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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. References

Objective To assess the effect of epidural versus systemic labour analgesia on funic acid–base status at birth.

Design A systematic review of trials, both randomised and non-randomised, comparing epidural with systemic opioid analgesia.

Population Babies of 2102 mothers taking part in trials comparing epidural with systemic analgesia in five countries.

Methods From the published and unpublished figures obtained from authors, fetal pH data from 12 studies (eight randomised) (1098 babies in the epidural group + 1004 controls) and base excess from 8 studies (four randomised) (856 epidural + 842 controls) were subjected to random effect meta-analysis.

Main outcome measures Umbilical artery pH and base excess values.

Results Fetal pH was higher in the epidural than in the control group in the randomised trials (difference +0.009, 95% CI +0.002 to +0.015), but when all studies were included, the difference was not significant (+0.004, 95% CI −0.005 to +0.014). Fetal base excess was higher in the epidural group in the four randomised studies (difference +0.779 mEq/L, 95% CI +0.056 to +1.502) and in all eight studies (difference +0.837 mEq/L, 95% CI +0.330 to +1.343).

Conclusion Umbilical artery pH is influenced by maternal hyperventilation. Base excess is therefore a better index of metabolic acidosis after labour. Epidural analgesia is associated with improved neonatal acid–base status, suggesting that placental exchange is well preserved in association with maternal sympathetic blockade and good analgesia. Although epidural analgesia may cause maternal hypotension and fever, longer second stage of labour and more instrumental vaginal deliveries, these potentially adverse factors appear to be outweighed by benefits to neonatal acid–base status.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. References

Epidural analgesia produces better pain relief and more maternal satisfaction than other methods of analgesia in labour1, but its possible adverse effects have been the focus of much attention in recent years. Many perceived complications stemmed from the fact that, appropriately, it was used more in induced and high risk than in normal spontaneous labours. A number of prospective studies, randomised trials and meta-analyses comparing it with systemic opioid analgesia have refuted concern that it may provoke an increase in the caesarean section rate1,2 and in the prevalence of postpartum backache3, and that it may adversely affect breastfeeding4. The most recent and comprehensive systematic review1, however, has confirmed an association between epidural analgesia and maternal hypotension, an increase in the duration of the second stage of labour, in the need for oxytocin and in instrumental vaginal delivery rate and a rise in maternal temperature during labour, although the latter only amounts to approximately 0.07°C/hour5.

Many British obstetricians and midwives assume that because epidural analgesia is associated with these maternal and obstetric changes, it must have adverse effects on the fetus and newborn, without pausing to consider whether there is direct evidence of any such detriment. Indeed, scant attention has been paid to indices of the baby's wellbeing, one meta-analysis even making no mention of neonatal effects2. If these potentially adverse intrapartum effects of epidural analgesia were harmful to the baby, this would be reflected in the neonatal acid–base status. Early studies published in 1974, however, reporting funic pH and base excess, suggested that epidural analgesia was associated with reduced fetal/neonatal acidosis and even appeared to protect the fetus from the detrimental effects of a prolonged second stage of labour6–9.

Acid–base balance measured in cord blood at delivery is a useful index of the recent intrauterine environment. The commonly recorded umbilical artery pH, however, is influenced by respiratory as well as metabolic factors. Maternal hyperventilation in painful labour tends to raise arterial pH in both maternal and fetal blood and may therefore mask fetal acidosis, but with epidural blockade, excessive hyperventilation is prevented by adequate analgesia, counteracting any possible respiratory alkalosis. Base excess is a more specific index of the metabolic component of acid–base balance, but unfortunately, although derived from pH, PCO2 and haemoglobin, and usually calculated automatically, it has rarely been reported in more recent published work. We have therefore explored whether there is any up-to-date evidence from randomised studies, both published and unpublished, that supports or refutes the earlier findings of a favourable effect of epidural analgesia on umbilical artery pH and base excess values. It is hoped that this work may improve understanding among those who inform pregnant women of this crucial aspect of neonatal welfare.

