You are here

Expert review – identification of intra-partum fetal compromise

European Journal of Obstetrics & Gynecology and Reproductive Biology, July 2015, Pages 1 - 6

Abstract

Whilst most cases of cerebral palsy occur as a consequence of an ante-natal insult, a significant proportion, particularly in the term fetus, are attributable to intra-partum hypoxia. Intra-partum monitoring using continuous fetal heart rate assessment has led to an increased incidence of operative 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 evaluates current intra-partum monitoring techniques as well as alternative approaches aimed at better identification of the fetus at risk of compromise in labour.

Keywords: Cerebral palsy, Intrapartum monitoring, Hypoxia, Fetal distress, Fetal compromise.

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 compromise 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] and [5], intra-partum events may still account for a significant proportion (between 9.6% and 14.5%) [6] and [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 predominant 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 (STAN©), 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 inclusion. 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 disagreement [16] as well as a lack of discriminatory power in identifying truly hypoxic fetuses. In order to reduce inter-observer disagreement 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 interpretation 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 reporting 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 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] and [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] and [38]. Whilst some publications [39] and [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 electrocardiogram (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] and [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. However, 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 compromise, 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] and [48] led one 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] and [56], whereas other studies have not replicated these findings [57] and [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 resistance 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 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] and [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 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.

