Analysing adverse effects of epidural analgesia in labour

Epidural analgesia is a widely available method of pain relief in labour in Western countries. This article analyses the various adverse outcomes of labour and birth after the administration of epidural analgesia. A literature review found that the use of intrapartum epidural analgesia for women with low-risk pregnancy has not only disempowered women but can also lead to maternal and fetal morbidity connected with major obstetric interventions, such as operative deliveries. Epidural analgesia also interferes with breastfeeding success and effective oxytocin circulation in the maternal blood-stream, and may even impact on childhood behavioural development.

 The rate of intrapartum epidural analgesia has been increasing rapidly in Western countries over the last few decades. In England, 25% of women who had spontaneous and induced onset of labour received epidural or spinal analgesia during labour between 2010 and 2011 (NHS Information Centre (NHSIC), 2011).

However, in Eastern countries, it is rare for epidural analgesia to be administered. For example, in a large tertiary antenatal hospital in Tokyo, Japan that delivers approximately 3000 births annually and has a maternal-fetal intensive care unit, which deals with complications such as severe pre-eclampsia, multiple births, pre-term deliveries (>22 weeks) and major fetal congenital diseases including cardiovascular diseases, no one receives intrapartum epidural analgesia.

However, in Eastern countries, it is rare for epidural analgesia to be administered. For example, in a large tertiary antenatal hospital in Tokyo, Japan that delivers approximately 3000 births annually and has a maternal-fetal intensive care unit, which deals with complications such as severe pre-eclampsia, multiple births, pre-term deliveries (>22 weeks) and major fetal congenital diseases including cardiovascular diseases, no one receives intrapartum epidural analgesia.

Over 75% of deliveries are spontaneous vaginal births in this hospital and less than 8% of deliveries are instrumental; the caesarean section rate remains less than 20%. Furthermore, the hospital is designated as a Baby Friendly Hospital by the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF), and nearly 80% of mothers are exclusively breastfeeding at 1 month postnatally (Japanese Red Cross Medical Centre, 2009).

In Japan childbirth with pain is seen as a normal physiological event. Although this is also the case in some other countries, childbirth with pain is culturally considered the norm in Japan, so the majority of women and health professionals do not consider pharmacological pain management, even inhaled analgesia such as Entonox, for labour pain. Therefore, women and midwives consider approaches for working with labour pain and in most hospitals epidural analgesia is given only when medically indicated, such as for a caesarean section.

Although epidural analgesia is often thought of as the most effective pain relief during labour, concerns arise as to why epidural analgesia is so readily provided to women with uncomplicated pregnancies in spite of the potential harm. Epidural analgesia can cause both short- and long-term morbidity and mortality, to both mothers and infants (Jones et al, 2012).

The National Institute for Health and Clinical Excellence (NICE) (2007) recommends informed consent for women before choosing epidural analgesia. However, it is doubtful whether labouring women in pain are able to make an appropriately calm moral judgement concerning the advantages and disadvantages before receiving epidural analgesia, and most labouring women seem not to have been informed of the risks during their pregnancy. Although women are informed of some of the risks prior to the procedure, they are not told about all risks such as instrumental and operative deliveries, oxytocin augmentation and interference with breastfeeding.

Risks associated with epidural analgesia

Instrumental deliveries and the associated injuries

The association between epidural analgesia and instrumental deliveries is already well recognised (NICE, 2007; Nguyen et al, 2010; Anim-Somuah et al, 2011; Eriksen et al, 2011). These are substantiated by a prospective cohort study performed by Lieberman et al (2005) who investigated fetal position during labour comparing the use of epidural analgesia with non-epidural analgesia.

This research found that intrapartum epidural analgesia resulted in a four-fold increase in the risk of a fetus rotating to an occiput posterior position and allowed an occipito-transverse position to stay transverse. Although the study included 1562 women initially, followed by a reduction by half due to exclusion criteria, insufficient data and withdrawal, the finding demonstrates generalisability with narrow confidence intervals.

