Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

The effects of maternal labour analgesia on the fetus

Felicity Reynolds, MBBS, MD, FRCA, FRCOG, ad eundem Emeritus Professor of
Obstetric Anaesthesia a
Anaesthetic Department, St Thomas’ Hospital, London SE1 7EH, UK

Keywords:
Maternal labour pain and stress are associated with progressive
labour analgesia fetal metabolic acidosis. Systemic opioid analgesia does little to
pethidine mitigate this stress, but opioids readily cross the placenta and
opioids cause fetal-neonatal depression and impair breast feeding. Pethi-
neuraxial analgesia dine remains the most widely used, but alternatives, with the
epidural analgesia possible exception of remifentanil, have little more to offer. Inha-
local anaesthetics lational analgesia using Entonox is more effective and, being
neonatal welfare
rapidly exhaled by the newborn, is less likely to produce lasting
umbilical artery acid-base balance
depression. Neuraxial analgesia has maternal physiological and
breast feeding
biochemical effects, some of which are potentially detrimental and
some favourable to the fetus. Actual neonatal outcome, however,
suggests that benefits outweigh detrimental influences. Meta-
analysis demonstrates that Apgar score is better after epidural than
systemic opioid analgesia, while neonatal acid-base balance is
improved by epidural compared to systemic analgesia and even
compared to no analgesia. Successful breast feeding is dependent
on many factors, therefore randomized trials are required to
elucidate the effect of labour analgesia.
Ó 2009 Elsevier Ltd. All rights reserved.

Introduction

A number of widely held misconceptions about the effects of maternal anaesthesia and analgesia on
the fetus have for many years hampered best practice in the UK. For example, despite old and new
evidence to the contrary, it is commonly believed that:

E-mail address: felicity.reynolds@btintenet.com

a
Of the on-time United Medical and Dental Schools of Guys and St Thomas’ Hospitals, now no longer in existence and
swallowed up by King’s College London.

1521-6934/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bpobgyn.2009.11.003
290 F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302

1. Unmodified labour is relatively harmless to the baby, and any pharmacological form of analgesia
must have adverse effects.
2. Epidural analgesia, the most invasive form of pain relief in labour, must also be the most damaging
to the fetus.
3. Pethidine should be avoided in the last hour of labour, to avoid neonatal sedation.

I cannot stress too strongly: these are indeed misconceptions, but they die hard. One common
problem is that, instead of examining the effect of any procedure on the newborn, various surrogate
outcomes such as maternal blood pressure, fetal heart rate, duration of labour, need for oxytocin,
delivery type and even maternal fever are assumed to equate with fetal/neonatal welfare. This is
erroneous. Another surrogate outcome that has in the past received too much attention is measure-
ment of drug concentration rather than drug effect. There are several genuine yardsticks of neonatal
welfare, for example: Apgar score, neurobehavioural score, acid-base balance and feeding. Although of
variable reliability, all merit attention. Sadly, many studies of labour analgesia fail to include any
measures of neonatal outcome.
Maternal analgesia in and around parturition may have direct pharmacological effects on the baby,
because of placental transfer of maternally administered drugs, or indirect effects secondary to phys-
iological or biochemical changes in the mother. These disparate means of affecting the fetus must be
borne in mind when considering each type of procedure.
It is important that all those wishing to keep mothers correctly informed should be fully conversant
with the evidence, so as to be competent to disabuse both fellow care-givers and lay consumers of their
misconceptions.

Effects of labour pain on the baby

Labour induces a massive catecholamine surge in the fetus, particularly in the second stage, which
helps to preserve blood flow to brain, heart and adrenal and to promote post-natal adaptive circulatory
changes and surfactant release. While this fetal stress response is favourable to the fetus, unmodified
‘natural’ labour produces maternal changes that are far from innocuous. Maternal hyperventilation in
response to pain has long been known to have adverse fetal effects.1,2 It leads to:

 respiratory alkalosis and a left shift in the oxygen dissociation curve (potentially disadvantageous
to placental transfer of oxygen).
 a compensatory metabolic acidosis, which becomes progressively more severe as labour advances
and is also conveyed to the fetus.3
 Episodes of hypoventilation, hence haemoglobin desaturation, between contractions.4
 Uterine vasoconstriction.1

Meanwhile the stress of labour also leads to release of maternal cortisol and catecholamines, which
may prolong labour and impair placental flow.5-7 Stress hormones also bring about lypolysis with
release of free fatty acids (readily transferable across the placenta) and hyperglycaemia, which will
exacerbate fetal hypoxia. All these changes tend to intensify fetal metabolic acidosis, which indeed
becomes progressively more severe as labour advances.3

