EUROPEAN ASSOCIATION OF PERINATAL MEDICINE (EAPM) Position statement: Use of appropriate terminology for situations related to inadequate fetal oxygenation in labor.

In high-resource countries, adverse perinatal outcomes are currently rare in term, non-malformed fetuses, undergoing labor, but they remain a leading cause of medico-legal dispute. Precise terminology is important to describe situations related to inadequate fetal oxygenation in labor, to ensure appropriate communication between healthcare professionals and adequate transmission of information to parents. This position statement provides consensus definitions from European perinatologists and midwives regarding the most appropriate terminology to describe situations related to inadequate fetal oxygenation in labor: suspected fetal hypoxia, severe newborn acidemia, newborn metabolic acidosis, and hypoxic-ischemic encephalopathy. It also identifies terms that are imprecise or nonspecific to this situation, and should therefore be avoided by healthcare professionals: fetal well-being, fetal stress, fetal distress, non-reassuring fetal state, and birth asphyxia.

An Update of Our Understanding of Fetal Heart Rate Patterns in Health and Disease.

UNDERSTANDING FETAL HEART RATE PATTERNS THAT MAY PREDICT ANTENATAL AND INTRAPARTUM NEURAL INJURY: Christopher A. Lear, Jenny A. Westgate, Austin Ugwumadu, Jan G. Nijhuis, Peter R. Stone, Antoniya Georgieva, Tomoaki Ikeda, Guido Wassink , Laura Bennet , Alistair J. Gunn Seminars in Pediatric Neurology Volume 28, December 2018, Pages 3-16 Electronic fetal heart rate (FHR) monitoring is widely used to assess fetal well-being throughout pregnancy and labor. Both antenatal and intrapartum FHR monitoring are associated with a high negative predictive value and a very poor positive predictive value. This in part reflects the physiological resilience of the healthy fetus and the remarkable effectiveness of fetal adaptations to even severe challenges. In this way, the majority of "abnormal" FHR patterns in fact reflect a fetus' appropriate adaptive responses to adverse in utero conditions. Understanding the physiology of these adaptations, how they are reflected in the FHR trace and in what conditions they can fail is therefore critical to appreciating both the potential uses and limitations of electronic FHR monitoring.

Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis.

BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). STUDY SELECTION AND DATA EXTRACTION: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2  = 62%, and 0.59 (95% CI 0.42, 0.82), I2  = 0 before; and 0.95 (95% CI 0.81, 1.11), I2  = 59%, and 0.90 (95% CI: 0.72, 1.12), I2  = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.

Fetal defenses against intrapartum head compression-implications for intrapartum decelerations and hypoxic-ischemic injury.

Uterine contractions during labor and engagement of the fetus in the birth canal can compress the fetal head. Its impact on the fetus is unclear and still controversial. In this integrative physiological review, we highlight evidence that decelerations are uncommonly associated with fetal head compression. Next, the fetus has an impressive ability to adapt to increased intracranial pressure through activation of the intracranial baroreflex, such that fetal cerebral perfusion is well-maintained during labor, except in the setting of prolonged systemic hypoxemia leading to secondary cardiovascular compromise. Thus, when it occurs, fetal head compression is not necessarily benign but does not seem to be a common contributor to intrapartum decelerations. Finally, the intracranial baroreflex and the peripheral chemoreflex (the response to acute hypoxemia) have overlapping efferent effects. We propose the hypothesis that these reflexes may work synergistically to promote fetal adaptation to labor.

A second look at intrapartum fetal surveillance and future directions.

Intrapartum fetal surveillance aims to predict significant fetal hypoxia and institute timely intervention to avoid fetal injury, and do so without unnecessary operative delivery of fetuses at no risk of intrapartum hypoxia. However, the configuration and application of current clinical guidelines inadvertently undermine these aims because of persistent failure to incorporate increased understanding of fetal cardiovascular physiology and adaptations to oxygen deprivation, advances in signal acquisition/processing, and related technologies. Consequently, the field on intrapartum fetal surveillance is stuck in rudimentary counts of the fetal R-R intervals and visual assessment of very common, but nonspecific fetal heart decelerations and fetal heart rate variability. The present authors argue that the time has come to move away from classifications of static morphological appearances of FHR decelerations, which do not assist the thinking clinician in understanding how the fetus defends itself and compensates for intrapartum hypoxic ischaemic insults or the patterns that suggest progressive loss of compensation. We also reappraise some of the controversial aspects of intrapartum fetal surveillance in modern obstetric practice, the current state of flux in training and certification, and contemplate the future of the field particularly in the context of the emerging role of artificial intelligence.

