CLINICAL REVIEW

I. Amer-Wahlin Æ B. Yli Æ S. Arulkumaran

Foetal ECG and STAN technology—a review

Received: 18 March 2005 / Accepted: 18 May 2005 / Published online: 17 June 2005� European Board and College of Obstetrics and Gynaecology 2005

Abstract Waveform analysis of the foetal electrocar-diogram (FECG) has been studied from physiological,signal processing and clinical aspects. Two randomisedcontrolled trials (RCT) have been performed during thelast 20 years, monitoring high-risk labours with cardi-otocography (CTG) only or combining CTG with theST waveform analysis of the FECG. A significant de-crease in neonates born with metabolic acidosis in cordartery blood was observed, along with a decrease ofoperative deliveries for foetal distress. Blinded assess-ment of neonatal outcome in the latest RCT revealed animprovement of the Apgar score and the need forintensive care and neonatal encephalopathy whenmonitoring with CTG in combination with FECG. Also,the interobserver agreement for ST analysis was higherthan for CTG alone. The system ability of the STANtechnology, including an educational model, was studiedin several European University clinics as an EU-sup-ported project. During the last 6 months, the projectconfirmed the incidence of metabolic acidosis (0.64%)and moderate/severe encephalopathy in the earlier RCTon using ST information in addition to CTG. Theavailable evidence suggests that the expected outcomecould be achieved in most clinics, with a special focus onsystematic teaching and training. Compared to STanalysis, foetal blood sampling (FBS) for pH analysis istechnically complicated and, because it only presentsmomentary information, needs to be repeated to giveadequate information. The STAN method providescontinuous on-line information. ST waveform analysis

in addition to CTG has the potential to give significantbenefits in reducing operative deliveries for foetal dis-tress and reducing the incidence of metabolic acidosis.However, this will depend on the appropriate educationand use of STAN according to the guidelines provided.

Keywords Foetal ECG Æ Cardiotocography ÆIntrapartum monitoring Æ Review

Introduction

Electronic foetal monitoring (EFM) is an importantobstetric tool and a generally accepted method for foetalsurveillance during pregnancy and labour. It has con-siderably improved our knowledge about the foetalcondition throughout gestation and, in particular, dur-ing labour. In the UK, EFM is recommended for foetalsurveillance of high-risk pregnancy in labour by theNational Institute of Clinical Excellence (NICE 2001).However, NICE does not recommend EFM monitoringof low-risk pregnancies, since there is no evidence ofbenefit in terms of the reduction of perinatal mortality ormorbidity [1]. This is mainly due to insufficient numbersin the trials to show reductions in these parameters,which have an extremely low incidence. According to theAmerican College of Obstetricians and Gynecologistshttp://www.acog.com/, EFM is no longer a requiredstandard for a high-risk patient, and the ACOG statesthat EFM does not have any benefit over auscultation.

The Dublin randomised controlled trial (RCT) offoetal heart rate (FHR) monitoring [2] was conductedon a large number of normal deliveries by conventionalstandards and did not show any difference in perinatalmortality between electronic monitoring and intermit-tent auscultation. Long-term follow-up [2] did not showany difference in outcome at 4 years of age [3]. However,it should be pointed out that, in the Dublin trial, car-diotocography (CTG) was introduced as a new moni-toring method into the hospital only a few months

I. Amer-Wahlin (&)Department of Obstetrics and Gynaecology,University Hospital, 221 85 Lund, SwedenE-mail: isis.amer-wahlin@gyn.lu.se

B. YliDepartment of Obstetrics and Gynaecology,Rikshospitalet University Hospital, Oslo, Norway

S. ArulkumaranDepartment of Obstetrics and Gynaecology,St. Georges Hospital, London, UK

Eur Clinics Obstet Gynaecol (2005) 1: 61–73DOI 10.1007/s11296-005-0017-2

before the RCT began, which raises questions about thestaff’s experience with this technique [4].

Nevertheless, EFM is applied in 75% of deliveries [5],and there is evidence to show that the operative deliveryrates are significantly increased with the use of EFM,especially if foetal scalp blood sampling (FBS) is notused as an adjunct to establish the foetal condition [1].The fourth ‘‘Confidential enquiry into stillbirths anddeaths in infancy (CESDI)’’ analysed the intrapartumdeaths that were due to asphyxia in babies greater than1,500 g with no chromosomal or congenital malforma-tion [6]. The conclusion was that 50% of the deathscould have been avoided if an alternative care wasprovided. The reasons identified for the poor outcomeswere; inability to interpret CTG recordings, failure toincorporate the clinical picture, delay in taking appro-priate action and poor communication. This is not en-tirely surprising, since the model of FHR interpretationis largely based on empirical observations of thousandsof hours of recordings during human labour [7]. Largeintraobserver and interobserver differences in the inter-pretation of CTG recordings have been reported and,apparently, even amongst experts [8–12]. Intelligentcomputer systems to increase consistency in the inter-pretation of CTG recordings have been suggested [13].However, even with consistent manual interpretation,the observations most associated with cerebral paresis(CP) in EFM, such as late decelerations and decreasedbeat-to-beat variability, have a false positive rate of99.8% [3, 14].

