ST Segment Analysis (STAN) as an Adjunct to Electronic Fetal Monitoring, Part II: Clinical Studies and Future Directions

Transcription

1 ST Segment Analysis (STAN) as an Adjunct to Electronic Fetal Monitoring, Part II: Clinical Studies and Future Directions Michael A. Belfort, MBBCH, MD, PhD*, George R. Saade, MD KEYWORDS ST segment analysis STAN Cardiotocography Fetal monitoring The prior article focused on the physiology and general system for interpretation of ST segment analysis (STAN) systems. This article focuses on prior clinical studies of STAN, and future research directions. THE PLYMOUTH TRIAL This was the first large randomized controlled trial in which intervention rates and neonatal outcomes in fetuses monitored with cardiotocography (CTG) alone were compared with those in fetuses monitored using the combination of ST waveform analysis plus CTG. 1 In this study of 2434 patients, there was a 43% reduction in operative interventions for fetal distress in the ST 1 CTG group. There was also a trend toward fewer cases of cord artery metabolic acidosis and low Apgar score. THE SWEDISH RANDOMIZED CONTROLLED TRIAL This was the second, large-scale randomized controlled trial to compare outcomes following use of CTG alone and CTG 1 ST waveform analysis. 2 The study included 4966 term fetuses in 3 large labor and delivery wards in Sweden. After exclusion of inadequate recordings and fetuses with malformations (n 5 574), the findings showed a 61% decrease in the number of fetuses born with umbilical cord arterial metabolic acidosis in the CTG 1 ST group. There was also a 28% decrease in operative Department of Obstetrics and Gynecology, Baylor College of Medicine, Texas Children s Hospital, Houston, TX, USA * Corresponding author. address: michael.belfort@hcahealthcare.com Clin Perinatol 38 (2011) doi: /j.clp perinatology.theclinics.com /11/$ see front matter Ó 2011 Published by Elsevier Inc.

2 160 Belfort & Saade interventions because of fetal distress in the STAN-monitored group. These findings were consistent with the results of the Plymouth trial. It was concluded that intrapartum monitoring with CTG combined with automatic ST waveform analysis increased the ability to identify fetal hypoxia and to intervene more appropriately, resulting in an improved perinatal outcome. FINNISH RANDOMIZED CONTROLLED TRIAL This study aimed to examine whether STAN could reduce the rate of neonatal acidemia and the rate of operative intervention during labor, compared with fetal heart rate (FHR) monitoring alone. 3 A total of 1483 women in active labor with a singleton term fetus in cephalic presentation were randomly assigned to STAN 1 FHR monitoring or to FHR monitoring alone. Fetal scalp sampling was optional in both groups. The main outcome measures were neonatal acidemia (umbilical artery ph <7.05 and base excess < 12 mmol/l), neonatal metabolic acidosis (umbilical artery ph <7.05 and base excess < 12 mmol/l) and operative interventions: cesarean section rate, vacuum outlet (VO) rate, and fetal scalp sampling rate. There were no statistically significant differences between the STAN group and FHR monitoring group in the incidence of neonatal acidemia (5.8% vs 4.7%) or metabolic acidosis (1.7% vs 0.7%). The cesarean section rate (6.4% vs 4.7%) and the VO rate (9.5% vs 10.7%) were also similar in the STAN and FHR monitoring groups. The incidence of fetal scalp sampling was lower (P<.001) in the STAN group (7.0%) than in the FHR monitoring group (15.6%). The investigators concluded that intrapartum fetal monitoring with STAN did not improve the neonatal outcome or decrease the cesarean section rate. However, the need for fetal blood sampling (FBS) during labor was lower in the STAN group. FRENCH RANDOMIZED CONTROLLED TRIAL This randomized trial was conducted in 2 French maternity centers. 4 Its objective was to assess whether knowledge of ST-segment analysis was associated with a reduction in operative deliveries for nonreassuring fetal status (NRFS) or with a need for at least 1 scalp ph during labor. A total of 799 women in labor at 36 weeks or more, with a single fetus with cephalic presentation, and either abnormal cardiotocographic trace or thick meconium-stained amniotic fluid were randomized to either monitoring with CTG alone (n 5 400) or CTG 1 STAN (n 5 399). Scalp ph sampling was an option in both groups. There was no difference between the groups in the primary outcome of operative delivery for NRFS. The proportion of patients who had at least 1 scalp ph measurement during labor was substantially lower in the CTG 1 STAN group as compared with CTG alone: 27% compared with 62% (relative risk, 0.44; 95% confidence interval [CI], ). There was no significant difference in a composite abnormal neonatal outcome between the groups (ph 7.05 or base deficit in extracellular fluid [BDecf] 12 mmol/l or 5-minute Apgar score 7 or neonatal intensive care unit admission or convulsions or neonatal death). THE COCHRANE REVIEW ON FETAL ELECTROCARDIOGRAM The above 4 randomized trials were included in the most recent Cochrane review on the topic. 