Method

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. References

A search was conducted, using a personal card index, published meta-analyses1,2, earlier reviews10 and also Medline and Embase using key words ‘epidural AND (meperidine OR opioid analgesia) AND (umbilical OR neonatal OR fetal) AND pH OR acid–base balance’, to identify studies, both randomised and observational, comparing epidural with other forms of labour analgesia, in which it appeared that umbilical cord blood was sampled at birth. The original papers were scrutinised and when incomplete data were published, we attempted to contact the authors to obtain additional unpublished umbilical artery pH and base excess values.

Where raw data were available, the effect of epidural use was re-estimated using linear regression with robust standard errors11. Where the authors gave separate data for different subgroups (different delivery types or second stage duration), the mean and standard deviation were calculated for the combined data and unpaired t tests with Satterthwaite's correction for unequal variance conducted. The treatments effects were combined using random effect meta-analysis both for randomised studies and for all studies12. Funnel plots and Eggar's test were used to check for heterogeneity and publication bias13. All calculations were carried out in Stata version 6.0 (Stata, College Station, Texas).

Table 1 describes the studies that have been included in the meta-analysis6–9,14–22. These include some studies in which old-fashioned epidural analgesia using local anaesthetic without opioid was used, and others using the more up-to-date low dose combinations. Four of the early studies were not randomised7–9,21,22 and one was quasi-random (alternate allocation)14, but they have been included in the full analyses for reasons that are given in the Discussion. In one early study6, acid–base balance was measured in blood drawn from ‘umbilical vessels’ at birth. In another, absolute values were reported for fetal scalp blood during labour7, while absolute values for cord blood data were not reported, but only trends during the second stage were given8. The author was able to provide the actual umbilical artery pH and base excess values for many more babies than were in the published series. All those for whom information on parity, delivery type, treatment group and umbilical artery acid–base data were available have been included in the present analysis.

Table 1.  Studies included in meta-analysis.
SourceType of trial and subjectsNature of epiduralnNature of control analgesian
  1. In the randomised trials, n is given as numbers that were protocol compliant over total numbers randomised to the treatment group.

  2. ‘mixed’ refers to parity; m = multipara; p = primipara.

  3. In the study by Deckardt et al.21, the epidural group contained only primipara, whereas the control group was of mixed parity.

Randomised trials     
Thalme et al.6, SwedenRandomised, uncomplicated, nullipara, established labourBupivacaine 0.25% + epinephrine boluses14/14Intramuscular pethidine 100 mg + chlorpromazine14/14
Jouppila and Hollmen14, FinlandAlternate, induced, mixed parturientsBupivacaine 0.5% + epinephrine boluses14/14Intramuscular pethidine 50 mg or nothing14/14
Thorp et al.15, USARandomised, uncomplicated, nullipara, spontaneous labourBupivacaine 0.25% bolus and 0.125% infusion48/48Intravenous pethidine 75 mg + promethazine every 90 minutes, prn45/45
Ramin et al.16, USARandomised, uncomplicated, mixed, spontaneous labourBupivacaine 0.25% bolus + infusion of 0.125% with fentanyl432/664Intravenous pethidine 50 mg + promethazine, prn437/666
Sharma et al.17, USARandomised, uncomplicated, mixed, spontaneous labourBupivacaine 0.25% bolus + infusion of 0.125% with fentanyl243/358PCA pethidine + initial promethazine259/357
Bofill et al.18, USARandomised, uncomplicated, nullipara, spontaneous labourBupivacaine 0.25% boluses ± fentanyl + infusion of 0.125% with fentanyl47/49Intravenous butorphanol ± promethazine hourly, prn39/51
Nikkola et al.19, FinlandRandomised, uncomplicated, nullipara, spontaneous labourBupivacaine 0.5% boluses10/10PCA fentanyl7/10
Clark et al.20, USARandomised, uncomplicated, nullipara, spontaneous labourBupivacaine 0.25% with fentanyl bolus + infusion of 0.125% with fentanyl147/156Intravenous pethidine every 90 minutes, prn78/162
Non-randomised trials     
Pearson and Davies7,8, UKUncomplicated, mixed, induced and spontaneousPlain bupivacaine 0.25% boluses17Intramuscular pethidine 100 mg or more ± promazine22
Pearson (unpublished)Mixed parturients, induced and spontaneousPlain bupivacaine 0.25% boluses19m, 36pIntramuscular pethidine 100 mg or more ± promazine or nil31m, 24p
Zador and Nilsson9, SwedenUncomplicated, mixed parturients, spontaneous labour1% or 0.5% lidocaine + epinephrine boluses49Nitrous oxide ± pethidine 50 mg in early labour ± diazepam71
Deckardt et al.21, GermanyUncomplicated, mixed parturients, induction not statedPlain bupivacaine 0.25% boluses15pIntramuscular pethidine/nitrous oxide or no analgesia16m, 15p
Shyken et al.22, USAUncomplicated, mixed parturients, spontaneous labourBupivacaine 0.125 or 0.25% ± fentanyl boluses49Narcotic/unspecified/general for caesarean (n= 16)45

