European Journal of Obstetrics & Gynecology and Reproductive Biology 190 (2015) 1–6

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Review

Expert review – identification of intra-partum fetal compromise

Tomas Prior a,b, Sailesh Kumar a,b,c,*
a
Centre for Fetal Care, Queen Charlotte’s and Chelsea Hospital, Du Cane Road, London W12 0HS, UK
b
Institute for Reproductive and Developmental Biology, Imperial College London, London W12 0HS, UK
c
Mater Research Institute/University of Queensland, Aubigny Place, Raymond Terrace, South Brisbane, QLD 4101, Australia

A R T I C L E I N F O A B S T R A C T

Article history: Whilst most cases of cerebral palsy occur as a consequence of an ante-natal insult, a significant
Received 3 September 2014 proportion, particularly in the term fetus, are attributable to intra-partum hypoxia. Intra-partum
Received in revised form 31 January 2015 monitoring using continuous fetal heart rate assessment has led to an increased incidence of operative
Accepted 7 April 2015
delivery without a concurrent reduction in the incidence of cerebral palsy. Despite this, birth asphyxia
remains the strongest and most consistent risk factor for cerebral palsy in term infants. This review
Keywords: evaluates current intra-partum monitoring techniques as well as alternative approaches aimed at better
Cerebral palsy
identification of the fetus at risk of compromise in labour.
Intrapartum monitoring
Hypoxia
ß 2015 Elsevier Ireland Ltd. All rights reserved.
Fetal distress
Fetal compromise

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Search strategy and selection criteria . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Techniques used for intra-partum monitoring . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Cardio-tocography . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Fetal pH and lactate levels . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Fetal electrocardiogram . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Fetal pulse oximetry . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Other techniques used to identify fetuses at risk of compromise in labour . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Doppler ultrasound . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Umbilical artery . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Middle cerebral artery . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Cerebro-umbilical ratio. . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Umbilical venous flow . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Biochemical markers of placental function . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Authors’ contribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Disclosure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Ethical approval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

* Corresponding author at: Mater Research Institute/University of Queensland, Level 3, Aubigny Place, Raymond Terrace, South Brisbane, Queensland 4101, Australia.
Tel.: +61 7 31632564.
E-mail address: skumar@mmri.mater.org.au (S. Kumar).

http://dx.doi.org/10.1016/j.ejogrb.2015.04.002
0301-2115/ß 2015 Elsevier Ireland Ltd. All rights reserved.
2 T. Prior, S. Kumar / European Journal of Obstetrics & Gynecology and Reproductive Biology 190 (2015) 1–6
Introduction
During labour the feto-placental relationship is tested to its
highest degree as uterine contractions can reduce blood flow in the
uterine artery by as much as 60% [1]. Whilst in some cases, such as
fetal growth restriction, an increased risk of intra-partum compro-
mise may be evident prior to labour, as much as 63% of cases of intra-
partum hypoxia occur in pregnancies with no prior antenatal risk
factors [2]. Despite improvements in antenatal and intra-partum
care, as well as the introduction of continuous fetal monitoring, rates
of cerebral palsy have not declined over the last 30 years [3]. Whilst
some evidence suggests that ante-partum events are responsible for
the majority of cases of cerebral palsy [4,5], intra-partum events may
still account for a significant proportion (between 9.6% and 14.5%)
[6,7], and possibly as much as 20% in term infants [8]. The debate
regarding causality is on-going, with a recent study suggesting that
the application of strict diagnostic criteria to hypoxic ischaemic
encephalopathy (HIE) revealing intra-partum events as the pre-
dominant antecedent in term babies [9]. Furthermore, a recent
systematic review concluded that birth asphyxia remained the
strongest and most consistent risk factor for cerebral palsy in term
infants [10]. These cases are over-represented in obstetric medico-
legal claims [11], and often result in a high quantum of damages [12].
Given the spiralling costs of medical malpractice insurance, and the
possibility of affected infants requiring a lifetime of medical support,
cerebral palsy as well as other neurological sequelae of intra-partum
hypoxic ischaemic encephalopathy, represent a significant financial
burden to healthcare providers around the world.