5 The objective of this review was to compare the effects of analysis of fetal electrocardiogram (ECG) waveforms during labor with alternative methods of fetal monitoring. Four trials using STAN were included in the meta-analysis and it showed that in comparison with continuous electronic fetal heart rate monitoring alone, the use

3 ST Segment Analysis 161 of adjunctive ST waveform analysis (4 trials, 9671 women) was associated with fewer babies with neonatal encephalopathy (4 trials, risk ratio (RR) 0.37, 95% CI ) (although the absolute number of babies with encephalopathy was low [n 5 19]), fewer fetal scalp samples during labor (4 trials, RR 0.65, 95% CI ), and fewer operative vaginal deliveries (4 trials, RR 0.89, 95% CI ). There was no statistically significant difference in the number of babies with severe metabolic acidosis at birth (cord ph <7.05 and base deficit >12 mmol/l) (RR 0.73, 95% CI , data from 8907 babies), cesarean section (4 trials, RR 0.93, 95% CI ), Apgar score less than 7 at 5 minutes (4 trials, RR 0.82, 95% CI ), or admissions to special care unit (4 trials, RR 0.90, 95% CI ). The Cochrane review concluded that these findings provide some support for the use of fetal ST waveform analysis when a decision has been made to undertake continuous electronic fetal heart rate monitoring during labor. However, the advantages need to be considered along with the disadvantages of needing to use an internal scalp electrode, after membrane rupture, for ECG waveform recordings. It should be noted that in all trials included in the Cochrane review, scalp ph assessment was allowed. Moreover, the method for cord blood base deficit calculation differed between the studies, with some using the extracellular fluid and others using blood. DUTCH RANDOMIZED CONTROLLED TRIAL A recent randomized trial was completed after the latest Cochrane review was updated, and therefore was not included in the previous section. 6 This was a multicenter randomized pragmatic trial in 3 academic and 6 nonacademic teaching hospitals in The Netherlands. The objective of the trial was to estimate the effectiveness of intrapartum fetal monitoring by CTG plus ST analysis using a strict protocol for performance of fetal blood sampling. Performance of fetal blood sampling was restricted to 3 situations: (1) start of STAN registration with an intermediary or abnormal CTG trace; (2) abnormal CTG trace for more than 60 minutes during the first stage without ST events; and (3) poor ECG signal quality in the presence of an intermediary or abnormal CTG trace. The reason for this protocol was to control performance of scalp ph, a factor that may have affected the results of prior trials in which scalp ph use was not left up to the discretion of the provider. The primary outcome measure was the incidence of metabolic acidosis, defined as an umbilical cord artery blood ph below 7.05 and a base deficit calculated in the extracellular fluid compartment (BDecf) above 12 mmol/l according to the Siggaard-Andersen acid-base chart algorithm. Although base deficit in blood is the value most commonly reported by umbilical cord blood analyzers, and the one often used in clinical practice, the investigators in this trial thought that BDecf better reflects the true metabolic component of acidosis. There were 2832 and 2849 women randomly assigned to monitoring by CTG with ST analysis (index) or CTG only (control). The fetal blood sampling rate was 10.6% in the index compared with 20.4% in the control group (relative risk 0.52; 95% CI ). The primary outcome occurred 0.7% in the index compared with 1.1% in the control group (relative risk 0.70; 95% CI ; number needed to treat 252). Using metabolic acidosis calculated in blood, these rates were 1.6% and 2.6%, respectively (relative risk 0.63; 95% CI ; number needed to treat 100). The number of operative deliveries, low Apgar scores, neonatal admissions, and newborns with hypoxic ischemic encephalopathy was comparable in both groups. Although this study did not show a difference in the primary outcome, it did show a lower rate of metabolic acidosis defined using base deficit in blood, the most

