Waveform analysis of the fetal ECG in labor in patients with intrahepatic cholestasis of pregnancy.

AIM: Intrahepatic cholestasis of pregnancy (ICP) is reported to be associated with an increased risk of sudden fetal death. The possible mechanism is thought to be cardiac arrhythmia. Prolonged QT interval of the electrocardiogram (ECG) is associated with arrhytmogenic events. The aim of the study was to compare the fetal ECG QT interval during labor in pregnancies complicated with ICP to healthy controls. METHODS: The fetal ECG and QT interval was reviewed retrospectively. The intrapartum QT interval was measured in 61 fetuses born to mothers with ICP and in a control group of similar size. The corrected QT interval (QTc) was calculated using Bazett's formula: QT/√RR. The occurrence of ST segment depression was also included in the analysis. RESULTS: The groups were similar regarding to maternal age, parity, BMI, gestational age and smoking habits. The rate of labor induction was significantly higher in ICP patients (P < 0.001). The QTc at the beginning and the end of recording was analyzed and there were no significant differences in these values between the ICP patients and healthy controls (P = 0.467). Most ICP patients used ursodeoxycholic acid (UDCA) for mediation. We analyzed separately patients who had elevated liver enzymes before labor. No significant differences in the QTc were noted in these patients either. Nor were there any significant ST depressions in ICP patients. CONCLUSIONS: The etiology of adverse perinatal outcome and even sudden fetal death in ICP is still controversial. No differences in QTc intervals and ST waveforms during labor were found in our study material.

Association between umbilical cord artery pCO2 and the Apgar score; elevated levels of pCO2 may be beneficial for neonatal vitality after moderate acidemia.

OBJECTIVE: To determine the association between 5-min Apgar score and umbilical cord artery carbon dioxide tension (pCO2). DESIGN: Observational study. SETTING: European hospital labor wards. POPULATION: Data from 36,432 newborns ≥36 gestational weeks were obtained from three sources: two trials of monitoring with fetal electrocardiogram (the Swedish randomized controlled trial and the European Union Fetal ECG trial) and Mölndal Hospital data. After validation of the acid-base values, 25,806 5-min Apgar scores were available for analysis. METHODS: Validation of the umbilical cord acid-base values was performed to obtain reliable data. 5-min Apgar score was regressed against cord artery pCO2 in a polynomial multilevel model. MAIN OUTCOME MEASURES: Five-min Apgar score, umbilical cord pCO2, pH, and base deficit. RESULTS: Overall, a higher cord artery pCO2 was found to be associated with lower 5-min Apgar scores. However, among newborns with moderate acidemia, lower umbilical cord artery pCO2 (≤median pCO2 for the specific cord artery pH) was associated with lower 5-min Apgar scores, with a relative risk of 2.0 (95% confidence interval: 1.4-2.8) for 5-min Apgar scores 0-6. CONCLUSIONS: Metabolic acidosis affects the newborn's vitality more than respiratory acidosis. In addition, elevated levels of pCO2 may be beneficial for fetuses with moderate acidemia, and thus cord artery pCO2 is a factor that should be considered when assessing the compromised newborn.

Swedish randomized controlled trial of cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram revisited: analysis of data according to standard versus modified intention-to-treat principle.

