Journal Pre-proof

Perinatal asphyxia from the obstetric standpoint

Meghan G. Hill, Kathryn L. Reed, Richard Brown, Newborn Brain Society Guidelines
and Publications Committee*

PII: S1744-165X(21)00067-6
DOI: https://doi.org/10.1016/j.siny.2021.101259
Reference: SFNM 101259

To appear in: Seminars in Fetal and Neonatal Medicine

Please cite this article as: Hill MG, Reed KL, Brown R, Newborn Brain Society Guidelines and
Publications Committee*, Perinatal asphyxia from the obstetric standpoint, Seminars in Fetal and
Neonatal Medicine, https://doi.org/10.1016/j.siny.2021.101259.

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 Perinatal asphyxia from the obstetric standpoint
Meghan G Hill1; Kathryn L. Reed2; Richard Brown3;
on behalf of the Newborn Brain Society Guidelines and Publications Committee*.
1
Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, The
University of Auckland, Auckland, New Zealand; 2Department of Obstetrics and Gynecology,
University of Arizona College of Medicine Tucson, Tucson, USA; 3Divisions of Obstetrics,
Maternal Fetal Medicine and Ultrasound, Department of Obstetrics & Gynaecology, McGill
University Health Centre, Montreal, Canada.
* Newborn Brain Society, PO Box 200783, Roxbury Crossing, MA 02120. Email:

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publications@newbornbrainsociety.org

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Meghan G Hill, MBBS, MS (Corresponding Author)
Senior Lecturer
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The Department of Obstetrics and Gynaecology
Faculty of Medical and Health Sciences
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The University of Auckland

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Private Bag 92019

Auckland Mail Centre
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Auckland 1142
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New Zealand
email: meghan.hill@auckland.ac.nz
Phone: +64 9373 7599 ext 89493

Kathryn L. Reed, MD
Professor Emeritus
University of Arizona College of Medicine Tucson
Department of Obstetrics and Gynecology
1501 N. Campbell Ave.
Tucson AZ 85724
email: kreed@obgyn.arizona.edu
Phone 520-626-6174
Dr Richard Brown MBBS FRCOG FACOG
Associate Professor
Director of the Divisions of Obstetrics, Maternal Fetal Medicine and Ultrasound
Department of Obstetrics & Gynaecology
McGill University
McGill University Health Centre
1001 Decarie Blvd, Montreal, Canada H4A 3J1
email: richard.brown@mcgill.ca

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The authors do not have anything to disclose.

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Abstract:
Perinatal asphyxia remains one of the major causes of morbidity and mortality for term newborns.
Though access to health care and birth attendants have decreased the rate, Neonatal
encephalopathy (NE) has not been eliminated. Worldwide, women at socioeconomic disadvantage
have the highest risk of delivering a neonate with NE. Neonates that will experience perinatal
asphyxia cannot be easily identified prospectively and the intrapartum testing available is not
specific enough to clearly indicate the best course of action in most cases. Despite this, training
programs that aim to decrease morbidity and mortality from all causes appear to be associated with
fewer cases of perinatal asphyxia. The current best approach is to support education and
communication of all people involved in the care of birthing women. Ideally, new technology will

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address identification of the fetus likely to be affected or the fetus who is beginning to experience
injury in advance of delivery.

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Key Words: Neonatal encephalopathy, Birth, Birth Injuries, Labor complications, Cesarean section
Abbreviations: NE, neonatal encephalopathy; CP, cerebral palsy; CTG, cardiotocography.
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Introduction
No text on perinatal asphyxia is complete without a discussion of the antepartum, intrapartum and
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immediate postpartum course of the neonates that will go on to be diagnosed with some form of
perinatal asphyxia. From the outset, it is important to recognize that the perspective of obstetric
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providers overseeing the care of women during their pregnancies, labours and postpartum courses
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vary significantly from that of the neonatologists and nurses caring for affected neonates.
Perinatal asphyxia is a potentially devastating and life-changing event for families and care
providers. Minimizing the rate of perinatal asphyxia is a clear priority, However, due to its rarity in
clinical practice in developed countries, any measures taken must be balanced against other
priorities such as maternal haemorrhagic and infective morbidity, operative complications and long-
term outcomes. This is viewed in combination with the risks to the fetus which closely match the
maternal ones. Fetal complications related to difficult operative deliveries, prematurity and infective
complications of parturition are more commonly encountered in obstetric practice than perinatal
asphyxia. A relative example is the single complication of postpartum haemorrhage of 500mL or
more, which occurs in approximately 20% of births, with haemorrhage >1000mL occurring in 4% of
births, as compared to the incidence of neonatal encephalopathy (NE), at approximately 0.3% of
births in developed countries 1,2. The striking difference is that most women who experience
haemorrhage in the developed world will have complete recovery with treatment, while NE
frequently has implications on the neonate and their family that are lifelong.
Obstetric care providers are acutely aware that there is not currently accurate testing to
differentiate the fetus that is becoming compromised from the one that is well within its means to
maintain physiologic homeostasis, with the majority of fetuses displaying abnormal fetal heart rate
tracings during labor 3,4. Two labours with apparently identical findings can have very different
outcomes, which makes decisions challenging. This is in stark contrast with the experience of
neonatologists. Term neonates admitted to neonatal intensive care units with perinatal asphyxia
have more predictable outcomes based on their clinical course of events, often suffering long term
disability resulting from the condition. Their counterparts with similar intrapartum courses that were

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undamaged are not admitted to the NICU so no comparison can be made. Therefore although
looking back at the perinatal course of affected neonates would seem to point to easy intervention