In one randomised trial, actual pH values were not reported, but only numbers of babies with pH values less than a particular cutoff point, but it was possible to obtain the absolute values from the authors16. It was also possible to obtain base excess values for individual patients in this and another large randomised trial17. In the latter trial, unpublished data for babies of non-compliant mothers were also obtained. Most of the data presented for these two large randomised trials are therefore previously unpublished.

In the study by Zador and Nilsson9, mean pH and base excess values were given separately for those in whom the second stage of labour was longer or shorter than 60 minutes. In the study reported by Shyken et al.22, results were separated into those delivering vaginally and those by caesarean section. The authors did not state whether the women who delivered by caesarean section under epidural anaesthesia had received epidural analgesia during labour. For the purpose of this meta-analysis in both these studies the data for all subjects were combined within each treatment group to avoid bias by omitting babies delivered by caesarean section.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. References

Table 2 gives the values for pH in individual studies and unpublished series. Meta-analysis of pH data is shown in Fig. 1 for randomised trials and Fig. 2 for all studies. In the randomised studies, there is a difference of +0.009 (95% CI +0.002 to +0.015, P= 0.007) in umbilical artery pH values between the epidural and systemic analgesia groups, favouring epidural analgesia. There is no significant heterogeneity between treatments. When all studies are included, the difference between treatment groups is not significant (+0.004; 95% CI −0.005 to +0.014), but there is significant heterogeneity (P= 0.015), revealing inconsistencies with the non-randomised studies, the main difference being between Shyken et al.22 and the rest, and a lesser difference (in the opposite direction) between Deckardt et al.21 and the rest.

Table 2.  Umbilical artery pH values (mean [standard deviation]) recorded after labour with or without epidural analgesia.
 n+nEpiduralControlsDifference (95% CI)
  1. Numbers differ from those in Table 1, as pH was not measured in all cases.

  2. Deckardt et al.21 data for primipara only, as multipara consisted of ‘controls’ only. Numbers analysed in the control group are uncertain.

  3. Shyken et al.22 separated results by mode of delivery: vaginal or caesarean section (CS). All were labouring women, but it is not stated whether women given epidural anaesthesia for caesarean section received it also during labour.

  4. The results of Zador and Nilsson9 were separated into those with a second stage <60 minutes or >60 minutes.

  5. The results for Ramin (unpublished) and Sharma (unpublished) are drawn from the populations in the published trials15,19.

  6. The results for Pearson in this table and Table 3 are unpublished and drawn from a larger population than in the published series.

  7. * Sample from ‘umbilical vessels’.

  8. ** Fetal scalp blood sampled at full dilatation.

  9. Epidural minus control.

  10. § Analysed by intention-to-treat.