The high frequency of non-reassuring patterns onEFM with interventions that lead to normal neonataloutcomes makes optimal management of labour diffi-cult. This ongoing debate about the effectiveness ofmonitoring to predict adverse foetal outcome [15–17]without increasing the operative delivery rates hasstimulated researchers and clinicians to identify andevaluate other forms of assessment. Computerisedanalysis of the waveform of foetal electrocardiograms(FECG), when used as an adjunct to FHR tracing,identifies the foetus that is likely to be compromisedand helps to reduce morbidity and reduce operativeinterventions when compared to EFM by CTG alone[18, 19].

The foetal electrocardiogram

The foetal ECG reflects the summation of electricalevents within the myocardial cells as seen from the bodysurface [20]. Electrical changes seen on the surface occurin relation to changes in action potentials in the ven-tricular myocardium over time. In normal healthymyocardium, the cells are in a polarised state (i.e. equalnumber of positive and negative charges) during diastolewith an accumulation of positive charges, which is bal-anced by an equal number of negatively charged ions,electrons extracellularly. This is the normal resting stateuntil depolarisation occurs. At this point, the distribu-

tion of negative and positive charges is reversed by aself-propagating wave from cell to cell through a ‘‘bat-tery condition’’; if the outer cell is positive and itsadjacent cells are negative, a local current will flow. TheP and QRS waves (Fig. 1) are the resulting electricalactivity produced by the propagation of the depolar-isation wave. The T wave represents the time differencebetween the repolarisation of different parts of themyocardium.

The sino-atrial node controls the action of the heartand the cells in this node are controlled by vagal andsympathetic nerves, as well as chemically. The P waveconfiguration and time constants are affected by changesin the autonomic nervous system controlling part of theheart pump function.

The P wave of the ECG (Fig. 1) corresponds to thecontraction of the atrium. The next sequence is thecontraction of the ventricles, represented by the wavesQ, R and S. The generation of these waves is a passiveevent and are, thus, very stable and easily detected,which makes it well suited for FHR measurements.

Pathophysiology of foetal electrocardiogram changesand experimental studies

Hypoxia may cause an alteration in the P–R time with aPR shortening in spite of an RR lengthening, but this ismore related to the foetal heart attempting to preservean optimal filling of the atrium in situations of a de-crease in blood returning to the heart [21–23].

The ST segment and T wave relate to the repolari-sation of myocardial cells in preparation for the nextcontraction. This repolarisation process is energy con-suming. An increase in T wave height occurs when theenergy balance within the myocardial cells is threatened.During hypoxia, this balance becomes negative and thecells produce energy by the b-adrenoceptor-mediatedanaerobic breakdown of glycogen reserves. This processnot only produces lactic acid, but also potassium ions(K+) [24], which affect myocardial cell membrane po-tential and cause a rise of the ST waveform.

When the energy balance cannot be maintained byvasodilatation or anaerobic metabolism, ischemia occurs

Fig. 1 Electrocardiogram

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in the endocardium [25]. This will alter the sequence ofrepolarisation, changing myocardial cell potentials and,thus, the direction of the current flow. A depression of STwith or without negative T wave will occur (Fig. 2) [26].

Pathophysiology of foetal electrocardiogram changes

Rosen and Kjellmer [28] observed progressive changes inthe ST interval prior to the bradycardia in the foetalECG tracings in experimental hypoxia.

The maintenance of foetal myocardial function andsurvival during hypoxia depends on myocardial glyco-genolysis, as described by Dawes et al. [29]. Withincreasing glycogenolysis, there is a further increase in Twave amplitude [30] and the correlation has been de-scribed as linear [25].

The ST waveform can be assessed qualitatively by itsshape, and quantitatively by the height of the T wave inrelation to the height of QRS (T/QRS ratio). Greene et al.[31] found a correlation between high T/QRS with per-sistently elevated ST waveforms and anaerobic metabo-lism in chronically instrumented lambs. The ST changesmay also occur by the general surge of stress hormones(adrenaline) occurring in response to labour [32–34].

The shape of the ST waveform can change, giving abiphasic ST [35], i.e. an ST segment sloping downwards

to become negative, followed by an initially lowered Twave, which turns positive in relation to the baseline.The physiology behind biphasic ST events is related tothe mechanical performance of the myocardium and therelationship between the inner (endocardium) and outer(epicardium) layers of the walls of the ventricles inparticular (Fig. 3).

Biphasic ST illustrates an imbalance between thesetwo layers: the perfusion pressure of the endocardium isalways the lower at the same time as the mechanicalstrain is always the larger. This means that, unless themyocardium is generally activated (b-receptor activationand enhanced Frank–Starling relationship, i.e. the abil-ity of the myocardium to respond to volume load), anydecrease in performance will cause biphasic ST. Thus,not only hypoxia, per se, may cause biphasic ST as a signof mal-adaptation, but also, basically, all factors sub-stantially altering the balance and the performancecharacteristics within the myocardial wall may institutethese events (prematurity, infections, maternal fever,myocardial dystrophy, cardiac malformations [37]).

In adults, ST depression with T wave elevation (abiphasic ST waveform) is also seen in myocardialischemia, and may represent an earlier stage in thedevelopment of myocardial ischemic hypoxia whenthe action potential change is not uniform throughoutthe myocardium. It is used to diagnose myocardialinfarction or coronary insufficiency [38]. The lesions aregenerally focal and occur in an otherwise intact indi-vidual. The foetus, on the other hand, is exposed toextraordinary alterations in its demand of pumpingblood, due to intermittent reductions in placenta bloodflow. Anything reducing myocardial performance underthese circumstances carries a risk of failing cardiovas-cular function and hypoxia.