OBJECTIVE: To undertake a renewed analysis of data from the previously published Swedish randomized controlled trial on intrapartum fetal monitoring with cardiotocography (CTG-only) vs. CTG plus ST analysis of fetal electrocardiogram (CTG+ST), using current standards of intention-to-treat (ITT) analysis and to compare the results with those of the modified ITT (mITT) and per protocol analyses. METHODS: Renewed extraction of data from the original database including all cases randomized according to primary case allocation (n=5 049). MAIN OUTCOME MEASURE: Metabolic acidosis in umbilical artery at birth (pH <7.05, base deficit in extracellular fluid >12.0 mmol/l) including samples of umbilical vein blood or neonatal blood if umbilical artery blood was missing. RESULTS: The metabolic acidosis rates were 0.66% (17 of 2 565) and 1.33% (33 of 2 484) in the CTG+ST and CTG-only groups, respectively [relative risk (RR) 0.50; 95% confidence interval (CI) 0.28-0.88; p=0.019]. The original mITT gave RR 0.47, 95%CI 0.25-0.86 (p=0.015), mITT with correction for 10 previously misclassified cases RR 0.48, 95%CI 0.24-0.96 (p=0.038) and per protocol analysis RR 0.40, 95%CI 0.20-0.80 (p=0.009). The level of significance of the difference in metabolic acidosis rates between the two groups remained unchanged in all analyses. CONCLUSION: Re-analysis of data according to the ITT principle showed that regardless of the method of analysis, the Swedish randomized controlled trial maintained its ability to demonstrate a significant reduction in metabolic acidosis rate when using CTG+ST analysis for fetal surveillance in labor.

3D evaluation of fetal brain structures: reference values and growth curves.

BACKGROUND: The development of the fetal central nervous system is one of the most important fields of research in perinatology. Since the early 1980s, 3 D ultrasound has become one of the major research tools in obstetrics and gynecology. OBJECTIVE: The aim of this study was to reconstruct thalamus, cerebellum and Cortex volumes of fetal brain and generate, for these volumes, growth curves related to gestational age. METHODS: We enrolled 344 pregnant women. Using "Tomographic Ultrasound Imaging" (TUI), in all cases we obtained a satisfying 3 D acquisition of fetal brain. We reconstructed offline thalamus, cerebellum and cortex volumes using "Virtual Organ Computer-Aided AnaLysis" (VOCAL) or 4 D View (GE Healthcare). RESULTS: Among the 344 fetuses examined, we obtained 314 thalamus volumes, 252 cerebellum volumes and 261 cortex volumes and we constructed the reference growth curves. CONCLUSION: Our study confirms the reliability of cerebral volumes evaluation using 3 D technology and how these cerebral structures grow through gestation.

Allopurinol reduces oxidative stress in the ovine fetal cardiovascular system after repeated episodes of ischemia-reperfusion.

In complicated labor, neonatal outcome may depend not only on the extent of fetal asphyxia and acidosis but also on the effects on the fetal cardiovascular system of reactive oxygen species (ROS) generated during the ischemia-reperfusion (I/R) associated with repeated compressions of the umbilical cord. This study tested the hypothesis that maternal treatment with clinical doses of the antioxidant allopurinol in the setting of fetal asphyxia would reduce oxidative stress in the fetal cardiovascular system. The hypothesis was tested in chronically instrumented fetal sheep in late gestation by investigating the effects of maternal treatment with therapeutic doses of allopurinol or vehicle on the fetal cardiovascular system during and after episodes of I/R. The latter were produced by repeated, measured compressions of the umbilical cord. The data show that maternal treatment with allopurinol helped maintain umbilical blood flow and it reduced fetal cardiac oxidative stress after I/R of the type associated with clinically relevant acidemia and repetitive fetal heart rate decelerations. The data support the hypothesis tested and suggest that maternal treatment with allopurinol may offer plausible clinical intervention in the management of perinatal asphyxia in complicated labor.

A randomised clinical trial of intrapartum fetal monitoring with computer analysis and alerts versus previously available monitoring.