Randomised trials    
Thalme et al.*612 + 127.28 [0.062]7.27 [0.057]+0.01 (−0.044 to +0.064)
Jouppila and Hollmen1414 + 147.26 [0.08]7.28 [0.06]−0.02 (−0.078 to +0.038)
Thorp et al.1547 + 417.26 [0.06]7.25 [0.06]+0.01 (−0.016 to +0.036)
Ramin (unpublished)423 + 4117.27 [0.074]7.26 [0.078]+0.003 (−0.007 to +0.014)
Sharma (compliant)235 + 2147.26 [0.076]7.25 [0.081]+0.011 (−0.003 to +0.026)
Sharma (all)302 + 2717.26 [0.073]7.24 [0.081]+0.020 (+0.007 to +0.032)
Bofill et al.§1849 + 517.27 [0.06]7.27 [0.08]+0 (−0.028 to +0.028)
Nikkola et al.§1910 + 87.24 [0.06]7.23 [0.11]+0.01 (−0.081 to +0.101)
Clark et al.20142 + 667.24 [0.05]7.23 [0.05]+0.01 (−0.002 to +0.002)
Observational studies    
Pearson and Davies**7,816 + 137.36 [0.044]7.31 [0.036]+0.05 (−0.006 to +0.106)
Pearson (unpublished)55 + 557.26 [0.073]7.25 [0.057]+0.01 (−0.016 to +0.033)
Zador and Nilsson9    
  Short21 + 567.26 [0.04]7.27 [0.05]+0.01 (−0.033 to +0.013)
  Long26 + 157.22 [0.05]7.19 [0.08]+0.03 (−0.019 to +0.079)
Deckardt et al.2115 + 16?7.29 [0.06]7.21 [0.10]+0.08 (+0.013 to +0.147)
Shyken et al.22    
  Vaginal25 + 297.26 [0.04]7.29 [0.04]−0.03 (−0.05 to −0.008)
  CS24 + 167.27 [0.04]7.27 [0.04]0 (−0.032 to +0.032)
image

Figure 1. Meta-analysis of difference (epidural minus control) between umbilical artery (**umbilical cord) pH values in eight randomised controlled trials of epidural versus systemic opioid analgesia. The vertical line represents unity, the size of the box gives an estimate of the weighting of the study and the horizontal lines are the 95% confidence intervals. [Weighting is based on the amount of information provided by the study, defined as 1/the square of the standard error of the estimate.] There is a significant difference (P= 0.007) between the two treatment groups, favouring epidural analgesia. +Includes unpublished data.

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image

Figure 2. Meta-analysis of difference (epidural minus control) between umbilical artery (**umbilical cord) pH values in all 12 studies of epidural versus systemic opioid analgesia. See caption to Fig. 1 for further explanation. The difference is no longer significant. +Includes unpublished data.

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Table 3 gives the values for base excess in individual studies and unpublished series. Analyses of data for base excess are shown in Figs 3 and 4. Only the small quasi-randomised study of Jouppila and Hollmen14 does not show improvement in base excess with epidural analgesia. The difference between base excess values in the two treatment groups is +0.779 mEq/L (CI +0.056 to +1.502) for the four randomised studies only and +0.837 mEq/L (CI +0.33 to +1.343) for all eight studies. Again there is significant heterogeneity with the non-randomised studies (P= 0.028).

Table 3.  Umbilical artery base excess (mEq/L) recorded after labour with or without epidural analgesia. Values are given as mean [SD].
 n+nEpiduralsControlsDifference (95% CI)
  1. Numbers differ from those in Table 1, as base excess was not measured in all cases.

  2. Deckardt et al.21: data for primipara only, as multipara consisted of ‘controls’ only.

  3. Shyken et al.22 separated results by mode of delivery: vaginal or caesarean section (CS). All were labouring women, but it is not stated whether women given epidural anaesthesia for caesarean section received it also during labour.

  4. The results of Zador and Nilsson9 were separated into those with a second stage <60 minutes or >60 minutes.

  5. The results for Ramin (unpublished) and Sharma (unpublished) are drawn from the populations in the published trials15,19.

  6. * Sample from ‘umbilical vessels’.

  7. ** Fetal scalp blood sampled at full dilatation.

