Effect of maternal hyperoxygenation on neonatal outcomes among women in labour with pathological cardiotocography: an open-label randomized controlled trial.

BACKGROUND: Hyperoxygenation has shown promise in improving suspicious fetal heart patterns in women in labor. However, the effect of hyperoxygenation on neonatal outcomes in women in labor with pathologic fetal heart rate tracing has not been studied. OBJECTIVE: This study aimed to evaluate the effect of fractional inspiration of oxygen of 80% compared with fractional inspiration of oxygen of 40% on neonatal outcomes in women with pathologic fetal heart rate tracing. STUDY DESIGN: This randomized, open-label, parallel arm, outcome assessor-blinded clinical trial was conducted in a large tertiary care university hospital. Singleton parturients aged ≥18 years at term gestation in active labor (cervical dilatation of ≥6 cm) with pathologic fetal heart rate tracing were recruited in the study. Pathologic fetal heart rate tracing was defined according to the International Federation of Gynecology and Obstetrics 2015 guidelines. The International Federation of Gynecology and Obstetrics classifies fetal heart rate tracings into 3 categories (normal, suspicious, and pathologic) based on rate, variability, and deceleration. Women in the intervention arm received oxygen at 10 L/min via a nonrebreathing mask, and those in the usual care arm received oxygen at 6 L/min with a simple face mask. Oxygen supplementation was continued until cord clamping. The primary outcome measure was a 5-minute Apgar score. The secondary outcome measures were the proportion of neonatal intensive care unit admission, umbilical cord blood gas variables, level of methyl malondialdehyde in the cord blood, and mode of delivery. RESULTS: Overall, 148 women (74 women in the high fractional inspiration of oxygen arm and 74 in the low fractional inspiration of oxygen arm) with pathologic fetal heart rate tracing were analyzed. The demographic data, obstetrical profiles, and comorbidities were comparable. The median 5-minute Apgar scores were 9 (interquartile range, 8-10) in the hyperoxygenation arm and 9 (interquartile range, 8-10) in the usual care arm (P=.12). Furthermore, the rate of neonatal intensive care unit admission (9.5% vs 12.2%; P=.6) and the requirement of positive pressure ventilation (6.8% vs 8.1%; P=.75) were comparable. Concerning cord blood gas parameters, the hyperoxygenation arm had a significantly higher base deficit in the umbilical vein and lactate level in the umbilical artery. The cesarean delivery rate was significantly lower in women who received hyperoxygenation (4.1% [3/74]) than in women who received normal oxygen supplementation (25.7% [19/74]) (P=.00). In addition, umbilical vein malondialdehyde level in the umbilical vein was lower in the hyperoxygenation group (8.28±4.65 µmol/L) than in the normal oxygen supplementation group (13.44±8.34 µmol/L) (P=.00). CONCLUSION: Hyperoxygenation did not improve the neonatal Apgar score in women with pathologic fetal heart rate tracing. In addition, neonatal intensive care unit admission rate and blood gas parameters remained comparable. Therefore, the results of this trial suggest that a high fractional inspiration of oxygen supplementation confers no benefit on neonatal outcomes in women with pathologic fetal heart rate tracings and normal oxygen saturation.

Intrapartum cardiotocography with simultaneous maternal heart rate registration improves neonatal outcome.

BACKGROUND: Intrapartum cardiotocographic monitoring of fetal heart rate by abdominal external ultrasound transducer without simultaneous maternal heart rate recording has been associated with increased risk of early neonatal death and other asphyxia-related neonatal outcomes. It is unclear, however, whether this increase in risk is independently associated with fetal surveillance method or is attributable to other factors. OBJECTIVE: This study aimed to compare different fetal surveillance methods and their association with adverse short- and long-term fetal and neonatal outcomes in a large retrospective cohort of spontaneous term deliveries. STUDY DESIGN: Fetal heart rate and maternal heart rate patterns were recorded by cardiotocography during labor in spontaneous term singleton cephalic vaginal deliveries in the Hospital District of Helsinki and Uusimaa, Finland between October 1, 2005, and September 30, 2023. According to the method of cardiotocography monitoring at birth, the cohort was divided into the following 3 groups: women with ultrasound transducer, women with both ultrasound transducer and maternal heart rate transducer, and women with internal fetal scalp electrode. Umbilical artery pH and base excess values, low 1- and 5-minute Apgar scores, need for intubation and resuscitation, neonatal intensive care unit admission for asphyxia, neonatal encephalopathy, and early neonatal death were used as outcome variables. RESULTS: Among the 213,798 deliveries that met the inclusion criteria, the monitoring type was external ultrasound transducer in 81,559 (38.1%), both external ultrasound transducer and maternal heart rate recording in 62,268 (29.1%), and fetal scalp electrode in 69,971 (32.7%) cases, respectively. The rates of both neonatal encephalopathy (odds ratio, 1.48; 95% confidence interval, 1.08-2.02) and severe acidemia (umbilical artery pH <7.00 and/or umbilical artery base excess ≤-12.0 mmol/L) (odds ratio, 2.03; 95% confidence interval, 1.65-2.50) were higher in fetuses of women with ultrasound transducer alone compared with those of women with concurrent external fetal and maternal heart rate recording. Monitoring with ultrasound transducer alone was also associated with increased risk of neonatal intubation for resuscitation (odds ratio, 1.22; 95% confidence interval, 1.03-1.44). A greater risk of severe neonatal acidemia was observed both in the ultrasound transducer (odds ratio, 2.78; 95% confidence interval, 2.23-3.48) and concurrent ultrasound transducer and maternal heart rate recording (odds ratio, 1.37; 95% confidence interval, 1.05-1.78) groups compared with those monitored with fetal scalp electrodes. No difference in risk of neonatal encephalopathy was found between newborns monitored with concurrent ultrasound transducer and maternal heart rate recording and those monitored with fetal scalp electrodes. CONCLUSION: The use of external ultrasound transducer monitoring of fetal heart rate without simultaneous maternal heart rate recording is associated with higher rates of neonatal encephalopathy and severe neonatal acidemia. We suggest that either external fetal heart rate monitoring with concurrent maternal heart rate recording or internal fetal scalp electrode be used routinely as a fetal surveillance tool in term deliveries.

Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

Re-evaluating fetal scalp pH thresholds: An examination of fetal pH variations during labor.

INTRODUCTION: Since the 1970s, fetal scalp blood sampling (FSBS) has been used as a second-line test of the acid-base status of the fetus to evaluate fetal well-being during labor. The commonly employed thresholds that delineate normal pH (>7.25), subnormal (7.20-7.25), and pathological pH (<7.20) guide clinical decisions. However, these experienced-based thresholds, based on observations and common sense, have yet to be confirmed. The aim of the study was to investigate if pH drop rate accelerates at the common thresholds (7.25 and 7.20) and to explore the possibility of identifying more accurate thresholds. MATERIAL AND METHODS: A retrospective study was conducted at a tertiary maternity hospital between June 2017 and July 2021. Patients with at least one FSBS during labor for category II fetal heart rate and delivery of a singleton cephalic infant were included. The rate of change in pH value between consecutive samples for each patient was calculated and plotted as a function of pH value. Linear regression models were used to model the evolution of the pH drop rate estimating slope and standard errors across predefined pH intervals. Exploration of alternative pH action thresholds was conducted. To explore the independence of the association between pH value and pH drop rate, multiple linear regression adjusted on age, body mass index, parity, oxytocin stimulation and suspected small for gestational age was performed. RESULTS: We included 2047 patients with at least one FSBS (total FSBS 3467); with 2047 umbilical cord blood pH, and a total of 5514 pH samples. Median pH values were 7.29 1 h before delivery, 7.26 30 min before delivery. The pH drop was slow between 7.40 and 7.30, then became more pronounced, with median rates of 0.0005 units/min at 7.25 and 0.0013 units/min at 7.20. Out of the alternative pH thresholds, 7.26 and 7.20 demonstrated the best alignment with our dataset. Multiple linear regression revealed that only pH value was significantly associated to the rate of pH change. CONCLUSIONS: Our study confirms the validity and reliability of current guideline thresholds for fetal scalp pH in category II fetal heart rate.

Evaluation and patient experience of wireless noninvasive fetal heart rate monitoring devices.

INTRODUCTION: In clinical practice, fetal heart rate monitoring is performed intermittently using Doppler ultrasound, typically for 30 minutes. In case of a non-reassuring heart rate pattern, monitoring is usually prolonged. Noninvasive fetal electrocardiography may be more suitable for prolonged monitoring due to improved patient comfort and signal quality. This study evaluates the performance and patient experience of four noninvasive electrocardiography devices to assess candidate devices for prolonged noninvasive fetal heart rate monitoring. MATERIAL AND METHODS: Non-critically sick women with a singleton pregnancy from 24 weeks of gestation were eligible for inclusion. Fetal heart rate monitoring was performed during standard care with a Doppler ultrasound device (Philips Avalon-FM30) alone or with this Doppler ultrasound device simultaneously with one of four noninvasive electrocardiography devices (Nemo Fetal Monitoring System, Philips Avalon-Beltless, Demcon Dipha-16 and Dräger Infinity-M300). Performance was evaluated by: success rate, positive percent agreement, bias, 95% limits of agreement, regression line, root mean square error and visual agreement using FIGO guidelines. Patient experience was captured using a self-made questionnaire. RESULTS: A total of 10 women were included per device. For fetal heart rate, Nemo performed best (success rate: 99.4%, positive percent agreement: 94.2%, root mean square error 5.1 BPM, bias: 0.5 BPM, 95% limits of agreement: -9.7 - 10.7 BPM, regression line: y = -0.1x + 11.1) and the cardiotocography tracings obtained simultaneously by Nemo and Avalon-FM30 received the same FIGO classification. Comparable results were found with the Avalon-Beltless from 36 weeks of gestation, whereas the Dipha-16 and Infinity-M300 performed significantly worse. The Avalon-Beltless, Nemo and Infinity-M300 closely matched the performance of the Avalon-FM30 for maternal heart rate, whereas the performance of the Dipha-16 deviated more. Patient experience scores were higher for the noninvasive electrocardiography devices. CONCLUSIONS: Both Nemo and Avalon-Beltless are suitable devices for (prolonged) noninvasive fetal heart rate monitoring, taking their intended use into account. But outside its intended use limit of 36 weeks' gestation, the Avalon-Beltless performs less well, comparable to the Dipha-16 and Infinity-M300, making them currently unsuitable for (prolonged) noninvasive fetal heart rate monitoring. Noninvasive electrocardiography devices appear to be preferred due to greater comfort and mobility.

Large-scale analysis of interobserver agreement and reliability in cardiotocography interpretation during labor using an online tool.