QRS and ST

In the late 1960s, Gennser and Nilsson [39] and Gelliand Gyulai [40] made attempts to characterise FECGFig. 2 Hypoxia and ST change [27]

Fig. 3 Biphasic ST fromWidmark [36]

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changes in humans and animals. Their studies showedthe lengthening of the PR and QT intervals, as well asST segment and T wave inversion in 50% of theasphyxiated animals.

Several experimental studies during the 1970s ob-served that hypoxia with acidaemia caused a progressiveincrease in the amplitude of the ST waveform in theexteriorised foetal lamb [28, 41–43]. An improvement ofthe signal processing and computer technology tookplace in this period and a group in Gothenburg, Swedenconcentrated on the ST waveform configuration and theT wave height.

They reported a strong correlation between theT/QRS ratio and the depletion of myocardial glycogenand creatinine-phosphate [30], and between the T/QRSratio and lactate rise [31]. Later, Hokegard et al. [25]demonstrated a strong correlation between the increasein T wave amplitude during hypoxia and the rate ofmyocardial glycogenolysis, as measured by a decrease inmyocardial glycogen creatinine-phosphate and adeno-sine triphosphate measured on serial biopsies from thehearts of foetal lambs.

Greene et al. [31] showed that, despite similar falls inpO2, one group of lambs displayed little change in STwaveform or lactate, while another group had markedST elevations that were related to the rate of lactateaccumulation. Lilja et al. [44] describe a linear correla-tion between cord venous blood lactate and T/QRS ra-tio. The authors also reported marked T wave and STsegment changes in relation to bradycardia and variabledecelerations. High catecholamine levels during hypoxiawere observed in foetuses with lactate and ST waveformchanges [45]. This was explained as a failure to com-pensate for hypoxia with increased blood flow and aswitch to anaerobic metabolism. Dagbjartsson et al. [46]found a correlation between T/QRS ratio increase andmyocardial workload in exteriorised lambs. Watanabeet al. [47] reported a correlation between the degree ofST elevation and the development of foetal acidosisduring repetitive cord occlusion in chronic foetal sheeppreparations.

The integrity of the CNS along these ECG changeswas assessed using somatosensory-evoked EEG re-sponses. The result indicated that the mature lamb foe-tus maintained its central nervous system integrity untilthere were signs of cardiovascular collapse and that STwaveform changes were associated with intact foetalcortical activity and preceded foetal death by hours [48].

During intrauterine asphyxia, hypoxia by itself ex-erts a depressant effect on myocardial functions. Thefoetus as a whole is dependent on the ability of theheart to perform, despite this depressant influence.b-adrenoceptor activation becomes a key to prevent areduction in myocardial performance. From the studieson the influence of exogenous b-mimetics [46], it ap-pears as if the b-receptor population may increase itssensitivity to b-receptor activation during mild andmoderate hypoxia. Mild hypoxia may induce STchanges by b-receptor activation, whilst severe hypoxia

may have a more direct effect on myocardial cells. Thisability may be reduced in growth-retarded foetuses.Widmark et al. [49] studied growth-retarded guineapigs and observed ST depression with or without neg-ative T waves, while the normally grown animalsshowed ST elevation (Fig 4). The controls showedhigher levels of catecholamines compared to thegrowth-retarded foetuses, probably because of depletedglycogen reserves—a direct sympathoadrenal responseto hypoxia and, consequently, ineffective myocardialanaerobic metabolism.

Recently, Westgate et al. [35] reported on ST wave-form changes during repeated umbilical cord occlusionsin near-term foetal sheep. They describe a progressivelyincreasing T/QRS ratio with increasing degree of hy-poxia by reducing the interval between cord occlusionsfrom 5 min to 2.5 min. The authors concluded that anincrease in T/QRS ratio indicates hypoxic stress and thatthe appearance of biphasic and negative ST waveformsbetween contractions may be a useful marker of devel-oping severe foetal decompensation.

Foetal electrocardiogram analysis in human parturition

The foetal ECG was demonstrated for the first time byCremer [50], only a few years after the first adult ECGregistration by Einthoven [51].

During the following 20 years, few papers appearedon FECG registered with abdominal leads. In the 1950s,major technical advances were made in characterisingtime intervals of the FECG. Experimentally observablechanges in cardiac function stimulated an interest in thepossibility of identifying critical hypoxia in humans. Atthis point, further research divided into two pathways;one pathway focussing on FHR, which was becomingthe standard part of intrapartum monitoring, the otherpathway was the development of technology for con-tinuous evaluation of the FECG waveform.

Fig. 4 ECG changes in normal and growth-retarded guinea pigfoetuses from Widmark [36]

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Hon and co-workers [52, 53] introduced a scalp clipfor direct application to the foetus and performed sev-eral technically very advanced computer-based studies.They managed to greatly improve the signal-to-noiseratio. Larks and co-workers [54, 55] studied the foetalQRS complex through abdominal leads and performed aclinical study with 84 subjects, suggesting that changes inthe ST segment could be a sign of unfavourable foetalenvironment.