BACKGROUND: Intrapartum fetal hypoxia remains an important cause of death and permanent handicap and in a significant proportion of cases there is evidence of suboptimal care related to fetal surveillance. Cardiotocographic (CTG) monitoring remains the basis of intrapartum surveillance, but its interpretation by healthcare professionals lacks reproducibility and the technology has not been shown to improve clinically important outcomes. The addition of fetal electrocardiogram analysis has increased the potential to avoid adverse outcomes, but CTG interpretation remains its main weakness. A program for computerised analysis of intrapartum fetal signals, incorporating real-time alerts for healthcare professionals, has recently been developed. There is a need to determine whether this technology can result in better perinatal outcomes. METHODS/DESIGN: This is a multicentre randomised clinical trial. Inclusion criteria are: women aged ≥ 16 years, able to provide written informed consent, singleton pregnancies ≥ 36 weeks, cephalic presentation, no known major fetal malformations, in labour but excluding active second stage, planned for continuous CTG monitoring, and no known contra-indication for vaginal delivery. Eligible women will be randomised using a computer-generated randomisation sequence to one of the two arms: continuous computer analysis of fetal monitoring signals with real-time alerts (intervention arm) or continuous CTG monitoring as previously performed (control arm). Electrocardiographic monitoring and fetal scalp blood sampling will be available in both arms. The primary outcome measure is the incidence of fetal metabolic acidosis (umbilical artery pH < 7.05, BDecf > 12 mmol/L). Secondary outcome measures are: caesarean section and instrumental vaginal delivery rates, use of fetal blood sampling, 5-minute Apgar score < 7, neonatal intensive care unit admission, moderate and severe neonatal encephalopathy with a marker of hypoxia, perinatal death, rate of internal monitoring, tracing quality, and signal loss. Analysis will follow an intention to treat principle. Incidences of primary and secondary outcomes will be compared between groups. Assuming a reduction in metabolic acidosis from 2.8% to 1.8%, using a two-sided test with alpha = 0.05, power = 0.80, and 10% loss to follow-up, 8133 women need to be randomised. DISCUSSION: This study will provide evidence of the impact of intrapartum monitoring with computer analysis and real-time alerts on the incidence of adverse perinatal outcomes, intrapartum interventions and signal quality. (Current controlled trials ISRCTN42314164).

Identifying newborns with umbilical cord blood metabolic acidosis by intrapartum cardiotography combined with fetal ECG ST analysis (STAN): comparison of the new and old FIGO systems to classify cardiotocograms.

Introduction: The intrapartum cardiotocography (CTG) classification system by FIGO in 2015 (FIGO2015) was introduced to simplify CTG interpretation, but it is not harmonized with the fetal ECG ST analysis (STAN) algorithm from 2007 (STAN2007), which is based on the FIGO CTG system from 1987. The study aimed to determine time courses and sensitivity between the systems in classifying CTG + ST events to indicate metabolic acidosis at birth.Material and methods: Forty-four cases with umbilical cord artery metabolic acidosis were retrieved from a European multicenter database. CTG patterns and timing of the first occurring significant ST events were evaluated post hoc in consensus by an expert panel and sensitivity statistics were performed. Wilcoxon's matched-pairs signed-ranks test and McNemar's test were used with a two-tailed p < .05 regarded significant.Results: STAN2007 had a higher sensitivity (73 versus 43%, p = .0002) and alarmed for metabolic acidosis in mean 34 min earlier than the FIGO2015 system did (p = .002). In every fourth case, the time difference was ≥20 min.Conclusions: In this simulation study, surveillance with STAN2007 combined with fetal ECG ST analysis had a significantly higher sensitivity and would have alarmed for metabolic acidosis significantly earlier than the new FIGO system would have.

FHR patterns that become significant in connection with ST waveform changes and metabolic acidosis at birth.

Introduction: Recent developments have produced new CTG classification systems and the question is to what extent these may affect the model of FHR + ST interpretation? The two new systems (FIGO2015 and SSOG2017) classify FHR + ST events differently from the current CTG classification system used in the STAN interpretation algorithm (STAN2007). Aim: Identify the predominant FHR patterns in connection with ST events in cases of cord artery metabolic acidosis missed by the different CTG classification systems. Indicate to what extent STAN clinical guidelines could be modified enhancing the sensitivity. Provide a pathophysiological rationale. Material and methods: Forty-four cases with umbilical cord artery metabolic acidosis were retrieved from a European multicenter database. Significant FHR + ST events were evaluated post hoc in consensus by an expert panel. Results: Eighteen cases were not identified as in need of intervention and regarded as negative in the sensitivity analysis. In 12 cases, ST changes occurred but the CTG was regarded as reassuring. Visual analysis of the FHR + ST tracings revealed specific FHR patterns: Conclusion: These findings indicate FHR + ST analysis may be undertaken regardless of CTG classification system provided there is a more physiologically oriented approach to FHR assessment in connection with an ST event.