BACKGROUND: While the effectiveness of cardiotocography in reducing neonatal morbidity is still debated, it remains the primary method for assessing fetal well-being during labor. Evaluating how accurately professionals interpret cardiotocography signals is essential for its effective use. The objective was to evaluate the accuracy of fetal hypoxia prediction by practitioners through the interpretation of cardiotocography signals and clinical variables during labor. MATERIAL AND METHODS: We conducted a cross-sectional online survey, involving 120 obstetric healthcare providers from several countries. One hundred cases, including fifty cases of fetal hypoxia, were randomly assigned to participants who were invited to predict the fetal outcome (binary criterion of pH with a threshold of 7.15) based on the cardiotocography signals and clinical variables. After describing the participants, we calculated (with a 95% confidence interval) the success rate, sensitivity and specificity to predict the fetal outcome for the whole population and according to pH ranges, professional groups and number of years of experience. Interobserver agreement and reliability were evaluated using the proportion of agreement and Cohen's kappa respectively. RESULTS: The overall ability to predict a pH level below 7.15 yielded a success rate of 0.58 (95% CI 0.56-0.60), a sensitivity of 0.58 (95% CI 0.56-0.60) and a specificity of 0.63 (95% CI 0.61-0.65). No significant difference in the success rates was observed with respect to profession and number of years of experience. The success rate was higher for the cases with a pH level below 7.05 (0.69) and above 7.20 (0.66) compared to those falling between 7.05 and 7.20 (0.48). The proportion of agreement between participants was good (0.82), with an overall kappa coefficient indicating substantial reliability (0.63). CONCLUSIONS: The use of an online tool enabled us to collect a large amount of data to analyze how practitioners interpret cardiotocography data during labor. Despite a good level of agreement and reliability among practitioners, the overall accuracy is poor, particularly for cases with a neonatal pH between 7.05 and 7.20. Factors such as profession and experience level do not present notable impact on the accuracy of the annotations. The implementation and use of a computerized cardiotocography analysis software has the potential to enhance the accuracy to detect fetal hypoxia, especially for ambiguous cardiotocography tracings.

Relative uteroplacental insufficiency of labor.

Relative uteroplacental insufficiency of labor (RUPI-L) is a clinical condition that refers to alterations in the fetal oxygen "demand-supply" equation caused by the onset of regular uterine activity. The term RUPI-L indicates a condition of "relative" uteroplacental insufficiency which is relative to a specific stressful circumstance, such as the onset of regular uterine activity. RUPI-L may be more prevalent in fetuses in which the ratio between the fetal oxygen supply and demand is already slightly reduced, such as in cases of subclinical placental insufficiency, post-term pregnancies, gestational diabetes, and other similar conditions. Prior to the onset of regular uterine activity, fetuses with a RUPI-L may present with normal features on the cardiotocography. However, with the onset of uterine contractions, these fetuses start to manifest abnormal fetal heart rate patterns which reflect the attempt to maintain adequate perfusion to essential central organs during episodes of transient reduction in oxygenation. If labor is allowed to continue without an appropriate intervention, progressively more frequent, and stronger uterine contractions may result in a rapid deterioration of the fetal oxygenation leading to hypoxia and acidosis. In this Commentary, we introduce the term relative uteroplacental insufficiency of labor and highlight the pathophysiology, as well as the common features observed in the fetal heart rate tracing and clinical implications.

Correlation of fetal heart rate dynamics to inflammatory markers and brain-derived neurotrophic factor during pregnancy.

OBJECTIVES: This study aims to show the relation between biomarkers in maternal and cord-blood samples and fetal heart rate variability (fHRV) metrics through a non-invasive fetal magnetocardiography (fMCG) technique. METHODS: Twenty-three women were enrolled for collection of maternal serum and fMCG tracings immediately prior to their scheduled cesarean delivery. The umbilical cord blood was collected for measurement of biomarker levels. The fMCG metrics were then correlated to the biomarker levels from the maternal serum and cord blood. RESULTS: Brain-derived neurotrophic factor (BDNF) had a moderate correlation with fetal parasympathetic activity (0.416) and fetal sympathovagal ratios (-0.309; -0.356). Interleukin (IL)-6 also had moderate-sized correlations but with an inverse relationship as compared to BDNF. These correlations were primarily in cord-blood samples and not in the maternal blood. CONCLUSIONS: In this small sample-sized exploratory study, we observed a moderate correlation between fHRV and cord-blood BDNF and IL-6 immediately preceding scheduled cesarean delivery at term. These findings need to be validated in a larger population.

Hybrid-FHR: a multi-modal AI approach for automated fetal acidosis diagnosis.