Effects of systemic labour analgesia on fetus and neonate

Any drug that depends for its effect on its presence in maternal blood and central nervous system
must readily cross the blood-brain barrier and therefore also the placenta.8 Hence, given time, such
a drug has a direct affect on the baby. Snow himself observed that excessive chloroform could produce
a sleepy baby, and advocated careful control of dosage.9 Nevertheless, in the next century, deep
sedation using hyoscine (twilight sleep) and then barbiturates became popular, to the detriment of
both mother and baby. In the mid 20th century it was acknowledged that analgesia might be preferable
to sedation, and nitrous oxide and pethidine were adopted in the UK.
 F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302 291

Inhalational analgesia

Nitrous oxide was initially used in labour as a hypoxic mixture of gas and air and, thanks to the
development by Tunstall in 1961 of Entonox (a 50–50 mixture with oxygen in a single cylinder),10 and
despite the contribution of nitrous oxide to greenhouse gases, it became and remains the most popular
analgesic for labour in the UK. Although nitrous oxide passes readily across the placenta, it is rapidly
excreted by the newborn lungs, and though maternal hypoxaemic episodes occur after hyperventi-
lation during contractions, these are offset by the increased FiO2 in Entonox and have little apparent
effect on Apgar score, neurologic and adaptive capacity scores or acid-base balance.11
All the modern volatile anaesthetic agents have been used as alternatives or adjuncts to nitrous
oxide at various times.11 The more prolonged and profound the maternal effect, the greater the
potential sedation in the newborn, but again, these modern and poorly soluble agents are rapidly
excreted by the newborn lungs in the usual way.

Systemic opioids

Opioids given to provide systemic analgesia in labour have extensive dose-dependent direct fetal
and neonatal effects, but as pain relief is less effective than with neuraxial analgesia, they are less able
to mitigate the adverse effects of labour pain. Therefore any indirect benefit is small, but direct
pharmacological effects on the baby readily occur.

Pethidine
In twilight sleep, a combination of morphine and hyoscine, the morphine element was kept to
a minimum, as it was perceived to endanger the fetus. Then in 1950 pethidine was made available to
midwives, in the belief that it had the analgesic effect of morphine, but without its side effects. It was
also widely believed to be a more powerful analgesic than nitrous oxide. Wrong on both counts! Quite
quickly the ineffectiveness of pethidine 12 and it adverse effects on the newborn 13 began to emerge,
but these findings are often ignored.
In the fetus, breathing movements, muscular activity, oxygen saturation, and short-term heart rate
variability are all reduced following maternal pethidine.14 The impact of these changes on outcome is
unclear, but there is no doubt that numerous adverse effects are observed also in the newborn.
Neonatal sequelae of pethidine are prolonged. Respiratory depression has been extensively docu-
mented and is at its worst if pethidine is given repeatedly and three hours or more before delivery, least
if given only within the last hour of labour.15,16 Large doses of pethidine depress the Apgar score,13 but
though smaller doses may not, it must be remembered that Apgar score is only applicable to the first
few minutes of life, a stimulating time for the newborn, who may later become severely depressed.
Indeed reduced oxygen saturation, increased carbon dioxide levels and metabolic acidosis have been
observed in the first few hours of life, even after small doses of pethidine.3,14,17 A placebo-controlled
trial of pethidine in over 400 women found that umbilical artery respiratory and metabolic acidosis
were more severe with pethidine than placebo.18 The incidence of acidosis was highest when pethidine
was given 5 h before birth. Various neurobehavioural studies have found that babies whose mothers
had pethidine are sleepy, less good at suckling 19 and slow to establish breast feeding 20; thermo-
regulation may also be impaired.21 Observational studies support an adverse effect of maternal
pethidine 20,22-24 and indeed of other opioids 25,26 on breast feeding.
The prolonged effects of pethidine on the baby may largely be attributed to the presence of its long-
acting active metabolite norpethidine.16 All the effects may be rapidly and apparently permanently
reversed by giving the newborn intramuscular naloxone in a dose of 60–100 mg/kg.19,27 This practice,
however, appears to have gone out of favour.