With this in mind, much effort has been placed on techniques
to identify fetal hypoxia during labour, and to enable delivery of
the fetus before neurological damage takes place. fetal cardio-
tocography (CTG), ST-segment analysis (STANß), and pulse
oximetry have all been adopted into clinical practice to varying
extents in maternity units around the world. The most commonly
used technique for intra-partum fetal monitoring (CTG), when
compared to intermittent auscultation, has not resulted in a
decrease in the incidence of cerebral palsy [13], but is responsible
for an increase in the rates of obstetric intervention [13]. Other
techniques such as assessment of the fetal biophysical profile and
amniotic fluid volume have been adopted in an attempt to identify
the fetus at risk of compromise, prior to the onset of labour. Much
of the technology currently used for intra-partum fetal monitoring
has poor positive predictive value for fetal compromise [14].
This review will consider the evidence supporting the use of
these techniques in identifying the fetus at risk of compromise and
enabling timely intervention to prevent long term neurological
sequelae.
Search strategy and selection criteria
A comprehensive search of PubMed was conducted. All articles
indexed on PubMed and published in English were considered
eligible for inclusion. Search terms including ‘‘fetal compromise’,
‘‘fetal distress’’, ‘‘caesarean’’, ‘‘neonatal outcomes’’, ‘‘acidosis’’, and
‘‘operative delivery’’ were combined with the names of monitoring
techniques to identify relevant articles. Where possible, evidence
from meta-analyses/systematic reviews was prioritised for inclu-
sion. All included articles were reviewed by both manuscript
authors (TP and SK).
Techniques used for intra-partum monitoring
Cardio-tocography
Fetal electronic cardio-tocography (CTG) was developed in
1957 as a means of continuous monitoring of the fetal heart rate.
Almost 60 years later, it remains the primary means of intra-partum
fetal monitoring throughout the world, particularly in developed
countries. Unfortunately, CTG has not resulted in the expected
reduction in cerebral palsy rates [13]. Despite its almost ubiquitous
use in current intra-partum care, CTG has been criticised for its high
false positive rate for fetal compromise. In some studies this rate is as
high as 99.8% [15]. Furthermore its use has paradoxically resulted
in an increased incidence of operative delivery for presumed fetal
compromise, with 11 extra Caesarean sections being performed to
prevent one case of neonatal seizure [13].
A major limitation of the CTG is the subjective nature of its
interpretation with significant intra and inter-observer disagree-
ment [16] as well as a lack of discriminatory power in identifying
truly hypoxic fetuses. In order to reduce inter-observer disagree-
ment in CTG interpretation, several organisations including FIGO
(International Federation of Gynaecology and Obstetrics) [17], the
American Congress of Obstetricians and Gynaecologists (ACOG)
[18], the Australian and New Zealand College of Obstetrics and
Gynaecology [19] and the National Institute for Health and Care
Excellence (NICE) in the UK [20], have all published guidelines for
accurate CTG interpretation in an attempt to limit bias and
subjectivity. Use of such guidelines has been suggested to lead to a
reduction in the incidence of hypoxic-ischaemic encephalopathy
[21]. Nevertheless, all these documents have disparities in their
definitions of different types of fetal heart rate decelerations and
their classification of suspicious and pathological heart rate
patterns. Despite these guidelines, problems with CTG interpreta-
tion and subsequent obstetric management remain by far the
leading cause of medico-legal litigation claims in Obstetrics [22].
Methods to quantify CTG recordings using models such as the
Fischer score have also been developed and used to help guide
management [23], however, subjective interpretation of the CTG is
still a pre-requisite for their use.
More recently, computerised CTG analysis has been developed
in order to circumvent the problems of poor inter-observer
variability of the FHR pattern [24]. These systems use software
packages to record and analyse CTG tracings, providing audio and
visual alerts according to pre-programmed characteristics. They
have been reported to improve accuracy in predicting fetal acidosis
at delivery [25], and perform better than obstetricians in
identifying compromised fetuses [26]. Whilst these results are
promising, robust, multicentre, randomised control trials are likely
to be required demonstrating an improvement in neonatal
outcomes, before such automated systems are universally adopted.