BACKGROUND: In clinical medicine, fetal heart rate (FHR) monitoring using cardiotocography (CTG) is one of the most commonly used methods for assessing fetal acidosis. However, as the visual interpretation of CTG depends on the subjective judgment of the clinician, this has led to high inter-observer and intra-observer variability, making it necessary to introduce automated diagnostic techniques. METHODS: In this study, we propose a computer-aided diagnostic algorithm (Hybrid-FHR) for fetal acidosis to assist physicians in making objective decisions and taking timely interventions. Hybrid-FHR uses multi-modal features, including one-dimensional FHR signals and three types of expert features designed based on prior knowledge (morphological time domain, frequency domain, and nonlinear). To extract the spatiotemporal feature representation of one-dimensional FHR signals, we designed a multi-scale squeeze and excitation temporal convolutional network (SE-TCN) backbone model based on dilated causal convolution, which can effectively capture the long-term dependence of FHR signals by expanding the receptive field of each layer's convolution kernel while maintaining a relatively small parameter size. In addition, we proposed a cross-modal feature fusion (CMFF) method that uses multi-head attention mechanisms to explore the relationships between different modalities, obtaining more informative feature representations and improving diagnostic accuracy. RESULTS: Our ablation experiments show that the Hybrid-FHR outperforms traditional previous methods, with average accuracy, specificity, sensitivity, precision, and F1 score of 96.8, 97.5, 96, 97.5, and 96.7%, respectively. CONCLUSIONS: Our algorithm enables automated CTG analysis, assisting healthcare professionals in the early identification of fetal acidosis and the prompt implementation of interventions.

Does maternal oxygen administration during non-reassuring fetal status affect the umbilical artery gas measures and neonatal outcomes?

PURPOSE: To clarify whether maternal oxygen administration during vaginal delivery improves umbilical artery (UA) gas measurements and neonatal outcomes. METHODS: Singleton pregnancies requiring operative vaginal delivery or emergency cesarean section (CS) due to non-reassuring fetal status (NRFS) during vaginal delivery at our hospital from 2018 to 2021 were retrospectively investigated. Intrapartum fetal wellbeing was evaluated based on the 5-tier fetal heart rate (FHR) pattern which is a delivery management method widely used in Japan. Operative vaginal deliveries or emergency CS was performed under integrated judgment in NRFS. Patients were divided into the oxygen group to whom oxygen (10 L/min) was supplied by a facemask and the room air group. The UA gas measurements and neonatal outcomes were compared. The oxygen administration was classified by conditions before and after the coronavirus disease 2019 pandemic. As a secondary evaluation, stratification of FHR pattern levels and factors associated with UA pH < 7.15 were examined. RESULTS: A total of 250 patients required obstetric surgical delivery due to NRFS, including 140 (56%) and 110 (44%) in the oxygen and room air groups, respectively. No differences in maternal background factors were found between both groups, except for maternal age. UA gas measurements and neonatal outcomes also showed no significant differences. No significant factors were extracted in the multivariate analysis for UA pH < 7.15. CONCLUSIONS: Trans-maternal oxygen administration for intrapartum NRFS did not affect neonatal cord blood gasses or neonatal outcomes. Thus, routine oxygen administration for intrapartum NRFS may not always be necessary.

The benefit of active management in true knot of the umbilical cord: a retrospective study.

PURPOSE: To compare perinatal outcomes between active and routine management in true knot of the umbilical cord (TKUC). METHODS: A retrospective study of singletons born beyond 22 6/7 weeks with TKUC. Active management included weekly fetal heart rate monitoring(FHRM) ≥ 30 weeks and labor induction at 36-37 weeks. Outcomes in active and routine management were compared, including composite asphyxia-related adverse outcome, fetal death, labor induction, Cesarean section (CS) or Instrumental delivery due to non-reassuring fetal heart rate (NRFHR), Apgar5 score < 7, cord Ph < 7, neonatal intensive care unit (NICU) admission and more. RESULTS: The Active (n = 59) and Routine (n = 1091) Management groups demonstrated similar rates of composite asphyxia-related adverse outcome (16.9% vs 16.8%, p = 0.97). Active Management resulted in higher rates of labor induction < 37 weeks (22% vs 1.7%, p < 0.001), CS (37.3% vs 19.2%, p = 0.003) and NICU admissions (13.6% vs 3%, p < 0.001). Fetal death occurred exclusively in the Routine Management group (1.8% vs 0%, p = 0.6). CONCLUSION: Compared with routine management, weekly FHRM and labor induction between 36 and 37 weeks in TKUC do not appear to reduce neonatal asphyxia. In its current form, active management is associated with higher rates of CS, induced prematurity and NICU admissions. Labor induction before 37 weeks should be avoided.

Is lower fetal heart rate variability a susceptibility marker to the impact of negative coparenting on infant regulatory capacity?

Lower fetal heart rate variability (FHRV) may be a prenatal endophenotypic susceptibility marker and increase the impact of both positive and negative coparenting on infant regulatory capacity. This study analyzed the moderator role of FHRV in the association between positive and negative coparenting and infant regulatory capacity at 3 months. The sample comprised 86 first-born infants and their mothers and fathers recruited at a public Health Service in Northern Portugal. FHRV was recorded during routine cardiotocography examination at the third trimester of gestation. Mothers and fathers reported on coparenting and infant regulatory capacity at 2 weeks and 3 months postpartum. FHRV moderated the association between mother's and father's negative coparenting at 2 weeks postpartum and infant regulatory capacity at three months. Infants with low FHRV presented higher regulatory capacity when mothers or fathers reported less negative coparenting, while lower regulatory capacity when mothers or fathers reported more negative coparenting, than infants with high FHRV. Findings suggested lower FHRV as a prenatal endophenotypic susceptibility marker that increases the impact of negative coparenting on infant regulatory capacity.