Pardi et al. [56] studied 234 labours and observedshortened PQ intervals and biphasic or absent P wavesin relation to variable decelerations. Marvell et al. [57],Lilja et al. [44] and Jenkins et al. [58] further developedthe technology and registered the FECG by foetal scalpelectrode.

Further larger observational studies were then per-formed with computerised analysis of the ST waveform.The system used was a processor system for ST wave-form analysis, filtering the signal for waveform analysisbetween 0.05 Hz and 100 Hz at a sampling frequency of500 Hz with 8-bit resolution [59].

The electrode lead configuration used is differentfrom that used by a conventional CTG recorder. Amaternal skin electrode is used as a reference electrode inorder to standardise the T wave vector to be unaffectedfrom foetal rotation [60]. The mean T/QRS ratio wasfound to remain relatively stable throughout labour andwas, therefore, the main issue in FECG recording [61,62]. Further studies suggested that the combination ofCTG and ST analysis would be superior to the T/QRSratio alone [63]. Rosen et al. [59, 64] reported on nega-tive ST changes in association with CTG changes.

Arulkumaran et al. [63] reported good signal qualityin 77% of registrations and found three cases of as-phyxia among 201 cases monitored by CTG and STanalysis, of which all had acute ST changes, CTGabnormalities and low Apgar scores at delivery. Johan-son et al. [65] observed that a T/QRS ratio >0.25 cor-rectly identified 2 out of 3 foetuses with scalp bloodmetabolic acidosis, the third having poor signal quality.Murphy et al. [66] published a descriptive study ofFECG in 86 pregnancies and found no correlation be-tween T/QRS and Apgar score, but a weak correlationwith cord artery base deficit (BD).

The method was further evaluated in a large RCT,comparing intervention rates and neonatal outcome in

labours monitored with CTG alone to those monitoredwith the combination of ST waveform analysis plusCTG [18]. In 2,434 cases, STAN 8801 (Cinventa Medi-cal, Molndal, Sweden) was used and a 43% reductionwas observed in operative interventions for foetal dis-tress in the ST+CTG group. The odds ratio was 1.96[95% CI=1.42–2.71] (p<0.001) for intervention in theCTG only group as compared to the CTG+ST group.There was also a trend towards the reduction of meta-bolic acidosis (p=0.09, odds ratio=0.38 [95%CI=0.13–1.07]) and fewer low-5-minute Apgar scores(p=0.12, odds ratio=0.62 [95% CI=0.35–1.08]) in theST waveform plus CTG.

This study indicated that the ST waveform coulddiscriminate significant CTG changes during labour,thus, improving the specificity of intrapartum monitor-ing. The trial also observed that current intrapartumCTG monitoring relies on subjective interpretation ofthe available information, illustrating the need to im-prove data presentation, preferably by providing con-tinuous assessment of significant ST events.

Computerised ST waveform analysis with the event log

Continuous computerised surveillance of the ECGwaveform was made possible with improvements intechnology. This was presented as an ST log function,providing direct statements on specific ST events(Table 1) and their change over time rather than a spe-cific T/QRS value. This development was tested in theEuropean community multicentre trial on ECG analysisduring labour [67].

Further improvements in signal processing occurredand a descriptive study in 12 Nordic labour wards wasperformed to test the sensitivity and specificity of the STclinical guidelines [68]. About 574 cases were recordedusing a prototype of the STAN S21 recorder with foetalECG data stored for subsequent computerised STanalysis. The STAN clinical guidelines were used tocombine the analysis of CTG and ST waveform changesand guide intervention. The clinical results with the newtechnology suggested that computerised ST waveformanalysis showed promise, and this set the scene forRCTs.

Table 1 ST changes indicating clinical intervention (ST waveform guidelines) - with preterminal CTG, intervention is indicated regardlessof ST

CTG

Suspicious Abnormal

ST changesEpisodic T/QRS rise <10 min) Increase >0.15 from baseline Increase >0.10 from baselineBaseline T/QRS rise ‡10 min) Increase >0.10 from baseline Increase >0.05 from baselineBiphasic STa Continuous (>5 min) or >two episodes

of coupled biphasic STContinuous (>2 min) or >one episodeof coupled biphasic ST

a ST segment depression with a component of the ST segment below the baseline of ECG

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Randomised controlled trials using the ST event log

The Swedish RCT (SRCT) [19] was then performed inthree Swedish labour wards with the main aim to im-prove neonatal outcome using cord artery metabolicacidosis as a marker of adverse situations. Metabolicacidosis was defined according to the consensusregarding the basic requirements for diagnosis of intra-partum asphyxia [14]. In this document, cord metabolicacidaemia is defined as pH<7.00 and BD‡12 mmol/L,indicative of intrapartum asphyxia.

Women with term foetuses in cephalic presentationentered the trial during labour after a clinical decision toapply a foetal scalp electrode for internal CTG record-ing. They were randomised to monitoring withCTG+ST analysis or CTG only (n=4,996).

Table 2 gives the outcome with regards to the pri-mary aim of the trial, a >50% reduction in cord arterymetabolic acidosis. Furthermore, when basic recom-mendations on how to use the device were fol-lowed—starting a recording in the first stage of labourand maintaining data collection within 20 min of deliv-ery (adequate recordings)—further improvements werenoted, indicating the relevance of these recommenda-tions.