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points when confronted with a tragic reality for the asphyxiated infant, this ignores all the possible
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interventions that might have (but were not) made in all the other cases with normal outcomes. This
variance in approach is problematic to advancement in the care of women and their neonates as it
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can shift the focus from problem solving to blame, which does not benefit the patient.
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Obstetric care providers tend to focus on long-term neurological disability when a poor outcome is
encountered. There is inevitable confusion regarding the ‘brain injury’ diagnoses. An important
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distinction is that NE is a clinical syndrome that may or may not result in long term disability. While
NE sometimes leads to cerebral palsy (CP), it is not the main contributer to the condition It has been
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reported that NE is the primary cause of CP in approximately 10-20% of cases 5,6. NE occurs due to
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inadequate oxygen delivery and can result in permanent brain injury. Though it can occur after birth
due to a number of causes (severe blood loss, cardiac arrest, septic shock, for example), when we
refer to NE in this chapter, we are referring specifically to injury to the fetal brain during the process
of birth. We are not discussing long-term outcomes, but rather the diagnosis of a clinical syndrome.
The clinical outcomes can vary and be difficult to predict from initial presentation with some
neonates apparently making a full recovery. However,the likelihood of a permanent brain injury
increases with the severity of the NE at presentation. CP is a permanent neurological disorder that
involves posture and movement. It occurs in approximately 2-3 per 1000 neonates in the developed
world 5. In general, CP is thought to arise subsequent to events occurring either during pregnancy or
shortly after birth; it is estimated that up to 90% of cases are unrelated to the process of birth itself
(CNS malformations, brain atrophy, genetic reasons, to provide a few examples)5-7. Nonetheless,
there remains significant confusion amongst care providers and the public surrounding the
contribution of intrapartum NE to the condition. The umbrella diagnosis of ‘brain injury’ is
particularly feared for obstetric care providers both because of the potential severity of the
conditions involved and the history of litigation related to these injuries.
It is easy to understand the desire to find an intervention that will prevent both NE and CP. It is also
likely that the rate of both conditions will decrease only a small amount from the rate that is
currently seen in developed countries until technology and ability to identify and prevent
contributory events improves. In this chapter, we will focus specifically on NE that is thought to
occur during the process of parturition, while recognizing that only some cases lead to CP. In
discussing NE, it is also important to recognize that the brain is not the only affected organ involved
in perinatal asphyxia. Affected neonates frequently have multiorgan dysfunction, inclusive of renal
and hepatic injuries, coagulopathy and some neonates, especially in low-resource settings, will

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succumb to the asphyxial event due to these global insults.

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Social determinants of health
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The information regarding social determinants of health tracks closely with place of birth. It is well-
established that neonates are more likely to be born alive and without perinatal asphyxia in
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developed countries 8-12. Barriers to care for women aiming to get pregnant (or indeed aiming not to
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get pregnant) are relevant to pregnancy outcomes 13,14. Within developed countries, there are
disproportionate rates of birth injury in different locations 14,15. Simple, preventable and easily
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treatable illnesses such as anaemia increase the risk of perinatal asphyxia as do antepartum
hospitalizations 11,16. The lack of specific guidance in this area is unsurprising as performing a clinical
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test or intervention is easier than creating a society without the inequities readily identified in every
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country. However, in 2019, the Center for Disease Control and Prevention attempted to make a
start, highlighting the importance of the social determinants of health on the wellbeing of all
people17 . Prominent factors include poverty, lack of access to education, incarceration and the
disruption that this brings about for whole families, inadequate access to health care and being
stigmatized due to many factors including race, culture, literacy and locality of residence are all
relevant 17,18 . Assessing which of these factors is the most important is difficult, but access to care
and associated opportunities (access to education, housing and equal employment) emerges
repeatedly through much of the literature pertaining to NE in both developing and developed
countries. Countries with better-funded public health care systems appear to have lower rates of NE
than those without 18 and maternal literacy is important 18 . Though much of the remainder of this
chapter will focus on intrapartum events, it is important to note that the most effective strategy to
decrease perinatal asphyxia is likely economic and highly related to reproductive autonomy for
women and families. Interventions during the short interval of labour and birth can only go so far in
improving outcomes. This is not an opinion, but rather a conclusion based on much evidence, some
of it referenced above.

Maternal comorbidities
The link between maternal comorbidities and perinatal asphyxia is undeniable. Most of these
comorbidities, such as hypertension and uterine scars, lead to unpredictable complications that
occur in only a minority of women.
Though risk factors are relatively common, treatment may be offered too late to make a difference
to the rates of birth asphyxia. Maternal pyrexia is associated with NE, and should be treated, but
once it has occurred cannot be prevented 19. Antepartum hospitalization is associated with NE, but
usually arises once a pregnancy complication has developed and therefore cannot be prevented 16.

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There are pregnancy complications associated with NE (these include common conditions such as

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hypertension and diabetes in pregnancy amongst others), but whether the risk they attribute to NE
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can be mitigated during birth is unclear 19. One treatable maternal comorbidity that is associated
with NE is anemia 16. There are multiple therapies including oral supplementation, intravenous
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supplementation or transfusion. However, there is no guide as to which these treatments, if any of
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them, mitigate the risk of NE.