References

  • [1] T. Janbu, B. Nesheim. Uterine artery blood velocities during contractions in pregnancy and labour related to intrauterine pressure. Br J Obstet Gynaecol. 1987;94(December (12)):1150-1155
  • [2] J.A. Low, H. Pickersgill, H. Killen, E.J. Derrick. The prediction and prevention of intrapartum fetal asphyxia in term pregnancies. Am J Obstet Gynecol. 2001;184(4):724-730
  • [3] S. Clark, L. Ghulmiyyah, G. Hankins. Antenatal antecedents and the impact of obstetric care in the etiology of cerebral palsy. Clin Obstet Gynecol. 2008;51(4):775-786 10.1097/GRF.0b013e318187099d
  • [4] E. Blair, F. Stanley. Intrapartum asphyxia: a rare cause of cerebral palsy. J Pediatr. 1988;112(April (4)):515-519
  • [5] J.M. Perlman. Intrapartum hypoxic-ischemic cerebral injury and subsequent cerebral palsy: medicolegal issues. Pediatrics. 1997;99(June (6)):851-859
  • [6] E.M. Graham, K.A. Ruis, A.L. Hartman, F.J. Northington, H.E. Fox. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol. 2008;199(6):587-595
  • [7] A. Okereafor, J. Allsop, S.J. Counsell, et al. Patterns of brain injury in neonates exposed to perinatal sentinel events. Pediatrics. 2008;121(May (5)):906-914
  • [8] P.L. Yudkin, A. Johnson, L.M. Clover, K.W. Murphy. Assessing the contribution of birth asphyxia to cerebral palsy in term singletons. Paediatr Perinat Epidemiol. 1995;9(April (2)):156-170 PubMed PMID: 7596893. Epub 1995/04/01.eng
  • [9] M. Martinez-Biarge, J. Diez-Sebastian, C.J. Wusthoff, E. Mercuri, F.M. Cowan. Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy. Pediatrics. 2013;132(October (4)):e952-e959
  • [10] S. McIntyre, D. Taitz, J. Keogh, S. Goldsmith, N. Badawi, E.V.E. Blair. A systematic review of risk factors for cerebral palsy in children born at term in developed countries. Dev Med Child Neurol. 2013;55(6):499-508
  • [11] S.L. Johnson, E. Blair, F.J. Stanley. Obstetric malpractice litigation and cerebral palsy in term infants. J Forensic Legal Med. 2011;18(3):97-100
  • [12] NHSLA. Ten year of maternity claims: an analysis of NHS litigation authority data. (, 2012, October)
  • [13] Z. Alfirevic, D. Devane, G. Gyte. Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour. Cochrane Database Syst Rev. 2006;19(July (3)) CD006066
  • [14] J.A. Low. Intrapartum fetal surveillance. Is it worthwhile?. Obstet Gynecol Clin N Am. 1999;26(December (4)):725-739
  • [15] K.B. Nelson, J.M. Dambrosia, T.Y. Ting, J.K. Grether. Uncertain value of electronic fetal monitoring in predicting cerebral palsy. N Engl J Med. 1996;334(10):613-619 PubMed PMID: 8592523
  • [16] D. Ayres-de-Campos, J. Bernardes, A. Costa-Pereira, L. Pereira-Leite. Inconsistencies in classification by experts of cardiotocograms and subsequent clinical decision. Br J Obstet Gynaecol. 1999;106(December (12)):1307-1310
  • [17] FIGO. Intrapartum surveillance: recommendations on current practice and overview of new developments. FIGO Study Group on the Assessment of New Technology. International Federation of Gynecology and Obstetrics. Int J Gynaecol Obstet. 1995;49(May (2)):213-221
  • [18] ACOG. Intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles. ACOG Pract Bull. 2009;106(December)
  • [19] RANZCOG Intrapartum Fetal Surveillance Clinical Guideline – third edition. (, 2014)
  • [20] NICE. Intrapartum Care Clinical Guideline (Draft for consultation). (National Institute for Health and Care Excellence, 2014, March)
  • [21] S. Byford, E. Weaver, C. Anstey. Has the incidence of hypoxic ischaemic encephalopathy in Queensland been reduced with improved education in fetal surveillance monitoring?. Aust N Z J Obstet Gynaecol. 2014;54(4):348-353
  • [22] B. Williams, S. Arulkumaran. Cardiotocography and medicolegal issues. Best Pract Res Clin Obstet Gynaecol. 2004;18(3):457-466