One such trial is currently in progress [27].
Despite a large retrospective population study recently report-
ing an association between the temporal increase in CTG use in the
United States with a reduction in neonatal mortality [28], the value
of CTG to identify intra-partum hypoxia and improve neonatal
outcomes remains the subjective of considerable debate [29].
However, the use of CTG use does result in a reduction in neonatal
seizures [30], and it should be noted that the majority of trials
evaluating CTG use included in systematic reviews such as those of
Alfirevic et al. [13], and in the preparation of NICE guidance, were
conducted some time ago, potentially limiting their ability to be
representative of contemporary practice.
Fetal pH and lactate levels
Intra-partum CTG monitoring is frequently augmented by the
use of fetal blood sampling (FBS). This procedure involves sampling
blood from the fetal scalp, for immediate analysis of the acid–base
or lactate status of the fetus. This technique, which has been in use
since the 1960s, has a greater specificity for a low Apgar score at
1 min than the CTG [31]. Following FBS, management decisions
may be based on fetal pH values, which show a greater correlation
 T. Prior, S. Kumar / European Journal of Obstetrics & Gynecology and Reproductive Biology 190 (2015) 1–6
with neonatal condition than pO2 or pCO2 [32]. However, the use of
FBS varies significantly between different maternity units and
different Obstetricians. Despite the reported improved specificity
over CTG alone, the use of FBS has not been shown to reduce the
number of Caesarean sections performed due to fetal distress [13]
or improve neonatal outcomes [31]. Furthermore, FBS is an
invasive procedure, and is not always easy to perform in labour. A
Cochrane review suggested that insufficient samples are obtained
in as many as 20% of cases [33]. Even in optimal conditions, FBS
provides information on the fetal condition only at the time of
sampling. Importantly, even with an scalp pH of >7.3, fetuses with
an abnormal CTG pattern are still at an increased risk of low Apgar
scores at delivery compared to those with a normal CTG [34].
Fetal lactate levels obtained from an intra-partum fetal blood
sample have been reported to be more predictive of neonatal
encephalopathy and low Apgar score than the pH [35]. The
optimum discriminatory value for fetal lactate is suggested to be
greater than or equal to 4.2 mmol/L [36], whilst a number of
published trials have used 4.8 mmol/L as a cut off value to define
metabolic acidosis [35,37]. Despite the promising results reported
by Kruger et al. [35], two randomised controlled trials comparing
the use of lactate and pH failed to demonstrate an improvement in
neonatal outcomes in the lactate analysis group, or a change in
operative delivery rates [37,38]. Whilst some publications [39,40]
did not demonstrate a correlation between lactate levels and
Apgar scores at delivery, an observational study published in
2011 suggested lactate levels do have a greater correlation with
metabolic acidosis at delivery than either scalp pH or base deficit
[41]. A systematic review in 2010 however concluded, that while
current evidence suggested the efficacy of fetal lactate was at least
equivalent to that of pH for the identification of the compromised
fetus, further studies designed to evaluate diagnostic accuracy
were required [33].
Fetal electrocardiogram
The difficulties associated with CTG analysis and interpretation
has encouraged continued development of other technologies to
help identify fetal compromise during labour. The fetal electrocar-
diogram (ECG) is one such technique, and it is used in some
maternity units to supplement the CTG when continuous fetal
monitoring is indicated. However, it can only be used following
rupture of membranes, and requires the application of a fetal scalp
electrode, making it unsuitable for all cases [42]. In the ovine
model, hypoxia causes measurable ST segment elevation and
alterations in the relationship of the PR-RR interval [43,44]. The use
of ST segment analysis to compliment fetal CTG has been evaluated
in several studies. The Plymouth randomised trial in 1993
compared CTG plus ST segment analysis with CTG alone in 1200
cases. A reduction in the incidence of operative delivery for fetal
compromise was the only statistically significant finding. Howev-
er, this reduction was amongst cases with CTG recordings classified
as normal/intermediate, with no reduction found in cases with
pathological CTG recordings [45] thereby limiting its impact.