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Place of birth
It is important to delineate between high and low-resource countries. There is ample evidence from
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low-resource settings that stillbirth, neonatal demise and birth asphyxia are more common than
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they are in the developed world 8-10,18,20. The rates of both stillbirth and NE have been decreasing
incrementally in England 12 where the rate currently sits at approximately 0.3%2. This is in contrast to
the rate than found in Zanzibar (approximately 3-5%) as suggested by data relating to intrapartum
stillbirth and APGAR scores 21. The rate approximates 49.5 per thousand in Tanzania18. Moreover,
seemingly simple, non-medical interventions appear to make the most difference to both maternal
and fetal outcomes 22. Factors such as transportation to medical care with trained birth attendants
can have a large impact in the developing world, as can preconception care and early access to
prenatal care 13,22. The low-hanging fruit that can be approached worldwide are common conditions,
for example the association noted between maternal anaemia and perinatal asphyxia 11. Literature
from Asia has revealed that early recognition of perinatal asphyxia with admission to a specialized
neonatal unit appears to improve outcomes in affected neonates 23,24 , while the simple introduction
of more fetal surveillance and a decrease in labour augmentationdecreased the rate of stillbirth in
Zanzibar.
While the above-mentioned interventions may be beneficial in these low-resource settings, the
same interventions may not be the best approach in developed countries. For example, labour
induction and augmentation is likely safer in high-resource settings when patients can be adequately
monitored for known complications. This being said, data regarding home birth in the United States
likewise indicates that birth in a hospital setting is safer for neonates. The American College of
Obstetricians and Gynecologists recommends women be informed that home birth is associated
with a doubling of the incidence of perinatal death from 1.8 to 3.9 per 1000 births and a tripling in
the incidence of neurological dysfunction or seizures in the neonate from 0.4 – 1.3 per 1000 births
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Identical interventions may have opposite effects in differently resourced systems. One example is

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induction of labour. Avoiding induction of labour when indicated may actually increase NE rates in
high-resource settings, while inability to perform adequate monitoring during induced labour in low-

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resource settings likely increases risk.
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In high-resource settings, protocols to transfer women likely to experience preterm birth to centers
with the resources to adequately care for the at-risk newborn are common. This does improve
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neonatal outcomes, and is especially relevant considering that low-birth weight neonates represent
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approximately 40% of the neonates that will experience brain injuries (though a minority of these
neonates will have NE) 5. However, even high-resource settings do not have infinite resources. Data
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does suggest that failure of in utero transfer remains a problem 26 and some in-utero transfers are
influenced not only by the level of care available, but also the ratio of Neonatal Intensive Care Unit
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(NICU) staff to patients at the referring tertiary care centres 27. There are inevitable consequences to
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a need to transfer a patient intrapartum. Delivery during transfer, away from the advanced care
required, is one known undesirable outcome.
Data from the United States indicates that the initial advances in perinatal outcomes have either
slowed, stopped or even deteriorated, as seen with the rising rate of preterm birth, even while
intrapartum surveillance and access to interventions during birth have increased 14. There are
disproportionate outcomes between states, with a lack of access to preconception care and other
socioeconomic determinants of health likely being related to these differences in outcomes 15.
Indeed in research performed in the United States, there were no correlations between rates of
prespecified ‘quality indicators’ and rates of neonatal morbidity 28. Possible conclusions would be
that ‘quality indicators’ for the intrapartum period are applied too late to make a difference to
outcomes, or that the indicators chosen may not be the correct ones to apply.
From all of this, what emerges is that the best outcomes occur in women who have good access to
care with no medical comorbidities or deprivation related to poverty or inadequate nutrition and
with birth occurring in a high-resource setting.

Parity and Labor Duration

The evidence regarding labour characteristics and parity is mixed. As a general rule, the first vaginal
birth for a woman takes the longest, with multiple publications and guidelines suggesting that
nulliparous women should be considered to be laboring normally with longer durations of both the
latent and active phases of labour. Likewise, the second stage is expected to be longer on average in
nulliparous as compared to parous women. However, the effect that this has on the rate of birth

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asphyxia is unknown. It is likely that labour itself is probably not the cause of birth asphyxia in most
spontaneous labours, and that inherent issues in either the placenta or fetus that predate the labour

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have a larger contribution to NE. Labour may be the last contributing factor for the at-risk
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fetus.Although stimulated labour does appear to be a risk factor in some settings 21, it is unclear if
the stimulated contractions cause the risk, or if underlying conditions including that indicating a
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need for augmentation or induction such as hypertension in pregnancy are the causal factors.
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Several studies have assessed parity and its association with NE. One study assessed this factor in
comparing women in Nepal with women in Western Australia 29. Nulliparous women did have a
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higher risk of neonates with NE in both locations 29. This would seem to suggest that parity and by
association, possibly labour duration may be associated with some cases. These findings have been
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reproduced in Canada, with maternal nulliparity being related to NE and a trend suggesting the
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duration of these first labours may be relevant 30. However, caution should be applied to these
conclusions. The vast majority of first labours, even protracted labours, will not result in asphyxiated
neonates. It is unclear what effect shortening these first labours (with either instrumental delivery or
caesarean) would have. A study looking at predictors of NE in Sweden reached an opposite
conclusion 31. Higher parity was associated with NE 31. Important predictors in this cohort were
abruption and uterine rupture 31. Abruption is a complication that generally has a sudden onset and
is hard to predict. Uterine rupture seldom occurs in the absence of a prior caesarean delivery. That is
to say, more caesareans in first labours to prevent NE may actually increase the risk of NE for all
subsequent children the woman has, thereby increasing the overall rate.