La más baja variabilidad del pulso cardíaco fetal (FHRV) pudiera ser un marcador determinante de la susceptibilidad endofenotípica prenatal y aumentar el impacto de la crianza compartida tanto positiva como negativa sobre la capacidad regulatoria del infante. Este estudio analizó el papel moderador de FHRV en la asociación entre la positiva y negativa crianza compartida y la capacidad regulatoria del infante a los tres meses. El grupo muestra estaba compuesto de 86 infantes primerizos y sus mamás y papás. Se grabó la FHRV durante una examinación de cardiotocografía de rutina en el tercer trimestre de la gestación. Las mamás y los papás reportaron acerca de la crianza compartida y la capacidad regulatoria del infante a las dos semanas y a los tres meses después del parto. La FHRV moderó la asociación entre la crianza compartida negativa de la mamá y del papá a las dos semanas después del parto y la capacidad regulatoria del infante a los tres meses. Los infantes con baja FHRV presentaron una capacidad regulatoria más alta cuando las mamás o los papás reportaron una crianza compartida menos negativa, mientras que la capacidad regulatoria más baja se dio cuando las mamás o los papás reportaron una crianza compartida más negativa, que los infantes con una FHRV alta. Los resultados señalan la más baja FHRV como un marcador determinante de la susceptibilidad endofenotípica prenatal que aumenta el impacto de la crianza compartida negativa sobre la capacidad regulatoria del infante. Los infantes con baja FHRV pueden ser aquellos que mejor desarrollan mecanismos de autorregulación en la presencia de una crianza compartida menos negativa, mientras que están bajo alto riesgo de problemas regulatorios en la presencia de una crianza compartida más negativa.

Une variabilité de la fréquence cardiaque fœtale (VFCF) plus basse pourrait être un marqueur de sensibilité endophénotypique prénatale et augmenter l'impact du coparentage positif et négatif sur la capacité régulatoire du nourrisson. Cette étude a analysé le rôle modérateur de la VFCF dans le lien entre le coparentage positif et négatif et la capacité régulatoire du nourrisson à trois mois. Cet échantillon a inlu 86 nourrisson premiers nés et leurs mères et pères. La VFCF a été enregistrée penfdant un examen de cardiotocographie de routine au troisième trimestre de la grossesse. Les mères et les pères ont fait état de leur coparentage et de la capacité régulatoire du nourrisson à deux semaines et à trois mois postpartum. La VFCF a modéré le lien entre le coparentage négatif de la mère et du père à deux mois postpartum et la capacité régulatoire du nourrisson à trois mois. Les nourrissons avec une VFCF basse ont présenté une capacité régulatoire plus élevée lorsque les mères ou les pères ont signalé moins de coparentage négatif, alors qu'ils ont présenté une capacité régulatoire plus basse lorsque les mères ou les pères ont signalé un coparentage plus négatif, que les nourrissons avec une VFCF élevée. Les résultats ont suggéré une VFCF plus basse comme un marqueur de sensibilité endophénotypique prénatale qui augmente l'impact de coparentage négatif sur la capacité régulatoire du nourrisson. Les enfants avec une VFCF basse peuvent être ceux qui développent mieux leurs mécanismes auto-régulatoires en présence de moins de coparentage négatif, tout en étant à haut risque de problèmes régulatoires en présence de plus de coparentage négatif.

Dissecting the contributions of the peripheral chemoreflex and myocardial hypoxia to fetal heart rate decelerations in near-term fetal sheep.

Brief repeated fetal hypoxaemia during labour can trigger intrapartum decelerations of the fetal heart rate (FHR) via the peripheral chemoreflex or the direct effects of myocardial hypoxia, but the relative contribution of these two mechanisms and how this balance changes with evolving fetal compromise remain unknown. In the present study, chronically instrumented near-term fetal sheep received surgical vagotomy (n = 8) or sham vagotomy (control, n = 11) to disable the peripheral chemoreflex and unmask myocardial hypoxia. One-minute complete umbilical cord occlusions (UCOs) were performed every 2.5 min for 4 h or until arterial pressure fell below 20 mmHg. Hypotension and severe acidaemia developed progressively after 65.7 ± 7.2 UCOs in control fetuses and 49.5 ± 7.8 UCOs after vagotomy. Vagotomy was associated with faster development of metabolic acidaemia and faster impairment of arterial pressure during UCOs without impairing centralization of blood flow or neurophysiological adaptation to UCOs. During the first half of the UCO series, before severe hypotension developed, vagotomy was associated with a marked increase in FHR during UCOs. After the onset of evolving severe hypotension, FHR fell faster in control fetuses during the first 20 s of UCOs, but FHR during the final 40 s of UCOs became progressively more similar between groups, with no difference in the nadir of decelerations. In conclusion, FHR decelerations were initiated and sustained by the peripheral chemoreflex at a time when fetuses were able to maintain arterial pressure. After the onset of evolving hypotension and acidaemia, the peripheral chemoreflex continued to initiate decelerations, but myocardial hypoxia became progressively more important in sustaining and deepening decelerations. KEY POINTS: Brief repeated hypoxaemia during labour can trigger fetal heart rate decelerations by either the peripheral chemoreflex or myocardial hypoxia, but how this balance changes with fetal compromise is unknown. Reflex control of fetal heart rate was disabled by vagotomy to unmask the effects of myocardial hypoxia in chronically instrumented fetal sheep. Fetuses were then subjected to repeated brief hypoxaemia consistent with the rates of uterine contractions during labour. We show that the peripheral chemoreflex controls brief decelerations in their entirety at a time when fetuses were able to maintain normal or increased arterial pressure. The peripheral chemoreflex still initiated decelerations even after the onset of evolving hypotension and acidaemia, but myocardial hypoxia made an increasing contribution to sustain and deepen decelerations.