Alternatives to pethidine
Various substitutes for pethidine have been introduced, with the intent of producing superior
labour analgesia without neonatal depression w a forlorn hope. Unfortunately, fetal and neonatal
outcomes for these alternative drugs have been even less thoroughly studied than those of pethidine,
surely an omission, in view of its many know adverse neonatal effects.
292 F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302

Older agents. In the 1980s various alternatives were investigated and compared with pethidine. The
findings have been summarised by Scrutton.14 Meptazinol was used in some centres, but any neonatal
benefit that was sometimes noted was offset by a greater tendency to maternal side effects. Pentazo-
cine, likewise, was sometimes found to produce less neonatal detriment than pethidine, but the
balance between maternal analgesia, tachyphylaxis and side effects was not favourable. Nalbuphine
produced apparently even more sedation than did pethidine, and a less good neonatal outcome. Both
pentazocine and nalbuphine have been found to cause significant fetal metabolic acidosis.28 Another
agent, butorphanol, not used in the UK though popular in the US, is apparently a superior analgesic with
milder fetal effects.28,29
In the belief that morphine itself might produce better labour analgesia than pethidine, Swedish
investigators conducted a randomized comparison of the two, both given intravenously in repeated
doses up to 0.15 mg/kg for morphine and 1.5 mg/kg for pethidine.30 Both produced maternal sedation,
neither lowered the pain score and there was no difference in Apgar scores between the two drugs.
In the UK, however, particularly in Scotland, diamorphine has received more attention than
morphine. One randomized study of intramuscular administration showed slightly better analgesia but
fewer low Apgar scores with diamorphine 7.5 mg than with pethidine 150 mg.31 Meanwhile, neonatal
sedation with a 10-mg dose, inadequate analgesia with 5 mg and an apparently increased need for
neonatal resuscitation led Rawal et al. 32 to study the transplacental disposition of diamorphine
metabolites following a single 7.5-mg maternal dose in labour. They found that the concentration in
cord blood of free morphine, the principle active metabolite, was significantly associated with the need
for neonatal resuscitation. Diamorphine, being more lipid soluble than morphine, can more readily
cross the placenta, during which process it undergoes hydrolysis to morphine. It is no magic bullet for
systemic labour analgesia.

The fentanyl family. Fentanyl, alfentanil and remifentanil have been used to provide systemic, usually
patient-controlled intravenous analgesia (PCIA) during labour.
In a randomized open study, women in labour received either intravenous fentanyl 50–100 mg/h or
pethidine 25–50 mg every 2–3 h.33 Analgesia was equivalent but maternal side effects were more severe
and neonatal naloxone was needed more frequently in the pethidine group. These findings are unexpected
and have not been reproduced. A study comparing fentanyl with alfentanil by PCIA found no difference in
Apgar or neurologic and adaptive capacity score (NACS), umbilical vein pH or naloxone requirements.34
Remifentanil appears to offer better hope of advantage. Apgar scores and NACS have been found
better with remifentanil than with pethidine, when used for PCIA,35,36 although the drug has not
always lived up to early promise and low umbilical base excess values have been reported.37 When
neuraxial analgesia is contraindicated, PCIA remifentanil may currently be the best option, but
monitoring both maternal and neonatal respiration has been advised. One wonders why no such
precautions are recommended for pethidine.

Tramadol. Several studies have compared intramuscular tramadol and pethidine, producing variable
results and little information about the newborn. In one randomized trial from Singapore, tramadol
100 mg and pethidine 75 mg produced equivalent analgesia but pethidine produced more maternal
side effects and a lower respiratory rate in the newborn.38 In another from Iran, comparing tramadol
100 mg with pethidine 50 mg, women given pethidine had longer labours, lower pain scores in the
second stage and more side effects, but no difference in Apgar scores.39 A third from Turkey comparing
the two drugs both in 100-mg doses, found greater pain relief with pethidine, more side effects with
tramadol and no difference in duration of labour or Apgar scores.40

Adjuncts
Systemic opioids should be combined with anti-emetics, as nausea, exacerbated by opioids, is such
a problem in labour, but more information is needed about their fetal/neonatal effects. Vella et al. found
that the addition of promethazine or metoclopramide to pethidine had no effect on Apgar scores
compared to placebo.41 Promethazine, however, though effective as an antiemetic, produces severe
maternal sedation and an anti-analgesic effect, so should not be used in this context.
 F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302 293

To gain a true comparative picture of the various opioids and adjuncts that are given systemically,
randomized studies that assess maternal and neonatal respiratory status, neonatal neurobehavioural
status, acid-base balance and breast feeding, and that use PCIA to ensure analgesic equivalence, are
needed.