  • [23] H. Wilken, B. Hackl, H. Wilken. Clinical experience obtained from antepartal CTG evaluation according to Fischer, Hammacher, Hodr and Kubli. First communication: Fischer score. Zentralbl Gynakol. 1980;102(1):12-16
  • [24] J. Bernardes, C. Moura, J. de Sa, L. Leite. The Porto system for automated cardiotocographic signal analysis. J Perinat Med. 1991;19(1–2):61-65
  • [25] A. Costa, D. Ayres-de-Campos, F. Costa, C. Santos, J. Bernardes. Prediction of neonatal acidemia by computer analysis of fetal heart rate and ST event signals. Am J Obstet Gynecol. 2009;201(5) 464.e1–6
  • [26] P. Nielsen, B. Stigsby, C. Nickelsen, J. Nim. Computer assessment of the intrapartum cardiotocogram, II. The value of compared with visual assessment. Acta Obstet Gynecol Scand. 1988;67(5):461-464
  • [27] D. Ayres-de-Campos, A. Ugwumadu, P. Banfield, et al. A randomised clinical trial of intrapartum fetal monitoring with computer analysis and alerts versus previously available monitoring. BMC Pregnancy Childbirth. 2010;10(October (28)):71 PubMed PMID: 21029466. Pubmed Central PMCID: 2987886. Epub 2010/10/30.eng
  • [28] C. Ananth, S. Chauhan, H. Chen, M. D’Alton, A. Vintzileos. Electronic fetal monitoring in the United States: temporal trends and adverse perinatal outcomes. Obstet Gynecol. 2013;121(May (5)):927-933
  • [29] R. Resnik. Electronic fetal monitoring: the debate goes on…and on…and on. Obstet Gynecol. 2013;121(May (5)):917-918
  • [30] S. Thacker, D. Stroup, M. Chang. Continuous electronic heart rate monitoring for fetal assessment during labor. Cochrane Database Syst Rev. 2006;(3):CD000063
  • [31] A.A. Mahendru, C.C. Lees. Is intrapartum fetal blood sampling a gold standard diagnostic tool for fetal distress?. Eur J Obstet Gynecol Reprod Biol. 2011;156(2):137-139
  • [32] I. Weisbrot, L. James, C. Prince, D. Holaday, V. Apgar. Acid–base homeostasis of the newborn infant during the first 24 hours of life. J Pediatr. 1958;52(April (4)):395-403
  • [33] C.E. East, L.R. Leader, P. Sheehan, N.E. Henshall, P.B. Colditz. Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace. Cochrane Database Syst Rev. 2010;2010(3):CD006174 PubMed PMID: 20238343. Epub/03/20.eng
  • [34] S. PJ. Is fetal blood sampling and pH estimation helpful or harmful?. Arch Dis Child. 1987;62(November (11)):1097-1098
  • [35] K. Kruger, B. Hallberg, M. Blennow, M. Kublickas, M. Westgren. Predictive value of fetal scalp blood lactate concentration and pH as markers of neurologic disability. Am J Obstet Gynecol. 1999;181(November (5 Pt 1)):1072-1078
  • [36] R.M. Allen, F.G. Bowling, J.J.N. Oats. Determining the fetal scalp lactate level that indicates the need for intervention in labour. Aust N Z J Obstet Gynaecol. 2004;44(6):549-552
  • [37] E. Wiberg-Itzel, C. Lipponer, M. Norman, et al. Determination of pH or lactate in fetal scalp blood in management of intrapartum fetal distress: randomised controlled multicentre trial. BMJ. 2008;336(7656):1284-1287
  • [38] M. Westgren, K. Kruger, S. Ek, et al. Lactate compared with pH analysis at fetal scalp blood sampling: a prospective randomised study. Br J Obstet Gynaecol. 1998;105(January (1)):29-33
  • [39] R. Ramanah, A. Martin, D. Riethmuller, R. Maillet, J.P. Schaal. Intérêt de la mesure des lactates au scalp fœtal au cours du travail. Étude comparative avec le pH au scalp. Gynécologie Obstétrique & Fertilité. 2005;33(3):107-112
  • [40] F. Borruto, C. Comparetto, A. Treisser. Prevention of cerebral palsy during labour: role of foetal lactate. Arch Gynecol Obstet. 2008;278(1):17-22 English
  • [41] A.M.F. Heinis, M.E. Spaanderman, J.M.T.K. Gunnewiek, F.K. Lotgering. Scalp blood lactate for intra-partum assessment of fetal metabolic acidosis. Acta Obstet Gynecol Scand. 2011;90(10):1107-1114