4 162 Belfort & Saade common method used in the United States. And this benefit was achieved despite performing 48% less fetal blood sampling when ST segment analysis was used. It should also be noted that the actual rates of metabolic acidosis using base deficit in extracellular fluid (1.1% in the control and 0.7% in the index group) were much lower than the 3.5% assumed in the sample size calculations. The trials described previously beg the question as to how would ST segment analysis perform when fetal blood sampling is not performed. In addition to the randomized trials summarized previously, a number of observational or follow-up studies have been published. NORDIC OBSERVATIONAL MULTICENTER STUDY This multicenter study, conducted at 8 Norwegian and 4 Swedish labor and delivery wards, had the objective of determining the diagnostic power of CTG 1 ST clinical guidelines at predicting fetal well-being using STAN technology. 7 The findings showed that the additional information obtained from continuous assessment of ST waveform analysis increased specificity and positive predictive value while maintaining sensitivity. The investigators concluded that the clinical guidelines provided improved diagnostic power in identifying those fetuses exposed to adverse events during labor. FOLLOW-UP OF THE CHILDREN FROM THE SWEDISH TRIAL The aim of this study was to evaluate the neonatal outcome of the Swedish randomized controlled trial, with a focus on the complicated or adverse neonatal cases. 8 The results showed a reduction in the incidence of newborn infants with marked neurologic symptoms in the CTG 1 ST group. Of the 29 fetuses from both arms with complicated or adverse outcomes, 22 fetuses had presented a STAN pattern that indicated a need for intervention according to the STAN clinical guidelines. There was a significant decrease in the number of live-born babies with moderate or severe neonatal encephalopathy in the FHR monitoring 1 ST group, as compared with the group of FHR monitoring alone. The investigators concluded that the most important finding of the study was the prevalence of ST changes that are detected at an appropriate point in time to allow for earlier and more consistent intervention. VIRTUAL STUDY REVIEWING STAN TRACINGS The aim of this study was to evaluate if the addition of ST waveform analysis to standard FHR tracing analysis would improve the consistency and accuracy of clinical decision making for intervention during labor. 9 Seven experienced European STAN users performed a blinded FHR analysis on the same 51 completed intrapartum cases containing examples of both healthy and compromised term fetuses. When ST waveform was added to the FHR tracing, the rate of intervention was significantly decreased for cases with ph higher than More importantly, the observer agreement demonstrated a marked improvement in the timing of appropriate intervention, from 68% to 92% with the addition of ST analysis. MULTICENTER, OBSERVATIONAL STUDY OF FETAL BLOOD SAMPLING VERSUS CTG D ST ANALYSIS The objective of this study was to determine whether CTG 1 ST clinical guidelines could identify cases of intrapartum acidosis with a degree of accuracy similar to that of fetal scalp ph sampling. 10 Data from the European multicenter project involving 10 European centers were evaluated. Of the 6999 term deliveries, 911 (13%) were

5 ST Segment Analysis 163 identified where a scalp-ph had been obtained and of these, 53 (5.8%) cases were shown to have umbilical cord artery acidemia (defined as a ph <7.06). Of these 53 cases, 20 were diagnosed as metabolic acidosis and 33 as respiratory acidosis after birth. Of the metabolic acidosis cases, 19 had CTG 1 ST information suggesting a sensitivity of 95% for detecting metabolic acidosis in STAN-monitored pregnancies. The investigators concluded that the optimal performance of fetal monitoring depended on the ability of the clinical staff to interpret recordings and manage cases appropriately, and that the techniques of FBS and CTG 1 ST analysis are very similar in their capability of identifying intrapartum hypoxia. The prime difference in the 2 methods lies in the immediacy of the availability of the information, in that the CTG 1 ST information is continuously displayed whereas FBS is intermittent and requires a specific invasive procedure. STAN S21 FETAL HEART MONITOR IN 637 PATIENTS The objective of this study was to assess the value of the STAN fetal heart monitor for intrapartum fetal monitoring. 