Furthermore, a recent meta-analysis suggested that the use of fetal
ECG to compliment conventional CTG did not lead to a reduction in
Caesarean or instrumental delivery for presumed fetal compro-
mise, or metabolic acidosis at delivery. The only significant finding
was a reduction in the number of fetal blood sampling procedures
performed [46]. Assessment of ST segment analysis (STAN) as a
means to improve neonatal outcomes and reduce interventions
has been hampered by a failure to follow guidelines associated
with this technology. The observation that in several trials
evaluating the use of ST segment analysis, cases of neonatal
encephalopathy or metabolic acidosis were often associated with a
deviation from intra-partum monitoring protocols [47,48] led one
3
author to conclude that the greatest limitation of ST segment
analysis was a failure to follow STAN guidelines [49]. Whilst ST
segment analysis may have potential, it crucially still requires
appropriate CTG interpretation [50].
Fetal pulse oximetry
Fetal pulse oximetry is another technique of some promise and
was first described in 1989 [51]. The normal range for fetal oxygen
saturation in labour is between 30% and 65% [52], with a reduction
to <20% occurring during acute cord compression [53]. Fetal pulse
oximetry readings at delivery have been reported to correlate with
both umbilical vein oxygenation, and cord blood pH [54]. The
evidence for clinical benefit is however equivocal, with some
randomised controlled trials showing that the use of fetal pulse
oximetry in labour reduces operative delivery rates for presumed
fetal compromise without an increase in adverse neonatal
outcomes [55,56], whereas other studies have not replicated these
findings [57,58]. Furthermore, the performance of fetal pulse
oximetry may be influenced by a number of different variables [59]
with both fetal hair and caput succedaneum [60] affecting readings
taken from the fetal scalp. Collectively, a Cochrane review in 2007
concluded that whilst the available evidence provided limited
support for the use of fetal pulse oximetry, this technology did not
lead to a reduction in Caesarean section rates [61].
Other techniques used to identify fetuses at risk of compromise in
labour
Given the high false positive rates associated with intra-partum
CTG monitoring, a selective approach to the use of this monitoring
tool would seem appropriate. Current guidance in the UK does not
recommend continuous CTG monitoring in labour for pregnancies
deemed ‘‘low risk’’ [62]. However, identifying a pregnancy as low
risk for intra-partum fetal compromise is difficult, as the majority
of cases of fetal hypoxia are known to occur in pregnancies with no
antenatal complications [2]. Identification of pregnancies at risk of
fetal compromise would help target intra-partum care, exposing
only those pregnancies at risk of fetal compromise, to continuous
CTG monitoring. Various techniques have been suggested as
potentially beneficial.
Doppler ultrasound
Much of the investigation of fetal haemodynamics has taken place
in cohorts of fetuses known to be growth restricted. Fetal growth
restriction is associated with increased resistance in the umbilical
artery, and cerebral redistribution, characterised by reduced resis-
tance in the cerebral circulation. Interestingly, evaluation of middle
cerebral artery Doppler indices in small for gestational age fetuses
with normal umbilical artery Doppler indices, have suggested that a
low middle cerebral artery pulsatility index, indicative of cerebral
redistribution, may occur in the absence of evidence of increased
placental resistance. Such a finding may also be correlated with
an increased incidence of Caesarean delivery, as well as the need
for neonatal unit admission [63]. These findings suggest that the
resistance indices of the umbilical and middle cerebral arteries, and
the identification of cerebral redistribution, may have value in
identifying fetuses at increased risk of compromise in labour. The
cerebro-umbilical ratio has been proposed as the most accurate
method of identifying cerebral redistribution [64].