Effects of neuraxial analgesia on fetus and neonate

The following sections describes findings in relation to neuraxial analgesia in general. Evidence for
variation in neonatal effects due to different drug combinations and routes of delivery will be
addressed in a later section.

Direct effects of neuraxial analgesia

Neuraxial analgesia does not depend for its effect on the presence of drug in maternal blood, so
adverse direct fetal drug effects are likely only if maternal systemic effects of the drugs given neu-
raxially reach a detectable threshold. Thus when lidocaine was used to provide continuous epidural
analgesia, drowsiness was observed in both mother and baby. Longer-acting local anaesthetics
(bupivacaine, ropivacaine, levobupivacaine), correctly sited, are more slowly absorbed, and systemic
effects are usually observed only after accidental i.v. administration. Although opioids are well rec-
ognised to produce direct fetal and neonatal depression and to impair breast-feeding when used
systemically, their potential to do so when used for neuraxial analgesia is less,42 though still present
with large dose.43,44

Indirect effects of neuraxial analgesia

Neuraxial analgesia does not obtund the valuable fetal stress response to labour. While direct fetal
effects are also unlikely, indirect effects resulting from maternal physiological and biochemical changes
are on the cards. It is often believed that, because neuraxial analgesia may have potentially adverse
maternal effects,45,46 it must be bad for the baby, but it also has beneficial effects 47–54 (Table 1). Not
least of these is the fact that effective neuraxial analgesia can reverse the adverse maternal effects on
the baby of labour itself (see above, Effects of labour pain). Outcome depends on the balance between
the two opposing forces; no assumptions should therefore be made as to overall neonatal effect
without direct neonatal assessment. Assessment of the fetus, though less crucial because it can be
misleading, has also been a focus of attention.

Fetal assessment

Cardiotocography
Cardiotocography during labour is not a reliable predictor of neonatal welfare. Despite its short-
comings, however, it is often considered mandatory for mothers receiving neuraxial analgesia. In
consequence loss of short-term variability, decelerations and major bradycardia may be noted,
although meta-analysis of controlled trials shows that fetal heart rate abnormalities are not increased
by epidural compared with systemic opioid analgesia 55 or by epidural fentanyl,56 though they are
increased by intrathecal opioids,57 but without increasing the caesarean section rate. Interestingly,

Table 1
Maternal changes produced by neuraxial analgesia that may affect the baby.

Potentially unfavourable maternal effects [45] Potentially favourable maternal effects

Hypotension  Reduced maternal stress hormones 47-50
Fever  Reduces hyperventilation 3
51
Increased need for oxytocin  Uterine vasodilatation due to sympathetic blockade
Prolonged second stage  Fewer episodes of Hb desaturation 52-54
Increased need for instrumental delivery  Analgesic effect not dependent on presence of drug
in the blood, so placental transfer is not an issue
294 F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302

caesarean section rate rather than actual neonatal wellbeing has always been of the focus of concern –
another surrogate outcome!
Various explanations have been put forward for these episodes of fetal bradycardia. They may be
associated with the rapid onset of analgesia, with a reduction in epinephrine allowing the unopposed
action of norepinephrine to provoke uterine vasoconstriction and hypertonus,7 reduced maternal
blood pressure and cardiac output, omission of local anaesthetic, which would otherwise block
sympathetic fibres and cause uterine vasodilatation, and omission of fluid preload, which would inhibit
uterine contractions and reduce the incidence of fetal heart rate decelerations. A combination of
ruptured membranes, an unengaged head and variable decelerations (signalling cord compression)
may be a predictor of fetal bradycardia.58 Provided the changes are brief and do not reflect poor
placental perfusion resulting from uterine hypertonus or vasoconstriction, maternal hypotension or
aortocaval compression, their presence appears to be irrelevant to fetal outcome.57
Logic dictates that oxytocin administration must be discontinued before siting a neuraxial block and
the external tocodynamometer belt must be replaced as soon as the procedure is completed, otherwise
once analgesia is achieved uterine contractions may be undetected.

Fetal blood flow

While uterine blood flow can be said to influence fetal wellbeing, umbilical flow may reflect it.
Current Doppler flow technology has generated many studies encompassing flow characteristics of
both sets of vessels. Most suggest that epidural analgesia has little impact on uterine 59–61 or umbilical
60–62
vessels, although a fall in resistance in preeclampsia has been recorded in both.59,62 No studies
demonstrated any correlation with neonatal outcome.