Circadian patterns of heart rate variability in fetal sheep after hypoxia-ischaemia: A biomarker of evolving brain injury.

Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and severe neurodevelopmental disability in survivors, including cerebral palsy, although there are no reliable biomarkers to detect at risk fetuses that may have suffered a transient period of severe HI. We investigated time and frequency domain measures of fetal heart rate variability (FHRV) for 3 weeks after HI in preterm fetal sheep at 0.7 gestation (equivalent to preterm humans) until 0.8 gestation (equivalent to term humans). We have previously shown that this is associated with delayed development of severe white and grey matter injury, including cystic white matter injury (WMI) resembling that observed in human preterm infants. HI was associated with suppression of time and frequency domain measures of FHRV and reduced their circadian rhythmicity during the first 3 days of recovery. By contrast, circadian rhythms of multiple measures of FHRV were exaggerated over the final 2 weeks of recovery, mediated by a greater reduction in FHRV during the morning nadir, but no change in the evening peak. These data suggest that the time of day at which FHRV measurements are taken affects their diagnostic utility. We further propose that circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury. KEY POINTS: Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and probably for disability in survivors, although there are no reliable biomarkers for antenatal brain injury. In preterm fetal sheep, acute HI that is known to lead to delayed development of severe white and grey matter injury over 3 weeks, was associated with early suppression of multiple time and frequency domain measures of fetal heart rate variability (FHRV) and loss of their circadian rhythms during the first 3 days after HI. Over the final 2 weeks of recovery after HI, exaggerated circadian rhythms of frequency domain FHRV measures were observed. The morning nadirs were lower with no change in the evening peak of FHRV. Circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury.

Combining early pregnancy bleeding with ultrasound measurements to assess spontaneous abortion risk among infertile patients.

BACKGROUND: Approximately 15% of all clinically recognized pregnancies in patients with infertility result in spontaneous abortion. However, despite its potential to have a profound and lasting effect on physical and emotional well-being, the natural history of spontaneous abortion in women with infertility has not been described. Although vaginal bleeding is a common symptom in pregnancies conceived via reproductive technologies, its prognostic value is not well understood. OBJECTIVE: This study aimed to evaluate the combination of early pregnancy bleeding and first-trimester ultrasound measurements to determine spontaneous abortion risk. STUDY DESIGN: This was a retrospective cohort study of patients with infertility who underwent autologous embryo transfer resulting in singleton intrauterine pregnancy confirmed by ultrasound from January 1, 2017, to December 31, 2019. Early pregnancy symptoms of bleeding occurring before gestational week 8 and measurements of crown-rump length and fetal heart rate from ultrasounds performed during gestational week 6 (6 0/7 to 6 6/7 weeks of gestation) and gestational week 7 (7 0/7 to 7 6/7 weeks of gestation) were recorded. Modified Poisson regression with robust error variance was adjusted a priori for patient age, embryo transfer day, and transfer of a preimplantation genetic-tested embryo to estimate the relative risk and 95% confidence interval of spontaneous abortion for dichotomous variables. The relative risks and positive predictive values for early pregnancy bleeding combined with ultrasound measurements on the occurrence of spontaneous abortion were calculated for patients who had an ultrasound performed during gestational week 6 and separately for patients who had an ultrasound performed during gestational week 7. The primary outcome was spontaneous abortion in the setting of vaginal bleeding with normal ultrasound parameters. The secondary outcomes were spontaneous abortion with vaginal bleeding and (1) abnormal crown-rump length, (2) abnormal fetal heart rate, and (3) both abnormal crown-rump length and abnormal fetal heart rate. RESULTS: Of the 1858 patients who were included (359 cases resulted in abortions and 1499 resulted in live births), 315 patients (17.0%) reported vaginal bleeding. When combined with ultrasound measurements from gestational week 6, bleeding was significantly associated with increased spontaneous abortion only when accompanied by absent fetal heart rate (relative risk, 5.36; 95% confidence interval, 3.36-8.55) or both absent fetal heart rate and absent fetal pole (relative risk, 9.67; 95% confidence interval, 7.45-12.56). Similarly, when combined with ultrasound measurements from gestational week 7, bleeding was significantly associated with increased spontaneous abortion only when accompanied by an abnormal assessment of fetal heart rate or crown-rump length (relative risk, 5.09; 95% confidence interval, 1.83-14.19) or both fetal heart rate and crown-rump length (relative risk, 14.82; 95% confidence interval, 10.54-20.83). With normal ultrasound measurements, bleeding was not associated with increased spontaneous abortion risk (relative risk: 1.05 [95% confidence interval, 0.61-1.78] in gestational week 6 and 0.80 [95% confidence interval, 0.36-1.74] in gestational week 7), and the live birth rate was comparable with that in patients with normal ultrasound measurements and no bleeding. CONCLUSION: Patients with a history of infertility who present after embryo transfer with symptoms of vaginal bleeding should be evaluated with a pregnancy ultrasound to accurately assess spontaneous abortion risk. In the setting of normal ultrasound measurements, patients can be reassured that their risk of spontaneous abortion is not increased and that their live birth rate is not decreased.

Pathophysiological interpretation of fetal heart rate tracings in clinical practice.