Cardiotocography and Clinical Risk Factors in Early Term Labor: A Retrospective Cohort Study Using Computerized Analysis With Oxford System.

Objective: The role of cardiotocography (CTG) in fetal risk assessment around the beginning of term labor is controversial. We used routinely collected clinical data in a large tertiary hospital to investigate whether infants with "severe compromise" at birth exhibited fetal heart rate abnormalities in their first-hour CTGs and/or other clinical risks, recorded as per routine care. Materials and Methods: Retrospective data from 27,927 parturitions (single UK tertiary site, 2001-2010) were analyzed. Cases were included if the pregnancy was singleton, ≥36 weeks' gestation, cephalic presentation, and if they had routine intrapartum CTG as per clinical care. Cases with congenital abnormalities, planned cesarean section (CS), or CS for reasons other than "presumed fetal compromise" were excluded. We analyzed first-hour intrapartum CTG recordings, using intrapartum Oxford System (OxSys) computer-based algorithms. To reflect the effect of routine clinical care, the data was stratified into three exclusive groups: infants delivered by CS for "presumed fetal compromise" within 2 h of starting the CTG (Emergency CS, n = 113); between 2 and 5 h of starting the CTG (Urgent CS, n = 203); and the rest of deliveries (Others, n = 27,611). First-hour CTG and clinical characteristics were compared between the groups, sub-divided to those with and without severe compromise: a composite outcome of stillbirth, neonatal death, neonatal seizures, encephalopathy, resuscitation followed by ≥48 h in neonatal intensive care unit. Two-sample t-test, X2 test, and Fisher's exact test were used for analysis. Results: Compared to babies without severe compromise, those with compromise had significantly higher proportion of cases with baseline fetal heart rate ≥150 bpm; non-reactive trace; reduced long-term and short-term variability; decelerative capacity; and no accelerations in the first-hour CTG across all groups. Prolonged decelerations(≥3 min) were also more common. Thick meconium and small for gestational age were consistently more common in compromised infants across all groups. There was more often thick meconium, maternal fever ≥38 C, sentinel events, and other clinical risk factors in the Emergency CS and Urgent CS compared to the Others group. Conclusion: A proportion of infants born with severe compromise had significantly different first-hour CTG features and clinical risk factors.

Physiological control of fetal heart rate variability during labour: implications and controversies.

The interpretation of fetal heart rate (FHR) patterns is the only available method to continuously monitor fetal well-being during labour. One of the most important yet contentious aspects of the FHR pattern is changes in FHR variability (FHRV). Some clinical studies suggest that loss of FHRV during labour is a sign of fetal compromise so this is reflected in practice guidelines. Surprisingly, there is little systematic evidence to support this observation. In this review we methodically dissect the potential pathways controlling FHRV during labour-like hypoxaemia. Before labour, FHRV is controlled by the combined activity of the parasympathetic and sympathetic nervous systems, in part regulated by a complex interplay between fetal sleep state and behaviour. By contrast, preclinical studies using multiple autonomic blockades have now shown that sympathetic neural control of FHRV was potently suppressed between periods of labour-like hypoxaemia, and thus, that the parasympathetic system is the sole neural regulator of FHRV once FHR decelerations are present during labour. We further discuss the pattern of changes in FHRV during progressive fetal compromise and highlight potential biochemical, behavioural and clinical factors that may regulate parasympathetic-mediated FHRV during labour. Further studies are needed to investigate the regulators of parasympathetic activity to better understand the dynamic changes in FHRV and their true utility during labour.

Fetal ST baseline T/QRS rise in normal CTG does not predict neonatal acidemia.