Fetal oxygenation
‘Normal’ fetal oxygen saturation during labour varies between 30 and 70%. With such built-in
variability, uncontrolled studies over short periods with small numbers of subjects, that purport to
show the effect of neuraxial analgesia, are valueless. Most, however, show no significant change in
saturation before and after the block.63 In a controlled study continued throughout active labour in 150
women, no significant difference in fetal oxygen saturation between the epidural and no-epidural
groups was detected.64

Neonatal assessment

Apgar score
Meta-analysis of randomized controlled trials showed that there were significantly fewer low Apgar
scores at one and five minutes with epidural than with systemic opioid analgesia.45 The epidurals were
of various types. A more recent multicentre comparison of PCIA fentanyl with patient-controlled
epidural analgesia (PCEA) using a bupivacaine-fentanyl combination found lower 1-minute Apgar
scores and greater need for active resuscitation and naloxone in the PCIA group.65

Neurobehavioural assessments
Over the years various neurobehavioural tests have been developed in an attempt to assess the
newborn further into the post-natal period. The most used by anaesthetists, the neurological and
adaptive capacity score (NACS) was designed to discriminate between drug effects and neonatal
asphyxia.66 It may not be very sensitive or reliable, but it does correlate with breast feeding. Meta-
analyses of randomized trials revealed no significant difference in NACS between epidural and systemic
opioid analgesia.45

Acid-base balance
While fetal assessments and Apgar and neurobehavioural scores have serious shortcomings,
umbilical artery acid-base balance is a generally considered reliable. Since neuraxial analgesia does not
depend for its effect on the presence of drug in maternal blood, it is most likely to affect the fetus
indirectly, via maternal changes. The acid-base status of umbilical arterial blood reflects the quality of
 F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302 295

8
no analgesia
* epidural

**
6

4
UA pH PCO2 base deficit

Fig. 1. Umbilical artery acid-base status in babies whose mothers had had epidural analgesia using a low-dose combination,
compared with babies of 110 matched pairs who had had no analgesia. Units: PCO2 kPa; base deficit mEq/L. *P ¼ 0.01; **P ¼ 0.009.
Data from Schocket et al. 70

the recent in utero environment and the efficiency of transplacental exchange. It is therefore an
appropriate yardstick for the potential effects of neuraxial analgesia.
Arterial pH reflects both respiratory and metabolic changes, thus during labour both maternal and
fetal values are influenced by the extent to which maternal pain stimulates hyperventilation. Base
excess therefore better reflects metabolic acidosis, which itself is an index of 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 opioid analgesia. The presence of adequate buffer base is therefore
important to the newborn.
In 1974, three studies found that, whereas normal labour was associated with a progressive dete-
rioration in base excess in mothers and babies, epidural analgesia appeared to mitigate this adverse
effect,3,67,68 and indeed protected the fetus from the adverse effects of a prolonged second stage of
labour. These consistent findings were widely ignored. Towards the end of the last century, accusations
that epidural analgesia increased the need for caesarean section and long-term backache spurred
researchers to conduct randomized trials comparing systemic with various types of neuraxial anal-
gesia, and many remembered to look at the babies. Meta-analysis of umbilical acid-base values from
these trials and some unpublished data 69 showed that both UA pH and base excess were improved
following epidural compared to systemic analgesia. Though the differences between treatment groups
was small, any improvement must represent a potential benefit, particularly to the at risk fetus.
It may be thought that this apparent benefit of neuraxial analgesia is simply due to the detrimental
effect of systemic opioid analgesia. Researchers from Dallas therefore compared umbilical artery acid-
base status in 110 babies whose mothers had epidural analgesia with babies of a matched cohort of
mothers who had no analgesia.70 They found no difference in pH, but a significantly higher PCO2 in the
epidural group, reflecting the absence of maternal hyperventilation, and lower base deficit (Fig. 1),
confirming a positive beneficial effect of epidural analgesia in reducing fetal metabolic acidosis.
There is no disputing that epidural analgesia in labour is associated with maternal fever, but if this
were of serious consequence to the baby it would be reflected in an increased neonatal acidosis,
whereas the reverse is true.