11 It was a prospective observational study involving 637 high-risk patients who were monitored using a STAN S21 fetal heart monitor. A total of 449 recordings were available for analysis. In 61 cases, ST changes requiring intervention occurred more than10 minutes before birth. In 35 (57%) of these cases, umbilical artery blood ph at delivery was lower than Eighteen (4.0%) neonates were born with metabolic acidosis (umbilical artery ph <7.05 and base deficit >12 mmol/l). Significant ST changes (18 31 minutes before birth) were present in all 5 cases with ph lower than 7.00 and in 6 of the 13 cases with ph of 7.00 to 7.04 (false-negative rate 1.6%). Neonatal follow-up showed no adverse outcomes. A total of 192 fetal blood samples (121 in the first stage and 71 in the second stage of labor) were taken from 142 women. Fetal scalp blood ph was lower than 7.15 in 10 samples, 7.15 to 7.19 in 11 samples, 7.20 to 7.24 in 30 samples, and 7.25 or higher in 141 samples. ST changes occurred in 8 (80%), 6 (55%), 9 (30%), and 15 (11%) of these cases, respectively. In 188 (29.5%) women, outcome could not be analyzed in relation to ST changes because of inadequate recording (time between end of recording and delivery >20 minutes or poor signal quality) or the absence of umbilical cord gases. In this group, 4 (2.1%) neonates with metabolic acidosis were born. In 3 of these cases the fetal ECG signal was of was poor quality and in 1 case the recording had ended 60 minutes before birth. The investigators concluded that because ST changes were present in all 5 cases with severe metabolic acidosis (umbilical artery ph <7.00), and in 46% of cases with mild metabolic acidosis, STAN 1 FHR monitor analysis was more specific in detecting fetal acidemia than FHR monitoring alone. OUTCOME OF 2 YEARS OF REGULAR USE IN THE CITY OF GOTHENBURG This study was designed to monitor the effects of the introduction of routine STAN methodology usage in a large Swedish city population. 12 It was a prospective observational study covering the total population of deliveries at term over a 2-year period. A total of 4830 of 14,687 term pregnancies were monitored using the STAN S 21 fetal heart monitor and its associated clinical guidelines. Cord artery metabolic acidosis, neonatal outcome, and rates of operative deliveries for fetal distress were assessed. The annual rate of STAN usage increased from 28.1% to 37.7% and was associated with a significant reduction in the metabolic acidosis rate in the total population from 0.76% to 0.44% (P <.05). The compliance with the clinical guidelines increased in cases requiring intervention. The rates for moderate/severe hypoxic neonatal encephalopathy were consistently low, 0.55 and 0.68 per 1000 deliveries, respectively, corresponding with

6 164 Belfort & Saade previous findings. The rate of operative delivery did not change over the 2-year study period. The investigators concluded that increasing STAN usage provided consistent improvements in fetal outcome equaling those noted in the Swedish randomized controlled trial, without increasing operative interventions for fetal distress. US MULTICENTER CLINICAL USAGE STUDY This study was designed to assess the ability of obstetricians in the United States to use this system appropriately for intrapartum care. 13 It was a prospective nonrandomized trial conducted in 6 selected sites including a range of facilities from community hospitals to university tertiary care centers. Appropriate use was measured by negative predictive value (NPV) of nonintervention for fetuses with nonreassuring FHR patterns, normal STAN readings, and normal neonatal outcomes with umbilical cord arterial ph higher than 7.12; and percent agreement (PA) for intervention decisions with 3 STAN experts who conducted retrospective case reviews blinded to outcome. A total of 530 patients were enrolled. An NPV of 95.2% was achieved, whereas PA between investigators and STAN experts was 84% and 90%, for intervention and nonintervention, respectively. No fetus with metabolic acidosis requiring intervention was missed by US clinicians. The investigators concluded that US clinicians used the STAN system appropriately in a manner similar to that of experienced STAN users. CANADIAN STUDY This study was undertaken to determine the ability of intrapartum electronic fetal heart rate monitoring (EFM) plus fetal ECG STAN monitoring to predict metabolic acidemia (defined as an umbilical cord artery ph <7.15 and base deficit >12 mmol L) at birth. 