Sentinel Events
In the next several sections of this chapter, we will discuss the prediction of birth asphyxia utilizing
different means. In medicine, a sentinel event is an indicator of presence of disease. Unfortunately,
there is no such phenomenon for NE. There are some clinical scenarios which make an asphyxial
event far more likely. These include acute and unpredictable insults such as major abdominal
trauma, placental abruption, uterine rupture and severe shoulder dystocia.
The majority of pregnancies in which there are risk factors for NE will result in normal outcomes,
making management of the ‘high risk’ patient problematic 19 . One study from Ireland utilized a case
control model with logistic regression and a classification and regression tree to assess factors
associated with NE 19 . Though this analysis was able to provide some prediction of which neonates
would be affected, the risk factors were common within both the cases and controls 19. A Swedish
cohort looked at factors associated with depressed neonates 32. The findings were that moderate
fetal heart rate variability was protective and that abdominal compression to hasten delivery, breech
presentations, and instrumental deliveries were associated with low APGARs 32. One problem is that

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the definition of birth asphyxia in this study was 5-minute APGAR of <7. Likely, many of the neonates

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meeting this definition went on to have completely normal development. An additional issue is that
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some of the factors, instrumental delivery, for example, may not be causal but merely associated
with NE (the instrumental deliveries may be performed for a concerning fetal indication that is itself
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the key risk factor for NE). Likewise, shoulder dystocia is an important risk factor for NE 31. However,
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the clinician cannot accurately predict this event, or its severity, in the majority of cases.
Even the factors above with the highest associations with NE are relatively unhelpful. A mentor to
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one of the authors was known to say “Breeches are always awful. Awful easy or awful hard. But
always awful.” This comment is especially helpful here – most breech deliveries result in normal
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neonates with no asphyxial injury, but when they are not straightforward, significant difficulty can
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be encountered in effecting the delivery, even for an experienced provider. One approach is to
recommend caesarean delivery for all breech presentations (which most providers do). However,
the development of NE is not a certainty with a breech vaginal birth. Despite the increased risk of
complications, most of these neonates still do well with the largest randomized controlled trial on
the subject showing that the rate of perinatal/neonatal mortality or serious neonatal morbidity was
5% in the offspring of women who planned a vaginal birth as opposed to 1.6% of those who planned
a caesarean 33. Another way to express this is that there is a 95% chance that neonates born breech
will have no obvious serious neonatal concerns.
Perhaps most helpful is a finding from the review of cases with poor outcomes by an expert panel
tasked with assessing cases of moderate and severe NE in addition to stillbirths and neonatal deaths
attributed to an asphyxial event during a 2-year period in the United Kingdom. In this study,
inadequate communication was a key factor in birth asphyxia in many cases. In fact a delay in
communication was the most common contributor in cases where the panel identified issues with
intrapartum management 34. The group also found high rates of ‘suboptimal care’ relating to
cardiotography (CTG) interpretation, a finding with inherent issues, as we will discuss in a later
section.

Diagnosis of asphyxia via CTG

As discussed previously, there is some confusion regarding the diagnoses of NE and CP. The
occurrence of CP is in most cases unpredictable and unrelated to birth asphyxia 35. Though CTG has
been widely implemented with one of the primary aims of its initial adoption being a decrease in the
rate of CP, this has not occurred 36. The rate in CP is stable despite a marked increase in the
caesarean delivery rate, most likely related to the high false positive rate of CTG 37. Concerningly,
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there is no agreed-upon interpretation of CTG , even amongst experts. The vast majority of fetuses
in labour will exhibit what is defined as ‘concerning’ or ‘abnormal’ CTG monitoring during normal

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labour, with no clear guidance on the action recommended 3. An estimated 80% or more of fetuses
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will display periods of abnormal CTG monitoring during labour 3, making it a particularly poor
discriminator, though there is some evidence that the more time spent with an abnormal CTG, the
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higher the chance of NICU admission and low APGARs 38. However, still, most of these fetuses will be
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born without hypoxia 38.

Though CTG technology cannot detect CP, there is some evidence that it may be more useful in
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identifying the fetus at risk for NE 39. However, there is still some question as to how useful CTG is to
this end, with some studies showing poor correlation between CTG and birth asphyxia 40. The
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prediction of seizures also appears to be possible with CTG, indicating that in some cases it may be
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useful for detecting acute, hypoxic insults 41. A cautious approach should be followed here, as there
are other factors that appear to be related to NE, that are likely not causal. The passage of
meconium, for example, is more likely in deliveries from which many obstetric and paediatric
complications arise. However, as previously mentioned, meconium passage poorly predicts
outcomes 42. Likewise, there is an association between NE and operative delivery 40. However, it is
likely that in most cases the operative delivery is associated with but not causative of NE.
Many studies have retrospectively assessed the ability of clinicians to predict NE utilizing
cardiotocography. A group in New Zealand compared cases of NE to normal outcomes 43. Experts
reviewing fetal monitoring would have changed delivery timing approximately 40% of the time 43.
Though this seems encouraging at first glance, this is less than half of the cases. Additionally, it is
important to note that saying you would do something in a research setting in which you are
provided cardiotocographs to review is far different from making that decision in a clinical setting
and getting it done. When given all clinical information about a patient and incorporating their own
physical examinations and interactions with the patients in question, it is unknown whether
clinicians would have made the same decisions. There is invariably delay involved in escalation of
care in every setting as clinicians are rarely caring for just one patient and an operating theatre or
team is not always available. Lastly it is unclear if the change in delivery timing would have resulted
in a change in outcomes, or whether the recognition would have been too late to prevent injury
even at the earlier timepoint. Irrespective of these findings, it does appear that at least under
controlled circumstances, there is some ability to know which fetuses are ‘in trouble’ from CTG,
though there are clearly significant limitations with the method. It is well established that there are
very high false positive rates with CTG 37, and that only the extremes of abnormal with CTG in any
way predict an injured fetus, some of the time 44.

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In addition to analysis of fetal heart rate via CTG, other methods of fetal analysis have been
evaluated to see if they might improve the detection of compromised fetuses. These have included

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evaluation of fetal pulse oximetry, fetal ECG and ECG ST segment analysis. Despite these methods
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having been introduced many years ago they remain purely research tools with equivocal data
regarding their utility.
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Preventable Risks
There are several pregnancy-related factors that increase the risk of NE. Most are unpredictable in
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nature. For example, uterine rupture and placental abruption are major contributors but have
sudden and usually unpredictable onset 31. Other conditions, such as breech presentation, can have
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risk markedly decreased with a caesarean delivery. Paradoxically, this then leads to a risk of uterine
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rupture in a subsequent pregnancy.