The onset of regular, strong, and progressive uterine contractions may result in both mechanical (compression of the fetal head and/or umbilical cord) and hypoxic (repetitive and sustained compression of the umbilical cord or reduction in uteroplacental oxygenation) stresses to a human fetus. Most fetuses are able to mount effective compensatory responses to avoid hypoxic-ischemic encephalopathy and perinatal death secondary to the onset of anaerobic metabolism within the myocardium, culminating in myocardial lactic acidosis. In addition, the presence of fetal hemoglobin, which has a higher affinity for oxygen even at low partial pressures of oxygen than the adult hemoglobin, especially increased amounts of fetal hemoglobin (ie, 180-220 g/L in fetuses vs 110-140 g/L in adults), helps the fetus to withstand hypoxic stresses during labor. Different national and international guidelines are currently being used for intrapartum fetal heart rate interpretation. These traditional classification systems for fetal heart rate interpretation during labor are based on grouping certain features of fetal heart rate (ie, baseline fetal heart rate, baseline variability, accelerations, and decelerations) into different categories (eg, category I, II, and III tracings, "normal, suspicious, and pathologic" or "normal, intermediary, and abnormal"). These guidelines differ from each other because of the features included within different categories and because of their arbitrary time limits stipulated for each feature to warrant an obstetrical intervention. This approach fails to individualize care because the "ranges of normality" for stipulated parameters apply to the population of human fetuses and not to the individual fetus in question. Moreover, different fetuses have different reserves and compensatory responses and different intrauterine environments (presence of meconium staining of amniotic fluid, intrauterine inflammation, and the nature of uterine activity). Pathophysiological interpretation of fetal heart rate tracing is based on the application of the knowledge of fetal responses to intrapartum mechanical and/or hypoxic stress in clinical practice. Both experimental animal studies and observational human studies suggest that, just like adults undertaking a treadmill exercise, human fetuses show predictable compensatory responses to a progressively evolving intrapartum hypoxic stress. These responses include the onset of decelerations to reduce myocardial workload and preserve aerobic metabolism, loss of accelerations to abolish nonessential somatic body movements, and catecholamine-mediated increases in the baseline fetal heart rate and effective redistribution and centralization to protect the fetal central organs (ie, the heart, brain, and adrenal glands), which are essential for intrauterine survival. Moreover, it is essential to incorporate the clinical context (progress of labor, fetal size and reserves, presence of meconium staining of amniotic fluid and intrauterine inflammation, and fetal anemia) and understand the features suggestive of fetal compromise in nonhypoxic pathways (eg, chorioamnionitis and fetomaternal hemorrhage). It is important to appreciate that the timely recognition of the speed of onset of intrapartum hypoxia (ie, acute, subacute, and gradually evolving) and preexisting uteroplacental insufficiency (ie, chronic hypoxia) on fetal heart rate tracing is crucial to improve perinatal outcomes.

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.

Three-tiered fetal heart rate interpretation system and adverse neonatal and maternal outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the rate of adverse neonatal or maternal outcomes in parturients with fetal heart rate tracings categorized as I, II or, III within the last 30 to 120 minutes of delivery. DATA SOURCES: The MEDLINE Ovid, Scopus, Embase, CINAHL, and Clinicaltrials.gov databases were searched electronically up to May 2022, using combinations of the relevant medical subject heading terms, keywords, and word variants that were considered suitable for the topic. STUDY ELIGIBILITY CRITERIA: Only observational studies of term infants reporting outcomes of interest with category I, II, or III fetal heart rate tracings were included. STUDY APPRAISAL AND SYNTHESIS METHODS: The coprimary outcome was the rate of either Apgar score <7 at 5 minutes or umbilical artery pH <7.00. Secondary outcomes were divided into neonatal and maternal adverse outcomes. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. Random-effect meta-analyses of proportions were used to estimate the pooled rates of each categorical outcome in fetal heart rate tracing category I, II, and III patterns, and random-effect head-to-head meta-analyses were used to directly compare fetal heart rate tracings category I vs II and fetal heart rate tracing category II vs III, expressing the results as summary odds ratio or as mean differences with relative 95% confidence intervals. RESULTS: Of the 671 articles reviewed, 3 publications met the inclusion criteria. Among them were 47,648 singletons at ≥37 weeks' gestation. Fetal heart rate tracings in the last 30 to 120 minutes before delivery were characterized in the following manner: 27.0% of deliveries had category I tracings, 72.9% had category II tracings, and 0.1% had category III tracings. A single study, which was rated to be of poor quality, contributed 82.1% of the data and it did not provide any data for category III fetal heart rate tracings. When compared with category I fetal heart rate tracings (0.74%), the incidence of an Apgar score <7 at 5 minutes were significantly higher among deliveries with category II fetal heart rate tracings (1.51%) (odds ratio, 1.56; 95% confidence interval, 1.23-1.99) and among those with category III tracings (14.63%) (odds ratio, 14.46; 95% confidence interval, 2.77-75.39). When compared with category II tracings, category III tracings also had a significantly higher likelihood of a low Apgar score at 5 minutes (odds ratio, 14.46; 95% confidence interval, 2.77-75.39). The incidence of an umbilical artery pH <7.00 were similar among those with category I and those with category II tracings (0.08% vs 0.24%; odds ratio, 2.85; 95% confidence interval, 0.41-19.55). When compared with category I tracings, the incidence of an umbilical artery pH <7.00 was significantly more common among those with category III tracings (31.04%; odds ratio, 161.56; 95% confidence interval, 25.18-1036.42); likewise, when compared with those with category II tracings, those with category III tracings had a significantly higher likelihood of having an umbilical artery pH <7.00 (odds ratio, 42.29; 95% confidence interval, 14.29-125.10). Hypoxic-ischemic encephalopathy occurred with similar frequency among those with categories I and those with category II tracings (0 vs 0.81%; odds ratio, 5.86; 95% confidence interval, 0.75-45.89) but was significantly more common among those with category III tracings (0 vs 18.97%; odds ratio, 61.43; 95% confidence interval, 7.49-503.50). Cesarean delivery occurred with similar frequency among those with category I (13.41%) and those with category II tracings (11.92%) (odds ratio, 0.87; 95% confidence interval, 0.72-1.05) but was significantly more common among those with with category III tracings (14.28%) (odds ratio, 3.97; 95% confidence interval, 1.62-9.75). When compared with those with category II tracings, cesarean delivery was more common among those with category III tracings (odds ratio, 4.55; 95% confidence interval, 1.88-11.01). CONCLUSION: Although the incidence of an Apgar score <7 at 5 minutes and umbilical artery pH <7.00 increased significantly with increasing fetal heart rate tracing category, about 98% of newborns with category II tracings do not have these adverse outcomes. The 3-tiered fetal heart rate tracing interpretation system provides an approximate but imprecise measurement of neonatal prognosis.

