Pitocin myths and side-effects

So many are being offered induction of labour, often without a good medical reason. This blog article will help you to make sense- and make informed choices- in this complex and controversial area.

So many inductions

In  Australia (2020) labour was induced in more than  1 in 3 pregnancies (35.5%), including almost half (45.8%) of first-time pregnancies. The US Vital Statistics (2021) reports 32.1% induction (2021), although women themselves report higher induction rates- as reported in the Listening to Mothers surveys. Rates are high in many other countries, suggesting that maternity-care interventions are being applied ‘too much, too soon’.

Why am I being offered an induction?

 If you have been offered an induction of labour without  a medical reason, especially in your first pregnancy, it is likely because of the 2019 ARRIVE trial.

This study found that routinely inducing labour at 39 weeks in a healthy, low-risk first-time pregnancy reduced the caesarean rate from 22.2% to 18.6% (16% reduction) with no other signficant benefits. (See my blog critique here and note the even greater reduction in caesareans- 25%-  from doula care.)

The ARRIVE trial has influenced practice world-wide because it provides supposedly the best evidence- a randomised controlled trial (RCT)- in this controversial area. However, RCTs have strict criteria for inclusion and treatment, and results may be different in real-life situations, outside experimental conditions. This problem is called ‘external validity.’ (See this discussion of the external validity of the ARRIVE trial.)

In fact, many studies have found that, in everyday practice settings, induction has minimal or even negative effects on caesarean rates, and may increase other risks. See this large study,  this study  and this high-quality review.  This is a controversial  area and results depend on the groups compared,  the timing of induction and the rates of induction in the group who were not initially induced  (‘expectantly managed.’) 

Has this improved outcomes?

Have the increasing numbers of inductions improved outcomes, as the ARRIVE trial suggested?

This study used US data to compare the outcomes for healthy, low-risk, first-time pregnancies before (2015-7) and after (2019) publication of the ARRIVE trial. Induction rates increased from 30% to 36% in this population, but their CS rate decreased only 0.6%. In addition, there were higher risks of some concerning outcomes in the induced groups, including more serious postpartum haemorrhage, lower newborn APGAR scores and more newborn breathing difficulties.

Could induction disrupt hormonal processes?

There are very complex and precise processes that lead to the physiological (spontaneous) onset of labour. These processes ensure that mother and baby are both perfectly prepared for an effective labour, birth and postpartum/newborn transitions, including breastfeeding and bonding. By definition, this readiness is not complete when birth is scheduled by induction or prelabour CS.

For a detailed review of the processes involved with the physiological onset of labour, see Chapter 2 , ‘Physiologic Onset of Labor and Scheduled Birth’ in my 2015 Hormonal Physiology report, linked from my website here and a more recent article here.

In addition, the method of induction may disrupt the natural hormonal flow of labour. As part of my PhD, I’ve been publishing studies with EU colleagues looking at oxytocin levels in women and babies in labour and the effects of interventions. Our upcoming reviews include studies of prostaglandins and rupture of membranes.

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Oxytocin and Induction: My PhD research

In our most recent publication we summarised all the studies that measured plasma (blood) oxytocin levels in women receiving synthetic oxytocin (Pitocin, Syntocinon).

We found that, even with the highest doses in labour, maternal oxytocin levels were maximum 3-4 times higher than levels in physiological labour. This is not high enough to cross the placenta or into the maternal brain and cause direct harm. (However, indirect effects are possible, including effects from the additional stress and pain of induction- see our discussion here)

We also found that newborn babies have naturally high oxytocin levels in labour, likely due to the stress and massage-like effects of uterine contractions. These high oxytocin levels help the baby cope with labour and adapt to life outside the womb. Being exposed to synthetic oxytocin did not further increase newborn oxytocin levels, indicating that synthetic oxytocin does not cross to the baby in labour.

My next blog will discuss these findings further- stay tuned! We are also researching the effects of epidural, opioids and prostaglandins in upcoming publications.