PURPOSE: Analysis of the ST segment of the fetal electrocardiogram (ECG) waveform is a relatively new adjunct to support the cardiotocograph in assessing the risk of significant intrapartum fetal acidosis. The use of ST analysis (STAN) combined with cardiotocography (CTG) was reported to significantly lower the incidence of metabolic acidosis. We aimed to assess the role of "baseline T/QRS rise" associated with a normal CTG on the risk of neonatal acidemia. STUDY DESIGN: This is a prospective cohort study performed at the Division of Perinatal Medicine of Policlinico Abano Terme, Italy. Women in labor with a singleton fetus in cephalic position beyond 36 weeks of gestation were monitored with STAN and CTG. PATIENTS AND METHODS: The relationship between "baseline T/QRS rise" and neonatal cord arterial acidemia and hypoxic distress were assessed using a linear mixed-model analysis. Magnitude of "baseline T/QRS rise", neonatal cord blood acidemia, electrolytes, lactacidemia, and glycemia levels were measured. RESULTS: "Baseline T/QRS rise" was not associated with neonatal acidemia in the presence of normal CTG, regardless of the magnitude of the T/QRS rise. However, in a linear mixed-model analysis, cord blood sodium levels were negatively (p = .033) associated with T/QRS ratio magnitude. CONCLUSIONS: In the presence of a normal CTG, "baseline T/QRS rise" does not predict neonatal acidemia or biochemical derangement. Greater knowledge of fetal ECG parameters including "baseline T/QRS rise" and their associations with normal, intermediary, and abnormal CTG tracing, is required in assessing the performance of the STAN.

Computer-based intrapartum fetal monitoring and beyond: A review of the 2nd Workshop on Signal Processing and Monitoring in Labor (October 2017, Oxford, UK).

The second Signal Processing and Monitoring in Labor workshop gathered researchers who utilize promising new research strategies and initiatives to tackle the challenges of intrapartum fetal monitoring. The workshop included a series of lectures and discussions focusing on: new algorithms and techniques for cardiotocogoraphy (CTG) and electrocardiogram acquisition and analyses; the results of a CTG evaluation challenge comparing state-of-the-art computerized methods and visual interpretation for the detection of arterial cord pH <7.05 at birth; the lack of consensus about the role of intrapartum acidemia in the etiology of fetal brain injury; the differences between methods for CTG analysis "mimicking" expert clinicians and those derived from "data-driven" analyses; a critical review of the results from two randomized controlled trials testing the former in clinical practice; and relevant insights from modern physiology-based studies. We concluded that the automated algorithms performed comparably to each other and to clinical assessment of the CTG. However, the sensitivity and specificity urgently need to be improved (both computerized and visual assessment). Data-driven CTG evaluation requires further work with large multicenter datasets based on well-defined labor outcomes. And before first tests in the clinic, there are important lessons to be learnt from clinical trials that tested automated algorithms mimicking expert CTG interpretation. In addition, transabdominal fetal electrocardiogram monitoring provides reliable CTG traces and variability estimates; and fetal electrocardiogram waveform analysis is subject to promising new research. There is a clear need for close collaboration between computing and clinical experts. We believe that progress will be possible with multidisciplinary collaborative research.

Fetal electrocardiography ST-segment analysis for intrapartum monitoring: a critical appraisal of conflicting evidence and a way forward.

BACKGROUND: In the past century, some areas of obstetric including intrapartum care have been slow to benefit from the dramatic advances in technology and medical care. Although fetal heart rate monitoring (cardiotocography) became available a half century ago, its interpretation often differs between institutions and countries, its diagnostic accuracy needs improvement, and a technology to help reduce the unnecessary obstetric interventions that have accompanied the cardiotocography is urgently needed. STUDY DESIGN: During the second half of the 20th century, key findings in animal experiments captured the close relationship between myocardial glycogenolysis, myocardial workload, and ST changes, thus demonstrating that ST waveform analysis of the fetal electrocardiogram can provide information on oxygenation of the fetal myocardium and establishing the physiological basis for the use of electrocardiogram in intrapartum fetal surveillance. RESULTS: Six randomized controlled trials, 10 meta-analyses, and more than 20 observational studies have evaluated the technology developed based on this principle. Nonetheless, despite this intensive assessment, differences in study protocols, inclusion criteria, enrollment rates, clinical guidelines, use of fetal blood sampling, and definitions of key outcome parameters, as well as inconsistencies in randomized controlled trial data handling and statistical methodology, have made this voluminous evidence difficult to interpret. Enormous resources spent on randomized controlled trials have failed to guarantee the generalizability of their results to other settings or their ability to reflect everyday clinical practice. CONCLUSION: The latest meta-analysis used revised data from primary randomized controlled trials and data from the largest randomized controlled trials from the United States to demonstrate a significant reduction of metabolic acidosis rates by 36% (odds ratio, 0.64; 95% confidence interval, 0.46-0.88) and operative vaginal delivery rates by 8% (relative risk, 0.92; 95% confidence interval, 0.86-0.99), compared with cardiotocography alone.