Optimizing the management of acute, prolonged decelerations and fetal bradycardia based on the understanding of fetal pathophysiology.

Any acute and profound reduction in fetal oxygenation increases the risk of anaerobic metabolism in the fetal myocardium and, hence, the risk of lactic acidosis. On the contrary, in a gradually evolving hypoxic stress, there is sufficient time to mount a catecholamine-mediated increase in the fetal heart rate to increase the cardiac output and redistribute oxygenated blood to maintain an aerobic metabolism in the fetal central organs. When the hypoxic stress is sudden, profound, and sustained, it is not possible to continue to maintain central organ perfusion by peripheral vasoconstriction and centralization. In case of acute deprivation of oxygen, the immediate chemoreflex response via the vagus nerve helps reduce fetal myocardial workload by a sudden drop of the baseline fetal heart rate. If this drop in the fetal heart rate continues for >2 minutes (American College of Obstetricians and Gynecologists' guideline) or 3 minutes (National Institute for Health and Care Excellence or physiological guideline), it is termed a prolonged deceleration, which occurs because of myocardial hypoxia, after the initial chemoreflex. The revised International Federation of Gynecology and Obstetrics guideline (2015) considers the prolonged deceleration to be a "pathologic" feature after 5 minutes. Acute intrapartum accidents (placental abruption, umbilical cord prolapse, and uterine rupture) should be excluded immediately, and if they are present, an urgent birth should be accomplished. If a reversible cause is found (maternal hypotension, uterine hypertonus or hyperstimulation, and sustained umbilical cord compression), immediate conservative measures (also called intrauterine fetal resuscitation) should be undertaken to reverse the underlying cause. In reversible causes of acute hypoxia, if the fetal heart rate variability is normal before the onset of deceleration, and normal within the first 3 minutes of the prolonged deceleration, then there is an increased likelihood of recovery of the fetal heart rate to its antecedent baseline within 9 minutes with the reversal of the underlying cause of acute and profound reduction in fetal oxygenation. The continuation of the prolonged deceleration for >10 minutes is termed "terminal bradycardia," and this increases the risk of hypoxic-ischemic injury to the deep gray matter of the brain (the thalami and the basal ganglia), predisposing to dyskinetic cerebral palsy. Therefore, any acute fetal hypoxia, which manifests as a prolonged deceleration on the fetal heart rate tracing, should be considered an intrapartum emergency requiring an immediate intervention to optimize perinatal outcome. In uterine hypertonus or hyperstimulation, if the prolonged deceleration persists despite stopping the uterotonic agent, then acute tocolysis is recommended to rapidly restore fetal oxygenation. Regular clinical audit of the management of acute hypoxia, including the "the onset of bradycardia to delivery interval," may help identify organizational and system issues, which may contribute to poor perinatal outcomes.

Abnormal fetal heart rate patterns caused by pathophysiologic processes other than fetal acidemia.

Fetal acidemia is a common final pathway to fetal death, and in many cases, to fetal central nervous system injury. However, certain fetal pathophysiological processes are associated with significant category II or category III fetal heart rate changes before the development of or in the absence of fetal acidemia. The most frequent of these processes include fetal infection and/or inflammation, anemia, fetal congenital heart disease, and fetal central nervous system injury. In the presence of significant category II or category III fetal heart rate patterns, clinicians should consider the possibility of the aforementioned fetal processes depending on the clinical circumstances. The common characteristic of these pathophysiological processes is that their associated fetal heart rate patterns are linked to increased adverse neonatal outcomes despite the absence of acidemia at birth. Therefore, in these cases, the fetal heart rate patterns may provide more insight about the fetal condition and pathophysiology than the acid-base status at birth. In addition, as successful timing of intrapartum interventions on the basis of evolution of fetal heart rate patterns aims to prevent fetal acidemia, it may not be logical to continue to use the fetal acid-base status at birth as the gold standard outcome to determine the predictive ability of category II or III fetal heart rate patterns. A more reasonable approach may be to use the umbilical cord blood acid-base status at birth as the gold standard for determining the appropriateness of the timing of our interventions.