  8. Epidural minus control.

Randomised trials    
Thalme et al.*612 + 11−7.9 [2.7]−10.1 [2.2]+2.2 (−0.011 to +4.411)
Jouppila and Hollmen1414 + 14−7.6 [3.9]−6.8 [2.7]−0.80 (−3.55 to +1.95)
Ramin (unpublished)423 + 413−3.71 [2.55]−4.08 [2.96]+0.38 (+0.003 to +0.75)
Sharma (compliant)241 + 217−4.64 [3.19]−5.87 [3.21]+1.23 (+0.64 to +1.82)
Sharma (all)308 + 274−4.61 [3.02]−5.76 [3.08]+1.14 (+0.65 to 1.64)
Observational studies    
Pearson and Davies**7,817 + 13−2.2 [2.06]−4.5 [1.80]+2.3 (−0.58 to +5.18)
Pearson (unpublished)55 + 55−6.81 [3.92]−8.57 [3.16]+1.76 (+0.42 to +3.11)
Zador and Nilsson9    
  Short21 + 56−3.94 [1.7]−4.23 [1.94]+0.29 (−0.64 to +1.22)
  Long26 + 15−5.0 [2.26]−8.27 [2.35]+3.27 (+1.68 to +4.86)
Deckardt et al.2115 + 16?−6.4 [2.2]−9.5 [4.5]+3.0 (+0.08 to +5.92)
Shyken et al.22    
  Vaginal25 + 29−3.9 [1.8]−4.8 [2.6]+0.90 (−0.34 to +2.14)
CS24 + 16−4.4 [1.9]−3.7 [2.2]−0.7 (−2.02 to +0.62)
image

Figure 3. Meta-analysis of difference (epidural minus control) between umbilical artery (**umbilical cord) base excess data from four randomised controlled trials of epidural versus systemic opioid analgesia. See caption to Fig. 1 for further explanation. There is a significant difference (P= 0.035) between the two treatment groups, favouring epidural analgesia. +Includes unpublished data.

Download figure to PowerPoint

image

Figure 4. Meta-analysis of difference (epidural minus control) between umbilical artery (**umbilical cord) base excess data from all eight studies of epidural versus systemic opioid analgesia. See caption to Fig. 1 for further explanation. There is a significant difference (P= 0.001) between the two treatment groups, favouring epidural analgesia. +Includes unpublished data.

Download figure to PowerPoint

In Tables 2 and 3, the data as originally published are presented as well as the additional material. This reveals a difference between the groups with long and short second stages in the study by Zador and Nilsson9. The inclusion of data for non-compliant as well as compliant women in Sharma's study has little impact on the results. In two small randomised studies, neonatal data were also analysed by intention-to-treat18,19. All participants are included by intention-to-treat in the meta-analysis. In the study by Pearson and Davies7,8, only results for those having apparently normal labours and without major neonatal acidosis were originally selected for publication. The results are thus akin to those of a randomised trial, where it is normal practice for uncomplicated labours only to be selected. The 110 participants included in the present analysis are not exclusive and, as in real life, the epidural group included more primiparae (Table 1), more inductions, more complicated labours and more abnormal deliveries. Despite this bias against epidurals, the results remain favourable, although less so, to the epidural group.

Certain other studies that gave some data about funic acid–base balance in epidural and non-epidural labours23–27 have been excluded for the reasons given in Table 4. The findings in these excluded studies were, however, consistent with those of this meta-analysis. A second randomised trial by Sharma et al.28 that included umbilical artery pH was published after this meta-analysis was completed.

Table 4.  Excluded studies.
SourceType of trial and reason for exclusionNature of epiduralnNature of control analgesian
  1. * Further details requested but not obtained.

Wiener et al.23, UKUnrandomised, retrospective selection of easy vaginal deliveries of fit babies only. UV pHPlain bupivacaine 0.5% boluses11Intramuscular pethidine 100–300 mg (total dose) only (n= 18) or + naloxone at delivery (n= 15)33
Swanström and Bratteby24, SwedenRandomised but controls included regional blocks. ‘Asphyxiated’ babies in separate group. UA pH and BELidocaine bolus or infusion35‘Control’ (nitrous oxide or nil)25
Paracervical ± pudendal block15
Asphyxia10
Philipsen and Jensen25, DenmarkRandomised, UV pH: means and ranges but no standard deviations*Plain bupivacaine 0.375% boluses57Pethidine 75 mg prn ± nitrous oxide55
Muir et al.26, USARandomised, reported only numbers with ‘cord’ pH <7.15*Patient controlled epidural bupivacaine plus pethidine28Patient-controlled intravenous pethidine22
Gambling et al.27, USARandomised, reported only numbers with ‘cord’ pH <7.20*Intrathecal sufentanil then epidural infusion of bupivacaine + fentanyl616Intravenous pethidine 50 mg + promethazine then meperidine 50 mg prn hourly607