During the second phase of the trial, after interimanalysis and retraining (due to protocol violations), areduction in cord artery metabolic acidosis from 1.48%to 0.50% was noted (odds ratio=0.33, p=0.045) [69].However, the size of the trial also allowed an assessmentof outcome related to monitoring among the 351 neo-nates that were admitted to the neonatal intensive careunit (NICU) (Table 3) [70].

Probable intrapartum asphyxia was identified in 29neonates, moderate to severe encephalopathy was sig-nificantly more frequent in neonates monitored by CTGonly (odds ratio=0.12, 95% CI=0.01–0.94).

The SRCT also showed a significant reduction inoperative delivery for foetal distress (ODFD) from 9.3%to 7.7% (odds ratio=0.83, 95% CI=0.69–0.99,p=0.047) [19]. The ODFD rates related to the twophases of the trial showed a greater reduction in oper-ative interventions during the second phase with greaterexperience and the introduction of structured case dis-cussions [69].

The outcome of the two RCTs has also been thesubject of a recent Cochrane Review [71]. The conclu-sion was that the data support the use of foetal STwaveform analysis when a decision has been made toundertake continuous electronic FHR monitoring dur-ing labour.

Need for education and training

The issue of providing a model for the dissemination ofknowledge and training is important with any newtechnology, something that did not occur with theintroduction of CTG [72]. The system ability of theSTAN technology, including an educational model, as anevery day tool at the delivery department was studied inseveral European University clinics between June 2000and June 2002 as an EU-supported project. This wasperformed through provision of a specific educationalmaterial package and regional workshops [73]. Thematernity units were equipped with STAN S21 units. Allcentres had an educational process of 2–3 months. Atotal of 7,823 cases were recorded. The technology wasused in term high-risk pregnancies in active labour withan indication for foetal monitoring with a scalp electrode.

Among the 6,303 cases recorded with cord acid basedata available, 63 cases had cord metabolic acidosisdefined as umbilical artery pH<7.05 and BDECF>12 mmol/L. Of these 63 cases, 15% did not showSTAN changes (8% did not have adequate data), 5%

Table 2 Cord artery metabolic acidosis rates in the SRCT on CTG versus CTG+ST

Mode of analysis STAN Control Odds ratio, 95% CI, p-value

Intention to treat 15 (0.69%) 31 (1.49%) 0.46, [0.25–0.86], 0.02No of cases 2,159 2,079Adequate recordingsa 11 (0.57%) 27 (1.44%) 0.39, [19–0.79], 0.01No of cases 1,926 1,871

aAdequate recordings=starting in first stage of labour and maintaining data collection within 20 min of delivery [19]

Table 3 Neonatal outcomeexcluding lethal malformations

a Asphyxia, neonatal deathb One sepsis, neonatal death,one asphyxia, death intra par-tumData modified from Norenet al. [68]

CTG(n=2,447)

CTG+ST(n=2,519)

Total(n=4,966)

Perinatal death 1a 2b 3Neonatal symptoms:Neuromuscular symptomsSeizures 3 0 3Increased neuromuscular tone 4 0 4Irritability only 1 3 4Metabolic acidosis and other symptoms 10 5 15Total 19 10 29

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had a preterminal CTG and 72% displayed ST changeswith a median time to delivery of 25 min (95% CI=19–35 min). About 70% of the cases had a normal Apgarscore at 5 min (‡7). Nine cases were born with cordartery metabolic acidosis and Apgar score <5, requiringspecial neonatal care. All had STAN events indicatingabnormality for 25 min or more, except one case withfoetal bleeding.

During the last 6 months, the project confirmed theincidence of metabolic acidosis (0.64%) and moderate/severe hypoxic ischemic encephalopathy (HIE) in theSRCT on using ST information in addition to CTG [35,74].

The available evidence suggests that the expectedoutcome could be achieved in most clinics, with specialfocus on systematic teaching and training. This includesthe need to follow strict criteria when interpreting CTGtraces. Although guidelines are provided for the inter-pretation of CTG, it is not always easy in clinicalpractice. In all the mentioned studies, CTG guidelines(Table 4) were used and have, thus, been tested forefficacy along with the ST waveform guidelines (Ta-ble 1). During the SRCT, the centre with the greatesttradition of CTG education obtained the greatest dif-ference between the two study groups, proving that thequality of CTG interpretation is of major importancewhen working with the STAN technology. This high-lights the need for consistency in CTG interpretation.

Dervaitis et al. [76] aimed at determining the abilityof the technology in a North American setting in rela-tion to the prediction of metabolic acidaemia (defined asan umbilical cord artery pH<7.15 and BD‡12 mmol/L)at birth. Attending physicians were blinded to the STanalysis information, using only available EFMaccording to current clinical practice. After delivery, twotrained observers blinded to neonatal outcome and STanalysis information performed visual classification ofthe EFM tracing in 10-min epochs according to FIGO

guidelines. ST events automatically detected by theSTAN S21 monitor (Neoventa Medical) were thencombined with the visual EFM classification as perSTAN clinical guidelines (Neoventa Medical).

The study cohort consisted of 176 women and only143 gave adequate recordings.