Another important question is: could labour induction-whether with synthetic oxytocin or other methods- affect longer-term outcomes such as breastfeeding, bonding and postpartum depression?  These outcomes have not been well studied in the highest-quality randomised trials and are part of my PhD studies.

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Brain development in the womb

There are also a growing number of studies suggesting worse development and educational outcomes in children born at shorter gestation, even at 39 vs 40 or 41 weeks. This is not surprising when we consider that the unborn baby’s brain is growing at a very fast rate at the end of pregnancy, making those last weeks of brain development very precious. (See Every Week Counts) Shortening gestation with induction could limit full brain development.  See also my discussion here.

However, some studies looking at induction and longer-term offspring outcomes have not found negative effects. Induction rates in the expectant groups are an important consideration in these studies. It is also important to note that these population-wide studies do not mean that being induced will have effects on individual children.

Are there benefits from labour induction?

There is no doubt that induction of labour reduces the chances of stillbirth. Babies that have been induced and born are obviously not at risk of stillbirth. This has been a major motivation for induction past 40-41 weeks, although the actual risks (and therefore benefits of induction) are small.

Some babies that are overdue do not cope as well with labour. This has been used to disallow access to midwifery care in birth centres or homebirth past 41 or 42 weeks. However, again the risks are small. If you are labouring after 41-42 weeks, your care provider or midwife may want to monitor you more closely.

Based on these considerations, induction at 41-42 weeks may prevent 2 perinatal deaths (around the time of birth) per 1000 babies. Looked at another way, 544 inductions would be needed to prevent the death of one baby.  This information may be helpful if you are overdue and offered an induction of labour.

The best decision 

Ultimately the best decision is one you make with your heart and womb, connected to your baby, as well as with the information from here and the resources below.  

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More induction resources:

Postdates induction of labour- balancing risks Rachel Reed- Midwife thinking

Ten things I wish women knew about induction- Sarah Wickham  and her books 

Induction of labour (Podcast)- Melanie the Midwife with Hannah Dahlen in The Great Birth Rebellion 

Inducing for due dates Evidence based birth   

Induction of labour articles Henci Goer  

Myth of the aging placenta –Sophie Messager 

Preventative induction of labor- does Mother Nature know best? (ARRIVE trial)  Lamaze international

Your body, your baby, your choice: Chapter 4 in  Gentle Birth, Gentle Mothering by Dr Sarah Buckley 

Acknowledgements:

Some of this information comes from a new publication as part of my PhD research: Maternal and newborn plasma oxytocin levels in response to maternal synthetic oxytocin administration during labour, birth and postpartum – a systematic review with implications for the function of the oxytocinergic system This was written with the good work and dedication of my colleagues Kerstin Uvnäs-Moberg, Zada Pajalic, Karolina Luegmair, Anette Ekström-Bergström, Anna Dencker, Claudia Massarotti, Alicja Kotlowska, Leonie Callaway, Sandra Morano, Ibone Olza & Claudia Meier Magistretti. This work was initiated within  EU COST IS1405 BIRTH: Building intrapartum research through health. 

Synthetic oxytocin (Pitocin, Syntocinon) is widely used in maternity care around the world. It is commonly administered to induce or to speed up (augment) labour, and to prevent or treat bleeding after birth (postpartum haemorrhage).

Like all maternity-care interventions, synthetic oxytocin may be beneficial, even life-saving, for mothers and babies in some situations. However, because of its widespread use, including in many healthy mothers and babies, it is important to understand the possible risks and side-effects.

This blog explores some important questions, including:

• Is synthetic oxytocin harmless because it mimics the natural oxytocin that women release during labour?
• Do high doses of synthetic oxytocin impact the mother’s own natural oxytocin release in labour?

In upcoming blog posts: (from mid-2023, make sure to sign up to my newsletter) 

• Does synthetic oxytocin cross into the brain during labour?
• Could synthetic oxytocin affect breastfeeding or bonding?
• Does synthetic oxytocin cross to the baby?
• Could synthetic oxytocin impact the baby’s developing oxytocin system, as found in animal studies?
• Could synthetic oxytocin even cause autism? (Also see this blog)

This information in this blog comes from a recent publication on Maternal oxytocin levels during physiological childbirth, which Dr Buckley is a co-author (more details below) and a new review from Dr Buckley and colleagues of oxytocin levels in women and newborns following maternal  synthetic oxytocin administration.