14 Women with singleton, term pregnancies who had a clinical indication for internal EFM with a fetal scalp electrode were included and attending physicians were blinded to the ST analysis information, only using available EFM as per current clinical practice. After delivery, 2 trained observers blinded to neonatal outcome and ST analysis information performed visual classification of the EFM tracing in 10-minute epochs according to International Federation of Gynecology and Obstetrics (FIGO) guidelines. ST events automatically detected by the STAN S21 monitor were combined with the visual EFM classification as per STAN clinical guidelines. The results indicated a sensitivity of 43%, specificity of 74%, NPV of 96%, and a positive predictive value (PPV) of 8% for metabolic acidemia at birth. Poor ECG quality, despite good EFM tracings (ECG signal loss), occurred 11% of the tracing time. The investigators concluded that STAN clinical guidelines have a poor PPV and a sensitivity of less than 50% for metabolic acidemia at birth. STRASBOURG STUDY This study was performed to determine the diagnostic value of fetal STAN in predicting neonatal acidosis. 15 The STAN S21 was used to monitor singleton fetuses in labor with abnormal FHR. Physicians later reviewed tracings to identify any ST events dictating intervention. Outcome measures were umbilical artery ph of 7.15 or lower and ph of 7.05 or lower at birth. The sensitivity, specificity, PPV, and NPV of a significant ST event to predict both outcomes were calculated. Data from 411 women were analyzed. The sensitivity of a significant ST event for a ph of 7.15 or lower (21.9%) was 38% (41/108), specificity 83% (252/303), PPV 45% (41/92) and NPV 79% (252/ 319), and for ph of 7.05 or lower, it was (3.4%), 62.5% (10/16), 79% (313/395), 11% (10/92), and 98% (313/319), respectively. The investigators concluded that in a population of patients who develop an abnormal FHR tracing during labor, the sensitivity of

7 ST Segment Analysis 165 STAN is moderate (only 40%) for predicting ph of 7.15 or lower and better (approximately 60%) for more severe acidosis (ph 7.05). We can assume that if a ph of 7.0 is used to denote significant metabolic acidosis, as in the United States, the sensitivity, specificity, PPV, and NPV would be at least equal to, if not better than, the results for a ph of RATIONALE FOR A CLINICAL TRIAL OF FETAL STAN It is thus clear that whereas data are encouraging, the utility of this new method of fetal monitoring is yet to be confirmed in a US population. There are 2 main reasons why another randomized controlled trial (RCT) is needed before widespread general use of STAN can be endorsed in the United States. First, STAN has not been evaluated with an RCT under the specific conditions of obstetric health care delivery in this country. No current study comparing usual management versus STAN management exists. It should be remembered that the use of STAN is not simply use of a technology but rather the use of a system of management. How our obstetric community adapts to this technology and its associated protocol is not something that can be assumed to mirror the experience in Europe. This is important because the US model for obstetric care delivery is different from that in European and other countries and the direct extrapolation of data from these countries to a US population is not necessarily appropriate. Second, although metabolic acidosis and some aspects of neonatal outcome have been studied, no RCT has specifically addressed a composite neonatal outcome as the primary outcome of interest. Although a decrease in operative delivery is a very important outcome in obstetric practice, the reduction in adverse neonatal outcomes is the ultimate goal for a monitoring system designed to reduce fetal and neonatal acidosis. The data that are currently available do not adequately address this issue. To this end then, the Maternal Fetal Medicine Units Networks of the National Institute of Child Health and Human Development (NICHD) has recently embarked on an RCT that is expected to enroll approximately 11,000 patients, to specifically compare the incidence of a composite neonatal outcome (see the next section) in patients treated with usual practice versus those in whom STAN is used. The primary research question is: Does fetal STAN, as an adjunct to conventional electronic fetal heart rate monitoring in pregnancies at 36 weeks or more, decrease the risk of fetal compromise, a composite adverse neonatal outcome defined as one or more of the following outcomes: intrapartum fetal death, neonatal death, Apgar score of 3 or lower at 5 