This phenomenon of fetal malposition could be due to the epidural analgesia blocking maternal bearing down efforts and reducing the peak level of oxytocin during the second stage, as well as relaxing pelvic floor muscles and thus interfering with fetal rotation (Simkin and Ancheta, 2011).

Instrumental deliveries are associated with major injuries for mothers and infants. FitzGerald et al (2007) claimed that there was a 40 times higher incident of anal sphincter tears in cases where epidural analgesia, forceps delivery and episiotomy were combined. In a study by Rooks et al (2009), over 60% of term neonates delivered instrumentally had asymptomatic subdural haemorrhage. This study also emphasised the greater risk of haemorrhage in neonates who were significantly exposed to a long second stage of labour (>2 hours). However, although the study classified births according to the mode of delivery, the researchers did not also classify according to whether epidural analgesia was used.

Epidural analgesia leads to a prolonged second stage of labour (Anim-Somuah et al, 2011). This, combined with fetal malposition caused by epidural analgesia occasionally leads to excessive moulding or caput succedaneum of the fetal vertex (Akmal and Paterson-Brown, 2009). Significantly increased moulding or caput succedaneum on the vertex, especially the sinciput, could give extra tension and stretch cranial vessels, causing haemorrhage particularly when delivery is instrumental, due to the further tension introduced by the traction on the head.

Nguyen et al (2010) found a six times higher risk of instrumental deliveries in multiparous women who were given epidural analgesia. Multiparous women are more likely to successfully undergo instrumental rotation to occiput anterior from occiput posterior or transverse positions than primiparous women (Shaffer et al, 2006).

Therefore, instrumental vaginal deliveries could take place rather than caesarean section when fetal malposition causes the arrest of labour. In nulliparous women, on the other hand, intrapartum epidural analgesia increases the risk of caesarean section. This will be discussed in the following section.

Caesarean section

Anim-Somuah et al (2011) conducted a Cochrane systematic review of 20 randomised controlled trials involving 6534 women, which compared the risk of caesarean section in women who had intrapartum epidural analgesia with risks of caesarean section for women who had opioids and those who had no pain relief in labour.

The review found that epidural analgesia had no impact on the risk of caesarean section. The 20 included studies, however, did not examine the same controls: three studies recruited only women with severe pre-eclampsia and included women in pre-term labour; one study involved pregnancy-induced hypertension and 5% of the labours were pre-term; three studies included a mixture of women in the latent and active phases of labour and who had spontaneous and induced labours. All of these factors potentially constitute confounding variables. For example, women with severe pre-eclampsia who are most likely to have a small for gestational age infant (Groom et al, 2007) would be likely to require immediate caesarean section. Janakiraman et al (2010) found that there is a higher rate of caesarean section in women with induced labour compared with women in spontaneous labour. Moreover, because the Cochrane study included both multiparous and primiparous women, the results cannot be generalised. This review, therefore, raises concerns around methodological quality. Subgroup analyses across these categories of participants should have been performed (Centre for Reviews and Dissemination, 2009).

The confounding factors that are discussed above were controlled for in two prospective longitudinal studies. Nguyen et al (2010) investigated the effect of epidural analgesia in the first stage of labour on the occurrence of caesarean section and instrumental vaginal deliveries in 2052 nulliparous and multiparous women with low-risk pregnancies. This research controlled for potential confounders, such as parity, maternal age, antepartum complications, and took into account factors such as, infant birth weight, gestation at birth and cervical dilatation less than 4 cm at admission. This study found that nulliparous women who received epidural analgesia during labour had a higher absolute risk for caesarean section.

Similarly, Eriksen et al (2011) also maximised internal validity in their prospective cohort study in which 2721 low-risk nulliparous women were involved by exerting a high degree of control over potential confounding factors. These were mostly similar to Nguyen et al’s study but also included specific maternal risk factors for caesarean section relating to height, age, body mass index and the birth weight of a baby. Both studies demonstrate rigour in providing detailed information about inclusion and exclusion factors. However, the detail of how epidural analgesia was administered is not indicated. Whether a top-up of epidural analgesia was given or continuous infusion during the end of the first stage and second stage may have affected the progress of labour.