Is synthetic oxytocin harmless, because it mimics the natural oxytocin that women release during labour?

It is true that the chemical structure of synthetic oxytocin is identical to the chemical structure of the natural (endogenous) oxytocin that our bodies produce during labour, as shown in this picture.

However, our own natural (endogenous) oxytocin is made in the brain and is released during labour into both the body, where pulses of oxytocin reach the uterus and promote the rhythmic contractions of labour, and also locally into the brain, where it has calming and pain-relieving effects.

As labour progresses, high oxytocin levels released within the brain help to counter the stress and pain of the strengthening contractions, which are caused by oxytocin stimulating the labouring female’s uterus. At the same time, oxytocin is activating her brain’s pleasure and reward centres in preparation for bonding with her newborn baby. (This process assists all mammals during labour, birth and postpartum )

In contrast, synthetic oxytocin is administered by intravenous (IV) infusion and in constant, high doses rather than in lower-levels and pulses. This can lead to maternal plasma oxytocin levels that are more than double those in a natural (physiological) labour, as measured in the blood. (See Oxytocin levels during physiological childbirth)

For these reasons, IV synthetic oxytocin causes contractions that are stronger and closer together than natural contractions, especially in early labour.

In addition, because synthetic oxytocin is administered into the body and not into the brain, it does not have the brain-based benefits of countering labour stress and pain, as natural oxytocin does. (See Oxytocin levels during physiological childbirth.) Therefore, the stress system may be more activated with high doses of synthetic oxytocin in labour, compared to physiological labour.

Those who are administered synthetic oxytocin also commonly receive epidurals to counter the increased pain, and epidurals reduce the natural release of oxytocin, as explained below and in this blog, which increases the need for synthetic oxytocin to fill the ‘hormonal gap.’

With this combination of epidural with synthetic oxytocin in labour, the natural stress-reducing benefits of endogenous oxytocin can be reduced or absent. (More about this below.) This combination might also explain some of the longer-term effects that have been reported for synthetic oxytocin, to be discussed in upcoming blog posts.

For the baby, the stronger and more frequent contractions will inevitably reduce blood and oxygen supply more than during physiological labour, increasing the risks of hypoxia (low oxygen), which is especially risky for the baby’s brain at this time. For this reason, administration of synthetic oxytocin in labour always requires monitoring of the baby’s heart rate to check for indications of hypoxia.

Some studies suggest extra risks of hypoxia and its possible long-term consequences for babies exposed to synthetic oxytocin in labour, although this area is not well studied. (See studies below.)

Synthetic oxytocin may also reduce activity in the uterine oxytocin receptors, although the mechanisms is not certain. This can decrease the effectiveness of oxytocin (natural or synthetic) to cause strong contractions, including after the birth. This explains why receiving synthetic oxytocin in labour increases the chance of postpartum haemorrhage and requires extra medications (including more synthetic oxytocin) to counter this risk. (More discussion of the possible mechanisms in upcoming posts.)

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Do high doses of synthetic oxytocin impact the natural oxytocin release in labour?

It is sometimes presumed that administering high doses of synthetic oxytocin in labour will reduce maternal natural (endogenous) oxytocin production. This is not likely, according to our current understandings, although this is very hard to measure as natural and synthetic oxytocin can’t be differentiated in the blood.

It is important to understand that oxytocin release from the brain in labour is not controlled by the usual ‘negative feedback’ systems, whereby high levels of a hormone or biological marker lead to feedback that reduces levels. For example, our heart rate and blood pressure are controlled such that a sudden increases are detected by our body systems and lead to changes that bring them back down to what is normal for each of us. This negative feedback is operative in most biological systems, and contributes to homeostasis- the maintaining of physiological stability in the face of external (or internal) changes.