Breast feeding
There is no doubt of the value of successful breast feeding, and of its importance as a measure of
neonatal welfare. Successful breast feeding depends on intention to breast-feed, parity, age, local
tradition, social class, education, maternal exhaustion, the amount of help and support that is provided
and, probably last of all the type of analgesia given in labour. The many confounding variables make
results of unrandomized trials unreliable. Yet observational studies, many even retrospective, often
Table 2

296
Breast feeding studies; epidural vs. other or no analgesia.

Type of study Epidural type (n) Controls (n) Outcome measures Findings
Rajan 1994 Subset of NBT Various No epidural Questionnaire at 6 weeks, Epidurals and Entonox no effect on breast
survey n ¼ 1064 breast, bottle or a mixture feeding. Abnormal delivery, induction, short
second stage, general anaesthesia and

F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302
pethidine reduced it
Halpern 1999 prospective mixed CSE or epi bupþsuf or No epidural (74) (some Telephone interview: 72% fully breast-feeding at 6–8 weeks. No
parity fentanyl (113) had systemic opioids) breast-feeding success at 6 factors relating to labour analgesia had any
weeks significant effect on feeding when leaving
hospital or 6 weeks later
Albani 1999 Prospective n/k No analgesia Feeding at discharge Vaginal: epidural 96.5% v. controls 97.8% (NS)
observational, caesarean section: regional 95% v. general
mixed parity anaesthesia 85% (P ¼ 0.002)
n ¼ 1920 vaginal
deliveries
Riordan 2000 Prospective parity Various drugs and doses, No mediation (37); i.v. IBFAT, LATCH assessment LATCH score better with no medication. IBFAT
n/k usually bupþfent (27) (52); both (13) not properly blinded. score no med>i.v. ¼ epidural>both. Low
Duration of breast-feeding IBFAT ¼ shorter feeding but unmedicated did
at telephone at 6 weeks not feed longer than the rest.
Ransjo-Arvidson Prospective parity Epidural bupivacaine or No analgesia (10); Video of infant behaviour Unmedicated infants more active
2001 n/k pethidine (?systemic) or mepivacaine pudendal immediately after delivery,
combination (12) block (6); assessed blindly.
Age and duration of first
suckling
Radzyminski Observational Ultra low dose No analgesia Premature infant No significant difference between groups in
2003 n ¼ 56 total bupivacaine þ fentanyl breastfeeding behaviour breast-feeding behaviour
scale at birth and at 24 h
Henderson 2003 observational PCEA bupþfent 5 mg/ml Support þ N2O þ peth Timing þ quality of 1st Still feeding at 6/12: epidural 38%; controls
nullipara (690) (302) feed. Duration of feeding 51%. Factors favouring longer breast feeding:
or still feeding at 6/12 tertiary education>older mothers>non-
smoker >no epidural
Baumgarder 2003 sequential mixed Not stated (115) No epidural (116) 2 successful feeds in 24 h Success in 24 h: epidural 69.6%; controls 81%;
parity LATCH score OR 0.53 (NS). Odds of success increased with
duration of epidural, to >1!
Volmanen 2004 retrospective, Bupivacaine (30) No epidural (34) Postal questionnaire Fully Fully breast-feeding: epidural 33%; controls
vaginal delivery þoccasional fentanyl (8) breast-feeding in 1st 12 71% (usual reason for failure: not enough
nullipara weeks milk) Factors favouring full breast feeding:
younger mothers, no epidural, NOT rooming
in, early skin contact, education.
Chang 2005 prospective cohort; Not stated (52) No analgesia 63 8–12 h initiation (LATCH) Breast-feeding effectiveness a NACS, no
mixed parity 4/52 continuation þ NACS difference between groups Still feeding 4/52:
8–12 h epidural 86%, controls 81% (NS)
 Wang 2005 observational Not stated (96) No epidural 74 Analgesia; mental state; Epidural better analgesia and mental state;
parity n/k time starting lactation; quicker lactation; more milk; higher prolactin
milk quantity; prolactin
Jordan 2005 retrospective Neuraxial (232) N2O and/or i.m. Feeding on hospital Bottle-feeding on discharge: N2O only: 32%;
cohort nullipara [containing opioid 158] pethidine (570) discharge in discharge i.m. pethidine: 41%; neuraxial local
summary (exclusive or anaesthetic alone: 44%; neuraxial with opioid
partial breast-feeding cf 53% (NS). Final logistic regression model