  • [42] I. Amer-Wahlin, S. Arulkumaran, H. Hagberg, K. Maršál, G.H.A. Visser. Fetal electrocardiogram: ST waveform analysis in intrapartum surveillance. BJOG: Int J Obstet Gynaecol. 2007;114(10):1191-1193
  • [43] K. Greene, G. Dawes, H. Lilja, K. Rosén. Changes in the ST waveform of the fetal lamb electrocardiogram with hypoxemia. Am J Obstet Gynecol. 1982;144(December (8)):950-958
  • [44] J. Neilson. Fetal electrocardiogram (ECG) for fetal monitoring during labour. Cochrane Database Syst Rev. 2012;18(April (4)):CD000116
  • [45] J. Westgate, M. Harris, J. Curnow, K. Greene. Plymouth randomized trial of cardiotocogram only versus ST waveform plus cardiotocogram for intrapartum monitoring in 2400 cases. Am J Obstet Gynecol. 1993;169(November (5)):1151-1160
  • [46] A. Salmelin, I. Wiklund, R. Bottinga, et al. Fetal monitoring with computerised ST analysis during labor: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2012;
  • [47] I. Amer-Wåhlin, C. Hellsten, H. Norén, et al. Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial. Lancet. 2001;358(9281):534-538
  • [48] V. Doria, A.T. Papageorghiou, A. Gustafsson, A. Ugwumadu, K. Farrer, S. Arulkumaran. Review of the first 1502 cases of ECG-ST waveform analysis during labour in a teaching hospital. BJOG: Int J Obstet Gynaecol. 2007;114(10):1202-1207
  • [49] M. Westerhuis, A. Kwee, A.A. Van Ginkel, A.P. Drogtrop, W.J.A. Gyselaers, G.H.A. Visser. Limitations of ST analysis in clinical practice: three cases of intrapartum metabolic acidosis. BJOG: Int J Obstet Gynaecol. 2007;114(10):1194-1201
  • [50] M. Doret, M. Massoud, A. Constans, P. Gaucherand. Use of peripartum ST analysis of fetal electrocardiogram without blood sampling: a large prospective cohort study. Eur J Obstet Gynecol Reprod Biol. 2011;156(1):35-40
  • [51] J. Gardosi, M. Carter, T. Becket. Continuous intrapartum monitoring of fetal oxygen saturation. Lancet. 1989;334(8664):692-693
  • [52] G.A. Dildy, J.A. Thorp, J.D. Yeast, S.L. Clark. The relationship between oxygen saturation and pH in umbilical blood: implications for intrapartum fetal oxygen saturation monitoring. Am J Obstet Gynecol. 1996;175(3):682-687
  • [53] N. Johnson, V. Johnson. Continuous fetal monitoring with a pulse oximeter: a case of cord compression. Am J Obstet Gynecol. 1989;161(November (5)):1295-1296
  • [54] H. McNamara, D. Chung, R. Lilford, N. Johnson. Do fetal pulse oximetry readings at delivery correlate with cord blood oxygenation and acidaemia?. Br J Obstet Gynaecol. 1992;99(September (9)):735-738
  • [55] T.J. Garite, G.A. Dildy, H. McNamara, et al. A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns. Am J Obstet Gynecol. 2000;183(5):1049-1058
  • [56] M. Kühnert, S. Schmidt. Intrapartum management of nonreassuring fetal heart rate patterns: a randomized controlled trial of fetal pulse oximetry. Am J Obstet Gynecol. 2004;191(6):1989-1995
  • [57] C.E. East, S.P. Brennecke, J.F. King, F.Y. Chan, P.B. Colditz. The effect of intrapartum fetal pulse oximetry, in the presence of a nonreassuring fetal heart rate pattern, on operative delivery rates: a multicenter, randomized, controlled trial (the FOREMOST trial). Am J Obstet Gynecol. 2006;194(3) 606.e1–16
  • [58] S.L. Bloom, C.Y. Spong, E. Thom, et al. Fetal pulse oximetry and cesarean delivery. N Engl J Med. 2006;355(21):2195-2202 PubMed PMID: 17124017
  • [59] C.E. East, P.B. Colditz. Intrapartum oximetry of the fetus. Anesth Analg. 2007;105(December (6S Suppl.)):S59-S65
  • [60] N. Johnson, V. Johnson, J. Fisher, B. Jobbings, J. Bannister, R. Lilford. Fetal monitoring with pulse oximetry. Br J Obstet Gynaecol. 1991;98(January (1)):36-41