Umbilical artery
Umbilical artery Doppler is now established as a screening
test to distinguish true fetal growth restriction secondary to
4 T. Prior, S. Kumar / European Journal of Obstetrics & Gynecology and Reproductive Biology 190 (2015) 1–6
suboptimal placentation in the context of a small for gestational
age fetus. In addition abnormal umbilical artery resistance
indices have been shown to correlate with pathological fetal
heart rate patterns [65]. Further studies have also demonstrated
that adverse neonatal outcomes are more common in fetuses
with abnormal umbilical artery resistance indices [66], even in
an appropriately grown cohort [67]. However, as with other
techniques, the use of umbilical artery Doppler as part of a labour
admission test has found it to have a poor correlation with
neonatal outcomes [68]. This conclusion was further supported
by systematic reviews published in 1999 and 2010, which
suggested that Umbilical artery Doppler velocimetry alone was a
poor predictor of adverse perinatal outcome [69,70].
Middle cerebral artery
The role of MCA Doppler in the management of fetal growth
restriction and fetal anaemia is now well established in clinical
practice, but it has also been used to risk stratify pregnancies prior
to labour. Cruz-Martinez et al. [71] evaluated MCA Doppler indices
in a cohort of small for gestational age fetuses and found that its
use could distinguish a sub-group of SGA fetuses at increased risk
of Caesarean delivery for non-reassuring fetal status and neonatal
acidosis. Leung et al. [72] demonstrated that the incidence of
Caesarean delivery for non-reassuring fetal status, following
successful ECV, was more common in fetuses with lower pre-
version MCA resistance indices. MCA resistance has also been
found to be a significant predictor of meconium stained liquor in
postdates pregnancy [73]. A direct relationship between MCA flow
and fetal hypoxia during labour has also been suggested. Kassanos
et al. [74] compared the MCA pulsatility in cohorts of fetuses with
oxygen saturations >30% and <30%. They found significantly lower
MCA PI values in the cohort with Oxygen saturations <30%. These
findings are suggestive of a relationship between MCA Doppler
indices and fetal wellbeing, and indicate that assessment of the
middle cerebral artery may have value in identifying appropriately
grown fetuses at risk of intra-partum compromise.
Cerebro-umbilical ratio
The cerebro-umbilical (C/U) ratio combines assessment of both
the umbilical artery and middle cerebral artery resistance indices
and represents the ratio of the MCA PI to the UA PI.
The C/U ratio has been suggested to be the most accurate
method of identifying a brain sparing fetal circulation [64], and as
such may have potential in identifying fetuses at risk of
compromise. The clinical utility of the C/U ratio was first proposed
in 1987, when observations showed that pregnancies complicated
by fetal growth restriction or hypertensive disorders frequently
had a fetal C/U ratio <1 [75]. Several authors have now
investigated the value of the C/U ratio as a tool for assessment
of fetal wellbeing. Devine et al. evaluated a number of techniques
used to monitor postdates pregnancy including the C/U ratio,
biophysical profile and AFI. They found a C/U ratio of <1.05 to be
the most accurate predictor of adverse outcome [76]. Habek et al.
examined the relationship between both the C/U ratio and fetal
biophysical profile, and perinatal outcomes [77], and observed that
the incidence of Caesarean delivery was significantly higher in
fetuses with a C/U ratio <1. More recently, Siristatidis et al.
measured the C/U ratio of fetuses during abnormal CTG recordings,
with caesarean section being indicated if the C/U ratio was <1 for
more than 2 min. They found the use of the C/U ratio led to a
significant reduction in rates of caesarean section, with no adverse
effect on neonatal outcome reported [78]. Recently, the C/U ratio,
when measured in early labour, has been reported to be
significantly lower in fetuses that subsequently require emergency
delivery due to presumed intra-partum compromise, whilst a high
C/U ratio appears protective of fetal compromise in labour [79].
Whilst the positive predictive value for Caesarean delivery for
presumed fetal compromise was low, the negative predictive value
in fetuses with the highest C/U ratios was 100%. Assessment of the
C/U ratio is less time consuming than the CTG or biophysical
profile, and may offer a better predictive test in appropriately
grown fetuses than admission CTG which is of no proven benefit
[80]. More recently, a composite risk score, amalgamating data
from multiple fetal vessels, has been shown to improve the positive
predictive value of this test whilst largely maintaining its excellent
negative predictive value for intra-partum fetal compromise [81].