Understanding Fetal Heart Rate Patterns That May Predict Antenatal and Intrapartum Neural Injury.

Electronic fetal heart rate (FHR) monitoring is widely used to assess fetal well-being throughout pregnancy and labor. Both antenatal and intrapartum FHR monitoring are associated with a high negative predictive value and a very poor positive predictive value. This in part reflects the physiological resilience of the healthy fetus and the remarkable effectiveness of fetal adaptations to even severe challenges. In this way, the majority of "abnormal" FHR patterns in fact reflect a fetus' appropriate adaptive responses to adverse in utero conditions. Understanding the physiology of these adaptations, how they are reflected in the FHR trace and in what conditions they can fail is therefore critical to appreciating both the potential uses and limitations of electronic FHR monitoring.

The peripheral chemoreflex: indefatigable guardian of fetal physiological adaptation to labour.

The fetus is consistently exposed to repeated periods of impaired oxygen (hypoxaemia) and nutrient supply in labour. This is balanced by the healthy fetus's remarkable anaerobic tolerance and impressive ability to mount protective adaptations to hypoxaemia. The most important mediator of fetal adaptations to brief repeated hypoxaemia is the peripheral chemoreflex, a rapid reflex response to acute falls in arterial oxygen tension. The overwhelming majority of fetuses are able to respond to repeated uterine contractions without developing hypotension or hypoxic-ischaemic injury. In contrast, fetuses who are either exposed to severe hypoxaemia, for example during uterine hyperstimulation, or enter labour with reduced anaerobic reserve (e.g. as shown by severe fetal growth restriction) are at increased risk of developing intermittent hypotension and cerebral hypoperfusion. It is remarkable to note that when fetuses develop hypotension during such repeated severe hypoxaemia, it is not mediated by impaired reflex adaptation, but by failure to maintain combined ventricular output, likely due to a combination of exhaustion of myocardial glycogen and evolving myocardial injury. The chemoreflex is suppressed by relatively long periods of severe hypoxaemia of 1.5-2 min, longer than the typical contraction. Even in this setting, the peripheral chemoreflex is consistently reactivated between contractions. These findings demonstrate that the peripheral chemoreflex is an indefatigable guardian of fetal adaptation to labour.

Impediments to a unified international approach to the interpretation and management of intrapartum cardiotocographs.

There is much inconsistency in management recommendations for cardiotocograms by international organizations. Impediments to achieving consensus include disagreement on the spectrum of risk of fetal acidemia, different fetal heart rate pattern display due to differing chart paper speed, and the necessity for ancillary testing in confirming fetal acidemia.

Central Fetal Monitoring With and Without Computer Analysis: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether intrapartum fetal monitoring with computer analysis and real-time alerts decreases the rate of newborn metabolic acidosis or obstetric intervention when compared with visual analysis. METHODS: A randomized clinical trial carried out in five hospitals in the United Kingdom evaluated women with singleton, vertex fetuses of 36 weeks of gestation or greater during labor. Continuous central fetal monitoring by computer analysis and online alerts (experimental arm) was compared with visual analysis (control arm). Fetal blood sampling and electrocardiographic ST waveform analysis were available in both arms. The primary outcome was incidence of newborn metabolic acidosis (pH less than 7.05 and base deficit greater than 12 mmol/L). Prespecified secondary outcomes included operative delivery, use of fetal blood sampling, low 5-minute Apgar score, neonatal intensive care unit admission, hypoxic-ischemic encephalopathy, and perinatal death. A sample size of 3,660 per group (N=7,320) was planned to be able to detect a reduction in the rate of metabolic acidosis from 2.8% to 1.8% (two-tailed α of 0.05 with 80% power). RESULTS: From August 2011 through July 2014, 32,306 women were assessed for eligibility and 7,730 were randomized: 3,961 to computer analysis and online alerts, and 3,769 to visual analysis. Baseline characteristics were similar in both groups. Metabolic acidosis occurred in 16 participants (0.40%) in the experimental arm and 22 participants (0.58%) in the control arm (relative risk 0.69 [0.36-1.31]). No statistically significant differences were found in the incidence of secondary outcomes. CONCLUSION: Compared with visual analysis, computer analysis of fetal monitoring signals with real-time alerts did not significantly reduce the rate of metabolic acidosis or obstetric intervention. A lower-than-expected rate of newborn metabolic acidosis was observed in both arms of the trial. CLINICAL TRIAL REGISTRATION: ISRCTN Registry, http://www.isrctn.com, ISRCTN42314164.