ST analysis of the fetal electrocardiogram - Comments on recent experimental data.

In their paper, Andriessen at al present a validation of fetal ECG analysis and the clinical STAN device in midgestation fetal lambs exposed to 25 minutes of umbilical cord occlusion. The study presents results that contrast remarkably from previously published experimental data which raises a number of questions and comments. The most striking finding of Andriessen et al is the recording of an extremely high number of alarms from the STAN equipment during control conditions when no alarms at all are expected. These patterns have never been seen, neither in the clinical situation nor in our own fetal sheep studies. The reason for this becomes apparent when their way of recording the FECG is scrutinized. In their assessment of STAN, Andriessen at al use an assumed negative aVF lead with the assumption that it will reflect the FECG in the same way as the unipolar scalp lead used clinically. The signal used for disqualification of STAN is itself not qualified to properly represent the fetal scalp lead signal that STAN is designed for. To question a proven technology is fully accepted but those attempting would be asked to argue along fully validated data and related analysis including questioning of their own data.

Effects of minimal acupuncture in children with infantile colic - a prospective, quasi-randomised single blind controlled trial.

BACKGROUND: Colic causes crying in 10-30% of infants and is one of the primary reasons parents seek health care. Treatments are generally not totally effective and some cause side effects. In this study we aimed to test the effect of light needling (minimal acupuncture) on crying. METHODS: Forty children (median six weeks of age) with excessive crying unresponsive to conventional therapies, were recruited from 21 Child Welfare Clinics within an area of western Sweden, and quasi-randomised to control or light needling treatment. Parents were unaware of which group their child was assigned to. Children were given light needling acupuncture on one point (LI4) on both hands for approximately 20 seconds on four occasions, or received the same care except needling. Parental assessment questionnaires were used pre- and post-treatment to assess crying intensity, frequency, duration of crying and pain related behaviour throughout the day in six hour periods. RESULTS: Light needling resulted in a significant reduction in the rated crying intensity (assessed by a numeric rating scale, 0 to 10). For example, during the morning time period 0600-1200 hours, the median (range) rated crying intensity changed from 6 (1 to 9) pre-treatment to 2 (0 to 5) post-treatment (P=0.002), in the light needling group. The corresponding ratings for the children in the control group was 6 (0 to 10) and 5 (0 to 10) respectively. The difference between the groups was significant (P=0.016). There were also significant differences between the groups for the afternoon (1200-1800 hours), and evening (1800-midnight) time periods. Pain related behaviour like facial expression, was also significantly less pronounced in the light needling group as compared to the control group post-treatment, (P=0.027). The parents rated the light needling as more effective in improving symptoms than the control group (P<0.001). CONCLUSION: Four treatments with light needling on one point in the hand may alleviate crying and pain related behaviour without any noted side effects.

Fetal ECG waveform analysis.

Fetal ECG waveform analysis as an adjunct to electronic fetal monitoring (EFM) has developed over the last 3 decades. From a multitude of potential parameters, ST waveform analysis has been documented to provide the information required to shift EFM from a screening device to a diagnostic tool that meets the standards of evidence-based medicine. This chapter details the experimental and clinical evolution of the STAN methodology for intrapartum fetal surveillance. Observational data formed the basis for cardiotocograph (CTG) and ST waveform analysis clinical guidelines. Data from two large, randomized controlled trials (6826 cases) are summarized together with the first analysis of the recently completed EU project of 7823 term fetuses monitored as part of the study to introduce ST analysis into clinical practice. The reduction in the incidence of newborns with marked neurological symptoms is supported by these findings. The detection of ST changes allowed earlier and more consistent intervention.

Do spectral bands of fetal heart rate variability associate with concomitant fetal scalp pH?