minutes, seizure(s), cord artery ph of 7.05 or lower and base deficit of 12 mmol/l or less, intubation for ventilation at delivery, or presence of neonatal encephalopathy. Secondary research questions this study will address include the following: Does knowledge of fetal ECG ST segment and T-wave analysis modify the risk of a cesarean delivery? Does knowledge of fetal ECG ST segment and T-wave analysis modify the risk of an operative vaginal delivery? What is the frequency and prognostic significance of different fetal heart rate patterns as defined by the NICHD Fetal Monitoring Workshop (2008)? Does the utility of fetal ECG ST segment and T-wave analysis change over time? The study is a randomized, controlled clinical trial of 11,000 women in labor at more than 36.0 weeks gestation randomized to 1 of 2 groups using the STAN S31 system: Fetal STAN electrode inserted and data available to caregivers (open device group)

8 166 Belfort & Saade Fetal STAN electrode inserted, but data masked to the caregivers (masked device group). CONCLUDING STATEMENTS Fetal monitoring with the STAN system has the potential to herald a new era in the detection of impending fetal compromise by the use of a new technology coupled with a systematized approach to the evaluation of the monitoring information. Unlike the initial introduction of electronic fetal monitoring, before supporting the widespread dissemination and sale of this device there is under way an in-depth assessment of this technology and its protocol of use in a US population, a welcome and responsible approach led by the NICHD and supported by the company that produces the device. This cooperation between the National Institutes of Health and industry in the evaluation and introduction of new health care technology is a model that hopefully will be replicated in other arenas in medicine. REFERENCES 1. Westgate J, Harris M, Curnow JS, et al. Plymouth randomized trial of cardiotocogram only versus ST waveform plus cardiotocogram for intrapartum monitoring in 2400 cases. Am J Obstet Gynecol 1993;169: Amer-Wåhlin I, Hellsten C, Norén H, et al. Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial. Lancet 2001;358: Ojala K, Vaarasmaki M, Makikallio K, et al. A comparison of intrapartum automated fetal electrocardiography and conventional cardiotocography a randomised controlled study. BJOG 2006;113: Vayssiere C, David E, Meyer N, et al. A French randomized controlled trial of STsegment analysis in a population with abnormal cardiotocograms during labor. Am J Obstet Gynecol 2007;197:299, e Neilson JP. Fetal electrocardiogram (ECG) for fetal monitoring during labour. Cochrane Database Syst Rev 2006;3:CD Westerhuis ME, Visser GH, Moons KG, et al. Cardiotocography plus ST analysis of fetal electrocardiogram compared with cardiotocography only for intrapartum monitoring: a randomized controlled trial. Obstet Gynecol 2010;115: Amer-Wåhlin I, Bördahl P, Eikeland T, et al. ST analysis of the fetal electrocardiogram during labour: Nordic observational multicentre study. J Matern Fetal Neonatal Med 2002;12: Norén H, Amer-Wåhlin I, Hagberg H, et al. Fetal electrocardiography in labor and neonatal outcome: data from the Swedish randomised controlled trial on intrapartum fetal monitoring. Am J Obstet Gynecol 2003;188: Ross GM, Devoe LD, Rosén KG. ST-segment analysis of the fetal ECG improves fetal heart rate (FHR) tracing interpretation and clinical decision making. J Matern Fetal Neonatal Med 2004;15: Luttkus AK, Norén H, Stupin JH, et al. Fetal scalp ph and ST analysis of the fetal ECG as an adjunct to CTG. A multi-centre, observational study. J Perinat Med 2004;32: Kwee A, van der Hoorn-van den Beld CW, Veerman J, et al. STAN S21 fetal heart monitor for fetal surveillance during labor: an observational study in 637 patients. J Matern Fetal Neonatal Med 2004;15(6):400 7.

9 ST Segment Analysis Norén H, Blad S, Carlsson A, et al. STAN in clinical practice the outcome of 2 years of regular use in the city of Gothenburg. Am J Obstet Gynecol 2006; 195: Devoe LD, Ross M, Wilde C, et al. United States multicenter clinical usage study of the STAN 21 electronic fetal monitoring system. Am J Obstet Gynecol 2006; 195: Dervaitis KL, Poole M, Schmidt G, et al. ST segment analysis of the fetal electrocardiogram plus electronic fetal heart rate monitoring in labor and its relationship to umbilical cord arterial blood gases. Am J Obstet Gynecol 2004;191: Vayssiere C, Haberstich R, Sebahoun V, et al. Fetal electrocardiogram STsegment analysis and prediction of neonatal acidosis. Int J Gynaecol Obstet 2007;97:110 4.