Both studies included low-risk nulliparous women with term singleton pregnancy as well as cephalic presentation. However, there was diversity in maternal characteristics, geography and the period of collecting data. Nevertheless, these two observational studies could be described as more representative of the target population, and by controlling confounding factors, the validity of these observational studies was strengthened. Furthermore, the methodological route may be more appropriate than randomised controlled trials due to impossibility of blinding to epidural analgesia.

Thus in randomised controlled trials objectivity is automatically compromised. Although randomised controlled trials are known as the gold standard of research, the best methodological approach to investigation of this type of intervention remains a challenge. Although there were some missing data during follow-up, the findings from both studies provide robust evidence that epidural analgesia heightens the risk for caesarean section in low-risk nulliparous women.

Oxytocin augmentation and infant behavioural development

Oxytocin is a crucial hormone which plays an important role for expulsive contractions during labour including the delivery of the fetus and the placenta. Epidural analgesia has a major impact on the essential hormones surrounding birth. The level of oxytocin circulation in the maternal blood stream declines with the use of epidural analgesia during labour (Goodfellow et al, 1983; Rahm et al, 2002). Epidural analgesia diminishes oxytocin receptor binding in myometrial cells, which results in desensitisation of oxytocin receptors in the uterus (Phaneuf et al, 2000; Robinson et al, 2003). Therefore, oxytocin augmentation is inevitably required in order to continue labour among women receiving epidural analgesia (Anim-Somuah et al, 2011).

Desensitisation can lead to uncoordinated contractions such as coupling and tripling of contractions and high frequency, low-intensity contractions (Mahlmeister, 2008). These patterns of contractions are occasionally observed in women with epidural analgesia and oxytocin augmentation. Such contractions cannot be easily resolved by increasing the dosage of oxytocin infusion because the primary cause is a desensitisation to oxytocin receptors and a subsequent decrease in their binding.

Kotaska et al (2006) searched all randomised controlled trials that compared epidural with opioid analgesia during labour in order to develop protocols of labour management for oxytocin augmentation. Eight trials met the criteria and seven of those showed that high doses of oxytocin used for labour augmentation did not increase the caesarean section rate while the only study that used low doses of oxytocin for labour augmentation had to be discontinued because the rate of caesarean section increased due to failure to progress of labour. The researchers expressed concern that a higher caesarean rate was associated with labour augmentation with low-dose oxytocin alongside the use of epidural analgesia and recommended high-dose oxytocin for labour augmentation instead. However, highdose oxytocin use causes hyperstimulation (Wei et al, 2010), which contributes to fetal hypoxia and fetal distress (Simpson and James, 2008).

Moreover, it is insufficient to base a change in practice on only one incomplete study that was used for the assessment of low-dose oxytocin. Mori et al (2011) suggested a need for further research regarding this subject due to insufficiency of current evidence.

Synthetic oxytocin (syntocinon) can cross the placenta and reach the fetal circulation (Odent, 2010). Although it remains unknown whether a large amount of oxytocin in fetal blood has similar desensitising effects to those on the maternal system, genomic and epigenetic evidence signifies that deletion or methylation of oxytocin receptors has been observed in the autistic brain (Gregory et al, 2009). One hypothesis that has been proposed is that synthetic oxytocin infusion during labour could deactivate fetal oxytocin receptors, which might be related to the development of autism (Wahl, 2004).

However, the hypothesis needs to be tested. Glasson et al (2004) performed a population-based study using birth data of 465 children who were diagnosed with autistic spectrum disorders to investigate the relationship between obstetric factors and the disorders. The findings demonstrate that the mothers of children with Asperger’s syndrome were more likely to have received epidural analgesia and oxytocin infusion during labour. The mothers of children with autism and pervasive developmental disorders were more likely to have had elective caesarean section, and to have experienced oxytocin infusion and fetal hypoxia such as fetal distress and a low Apgar score at one minute. These relationships were significant. Nevertheless, the association between obstetric pharmacological interventions

and child behavioural development still remains controversial.