F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302
bottle-feeding) predictors of bottle-feeding: maternal age,
feeding intention, caesarean section and
fentanyl (dose-dependent [bottle feeding)
Beilin 2005 randomised Infusion of bupivacaine Epidural infusion: Day 1: maternal Maternal assessment at 24 h correlated with
double-blind with low-dose fentanyl bupivacaine alone (0F, questionnaire, lactation NACS and subsequent performance, lactation
multiparae who (LF, n ¼ 59) or high-dose n ¼ 60) consultant assessment, consultant’s did neither. Not breast-feeding at
had previously (HF, n ¼ 57) NACS. Telephone enquiry 6 6 weeks: 0F: 2%; LF: 6%; HF: 19% (P ¼ 0.002)
breast-fed weeks
Torvaldsen 2006 prospective cohort; PCEA bupþ fent 3.3 mg/ Non-pharmacologic/ Questionnaires on Only less educated did not breast-feed at all.
singleton mixed mL ALL had i.m. N2O/pethidine (762) discharge and 8, 16 and 24 Predictors of partial breast-feeding 1st week:
parity. No selection pethidine (416) weeks: fully, partial or not young mothers>less education>delivery type
of those intending to breast-feeding. Hazard & analg. GA>epi > N2O>none>pethidine!
breast-feed ratio of stopping feeding in After adjusting for delivery type and parity,
24 weeks epidural effect NS. Breast-feeding at 24
weeks: no analg 72%; no epidural 64%;
epidural: 52%. Predictors of stopping in 24
weeks: young>education>analg
Willund 2009 retrospective all Usually bupþsufentanil Nothing or paracervical Breast feeding in 1st 4 h; Babies in the epidural group were less likely
epidurals; controls bolus or infusion  and/or pudendal block artificial milk given; breast to breast feed in the first 4 h (OR3.79), more
matched for parity, paracervical and/or No opioid (351) feeding at discharge likely to be given artificial supplement (OR
age and gestation pudendal block (351) 2.19) and less likely to be breast feeding at
discharge (OR 1.79)
Wilson 2009 COMET plus no- CSEþlow-dose bupþfent Pethidine (151) or no Interviewed 24–48 h Number initiating breast feeding: all epidural
epidural controls bolus (351) or LDI: low- analgesia (200) ?initiated breast feeding. groups and no-pethidine group NS; pethidine
matched for parity, dose bupþfent infusion Postal questionnaire 12 group lower initiation rates. Duration NS
del type and (350) or high-dose bup months: duration of breast
ethnicity bolus (353) feeding

NBT: National Birthday Trust

297
298 F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302

with small numbers, purporting to show the effects of analgesia on breast feeding, are still reported.
Some do not distinguish between different types of analgesia or confuse systemic with neuraxial
routes of administration.71–73 Unsurprisingly, therefore, such trials demonstrate variable effects of
neuraxial analgesia on breast feeding 71–85 (Table 2), many finding no adverse effect from neuraxial
analgesia.74–76,78,82,83,85 Only those purporting to show adverse effects from epidural analgesia receive
much publicity. As Leighton and Halpern point out, some hospitals have policies for the care of women
who have had neuraxial analgesia that mitigate against establishment of breast feeding; where early
maternal-infant separation is minimized, epidural analgesia has no adverse effect on lactation
success.55
Meanwhile, one observational study and one randomized trial have suggested (perhaps unsur-
prisingly) an adverse effect on breast feeding of large epidural doses of fentanyl.43,44 Opioids even
given epidurally must enter the maternal circulation before they are eliminated. When prolonged
epidural analgesia for labour using a local anaesthetic-opioid combination is extended for emergency
caesarean section, it is unwise for the baby’s sake to give further opioid epidurally or systemically until
after delivery.