When assessing systems, safe levels of staffing are important. Clear hierarchies and an ability to
question management without fear of ridicule or retaliation are desirable. Though there does not
appear to be literature linking a ‘safety culture’ to decreases in rates of NE, there is evidence that
increasing the percentage of patients for whom care escalation is sought, via transfer from primary
to secondary care during labour decreases the rate of birth asphyxia 45.
Optimal treatment of a neonate with an asphyxial injury is also important. Where logistically
possible, women should be transferred to a higher level of care if their infant would be better served
at another center. NICU facilities with inadequate staffing levels present a preventable risk, as does
failure of in-utero transfer 26 27. Likewise, early recognition and treatment of a neonate with NE does
appear to improve outcomes 23,24.
Threshold for C Section
After a child is born with NE, it is not uncommon for the parents and indeed a provider’s colleagues
to speculate that the outcome would have been different had a caesarean been performed earlier,
or performed instead of a vaginal delivery. Indeed a randomized controlled trial has documented
this type of hindsight bias in expert clinicians 46. Obstetricians are frequently taught that ‘minutes
matter’. However, one study assessing outcomes from caesareans performed for emergency
indications found that those occurring more than 30 minutes after the decision to proceed to
delivery was made were not associated with worse neonatal outcomes than those performed more
expediently 47.
Despite clear evidence that CP and other developmental disabilities cannot be predicted with any
accuracy utilizing CTG or other clinical signs and that caesareans also do not appear to prevent it
36,39,41

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, NE has become the new condition of focus, which clinicians are thought to be able to predict
despite shaky evidence that this is possible 40.. An example of this is the passage of meconium, which

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is a very common occurrence, and linked to multiple conditions. While it is associated with
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neurological injury, this factor has very high false positive and false negative rates 4,42. One study
from Israel compared labours with clear amniotic fluid to those with thin or thick meconium. The
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rate of a 5 minute APGAR score of <7 was 0.4% in neonates who had clear amniotic fluid compared
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to 3.6% in those with thick meconium, though the difference was not statistically significant.
Worldwide, there is an increase in caesarean delivery rates without a significant decrease in
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complications. It is becoming clear that reducing operative delivery in isolation is likely not the best
indicator of quality 48.
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Work assessing maternal and fetal outcomes from the United States also addressed birth
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complications utilizing quality indicators 49,50. Data from multiple hospitals was included and rates of
maternal severe perineal laceration, caesarean delivery and neonatal APGAR scores <7 at 5 minutes
were some of the findings reported. In this work, there was no association between increased
caesarean delivery rates and 5 minute APGAR scores 49,50. This could be for several reasons, one
being that there were different rates of prematurity between hospitals and this is something
providers cannot modify 49. Another explanation may be that an expeditious delivery performed
during a difficult labour may not be effective in preventing neurological damage. In fact, being able
to predict which fetuses will be damaged by labour and performing the caesarean before the onset
of labour may be the solution. This candidate solution is however something that is unable to be
done on a large scale currently.
So can any guidance be arrived upon in relation to caesarean threshold? Some literature indicates
that substandard care is involved in about half of the poor outcomes encountered when they are
reviewed 51 though we should be mindful of the presence of hindsight bias in case reviews 46. When
a determination of ‘substandard care’ is made, often the intervention thought to be needed is not
caesarean delivery. A review of complications in Norwegian maternity units frequently cited other
candidate management such as different techniques to relieve of shoulder dystocia, for example.
Failure to escalate care was a consistent theme in the three areas (obstetric care in birth asphyxia,
shoulder dystocia and postpartum haemorrhage) investigated 51 . This concurs with other evidence
that communication is key in providing good care, with this being a common contributor to poor
outcomes when causation is assessed 34. What has also emerged in developed countries is that
appropriate access to secondary care for pregnancy and delivery management and and timely
escalation to secondary care intrapartum can make a difference 45. A nationwide cohort study from
the Netherlands documented a modest, but statistically significant decrease in birth asphyxia over a

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10-year period. This correlated with a 4% increase in the rate of secondary care referral in labour
and a 2% increase in the rate of intervention for fetal distress 45. Importantly, this highlights that not

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all cases of care escalation resulted in intervention, but some did, and the rate of birth asphyxia fell.
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The solution is likely not a set of specific physical symptoms or technological signs that are absolute
indications for caesarean delivery. It may be that open communication, timely input from colleagues
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in secondary care and expedient delivery when there is a concern may make the biggest difference.
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The blame game – remaining objective in high stress situations

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Tragic outcomes resulting from birth are also major events for healthcare professionals. Internal
factors (guilt, personal case history, position within teams and relationships with colleagues) and
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external factors (litigation, patient complaints, investigations regarding competence) can produce
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emotional, rather than evidence-based approaches to future provision of care. The history of blame
for any unfortunate outcome is well-known to obstetric providers 52. Often, cases that would
objectively seem to have been handled within guidelines result in large settlements. Neurologically
impaired newborns are the most common reason for litigation related to obstetric care, with one
report detailing this being responsible for 27.4% of claims 53. Litigation is more related to the severity
of the injury than to the skill of the birth attendant or whether the management was of high quality
54
.
There have been multiple studies in the United States assessing the provision of obstetric care as it
relates to neonatal outcomes. The studies indicated that the type of care provided, and quality
indicators utilized did not appear to account for the differences in outcomes between centres 28,55.
This indicates that the important and modifiable factors are likely more complicated than care
bundles (prespecified processes incorporating multiple elements with the intention of improving
outcomes), type of provider or setting that can be applied to the labour process itself.
Unfortunately, we appear to be naïve to the important factors. The lack of a universal clinical dogma
is easily evidenced by the markedly different guidelines that exist internationally. In spite of the
evidence to the contrary, clinicians still tend to assign and accept blame for outcomes that are, in
many cases difficult to predict, and most often partly or entirely out of their control. Perhaps the
most convincing evidence regarding this is an elegant randomized controlled trial, which
investigated hindsight bias regarding CTG interpretation 46. Providers were given three cases. The
first and second cases were both CTGs with specified outcomes and the groups agreed on
interpretation and management. For the third case, all participants were provided with the same
CTG but a different neonatal outcome (one group was told the neonate was healthy, the other was
told the neonate had NE). Somewhat unsurprisingly, the groups differed here, with a statistically