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. References

Arterial pH reflects both a respiratory and a metabolic component; thus, during labour, both maternal and fetal values are influenced by the extent to which a mother in pain is stimulated to hyperventilate. Systemic analgesia is often not sufficiently effective to prevent this hyperventilation. Base excess is therefore a more specific index of metabolic acidosis, and hence, fetal hypoxia. Once born, a baby can no longer rely on maternal ventilation to maintain acid–base balance, and neonatal respiration may be depressed following maternal systemic opioid analgesia6. The presence of adequate buffer base is therefore important to the newborn. Base excess is designed to be zero in normal circumstances, but it is difficult to say what constitutes normality in the perinatal period. The normal umbilical artery pH is said to be >7.2 and base excess −10 to 0 mEq/L29. Table 3 shows that mean figures for base excess vary widely between studies, while many individual values fall outside the ‘normal’ range.

Epidural analgesia is used in the UK more frequently in longer and more complex labours; thus inclusion of unrandomised studies would be expected to introduce bias against epidural analgesia, and reduce its apparent benefit to the baby. When considering only randomised studies, epidural analgesia has a favourable effect on funic pH, while if unrandomised studies are included, the difference in pH between treatment groups is not significant. Yet there is a statistically significant improvement in base excess both in randomised studies and when all studies are included. In the control groups, therefore, the fetus suffers a more severe metabolic acidosis, which is not fully compensated by maternal hyperventilation. The small but significant improvement with epidurals could represent a crucial advantage for the at risk fetus, in whom surveys have shown improvement in mortality with epidurals30, and it certainly demonstrates an absence of any fetal detriment.

Methods of assessing the newborn

Many methods have been used to assess the wellbeing of fetus and newborn. Perinatal mortality is now too low to be a useful yardstick, particularly since it is common practice to select only normal labours for randomised controlled trials. An early observational study, however, found reduced early neonatal mortality among low birthweight infants in the epidural group compared with the non-epidural group30. The Apgar score, a method that has been used universally for many years, can be applied only within a few minutes of birth, a stimulating time for the newborn. A baby who has been exposed in utero to systemic drugs may therefore perform well at birth but may later become drowsy31. Nevertheless, a meta-analysis has demonstrated that Apgar score may be adversely affected by systemic compared with epidural analgesia1.

More recently, investigators have turned to neonatal neurobehavioural scoring, which is applicable in the first few hours or days of life rather than minutes, in the hope that it may be more relevant and more sensitive. Doubt, however, has been cast on the validity of the most popular approach32, the Neurological and Adaptive Score (NACS), which was designed to discriminate between drug effects and neonatal asphyxia33. The differences between neurobehavioural scores for epidural and systemic analgesia are variable and inconsistent34 and a meta-analysis yielded no significant difference35. The number of babies needing resuscitation with naloxone is also sometimes reported17,27,28, which reflects the doses of opioid used in the control groups. The numbers needing intensive care are rarely reported in randomised trials, and are also too few (0.065%)17–19 to provide a sensitive index of neonatal welfare. Among the more widely used methods of neonatal assessment, this only leaves funic acid–base status, which has the additional advantage that it is applicable to all labours.

The recent systematic review by Leighton and Halpern1 demonstrates that, despite a greater risk of maternal hypotension, a mean increase of 15 minutes in the duration of the second stage of labour, a 2-fold increase in the rate of instrumental delivery, a 2.8-fold increase in the need for oxytocin and a 5.6-fold increase in the risk of maternal fever with the epidural analgesia, the odds ratio for a 1-minute Apgar score <7 was 0.54 (P < 0.05), for a 5-minute Apgar score <7 was 0.54 (NS) and for needing naloxone was 0.20 (P < 0.01)—consistently in favour of epidural analgesia. The incidence of low umbilical artery pH or severe asphyxia did not differ significantly between groups. That we found a significant difference in pH values between groups may reflect the greater sensitivity of using mean and standard deviations for meta-analysis involving continuous variables.

Mechanisms by which labour analgesia may affect the baby

Analgesia may affect the baby either because the drugs reach active concentrations in the plasma (as is the case with systemic analgesia), or because they affect maternal physiology or biochemistry. The latter is the more likely mechanism with epidural analgesia, which does not depend for its effect on the presence of a drug in maternal blood. The acid–base status of umbilical arterial blood reflects the intrauterine environment and the efficiency of transplacental exchange. It is therefore an appropriate yardstick for the potential effects of epidural analgesia.