However, labour is not a homeostatic process! In labour, contractions need to strengthen rather than remain stable, and eventually be strong enough to push the baby from the mother’s uterus. This strengthening requires positive, rather than negative, feedback systems, also called ‘feed-forward cycles.’

This diagram shows one feed-forward cycle in labour, where strong uterine contractions cause pressure on the cervix area  and generate sensory feedback to the brain that increases brain  oxytocin release, including release to the uterus. This causes even stronger contractions and sensations, more sensory feedback and more oxytocin release.

This feed-forward cycle, also known as the Ferguson reflex, provides the high levels of oxytocin (average 3-4-fold increased at birth) that are needed for the birthing mother to have an effective pushing stage.(See Oxytocin levels during physiological childbirth)

The administration of synthetic oxytocin (without epidurals) will not reduce this cycle, or the stimulation of natural oxytocin release. In fact, in some circumstances, synthetic oxytocin may even accelerate this feed-forward cycle (and increase brain oxytocin) by causing stronger contractions with greater sensations. (More details in upcoming blog posts.)

However, when epidurals are co-administered, the sensations from contractions, which fuel this feed-forward cycle, are abolished, which slows or even stops the cycle, and consequently slows or stops oxytocin release, as described in this blog.

The combination of epidurals with high doses of synthetic oxytocin can therefore increase physiological stress in labour but reduce oxytocin release, including within the brain, which would usually counteract this stress in labour.

In summary

Synthetic oxytocin is chemically identical to the natural oxytocin released in labour and birth. However it has different effects because it is administered IV rather than into the brain.

In contrast, natural oxytocin  is released from and into the brain in labour, and gives calming, pain relieving effects that counteract labour stress and pain. Within the brain, natural oxytocin also activates reward and pleasure centres in preparation for bonding with the newborn baby.

While synthetic oxytocin may not directly reduce the natural release of oxytocin, the common co-intervention of epidural analgesia does significantly reduce oxytocin release. Epidurals can slow labour and reduce oxytocin’s anti-stress, anti-inflammatory and anti-oxidant benefits. This combination might explain some of the longer-term effects that have been found for synthetic oxytocin, which will be discussed further in later blogs.

In addition,  prolonged, high doses of synthetic oxytocin increase the risk of bleeding after birth (postpartum haemorrhage). This likely reflects disruption to uterine oxytocin receptors, making the uterus less responsive to oxytocin and increasing the risk of bleeding, although the mechanism is debated.

Upcoming blog posts:

• Does synthetic oxytocin cross into the brain during labour?
• Could synthetic oxytocin interfere with the new mother’s ability to bond with her baby?
• Could synthetic oxytocin impact breastfeeding success?
• Does synthetic oxytocin cross to the baby?
• Could synthetic oxytocin impact the baby’s developing oxytocin system, as found in animal studies?
• Could synthetic oxytocin even cause autism? (Also see this blog)

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References and resources

Much of this information comes from a new publication on Maternal oxytocin levels during physiological childbirth: A systematic review with implications for uterine contractions and central actions of oxytocin  This was written with the good work and dedication of colleagues Kerstin Uvnas Moberg, Anette Ekstrom-Bergstrom  and other European co-authors. This work was partly funded by  EU COST IS1405 BIRTH: Building intrapartum research through health. 

Ecstatic Birth ebook

Hormonal Physiology of Childbearing report Sarah’s 2015 report with lots of information about oxytocin (Free download)

Sarah’s 2-part blog on epidural effects, including oxytocin

Impacts of synthetic oxytocin in labour:

• Oscarsson 06: Higher newborn risks in a population study
• Clark 2008: Preventable adverse newborn outcomes 
• Buchanan 12:  Worse outcomes for mothers and babies
• Drummond 18: Legal views on synthetic oxytocin in labour

Note that these studies are observational and do not imply causation. However, there is very little high-quality research available in this area. 

Bugg 13 : Augmentation with synthetic oxytocin has minimal benefits (Cochrane review)

Rahm 2012 : Epidurals reduce oxytocin