BACKGROUND: Objective information on specific fetal heart rate (FHR) parameters would be advantageous when assessing fetal responses to hypoxia. Small, visually undetectable changes in FHR variability can be quantified by power spectral analysis of FHR variability. AIMS: To investigate the effect of intrapartum hypoxia and acidemia on spectral powers of FHR variability. STUDY DESIGN: This is a retrospective observational clinical study with data from an EU multicenter project. SUBJECTS: We had 462 fetuses with a normal pH-value (pH>7.20; controls) in fetal scalp blood sample (FBS) and 81 fetuses with a low scalp pH-value (≤ 7.20; low-FBS pH-fetuses). The low-FBS pH-fetuses were further divided into two subgroups according to the degree of acidemia: fetuses with FBS pH7.11-7.20 (n = 58) and fetuses with FBS pH ≤7.10 (n = 23). OUTCOME MEASURES: Spectral powers of FHR variability in relation to the concomitant FBS pH-value. RESULTS: Fetuses with FBS pH ≤7.20 had increased spectral powers of FHR variability compared with controls (2.49 AU vs. 2.23 AU; p = 0.038). However, the subgroup of most affected fetuses (those with FBS pH ≤7.10) had significantly lower FHR variability spectral powers when compared to fetuses with FBS pH7.11-7.20. CONCLUSIONS: This study shows that spectral powers of FHR variability change as a fetus becomes hypoxic, and that spectral powers decrease with deepening fetal acidemia.

Developmental outcome at 6.5 years after acidosis in term newborns: a population-based study.

OBJECTIVES: Infants who develop encephalopathy after perinatal asphyxia have an increased risk of death and adverse neurologic outcome. Conflicting results exist concerning outcome in healthy infants with metabolic acidosis at birth. The aim of the current study was to evaluate whether metabolic acidosis at birth in term infants who appear healthy is associated with long-term developmental abnormalities. METHODS: From a population-based cohort (14,687 deliveries), 78 infants were prospectively identified as having metabolic acidosis (umbilical artery pH < 7.05 and base deficit in the extracellular fluid >12.0 mmol/L). Two matched controls per case were selected. The child health and school health care records were scrutinized for developmental abnormalities. RESULTS: Outcome measures at 6.5 years of age for 227 of 234 children (97%) were obtained. No differences were found concerning neurologic or behavioral problems in need of referral action or neurodevelopmental diagnosis in comparison of control children with acidotic children who had appeared healthy at birth, ie, had not required special neonatal care or had no signs of encephalopathy. CONCLUSIONS: Infants born with cord metabolic acidosis and who appear well do not have an increased risk for neurologic or behavioral problems in need of referral actions or special teaching approaches at the age of 6.5 years.

Fetal scalp pH and ST analysis of the fetal ECG as an adjunct to cardiotocography to predict fetal acidosis in labor--a multi-center, case controlled study.

OBJECTIVE: To assess the relationship between scalp pH (FBS) and ST analysis in situations of acidosis with special emphasis on the timing of cardiotocography (CTG), FBS and ST changes during labor. STUDY DESIGN: From a European Union multicenter study on clinical implementation of the STAN methodology, 911 cases were identified where a scalp-pH had been obtained. In 53 cases, marked cord artery acidosis was found (cord artery pH<7.06) and 44 cases showed moderate acidemia at birth (pH 7.06-7.09). Comparisons were made with 97 control cases (pH>or=7.20). RESULTS: Of those cases with FHR+ST events recorded within 16 min of delivery, 61% (17/28) had a cord artery pH>or=7.20. The corresponding figure for cases where STAN indications occurred for more than 16 min was 19% (13/69) (OR 6.66, 2.53-17.55, P<0.001). Out of the 121 cases with an abnormal CTG, 84 (69%) showed a cord artery pH of <7.10. STAN indicated abnormality in 83% (70 out of 84). The corresponding figure for scalp pH<7.20 was 43% (36/84). In the case of CTG changes at the start of an adequate recording STAN guidelines provided information on developing acidosis in all cases but one (16 out of 17) in the marked acidosis group. STAN guidelines indicated abnormality prior to an abnormal FBS in 14 out of 17 cases. The median duration between STAN indications to intervention and an abnormal FBS was 29 (95% CI 11-74) min. CONCLUSIONS: ST analysis, as an adjunct to CTG, identifies adverse fetal conditions during labor similar to that of FBS but on a more consistent basis. The timing of CTG+ST changes relates to the level of acidosis at birth.

