO 2 and lactate concentration at T 0 , compared with neonates in the general anaesthesia group ( n = 6), but only the difference in lactate concentration was statistically sig- nificant (P = 0.03).

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 T 0 ), and again 45 seconds later (T 45 ), in unclamped umbilical cords with intact pulsations after vaginal delivery and caesarean delivery

Vaginal Caesarean

T 0

T 45

Vaginal versus

caesarean

Significance of difference ( P )

Vaginal

Caesarean

Vaginal

Caesarean

Median (range)

Median (range)

Median (range)

Median (range)

n

n

T 0

T 45

58

39

7.235 (7.0087.379) 7.305 (7.1627.397) 7.207 (7.005 7.384) 7.296 (7.1167.424) <0.0001 <0.0001

58

39

7.55 (5.2411.6)

7.30 (5.869.56) 1.99 (1.183.72)

7.87 (5.94 11.8) 2.66 (1.09 4.94) 5.5 (2.3 13.3)

7.57 (5.5610.4)

0.3

0.03

57

39

2.31 (0.627.93)

2.28 (1.183.25)

0.1

0.02

56

37

4.8 (2.013.3)

1.8 (1.1 4.8)

2.2 (1.56.2)

<0.0001 <0.0001

57

38

0.507 (0.0510.625) 0.452 (0.4090.585) 0.514 (0.423 0.635) 0.460 (0.3720.583) <0.0001 <0.0001

57

38

167 (134 205)

148 (133 191)

168 (138 208)

151 (121 191)

<0.0001 <0.0001

pH P CO 2 (kPa) P O 2 (kPa) Lactate (mmol/l) Hct ctHb (g/l)

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 T 0 ), and again 45 seconds later (T 45 ), in unclamped umbilical cords with intact pulsations after vaginal delivery and caesarean delivery

Vaginal Caesarean

T 0

T 45

Vaginal versus

caesarean

Vaginal

Caesarean

Vaginal

Caesarean

Median (range)

Median (range)

Median (range)

Median (range)

Significance of difference ( P )

n

n

T 0

T 45

64

41

7.331 (7.0687.471) 7.371 (7.3207.479) 7.329 (7.470 7.474) 7.367 (7.3187.469) <0.0001 <0.0001

64

41

5.49 (3.919.70)

5.78 (4.377.46) 3.46 (1.877.45)

5.42 (4.05 9.54) 3.68 (1.52 7.38) 4.7 (2.1 10.8)

5.77 (4.697.54)

0.2

0.1

63

41

3.57 (1.4615.70)

3.46 (1.406.43)

0.6

0.9

60

40

4.6 (1.910.9)

1.5 (1.1 2.7)

1.6 (1.23.0)

<0.0001 <0.0001

63

38

0.515 (0.4010.648) 0.455 (0.4100.585) 0.513 (0.058 0.633) 0.456 (0.3890.590) <0.0001 <0.0001

64

39

168 (131 212)

148 (133 191)

168 (126 208)

149 (127 193)

<0.0001 <0.0001

pH P CO 2 (kPa) P O 2 (kPa) Lactate (mmol/l) Hct ctHb (g/l)

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 P CO 2 in the group delivered vaginally. The similar increases in lactate concentration in the two groups indicate that considerable hidden acido- sis was also present in the group delivered by caesarean section.

The lack of change in venous P CO 2 indicates that placen- tal perfusion and gas exchange were maintained during the first 45 seconds, after both vaginal and abdominal deliver- ies. Thus, the temporal increase in arterial P CO 2 must be a result of CO 2 inflow from the newborn, and not from the placenta, or of an accumulation of CO 2 in the blood cir- cuit. Moreover, the significant increase in P O 2 indicates the rapid establishment of functional pulmonary ventilation, which would result in the escape of CO 2 and in a lowering of P CO 2 unless there was a considerable continuing fetal

Mokarami et al.

Vaginal delivery Caesarean delivery

Vaginal delivery

Vaginal delivery Caesarean delivery

Caesarean delivery

* 7,32 8,6 *** 8,4 7,30 8,2 7,28 8,0 7,26 NS 7,8 **** 7,24 7,6
*
7,32
8,6
***
8,4
7,30
8,2
7,28
8,0
7,26
NS
7,8
****
7,24
7,6
7,22
7,4
7,20
7,2
7,18
7,0
****
2,9
6,5
***
2,8
6,0
2,7
5,5
2,6
5,0
*
2,5
4,5
2,4
4,0
2,3
3,5
****
2,2
3,0
2,1
2,5
2,0
2,0
1,9
1,5
175
54
****
****
53
170
52
165
51
50
**
160
*
49
155
48
47
150
46
145
45
pH
Hct (%)
P 2O (kPa)
P
ctHb (g/L)
Lactate (mmol/L)
2CO (kPa)

T 0

T 45

T 0

T 45

Figure 2. Measurements of arterial umbilical cord blood gases, and concentrations of lactate, haematocrit (Hct), and total haemoglobin (ctHb) obtained immediately after birth ( T 0 ), and then again 45 seconds later (T 45 ), 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 T 0 and T 45 : *P < 0.05; ** P < 0.01; *** P < 0.001; ****P < 0.0001; NS, not significant.

contribution. As it is unlikely that the CO 2 contribution was a result of a sudden rise in neonatal metabolism, a washout of CO 2 from peripheral tissues is the most plausi- ble explanation for this finding. After 45 seconds, arterial blood showed a small but sig- nificant 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 acid base and lactate changes. According to Stewart’s physicochemical concept, a change towards alkalosis should occur during haemocon- centration, as dehydration results in a higher [OH ]. 13 In the present study, the changes in haemoconcentration par- alleled changes towards acidosis in the artery, indicating

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 umbil- ical artery pH < 7.10 in the first samples. Both these new- borns 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

Acidbase changes after delayed umbilical cord sampling

from 7.06 to 7.02; P CO 2 changed from 10.0 to 10.5 kPa; BE changed from 12.7 to 15.3 mmol/l; and lactate chan- ged 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, P CO 2 changed from 11.2 to 11.8 kPa, BE changed from 14.9 to 14.4 mmol/l, and lactate concen-

tration was 13.3 mmol/l at both time points. These obser- vations 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 phenome- non 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 precau- tions in terms of prehydration and vasopressor administra- tion, spinal anaesthesia in particular is frequently associated with maternal hypotension and lower umbilical cord arte- rial pH. 14 18 Vasopressor substances can cross the pla- centa, 14,19 22 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 mod- ern techniques for spinal anaesthesia, this side effect is dif- ficult to avoid. 26 An interesting finding was that at T 0 , P O 2 was similar in the groups delivered vaginally and by caesarean sections, but at T 45 it was significantly higher in the group delivered vaginally, as a result of a steeper increase. This demon- strates the protective role of vaginal delivery, with the more effective release of lung surfactant and alveolar expansion, absorption of pulmonary fluid, and rapid circulatory tran- sition 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 chronologi- cal 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 newborn’s status and lead to a false diagnosis of acido- sis, 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 inter- vals 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 haemocon- centration occurred in arterial blood, and haemodilution occurred in venous blood, but these changes could not explain the change in acid base 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 Cen-

tral Ethical Review Board, Stockholm, Sweden (reference

number O 50 200), and all the women gave their informed

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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