  • [61] C. East, F. Chan, P. Colditz, L. Begg. Fetal pulse oximetry for fetal assessment in labour. Cochrane Database Syst Rev. 2007;18(April (2)):CD004075
  • [62] NICE. CG55: Intraspartum Care.
  • [63] R. Hershkovitz, J.C.P. Kingdom, M. Geary, C.H. Rodeck. Fetal cerebral blood flow redistribution in late gestation: identification of compromise in small fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol. 2000;15(3):209-212
  • [64] P. Arbeille, D. Maulik, A. Fignon, et al. Assessment of the fetal pO2 changes by cerebral and umbilical Doppler on lamb fetuses during acute hypoxia. Ultrasound Med Biol. 1995;21(7):861-870
  • [65] H. Brar, L. Platt, R. Paul. Fetal umbilical blood flow velocity waveforms using Doppler ultrasonography in patients with late decelerations. Obstet Gynecol Clin N Am. 1989;73(March (3 Pt 1)):363-366
  • [66] D. Ogunyemi, R. Stanley, C. Lynch, D. Edwards, T. Fukushima. Umbilical artery velocimetry in predicting perinatal outcome with intrapartum fetal distress. Obstet Gynecol Clin N Am. 1992;80(September (3 Pt 1)):377-380
  • [67] B.H. Yoon, I.H. Oh, P.R. Lee, W.J. Kim, H.C. Syn, S.W. Kim. Is an abnormal Doppler umbilical artery waveform ratio a risk factor for poor perinatal outcome in the non-small for gestational age fetus?. Am J Perinatol. 1993;10(3):245-249 PubMed PMID: 101055S2007994730
  • [68] F. Chan, C. Lam, Y. Lam, W. To, T. Pun, C. Lee. Umbilical artery Doppler velocimetry compared with fetal heart rate monitoring as a labor admission test. Eur J Obstet Gynecol Reprod Biol. 1994;54(March (1)):1-6
  • [69] T. Farrell, P. Chien, A. Gordon. Intrapartum umbilical artery Doppler velocimetry as a predictor of adverse perinatal outcome: a systematic review. Br J Obstet Gynaecol. 1999;106(August (8)):783-792
  • [70] Z. Alfirevic, T. Stampalija, G.M. Gyte. Fetal and umbilical Doppler ultrasound in normal pregnancy. Cochrane Database Syst Rev. 2010;8(8):CD001450 PubMed PMID: 20687066. Epub 2010/08/06.eng
  • [71] R. Cruz-Martínez, F. Figueras, E. Hernandez-Andrade, D. Oros, E. Gratacos. Fetal brain Doppler to predict cesarean delivery for nonreassuring fetal status in term small-for-gestational-age fetuses. Obstet Gynecol. 2011;117(March (3)):618-626
  • [72] T.Y. Leung, W.Y. Fok, L.W. Chan, L.W. Law, T.K. Lau. Prediction of intrapartum Cesarean delivery for non-reassuring fetal status after a successful external cephalic version by a low pre-version pulsatility index of the fetal middle cerebral artery. Ultrasound Obstet Gynecol. 2006;27(4):416-419
  • [73] H. Lam, W.C. Leung, C.P. Lee, T.T. Lao. The use of fetal Doppler cerebroplacental blood flow and amniotic fluid volume measurement in the surveillance of postdated pregnancies. Acta Obstet Gynecol Scand. 2005;84(9):844-848
  • [74] D. Kassanos, C. Siristatidis, N. Vitoratos, E. Salamalekis, G. Creatsas. The clinical significance of Doppler findings in fetal middle cerebral artery during labor. Eur J Obstet Gynecol Reprod Biol. 2003;109(1):45-50
  • [75] J. Wladimiroff, J. vd Wijngaard, S. Degani, M. Noordam, J. van Eyck, H. Tonge. Cerebral and umbilical arterial blood flow velocity waveforms in normal and growth-retarded pregnancies. Obstet Gynecol Clin N Am. 1987;69(May (5)):705-709
  • [76] P. Devine, L. Bracero, A. Lysikiewicz, R. Evans, S. Womack, D. Byrne. Middle cerebral to umbilical artery Doppler ratio in post-date pregnancies. Obstet Gynecol. 1994;84(November (5)):856-860
  • [77] D. Habek, B. Hodek, R. Herman, D. Jugović, J. Cerkez Habek, A. Salihagić. Fetal biophysical profile and cerebro-umbilical ratio in assessment of perinatal outcome in growth-restricted fetuses. Fetal Diagn Ther. 2003;18(January–February (1)):12-16