A screening test such as this could be used to supplement current
intra-partum monitoring regimes.
Umbilical venous flow
Almost three decades after altered umbilical venous flow was
first reported in growth restricted fetuses [82], the clinical utility of
this measurement remains limited outside the growth restriction
setting [83]. Alterations in umbilical venous flow have been
observed in fetuses with CTG abnormalities in labour that were
subsequently delivered by emergency caesarean section [84].
Subsequent investigations have confirmed that the presence of
umbilical venous pulsation is associated with an increased
incidence of operative delivery for presumed fetal compromise
even in uncomplicated pregnancies [85]. Our group has recently
shown that quantitative assessment of umbilical venous flow can
identify fetuses at increased risk of subsequent caesarean delivery
for presumed fetal compromise in labour [86].
Biochemical markers of placental function
A number of biochemical markers have now been associated
with placental dysfunction and adverse perinatal outcomes.
Perhaps the most established relationship is that of low maternal
serum levels of pregnancy associated plasma protein A (PAPP-A)
with subsequent fetal growth restriction [87]. Low PAPP-A,
measured during first trimester screening, has also been associated
with an increased risk of intra-partum fetal compromise and
emergency delivery [88]. Other biochemical markers of placental
function include human placental lactogen (hPL) [89], placental
growth factor (PlGF) [90], amongst others [91]. Low levels of
placental growth factor has been strongly linked to pre-eclampsia,
with the reduction in circulating PlGF thought to occur secondary
to an excess of the anti-angiogenic protein, soluble fms-like
Tyrosine Kinase 1 (sFlt1) [92]. An increase in concentrations of
sFlt1 in the maternal circulation has also been reported in fetal
growth restriction [93]. Another area of interest is that of hypoxia
induced microRNAs in maternal blood, with recent studies
suggesting an association between elevated microRNA levels
and fetal hypoxia [94]. Given that in many cases, intra-partum fetal
compromise is likely to be associated with placental dysfunction
[79], it is possible that assessment of these markers of placental
function or dysfunction may be predictive of fetal compromise.
Conclusions
Multiple different techniques now exist to aid the identification
of intra-partum fetal compromise. Currently, these methods have
not led to a reduction in the incidence of cerebral palsy in term
infants, despite increasing intervention rates. Given the absence of
a ‘‘gold standard’’ test for intra-partum fetal compromise, an
alternative approach to intra-partum monitoring is required, with
better identification of those fetuses at risk enabling a more
targeted approach to intra-partum care and delivery. Further
 T. Prior, S. Kumar / European Journal of Obstetrics & Gynecology and Reproductive Biology 190 (2015) 1–6
research on this field could utilise biomarkers of placental function,
such as PlGF, VEGF, sFlt1, and hypoxia induced microRNAs to aid
prediction of subsequent fetal compromise in labour. Combining
such biomarkers with Doppler ultrasound of selected feto-
placental vessels could result in an effective algorithm to predict
those pregnancies at risk of compromise, prior to labour. The use of
such a model, to supplement current intra-partum monitoring
techniques, has the potential to both reduce unnecessary
intervention, and improve neonatal outcomes. Furthermore, it
may also help by alleviating concerns about intra-partum fetal
wellbeing in women who choose to deliver at home, or in other
settings with minimal or no fetal monitoring.
Authors’ contribution
Both Dr Tomas prior and Professor Sailesh Kumar were
responsible for the literature review, planning and manuscript
preparation for this article.
Funding
Dr T Prior was funded by Moonbeam Trust (Charity No.
1110691). Both authors were funded by the Imperial College
Healthcare NHS Trust comprehensive Biomedical Research Centre
(BRC) scheme. The funders had no role in the conceptualisation,
planning or preparation of the manuscript.
Disclosure
The authors report no conflict of interest.
Ethical approval
No formal HREC review was required for this review article.
Acknowledgments
There are no specific acknowledgements for this article.
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