When applying STAN clinical guidelines from asample of 143 women, the data indicated a sensitivity of43%, specificity of 74%, negative predictive value of96% and a positive predictive value of 8% for metabolicacidaemia at birth. Poor ECG quality, despite goodEFM tracings (ECG signal loss), occurred 11% of thetracing time. This may be due to the use of standardscalp electrodes. Specially designed electrodes (Gold-trace) should give better continuous records.

The study was set up with ST blinded to the staffduring the recording and the analysis was done retro-spectively (blinded to clinical information). According toSTAN guidelines, the approach to STAN events in thefirst stage and second stage of labour is different. Only inthe second stage of labour do the STAN guidelinesrecommend immediate delivery in case of a significantST event in combination with a non-reassuring FHR.The result of an analysis taken out of the clinical rela-tions is a risk of increasing the rate of STAN indicationsto intervene. In this study, the rate of indication tointervene was 27%, which is twice as high as in TheNetherlands study [77] describing The Netherlands’experience in the EU project. In that study, 449 caseshad data available for the analysis of outcome in rela-tion to ST changes.

Finally, the main aim of the Canadian trial was toimprove neonatal outcome using cord artery metabolicacidosis as a marker of adverse situations and theyconclude that STAN has a poor positive predictive valueand a sensitivity of less than 50% for metabolic acida-emia at birth. However, they define metabolic acidosis aspH<7.15 and standard BD‡12 mmol/L. Standard BD

Table 4 Interpretation of the CTG

CTG characteristics

Baseline heart rate Variability, reactivity Decelerations

CTG classificationNormal 110–150 bpm 5–25 bpm

Accelerations presentEarly decelerationsUncomplicated variabledecelerations with duration<60 s and loss <60 bpm

Suspicious 100–110 bpm150–170 bpmShort episode of bradycardia<100 bpm

>25 bpm withoutaccelerations<5 bpm for >40 min

Uncomplicated variable decelerationswith duration <60 s and loss >60 bpm

Abnormal >170 bpmPersistent bradycardia <100 bpmCombination of severalcharacteristics of suspicious CTG

<5 bpm for >60 minSinusoidal pattern

Complicated variable decelerationswith duration >60 s

Preterminal Total lack of variability and reactivitywith or without decelerationsand/or bradycardia

Modified from the FIGO guidelines [75]

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will overestimate metabolic acidosis in case of highpCO2. Accumulation of pCO2 is part of a normaldelivery, and, thus, BD calculated as the buffer distri-bution of the extra cellular fluid (ecf) should be used [78,79]. A low cord pH, per se, will reflect an accumulationof pCO2 and the metabolic component will onlymarginally contribute. This is the explanation whyneonates manage very well, in spite of low pH readingsfrom cord blood samples.

The Canadian authors recognise this and state thatnone of their cases met the criteria of metabolic acidosisused at SRCT. This makes a discussion of sensitivity/specificity in relation to previously published studiesimpossible.

Foetal scalp blood sampling, STAN or both?

The effectiveness of FBS in clinical practice has beenquestioned. In the Plymouth trial, despite the use of astrict protocol, 39% of cases had FBS performedunnecessarily, and 33% of cases did not have it per-formed when it was indicated [80]. The decision to useFBS depends on the CTG interpretation. If the level ofCTG interpretation is suboptimal, the value of moni-toring with FBS is limited [81].

Olofsson [74] discusses this matter observing that, inthe SRCT, FBS was performed in 10.7% of cases in theCTG group and in 9.3% of cases in the CTG+ST group(RR=0.87, 95% CI=0.74–1.03; p=0.12) [19]. In thesecond part of the study, after the interim analysis andre-training, the corresponding figures were 11.8% vs.8.9% (p=0.02). The difference is not statistically sig-nificant, but could indicate that, along with acceptanceof STAN, there is a need for FBS to confirm a falsepositive CTG trace in the absence of an ST event.

In a recently completed analysis of FBS in the EUdatabase with 6,999 term deliveries [82], FBS was per-formed in 911 cases (13%). Fifty-three cases were bornwith cord acidaemia (pH<7.06) where FBS was ob-tained, corresponding to only 5.8% of all cases withFBS. Luttkus et al. [82] describe that, of the 20 caseswith metabolic acidosis, 19 had adequate STAN infor-mation. One case with adequate data out of these 19cases was not identified by STAN giving a sensitivity of95%. Among the 20 cases with metabolic acidosis, 11had FBS obtained after STAN guidelines had identifiedabnormality. In eight of these cases, a progressive rise inT/QRS baseline occurred. A close negative linear rela-tionship was noted between the time of a significant T/QRS rise and scalp pH (r= �0.73, p=0.004), showing adecrease by 0.01 units for every minute of the scalp pHduring the second stage of labour.

Of the 33 cases with respiratory acidaemia, 29 hadadequate STAN recordings, out of which, 25 cases(86.2%) were identified as in need of intervention. Thecorresponding figure for CTG+FBS was 18 cases withFBS, obtained within 60 min of delivery, out of which,12 cases had an FBS with a pH of <7.20 (66.7%).

Differences between FBS and ST analysis relate lar-gely to the availability of information. One of the knownshortcomings of FBS in that it is not used when requiredand it is used when not required [80]. The FBS proce-dure is technically complicated and time-consuming and,because it only presents momentary information, needsto be repeated to give adequate information. The STANmethod provides continuous on-line information aboutthe foetal status. Due to the low incidence of metabolicacidosis at birth, extraordinary efforts would be neededto perform a study comparing FBS and STAN to resolvethe question on whether CTG+ST can replace FBS.Such a comparison can only be made if the acquaintanceof both methods is equal. Meanwhile, only opinionsbased on observational data are available.