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significant increase in finding fault in the management when they were told the neonate suffered NE
(37% versus 72%, P = 0.0001) 46.

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Some have suggested that obtaining umbilical cord blood for gases is helpful in cases where an
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infant is born with low Apgar scores or in an emergency situation (scenarios in which a diagnosis of
NE is more likely to follow). Certainly there are case reports where cord blood gases have
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‘exhonorated’ a clinician when there has been a poor outcome by indicating an event remote from
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delivery 56. Though favorable cord blood gases may indicate that encephalopathy due to poor
oxygenation did not occur immediately prior to the birth, they do no in any way improve things for
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the patient. For this reason it is hard to recommend cord blood gases for any clinical reason.
Compounding this is the reality that in many healthcare systems, the patient receives a bill for any
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testing performed. It is difficult to justify women paying for tests used purely to defend the
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delivering provider.
Similarly, placental pathology can be a helpful adjunct to other testing. As discussed in a following
section, important causal pathways can likely be identified in a significant proportion of cases where
the neonate is diagnosed with NE. Unfortunately we do not presently have effective predictive
imaging or testing as to which fetuses has abnormalities in their placentas until after birth.
So where to go from here? Clinicians should strive to communicate better amongst themselves and
recognize the limitations of current technology to predict outcomes. The approach should not stop
at clinicians but should also include scientists researching the area, quality reviewers and officers of
the courts. Families with affected children need expensive care and our society should provide for
them, whether or not there is an obvious person to blame. A system that requires assignation of
fault for a person to access medical care is flawed and should be improved.
Recognizing that most outcomes are not attributable to a singular ‘fault’ does not mean a departure
from quality improvement or self-reflection and practice improvement, but rather a recognition that
bad outcomes can bring out the worst in all of us. Though medical mismanagement will be identified
51
in a large proportion of retrospective reviews of known poor outcomes , communication is
frequently a contributor in these cases 34. The way forward includes better collaboration, open
channels of communication and development of better systems to identify and treat those at risk. A
commitment to training the next generations of providers and ensuring their competency is
necessary 57.

Neonatal resuscitation – birth room variation

As already stated, communication appears to be lacking in a significant proportion of cases where NE
was thought to be preventable. Communication between nurses, midwives and obstetric providers is

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important but these are not the only necessary parties to the communication. The conversation
regarding the high-risk births should involve neonatologists, neonatal nurses and anaesthetists.

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When an asphyxiated infant is delivered, the availability of skilled attendants to provide
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resuscitation is paramount. A delay in oxygenation of even a few minutes may have a profound
effect on neonatal outcome. Simulation can assist in preparing teams for emergencies, and there are
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many courses available for training internationally. There is also evidence that standardized neonatal
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resuscitation training appears to improve outcomes 58,59. Though the delivering provider turns their
responsibility to the mother after the birth has occurred, part of the responsibility for successful
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neonatal resuscitation lies with communication between those that will assume care of the neonate.
Teams tasked with resuscitating an infant rely on information that is as accurate as possible to
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prepare for a resuscitation, as well as sufficient notice so that they may be in attendance when the
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neonate is born. In many cases this pertains to operating theatres, as many neonates with NE are
delivered by caesarean after events such as abruption or uterine rupture 31. Ideally, the most
effective resuscitation possible is a shared responsibility between obstetric and neonatal care
providers, though this is not the way most hospital teams are classically identified. Discussions about
the immediate post delivery care, including delayed cord clamping when feasible, keeping the
newborn warm and providing a length of cord that permits the placement of catheters is relevant.
When litigation is then encountered (as it inevitably is in many developed countries), the team
approach can be strained. Focusing on shared responsibility and improving hospital rather than
individual outcomes is likely the most constructive approach. An awareness in team leaders and
participants that litigation is more related to outcome than whether the standard of care was met
can be a useful insight 54.

Variations between centers

Different centers serve different patient populations and have different availability of interventions
which may improve outcomes in rare clinical scenarios. Centres with specialized equipment and
clinicians with expertise in neonatal intensive care are more prepared to receive an infant with NE 60.
It is therefore unsurprising that the rates of NE do differ between centers. Attempts to assess which
type of care makes the biggest difference to morbidity between centers have been unsuccessful in
identifying this as a causal factor 55. One study from the United States looked at over 115,000 births
in 25 hospitals. Trained case abstractors were utilized to process the data. Over half of the variations
between centers were considered unexplained, and 20-40% of the variation in outcomes were
related to differences in the patient population treated 55. Likewise, quality indicators such as
caesarean rates in low-risk women and rates of elective delivery between 37 and 39 weeks, do not
appear to guide optimal processes for obstetric care 28.

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Quality metric work from the United States attempted to identify predictive factors. Though the data

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did seem to suggest some obvious conclusions; for example, while hospitals with the highest severe
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perineal laceration rates appeared to have some of the lowest caesarean delivery rates 49, there was
little association between caesarean rates and birth asphyxia. The surrogate for NE in this work was
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5-minute APGAR score of <7, and this appeared to be unrelated to the caesarean delivery rate 49 41.
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This is not to say that there are not important differences between centers that change the
incidence of NE, but rather that the differences may reflect differences in populations being cared
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for in addition to differences in management provided, once in labour.