A comparative study of fetal heart rate variability analysis techniques.

This study examines a novel methodology for continuous fetal heart rate variability (FHRV) assessment in a non-stationary intrapartum fetal heart rate (FHR). The specific aim was to investigate simple statistics, dimension estimates and entropy estimates as methods to discriminate situations of low FHRV related to non-reassuring fetal status or as a consequence of sedatives given to the mother. Using a t-test it is found that the dimension of the zero set and sample entropy reveal a difference in mean distribution of significance >99%. Thus it may prove possible to build a discriminating system based on either one or a combination of these techniques.

Fetal electrocardiogram waveform analysis in labour.

PURPOSE OF REVIEW: ST-waveform analysis of the fetal electrocardiogram (ECG) has emerged from experimental and observational studies to clinical use based on the outcome of two large randomized controlled trials and a European Union-supported project on the structured dissemination of knowledge and experience by establishing regional centres of excellence. The review focuses on the outcome from the host of studies and those recently published. RECENT FINDINGS: The database is dominated by a Swedish randomized controlled trial demonstrating not only improved outcome with regard to cord-artery metabolic acidosis and fewer operative interventions for non-reassuring fetal state but, most importantly, the marked and significant reduction in the risk of neonates showing signs of moderate or severe neonatal encephalopathy. The first report from the European Union project is presented, verifying the clinical relevance of the STAN methodology. The outcome of the large European Union project of 8000 deliveries confirms the observations of the randomized controlled trials. A study on the outcome shows improvements in accuracy and consistency among clinicians when automated ST analysis is added to the fetal heart rate trace. SUMMARY: After years of dedicated research, it appears as though ST analysis of the fetal ECG has become an additional source of information allowing detailed analysis of fetal responses and more accurate identification of a non-reassuring fetal status. The technology provides continuous information throughout labour. As with any new methodology, structured efforts on training and user feedback are required to fully implement the STAN methodology in clinical practice.

Marked fetal acidosis and specific changes in power spectrum analysis of fetal heart rate variability recorded during the last hour of labour.

OBJECTIVE: To assess whether intrapartum acidosis affects specific components of fetal heart rate variability. DESIGN: Prospective clinical study. SETTING: Twelve Nordic delivery units. SUBJECTS: Fetal heart rate variability was studied in 334 fetuses divided into two groups according to cord pH value: the acidotic group (cord arterial pH < 7.05 at birth, n= 15) and the control group (cord arterial pH > or =7.05 at birth, n= 319). METHODS: In spectral analysis of fetal heart rate variability, frequencies were integrated over the total frequency band (0.04-1.0 Hz), low-frequency band (0.04-0.15 Hz) and high-frequency band (0.15-1.0 Hz). We also calculated the low-to-high frequency ratio. MAIN OUTCOME MEASURES: The spectral bands of fetal heart rate variability were compared between the acidotic and control fetuses. RESULTS: We found that during the last hour of monitoring, baseline fetal heart rate gradually decreased, whereas total, low-frequency and high-frequency fetal heart rate variability initially increased but then, near the delivery, decreased in the acidotic fetuses when compared with the controls. Low-to-high frequency ratio was greater in the acidotic group during the whole study period (P= 0.002). Cord artery pH was inversely associated with total fetal heart rate variability (P < 0.001), low-frequency fetal heart rate variability (P < 0.001) and low-to-high frequency ratio (P= 0.004). CONCLUSIONS: Marked fetal acidosis was associated with frequency-specific changes in fetal heart rate variability as reflecting the compensation ability of autonomic nervous activation during the last hour of labour.