According to the documentation available, the use ofFBS in addition to CTG+STAN provides additionalinformation in:

– Cases where the recording started with persistentlyabnormal CTG patterns when ST is normal. Since welack previous information, foetal resources are un-known. FBS could also be a support feature duringthe training phase.

– Verification of recovery after a significant FHR+STevent in the first stage of labour. At least 20 minshould pass before the FBS is obtained.

Interobserver agreement and sensitivity

In a recently published study, Ross et al. [83] tested thehypothesis that additional ST waveform analysis tostandard FHR improves the consistency and accuracy ofclinical decision making, specifically, obstetric interven-tion during labour.

Seven STAN users, who were trained and experi-enced in combined FHR and ST monitoring, reviewed51 foetal monitor tracings (Fig. 5), ranging from 2 h to4 h in length, containing healthy and compromised termfoetuses from an extensive clinical archive. The review-ers had no information on the outcome when assessingthe cases. Among the 51 cases, nine had cord arterypH<7.05, ten cases had cord artery pH=7.05–7.14 and32 cases had cord artery >7.15.

Reviews were conducted in two sessions and at dif-ferent times. The first session presented only the FHRand uterine contraction information, following which,the participants determined the time at which interven-tion (decision for operative vaginal or caesarean sectiondelivery) was indicated. In the second session, the par-ticipants were provided with a randomised sequence ofthe same tracings with the addition of ST segmentinformation, as produced by the STAN monitor system(Neoventa Medical, Gothenburg, Sweden). Observeragreement was based on the proportion of participantswho agreed on the need for an intervention and theagreement on the timing of the intervention within20 min before or after the median time of intervention.

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Observer agreement increased significantly forrequired intervention when the ST segment informationwas available for tracing analysis as compared with a re-view of the standard tracing alone (0.96 vs. 0.80, p<0.05)and the timing of intervention (0.92 vs. 0.66, p<0.05).Similarly, correct identification of an indication to inter-vene on foetuses with abnormal outcomes increased from86% to 93%, while unneeded interventions on normalfoetuses decreased from 43% to 6% (Ross et al. [83]).

Recently, the recordings from neonates with meta-bolic acidaemia at birth and controls in the SRCT werecompared [84]. The aim was to identify the rates ofabnormal ST segment patterns of the ECG and CTGabnormalities.

Two obstetricians independently assessed the CTGand ST traces of 41 foetuses with metabolic acidaemia atbirth and 101 controls, blinded to the group, outcomeand all clinical data in the SRCT. The interobserveragreement in the interpretation of the ST analysis andCTG was evaluated, as well as rates of CTG and STabnormalities and decisions to intervene.

CTG was classified as abnormal in 50% of acidaemiccases and 20% of controls. It was judged to be anindication for intervention in 45% of cases with acida-emia and 15% of controls. ST events occurred in 63% ofcases with acidaemia and in 34% of controls, and theguidelines indicated intervention in combination withthe CTG in 56% of cases with acidaemia and 8% ofcontrols. The proportion of agreement between the twoinitial observers was significantly higher for ST abnor-malities (94%) than for CTG abnormalities (73%), andfor indication to intervene according to CTG+ST(89%) than according to CTG alone (76%). The sensi-tivity of both methods was probably underestimated, asthe last 10 min of the recordings were not evaluated.

False negative and false positive rates

In the SRCT [19], of 4,966 cases, 41 cases with adequaterecordings had metabolic acidosis (pH<7.05 and BDECF>12 mmol/L). In 26 cases, an indication to inter-vene according to CTG+STAN guidelines was found.In six cases, the signal quality was not good enough atthe end of the recordings, making analysis of the STsegment impossible. The remaining eight cases hadnormal ST segments, which corresponds to a false neg-ative rate of 1.6-2 per 1,000 cases recorded on STAN.Five neonates of these eight were not affected by labour,and were not in need of NICU.

In the CTG+ST group, three cases were not identi-fied out of 2,159 with cord data available and 15 dis-playing metabolic acidosis acid, giving a sensitivity of80%. The negative predicitive value, i.e. in the casewhere STAN says normal—what is the likelihood of nothaving metabolic acidosis—was 99.8%.

In the EU project, of the 6,303 cases recorded [73, 85],the false negative rate was 1.6 cases per 1,000 cases re-corded on STAN. It should be mentioned that all caseswith severe asphyxia defined as metabolic acidosis, lowApgar score and NICU need were identified by STANboth in the SRCT and the EU project.

The ST events in combination with normal CTG area sign of arousal and, thus, should never lead to inter-vention. They occur in about 8% of normal registrations[67, 84].

Conclusion

During the last 20 years, considerable change has ta-ken place in obstetric practice. The caesarean sectionrate has increased and the use of cardiotocography

Fig. 5 STAN registration with ST, the flags indicating ST events

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(CTG) is widespread. The limitations are, however,well recognised regarding the identification of infantsat risk of asphyxia [86]. The interpretation of CTG bymidwives and obstetric staff is of concern and hasbeen highlighted by several reports (Annual Reportof the Confidential Enquiry into Stillbirths andDeaths in Infancy, Maternal and Child Healthresearch Consortium, UK 1998) [87–89]. Some authorsreport the overall incidence of hypoxic seizures in terminfants not being reduced, despite evidence ofimproved obstetric practice in the identification anddelivery of high-risk foetuses [90], and, even in studieswhere the incidence of hypoxic seizures was decreased,there were no long-term consequences of their decrease[91].