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National patient safety program to manage obstetric risk efficiently

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Changes in policies at a national level can make a difference to patient outcomes. However, change
is never easy, and there are cases where policies cannot, or should not apply. The implied benefits of
a new way of doing things are not always realized in clinical outcomes – something that the
implementation of CTG to prevent CP has shown us.
While retrospective studies have suggested that the application of set interpretation of CTG or
clinical factors can predict and therefore prevent bad outcomes 43, this has not been reproduced
convincingly with prospective studies. Fields such as critical care, anaesthesiology and surgery have
61
been able to show that application of quality indicators can improve outcomes . However, the
same has not been found consistently with the provision of obstetric care61. Multiple studies
assessing quality indicators and assessment algorithms for fetal monitoring have failed to show real
decreases in risk to the fetus or mother 28,61. The reason for this may be related to the duration of
pregnancy, with interventions aimed at the last few hours of the process being applied too late.
Alternatively it may be that the complexity of the factors involved is too great for us to identify the
best indicators to choose.
Various healthcare systems exist internationally, all with competing merits and drawbacks, not to
mention different patient populations to serve. What is clear, is that access to health care,
preferably commencing from prior to pregnancy is desirable to improve outcomes. There is
consistent international literature showing that access to basic care, both antenatally and at the
time of birth, and to escalation of care when problems arise, are the most important factors that are
modifiable when trying to prevent morbidity and mortality from all causes 21,22,48. Data from a rural
hospital in South Africa showed an improvement in overall perinatal mortality with increased access
to care and escalation pathways (on site caesarean availability after hours, for example) 22. One

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noteworthy finding was that the percentage of cases of fetal and infant mortality attributable to
asphyxia rose whilst those attributable to antepartum haemorrhage, infection and hypertension fell

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22
. This reinforces the difficulty in the prediction of this outcome and suggests that perhaps the aim
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should be to decrease overall morbidity and mortality, rather than specifically focusing upon birth
asphyxia.
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In the developed world, there continues to be debate about whether intervention is warranted in
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low-risk pregnancies and about when a pregnancy ceases to be low risk. One trial aimed at
improving outcomes for women with a prior caesarean birth is currently underway, and will
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hopefully be able to provide some guidance on approaches for high-resource settings 62. There is
also considerable evidence indicating that ‘elective’ induction of labour at a “term” gestation
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decreases the rate of stillbirth and caesarean delivery 63,64. This data echoes what was already known
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regarding neonatal outcomes in the United States; that adversity is less likely in neonates delivered
between 39 and 40+6/7 weeks gestational age 65,66. The Swedes have also published data indicating
that the risk of neonatal seizures and APGARs of <4 at 5 minutes is higher in neonates delivered at
42 weeks or more 67. Though ongoing conversations are occurring about the applicability of these
findings to all health care settings, the evidence is hard to ignore. It may be that if there is little to
gain from a maternal or fetal standpoint, then remaining pregnant past 39, 40 or 41 weeks becomes
undesirable. The new standard of care may become a recommendation for delivery at a prespecified
gestational age if it has not occurred naturally. The American College of Obstetricians and
Gynecologists has already started a move in this direction, with labelling gestations at 41 weeks late-
term and those at 42 weeks post-term 68. The College has also recommended induction at 42 weeks
and states it should be considered at 41 weeks 68. If perinatal mortality and birth asphyxia were the
only concerns (clearly they are not), it would be hard to argue that there is significant advantage to
continued gestation past 39 weeks, and certainly not past 41 weeks gestational age.
Systems issues that are identified by literature review reflect the value of adequate staffing,
availability of transfer to a tertiary care centre prior to delivery and communication in situations
where care likely needs to be escalated 26,27,34. Prematurity contributes to complication rates, and
providers cannot control this variable. Maintaining beds in the most suitable places for these
neonates to be born is important for outcomes. as access to advanced care for neonates appears to
improve outcomes in asphyxiated neonates 60. Creating guidelines that give support to escalation of
care may be useful from a systems point of view. Providing the training to staff so that they have
competency in recognition of the abnormal and in the escalation pathways is vital 57.
An example of approaches to national programs are the Advances in Labour and Risk Management
(ALARM) and Managing Obstetrical Risk Efficiently (moreOB) programs that have existed in Canada
for many years 69. These programs have been employed in numerous hospitals and have been

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supported at regional levels by provincial health ministries and provincial medical colleges. The

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programs aim to address some of the factors alluded to above. Elements include requiring all staff in
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the obstetric service (medical and nursing) to access the same core knowledge bases, training on
evaluating CTGs, and a commitment to optimize the culture within labour wards to allow rapid
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bidirectional communication and to undertake skills drills and simulations to put into practice the
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knowledge and communication skills. Outcomes are tracked by year and the rates of severe
newborn morbidity in Alberta were shown to reduce by over 15% after completion of modules 2 and
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3 of moreOB in the province. The definition used for severe neonatal morbidity is not specific to NE
so it is difficult to know the impact of the improvement in regards to asphyxial injury 70. The lack of
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specificity is likely unimportant though. The data from Canada mirrors the above-discussed findings
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from other settings – that great improvements can be made with real decreases in neonatal
morbidity and mortality, but singularly effecting a change in the rate of NE is especially challenging.
In the United Kingdom, the introduction of skills drills and emergency obstetrical training to attempt
to reduce risk and litigation in a program overseen by the Clinical Negligence Scheme for Trusts,
halved the rates of NE 71 . While this is again encouraging, it is important to note that the change in
rate of NE was for all NE. However, this change in rate reflected a decrease in cases of mild NE – the
rate of moderate or severe NE was not statistically significantly decreased. This is relevant as most
neonates with mild NE will have good outcomes. The most benefit would be attained in prevention
of severe cases, something which remains a challenge. During the same period, the decreases in NE
were also accompanied by an increase in the caesarean delivery rate, which may or may not have
been related to the rate of NE.
Irrespective of the shortcomings of the programmes in the UK and Canada, it is difficult to argue that
there is not some overall benefit to increased training, drills for emergency situations and
improvements in communication. These programs had multiple facets and hence no one
intervention can be considered the ‘prevention’ tool for NE. But the overall results are encouraging.
These types of programs are not necessarily resource intensive and could be applied in lower
resource settings with the support of local governmental and health organisations.