Agreement and accuracy using the FIGO, ACOG and NICE cardiotocography interpretation guidelines.

INTRODUCTION: One of the limitations reported with cardiotocography is the modest interobserver agreement observed in tracing interpretation. This study compared agreement, reliability and accuracy of cardiotocography interpretation using the International Federation of Gynecology and Obstetrics, American College of Obstetrics and Gynecology and National Institute for Health and Care Excellence guidelines. MATERIAL AND METHODS: A total of 151 tracings were evaluated by 27 clinicians from three centers where International Federation of Gynecology and Obstetrics, American College of Obstetrics and Gynecology and National Institute for Health and Care Excellence guidelines were routinely used. Interobserver agreement was evaluated using the proportions of agreement and reliability with the κ statistic. The accuracy of tracings classified as "pathological/category III" was assessed for prediction of newborn acidemia. For all measures, 95% confidence interval were calculated. RESULTS: Cardiotocography classifications were more distributed with International Federation of Gynecology and Obstetrics (9, 52, 39%) and National Institute for Health and Care Excellence (30, 33, 37%) than with American College of Obstetrics and Gynecology (13, 81, 6%). The category with the highest agreement was American College of Obstetrics and Gynecology category II (proportions of agreement = 0.73, 95% confidence interval 0.70-76), and the ones with the lowest agreement were American College of Obstetrics and Gynecology categories I and III. Reliability was significantly higher with International Federation of Gynecology and Obstetrics (κ = 0.37, 95% confidence interval 0.31-0.43), and National Institute for Health and Care Excellence (κ = 0.33, 95% confidence interval 0.28-0.39) than with American College of Obstetrics and Gynecology (κ = 0.15, 95% confidence interval 0.10-0.21); however, all represent only slight/fair reliability. International Federation of Gynecology and Obstetrics and National Institute for Health and Care Excellence showed a trend towards higher sensitivities in prediction of newborn acidemia (89 and 97%, respectively) than American College of Obstetrics and Gynecology (32%), but the latter achieved a significantly higher specificity (95%). CONCLUSIONS: With American College of Obstetrics and Gynecology guidelines there is high agreement in category II, low reliability, low sensitivity and high specificity in prediction of acidemia. With International Federation of Gynecology and Obstetrics and National Institute for Health and Care Excellence guidelines there is higher reliability, a trend towards higher sensitivity, and lower specificity in prediction of acidemia.

Understanding cardiotocographic patterns associated with intrapartum fetal hypoxia and neurologic injury.

Widespread use of fetal heart rate monitoring for intrapartum fetal surveillance preceded our detailed understanding of the behaviour and regulation of the fetal cardiovascular system during labour. The fetal heart rate is sensitive to fetal hypoxaemia and hypoxia, but lacks specificity for fetal acidosis, the end point of unmitigated hypoxaemia and hypoxia. Original interpretations of fetal heart rate patterns equated decelerations to 'fetal distress' and mandated operative intervention. Since then, obstetricians have been trained to focus on the morphological appearances of fetal heart rate decelerations rather than to understand the underlying physiological mechanisms, how the fetus compensates and defends itself, and those patterns that suggest progressive loss of compensation. Consequently, operative interventions are commonly undertaken to 'rescue' fetuses that display benign signs of fetal heart rate adaption to events in labour. Failure to recognise abnormal fetal heart rate patterns remains the leading cause of avoidable brain injury and litigation. In this chapter the general characteristics of the fetal heart rate, the changes in fetal heart rate pattern that may occur during labour, and the patterns that suggest failure of the fetal compensatory mechanisms leading to injury are discussed.