  • [78] C. Siristatidis, D. Kassanos, G. Salamalekis, M. Creatsa, C. Chrelias, G. Creatsas. Cardiotocography alone versus cardiotocography plus Doppler evaluation of the fetal middle cerebral and umbilical artery for intrapartum fetal monitoring: a Greek prospective controlled trial. J Matern-Fetal Neonat Med. 2012;25(7):1183-1187 PubMed PMID: 21916811
  • [79] T. Prior, E. Mullins, P. Bennett, S. Kumar. Prediction of intrapartum fetal compromise using the cerebroumbilical ratio: a prospective observational study. Am J Obstet Gynecol. 2013;208(2) 124.e1–6
  • [80] E. Blix. The admission CTG: is there any evidence for still using the test?. Acta Obstet Gynecol Scand. 2013;92(6):613-619
  • [81] T. Prior, E. Mullins, P. Bennett, S. Kumar. Prediction of fetal compromise in labor. Obstet Gynecol Clin N Am. 2014;123(June (6)):1263-1271
  • [82] R. Gill, G. Kossoff, P. Warren, W. Garrett. Umbilical venous flow in normal and complicated pregnancy. Ultrasound Med Biol. 1984;10(May–June (3)):349-363
  • [83] S. Boito, P.C. Struijk, N.T.C. Ursem, T. Stijnen, J.W. Wladimiroff. Umbilical venous volume flow in the normally developing and growth-restricted human fetus. Ultrasound Obstet Gynecol. 2002;19(4):344-349
  • [84] G. Lingman, J. Laurin, K. Marsál. Circulatory changes in fetuses with imminent asphyxia. Biol Neonat. 1986;49(2):66-73
  • [85] G.S. Ghosh, J. Fu, P. Olofsson, S. Gudmundsson. Pulsations in the umbilical vein during labor are associated with increased risk of operative delivery for fetal distress. Ultrasound Obstet Gynecol. 2009;34(2):177-181
  • [86] T. Prior, E. Mullins, P. Bennett, S. Kumar. Umbilical venous flow rate in term fetuses: can variations in flow predict intrapartum compromise?. Am J Obstet Gynecol. 2014;210(January (1)):61
  • [87] M.R. Johnson, A.F. Riddle, J.G. Grudzinskas, V. Sharma, W.P. Collins, K.H. Nicolaides. Reduced circulating placental protein concentrations during the first trimester are associated with preterm labour and low birth weight. Hum Reprod. 1993;8(November (11)):1942-1947 PubMed PMID: 7507132. Epub 1993/11/01.eng
  • [88] S. Uccella, G.F. Colombo, C.M. Bulgheroni, et al. First-trimester maternal serum screening and the risk for fetal distress during labor. Am J Obstet Gynecol. 2009;201(2) 166.e1–6
  • [89] D. MacDonald, J. Scott, R. Gemmell, D. Mack. A prospective study of three biochemical fetoplacental tests: serum human placental lactogen, pregnancy-specific beta 1-glycoprotein, and urinary estrogens, and their relationship to placental insufficiency. Am J Obstet Gynecol. 1983;147(October (4)):430-436
  • [90] S.J. Benton, Y. Hu, F. Xie, et al. Can placental growth factor in maternal circulation identify fetuses with placental intrauterine growth restriction?. Am J Obstet Gynecol. 2012;206(2) 163.e1–7
  • [91] A. Conde-Agudelo, A.T. Papageorghiou, S.H. Kennedy, J. Villar. Novel biomarkers for predicting intrauterine growth restriction: a systematic review and meta-analysis. BJOG: Int J Obstet Gynaecol. 2013;120(6):681-694
  • [92] R.J. Levine, S.E. Maynard, C. Qian, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672-683 PubMed PMID: 14764923
  • [93] H. Stepan, T. Krämer, R. Faber. Maternal plasma concentrations of soluble endoglin in pregnancies with intrauterine growth restriction. J Clin Endocrinol Metab. 2007;92(July (7)):2831-2834
  • [94] C.L. Whitehead, W.T. Teh, S.P. Walker, C. Leung, L. Larmour, S. Tong. Circulating microRNAs in maternal blood as potential biomarkers for fetal hypoxia in-utero. PLOS ONE. 2013;8(11):e78487

Footnotes

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

Corresponding author at: Mater Research Institute/University of Queensland, Level 3, Aubigny Place, Raymond Terrace, South Brisbane, Queensland 4101, Australia. Tel.: +61 7 31632564.