Thus, our methods of detecting hypoxia during la-bour are often not sufficiently sensitive and not utilisedin an optimal fashion. The issue addressed in the currentreview is to what extent more appropriate use of theinformation contained in the CTG in combination withthe fetal electrocardiogram (FECG) would improvematters.

Data from the Plymouth randomised trial [92]showed members of staff improved in their capacity tocorrectly identify a normal CTG in cases where theyobtained support from a likewise normal ST waveform.In the Swedish randomised controlled trials (SRCT)[19], 25 of 29 foetuses with probable intrapartum as-phyxia had an abnormal or preterminal CTG [70]. Inmany of these cases, intervention was delayed or absent.It was concluded that the decreased number of neonateswith metabolic acidosis in the group monitored withSTAN might be explained by the fact that the methodgives a more comprehensive warning in cases of foetalhypoxia than CTG alone. Since CTG changes often arenot specific for hypoxia, there may be a tendency of thestaff to neglect abnormal traces. Combined CTG and STchanges are a more specific sign of hypoxia than CTGchanges alone, and, thereby, are not as easily neglected.Furthermore, the ‘‘log function’’ of the monitoring

system may alert the staff more accurately than changesin the CTG trace alone.

It is necessary to recognise that a consistent CTGinterpretation according to guidelines is necessary toobtain expected improvement. A preterminal CTGtrace, defined as complete loss of variability and reac-tivity, with or without decelerations and / or bradycar-dia, warrants intervention, even without anyaccompanying ST changes, as this may be the only signof severe hypoxia in cases exposed to the point where theadaptive mechanisms are failing. It is also important tonotice that, in hypoxic foetuses with a rise in the T/QRS-ratio, further rises should not be expected with a with-standing hypoxia. Instead, one warning in the ST logshould be considered sufficient evidence to intervene on,if labour is in the second stage. ST analysis also requiresclose attention to the quality of the foetal ECG signal. Inthe case of signal disturbance caused by a scalp ormaternal skin electrode becoming dislodged, the foetalheart rate should be recorded without the ST.

In summary (Table 5), the available evidence hasdemonstrated that the addition of ST waveform analysisto conventional CTG provides additional informationand also focuses one to interpret the CTG more pre-cisely. This improves the ability to identify intrapartumhypoxia and to reduce the incidence of newborns withmarked neurological symptoms. The detailed compara-tive analysis of CTG and ST recordings showed that theincorporation of ST analysis provides for better inte-robserver and intraobserver reproducibility, and betterspecificity as regards to pregnancy outcome than CTGalone. However, the performance of foetal monitoring isstill dependent on the ability of the staff to interpretCTG recordings and to manage the cases according tospecific guidelines. [93]. Education and preparation ofthe staff during a sufficiently long period and continuouscase evaluation was necessary during the SRCT toachieve the defined goals [69]. The protocol violationsrevealed at interim analyses pointed out the problems ofimplementation.

Table 5 STAN summaryWhat is known? Studied in pregnancies >36 weeks

Mother: reduction operative delivery for foetal distress(ODFD) without increasing operative deliveries for other reasonsNeonates: reduction in number of children bornwith metabolic acidosis, reduction in number of childrenhaving hypoxic ischemic encephalopathy (HIE)False positive rate: definitionFalse negative for metabolic acidosis: 1.6-2 per 1,000Correct implementation is mandatory evidence fromobservational studies

STAN+FBS Recording started with non-reassuring CTG patterns and withoutST event. Since we lack previous information, we lack informationregarding foetal resourcesVerification of recovery after a significant foetal heart rate (FHR)+ST event in the first stage of labour. At least 20 min shouldpass before foetal blood sampling (FBS) is obtained

Implication for furtherresearch

Effects on long-term outcomeComputerised analysis of CTG patternsCTG+ST in preterm labourSTAN patterns in specific pathophysiologic situations

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There is no intrapartum test that can accuratelypredict all the cases of poor neonatal outcome and theuse of STAN technology is no exception. It is evidentthat foetal heart rate (FHR) alone is outdated, giving, atbest, an approximation of the final outcome. Also, foetalassessment must be made with an understanding of theoverall clinical situation; cellular damage in the foetuscan occur in a wide variety of circumstances. Clinicalinformation and the use of ST waveform analysis forfoetal assessment in addition to CTG have the potentialto give significant benefits in reducing operative deliv-eries for foetal distress and reducing the incidence ofmetabolic acidosis. However, this will depend on theappropriate use of STAN according to the guidelinesprovided.

Along with further development of electronic foetalmonitoring (EFM), we should continue aiming atapplying computing systems to reduce our uncertaintiesin dealing with abnormalities of the FHR. Enlargementof the window of foetal assessment is another achieve-ment for the future, providing us with information onevents that have preceded the onset of labour and,hopefully, reducing the intrapartum scenarios, resultingin neurologic handicap for the child and litigation forthe obstetrician.

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