Effect on the baby of variation in routes of delivery and drug combinations

The field of neuraxial analgesia in labour is replete with randomized comparisons of different drugs
and modes of administration, but for neonatal outcome many report only the Apgar score, which is
barely sensitive enough to detect such subtle changes as are likely to arise.
Neuraxial analgesia may be initiated using an epidural bolus or a combined spinal-epidural
approach and may be continued using boluses, infusion or PCEA. None of these variations has been
shown to have an impact on the newborn.86,87 Several randomized studies have been conducted to
explore the suggestion that early initiation of epidural analgesia might increase the caesarean section
rate. All have refuted this, and in so doing also demonstrated that timing of initiation had no impact on
Apgar score 88,89 or funic acid-base status.88
A randomized comparison of single-shot spinal analgesia using low-dose bupivacaine-sufentanil
and paracervical block using bupivacaine alone, however, showed that though analgesia was better in
the spinal group, umbilical artery pH was significantly lower.90 This is an interesting finding, consistent
with the significant detrimental effect on funic acid-base balance of spinal compared with general and
epidural anaesthesia for caesarean section.91
Of the local anaesthetics themselves, from the fetal viewpoint there is little difference between
bupivacaine, levobupivacaine and ropivacaine. Lidocaine is unsuitable for the purpose.
The commonest adjunct to local anaesthetics, fentanyl, has been extensively studied. The best
evidence comes from a randomized double-blind comparison of low-dose bupivacaine plus fentanyl
and bupivacaine alone, titrated to produce equal analgesia, in 400 labouring women.92 There were no
significant differences between the groups in Apgar scores or umbilical artery pH, but 24-h NACS was
significantly less good in the fentanyl group. A mildly depressed NACS with fentanyl has been recorded
in other studies 93,94 and would support the finding that larger doses of fentanyl have been associated
with slightly impaired breast feeding.43,44 A double-blind comparison of three loading doses of
epidural fentanyl found no difference in Apgar scores between 50, 75 or 100 mg.95 While epidural
fentanyl may increase the number of episodes of maternal desaturation, such episodes have not been
found to correlate with funic pH or NACS.94 Any differences between epidural sufentanil and fentanyl
are slight.96 Intrathecal sufentanil, on the other hand, is associated with a significantly disturbed fetal
heart trace and uterine hyperactivity,57,97 though again the difference between sufentanil and fentanyl
may be slight.98
Any adverse effects of epidural fentanyl on the baby are mild compared with the outstanding
maternal benefit and increased safety of the low-dose combination. The same cannot be said of some
other agents that may be combined with local anaesthetic for neuraxial analgesia. Adverse neonatal
effects of clonidine and epinephrine should not be ignored. Both epidural and intrathecal clonidine
may potentiate analgesia with local anaesthetics, but the addition of clonidine to epidural ropivacaine
was associated with reduce Apgar score and NACS,99 while a 30–mg intrathecal dose worsened fetal
heart rate abnormalities and umbilical artery pH.100 In one randomized trial the addition of
 F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302 299

epinephrine 1:800,000 to epidural levobupivacaine and sufentanil was associated with reduced Apgar
scores at 1 and 5 min 101 though in another, the addition of 1:200,000 epinephrine to a bupivacaine
infusion had no significant effect on Apgar score, umbilical artery pH or respiratory gases.102 The
increase in maternal motor block anyway makes the addition of epinephrine to epidural local anaes-
thetic unsuitable during labour.

Summary and conclusions

Systemic opioids, in addition to producing less effective analgesia than neuraxial techniques, also
have a less favourable effect on the newborn. Nitrous oxide in the form of Entonox is not only more
effective than systemic opioids, it is also less likely to depress the newborn.
There is no disputing that epidural analgesia in labour is associated with maternal fever, but if this
were of serious consequence to the baby it would be reflected in an increased neonatal acidosis,
whereas the reverse is true. Expectant mothers should be reassured that, although epidural analgesia
may be associated with some short-term maternal side effects, its effects on the baby, when compared
with systemic analgesia, are more consistently beneficial in terms not only of Apgar score but also of
acid-base status, and it is less likely than systemic opioids to impair breast feeding.

Practice points

 Be aware that maternal labour pain and stress are associated with progressive fetal metabolic
acidosis.
 Nitrous oxide relieves pain more effectively than pethidine, and if Entonox is found to be
insufficient, it is useless offering pethidine.
 Pethidine produces neonatal depression, which is most severe when given 3–5 hours before
birth, but very slight if given only within an hour of delivery.
 Logic dictates that oxytocin administration must be discontinued before siting a neuraxial
block and the external tocodynamometer belt must be replaced as soon as the procedure is
completed, otherwise once analgesia is achieved uterine contractions may be undetected.
 Expectant mothers should be reassured that, although epidural analgesia may be associated
with some short-term maternal side effects, its effects on the baby, when compared with
systemic analgesia, are more consistently beneficial in terms not only of Apgar score but also
of acid-base status, and it is less likely to impair breast feeding.
 When prolonged epidural analgesia for labour using a local anaesthetic-opioid combination
is extended for emergency caesarean section, it is unwise for the baby’s sake to give further
opioid epidurally or systemically until after birth.
 Neuraxial labour analgesia should not be augmented with clonidine or epinephrine, both of
which tend to have detrimental neonatal effects.
 There is no disputing that epidural analgesia in labour is associated with maternal fever, but if
this were of serious consequence to the baby it would be reflected in an increased neonatal
metabolic acidosis, whereas the reverse is true.

Research agenda

To gain a true comparative picture of the various agents and types of analgesia that are used in
labour, randomized studies that use PCIA (or PCEA) to ensure analgesic equivalence and that
assess maternal and neonatal respiratory status, neonatal neurobehavioural status, acid-base
balance and breast feeding, are needed.
300 F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289–302

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