If I knew then what I know now – Placental findings in cases of NE

NE has been thought to be the result of the birth process and, historically, placental findings have
not been considered important. As more information emerges on post-hoc placenta pathology from
neonates affected and unaffected with NE, reevaluation of that theory is required. It may be that NE
is far more likely to happen as a ‘second hit’ phenomenon, or that the condition is worsened rather
than caused by birth events in many cases 72. Case-control and retrospective cohort studies have

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consistently documented higher rates of fetal thrombotic vasculopathy, accelerated villous

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maturation, in addition to markers of inflammation and infection, such as chronic villitis, in
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pregnancies resulting in neonates with NE 72-75. There appears to be a relationship between intra-
amniotic infection and NE. Sepsis is known to cause vasodilation and low tissue perfusion in adults
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and may have a similar effect in the fetus, potentially worsening preexisting damage. Some evidence
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suggests that the histologic findings, when compounded, worsen the prognosis of NE 74, with
imaging work indicating villitis in the placenta is highly associated with severe NE 75. Though other
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clinical findings such as abnormal cardiotocographs are also more common in these presentations 72,
it seems likely that rapid deterioration in the fetus (and also the cardiotocograph) would occur in a
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pregnancy, in which the placenta and as a result the fetal brain was already compromised. As we
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move forward in optimally diagnosing and treating NE, the application of responsibility to the
individual or team who catches the baby at the bottom of the cliff is unhelpful, especially when we
consider the cliff to be made up of intrapartum events. There is now considerable evidence from
placental pathology, neonatal imaging and a multitude of studies relating to comorbidities and
socioeconomic disadvantage that indicate that events in labour perhaps occupy the precipice alone.

Research
Identifying the fetus with underlying injury or risk is of paramount importance in the obstetric field.
The existing testing available, such as ultrasound and cardiotocography poorly predicts NE. Many
researchers have applied algorithms to these tests in an attempt to predict the disease. None have
succeeded in making either more useful or accurate. Further reflection on cardiotocography
especially is unlikely to improve its positive predictive value. New imaging techniques of the fetal
brain via ultrasonography may prove useful, however. Work in this space should include a focus on
the fetal brain and signs of malperfusion or injury prior to birth.
Research regarding placental health is also a key area to identify fetuses at risk, considering most of
the existing data only applies to placental findings after birth, at a time where this is of scientific
interest, but of little clinical help as it relates to NE. Post-birth photographic computer recognition
programs are being piloted and may provide an affordable way to identify which placentas should be
selected for histologic examination and this may be relevant to neonates, who go on to be
diagnosed with disabilities later in childhood 76. Utilizing computers to interpret histology may also
prove a cost effective way to perform placental histologic examination going forward 77. The Human
Placenta Project was formed recently and is “a collaborative research effort to understand the role
of the placenta in health and disease” 78. Placental imaging as well as functional research has been

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supported and publicized through this platfrom. Ideally, collaborative clinical research will also focus

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on early identification and treatment of affected neonates as well.

Future Directions
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As the aim is to improve birth outcomes, bias and emotion tend to be obstacles. What we have
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evidence for, is an approach in which all women receive prenatal care, intrapartum care and have
access to escalation of care (with varying degrees of intervention) as indicated. Social determinants
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of health are important factors in modifying the rate of NE. Retrospective reviews of cases have
obvious biases applied by a known outcome, but they do seem to indicate that communication
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between members of the healthcare team is important and that care providers do not always
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interpret abnormal data with concern. Part of the reason for the latter is the inadequacy of current
tests to predict NE. Several decades have been spent now proving and proving again that
implementation of CTG and an increasing caesarean delivery rate cannot eliminate birth asphyxia.
These are specific tools that will assist in some, but not all cases. Tests that better predict the
outcome are required. Technological innovations are needed to permit better detection of the at-
risk fetus and that such developments would likely do the most to lower the rate further in high-
resource settings.

Practice Points
- The rates of birth asphyxia are the lowest in developed countries.
- Access to prenatal care and the social determinants of health are the most important
factors related to birth asphyxia.
 - The pregnancy-related risk factors for birth asphyxia are common and generally not
informative as to which foetuses are likely to be affected at birth.
- Cardiotocography, ultrasound and other fetal monitoring methods poorly predict
birth asphyxia.
- There is some evidence that continuous training of all staff involved in the care of
women (such as standardized CTG interpretation, skills drills, simulation and
communication exercises) improves outcomes. Part of this effect may relate to birth
asphyxia.
- Reducing overall morbidity and mortality appears to be the best approach to
preventing birth asphyxia.

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Research Directions
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Our technology needs to improve to better identify the at-risk fetus that would
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benefit from expedited delivery.
- Innovation is required to accurately detect foetuses experiencing intrapartum
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asphyxia.
- Current intrapartum testing provides some indication as to whole-body hypoxia or
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acidosis but does not inform us regarding the function of the fetal brain. Research
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should focus on this organ.

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