Several studies that followed the introduction of ion-sensitive electrodes in the 1970s showed that painful labour led not only to maternal respiratory alkalosis, but also to progressive metabolic acidosis, which was transmitted to the fetus during the first stage of labour6,7,36, while the second stage was associated with further deterioration in fetal acid–base balance6,8. These early studies, however, suggested that in the presence of epidural analgesia, both maternal and fetal metabolic acidosis were less severe and the second stage was not associated with the same deterioration in maternal or fetal acid–base balance8. Indeed, the study by Zador and Nilsson9 showed that this apparent protective effect of epidural analgesia was seen in the subgroup in which the second stage lasted longer than 60 minutes. These findings suggested that, although epidural analgesia may prolong the second stage1, this does not necessarily result in worsening fetal acidosis.

Although hypotension may occur following regional anaesthesia for caesarean section, and if prolonged may have a detrimental effect on newborn acid–base balance37,38, the frequency and degree of hypotension are less following the smaller doses required for analgesia in labour. Numerous studies, cited by Hollmen39, have shown using various techniques that sympathetic blockade from lumbar epidural analgesia tends to improve maternal placental blood flow, and to have no detrimental effect on umbilical blood flow40,41. Respiratory gas exchange, which is flow dependent, should therefore be favoured. Moreover, epidural analgesia without opioid prevents episodes of maternal desaturation that otherwise occur during painful labour, particularly when systemic analgesia is used21,42. The reduction in maternal hyperventilation36,43 and in the levels of maternal stress hormones44,45, which are both associated with regional analgesia, may also improve transplacental gas exchange. Similar improvements in stress responses are seen when low dose local anaesthetic and opioid combinations are used46,47.

Thus, there are theoretical reasons why fetal acid–base status during labour may both improve and deteriorate with epidural analgesia, and the present analysis suggests that, in practice, it is the beneficial effects that prevail.

Improvements in analgesic techniques

In the past 20 years, the practice of epidural analgesia has changed in that other drugs such as opioids are added to the local anaesthetic. This enables a smaller dose of local anaesthetic to be used, thereby reducing the local anaesthetic side effects of hypotension and muscle weakness and also reducing the danger from misplacement of a dose. Although large doses of opioids given epidurally or intrathecally have been known to cause neonatal depression34, the modest doses in current use have no measurable adverse neonatal effects48. The comparative lack of neonatal effect of epidural as opposed to systemic opioids is reflected in the greater need for resuscitation with naloxone in the non-epidural groups1. Moreover, although the improvement in funic acid–base balance was first demonstrated at a time when local anaesthetic was used without opioid6–9, similar beneficial effects have been found in the more recent randomised trials in which low dose combinations were used16–18,20. These four studies contributed 916 of the total of 952 women in this meta-analysis who were randomised. It appears that replacing systemic with modest doses of neuraxial opioids not only produces superior analgesia but also reduces neonatal complications. The COMET study49 did not compare epidural with systemic analgesia, but rather, compared using plain bupivacaine epidural analgesia with combined spinal epidural analgesia using epidural top-up injections of local anaesthetic and opioid solutions, and also with a continuous infusion of the mixture of drugs. The continuous infusion of bupivacaine and opioid was associated with an increased need for neonatal resuscitation. Women in this group, however, received the same total dose of bupivacaine as in the first group, but received opioid as well, which may explain these findings. These findings disagree with those of Porter et al.48.

Changes in practice might also affect the control groups. Table 1 shows that intramuscular pethidine was used in only 28 women in the randomised trials, and various more sophisticated intravenous and patient controlled analgesia regimens were used in the remainder. These were successful in improving compliance and reducing crossover, but possibly at a cost of greater need for naloxone.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. References

Expectant mothers can be reassured that, although epidural analgesia may be associated with some short term maternal side effects, it does not exacerbate fetal acidosis, and if anything, may partially protect the fetus from fetal hypoxia. It is important to dispel the notion that epidural analgesia is in some way harmful to babies.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. References

The authors would like to thank Jim Pearson for entrusting to us his original lab book and for use of his raw data.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Method
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. References
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