Negative impact on breastfeeding success

A negative association between epidural analgesia and breastfeeding seems to be apparent.

In a retrospective study, Wiklund et al (2009) investigated the early breastfeeding behaviour of 351 full-term infants whose mothers requested epidural analgesia during labour and compared them with mothers who did not have this form of pain relief. The authors concluded that epidural analgesia and the use of oxytocin augmentation obstructed breastfeeding success. Usually oxytocin stimulates contraction of mammary myoepithelial cells, thereby triggering ejection of milk. Jordan et al (2009) performed a retrospective cohort study on a large obstetric data set in Wales and measured associations between routine drugs in labour including epidural analgesia and breastfeeding.

They found that the use of epidural analgesia during labour correlated with a reduction in the rate of breastfeeding in all subgroups, which were strictly controlled for multiple confounders, such as induction of labour, parity and social class. However, the drugs and doses used for epidural analgesia were not recorded. The findings of both studies provide feasible negative correlations between epidural analgesia in labour and breastfeeding success.

Wilson et al (2010) performed a randomised controlled trial involving 1054 nulliparous women to examine the effects of various forms of analgesia on initiation and continuation of breastfeeding at 12 months after birth. The women were divided into five groups: high-dose epidural analgesia; combined spinal epidural; low-dose infusion; no epidural with pethidine; and no pharmacological pain relief. The findings showed that initiation of breastfeeding was no different among these groups. However, control groups were impossible to blind, and women’s level of knowledge and views regarding initiation of breastfeeding were likely to vary. Nevertheless, women without pain relief had the greatest duration of breastfeeding among the groups.

An Australian prospective cohort study concluded that women who received intrapartum epidural analgesia were less likely to breastfeed exclusively and to continue breastfeeding in the 24 weeks postpartum (Torvaldsen et al, 2006). This negative correlation may be caused by low oxytocin levels in maternal blood after birth that impact on maternal-infant initial bonding at birth or interfere with patterns of oxytocin secretion for lactation (Jordan et al, 2009). Another possible cause is that epidural solutions, which can cross the placenta by diffusion, may make an infant drowsy and may disturb the initiation of breastfeeding (NICE, 2007).

Although all women have a right to choose their maternity care and treatment, the maternity service should always improve safety and promote better health for both women and their infants (Department of Health, 2007). From an ethical point of view, non-maleficence may outweigh women’s autonomy. However, this is a similar argument to the debate surrounding whether or not caesarean section should be offered at maternal request (Bewley and Cockburn, 2004).

Caesarean section is not provided as a routine choice because of the known evidence that this procedure increases the risk of severe morbidity and mortality for women and their infants (Liu et al, 2007). NICE (2011) has emphasised that women requesting caesarean section should discuss the reason and their anxiety regarding childbirth with appropriate specialists. Importantly, the fear that women express (Nilsson and Lundgren, 2009; Sercekus and Okumus, 2009) is also the reason why women request epidural analgesia. Therefore, surely the use of epidural analgesia during labour has to be questioned in the same way?

Conclusions

Women who receive epidural analgesia are disempowered by the process of medicalisation, and may be more likely to receive further interventions, some of which result in instrumental or operative deliveries. In order to empower women to give birth normally, epidural analgesia needs to be reconsidered as a common choice for pain relief during labour. Midwives should give women relevant information regarding the potential adverse outcomes of administration of epidural analgesia during pregnancy, and explore women’s feelings and fears about pain in labour.

They should offer appropriate holistic support throughout the pregnancy and intrapartum period such as one-to-one midwifery care, encouragement, reassurance, immersion in water, relaxation and massage (Jones et al, 2012).