Heart rate markers for prediction of fetal acidosis in an experimental study on fetal sheep.

To overcome the difficulties in interpreting fetal heart rate (FHR), several tools based on the autonomic nervous system and heart rate variability (HRV) have been developed. The objective of this study was to use FHR and HRV parameters for the prediction of fetal hypoxia. It was an experimental study in the instrumented fetal sheep. Repeated umbilical cord occlusions were performed to achieve severe acidosis. Hemodynamic parameters, ECG, and blood gases were analyzed. The variables used were heart rate baseline, HRV analysis (RMSSD, SDNN, LF, HF, HFnu, Fetal Stress Index (FSI), …), and morphological analysis of decelerations. The gold standard used to classify hypoxia was the fetal arterial pH (pH < 7.10). Different multivariable statistical methods (logistic regression and decision trees) were applied for the detection of acidosis. 21 lambs were instrumented. A total of 130 pairs of FHR/fetal pH analysis were obtained of which 29 in the acidosis group and 101 in the non-acidosis group. After logistic regression model with bootstrap resampling and stepwise backward selection, only one variable was selected, FSI. The AUC of FSI alone in this model was 0.81 with a sensitivity of 0.66, specificity of 0.88, PPV of 0.61, and NPV of 0.90 considering a threshold of 68. Decision trees with CHAID and CART algorithms showed a sensitivity of 0.48 and 0.59, respectively, and a specificity of 0.94 for both. All employed methods identified HRV variables as the most predictive of acidosis. The primary variables selected automatically were those from the HRV. Supporting the use of FHRV measures for the screening of fetal acidosis during labour is interesting.

Fetal heart rate variability analysis for neonatal acidosis prediction.

Fetal well-being during labor is usually assessed by visual analysis of a fetal heart rate (FHR) tracing. Our primary objective was to evaluate the ability of automated heart rate variability (HRV) analysis methods, including our new fetal stress index (FSI), to predict neonatal acidosis. 552 intrapartum recordings were analyzed. The analysis occurred in the last 90 min before birth and was conducted during two 5-min intervals: (i) a stable period of FHR and (ii) the period corresponding to the maximum FSI value. For each period, we computed the mean FHR, FSI, short-term variability (STV), and long-term variability (LTV). Visual FHR interpretation was performed using the FIGO classification. The population was separated into two groups: (i) an acidotic group with an arterial pH at birth ≤ 7.10 and a control group. Prediction of a neonatal pH ≤ 7.10 was assessed by computing the receiver-operating characteristic area under the curve (AUC). FHR, FSI, STV, and LTV did not differ significantly between groups during the stable period. During the FSI max peak period, LTV and STV correlated significantly in the acidotic group (- 5.85 ± 2.19, p = 0.010 and - 0.62 ± 0.29, p = 0.037, respectively). The AUC values were 0.569 for FIGO classification, 0.595 for STV, and 0.622 for LTV. The multivariate model (FIGO, FSI, FC, STV, LTV) had the greatest accuracy for predicting acidosis (AUC = 0.719). FSI was not predictive of neonatal acidosis probably because of the low quality of the FHR signal in cardiotocography. When used separately, HRV indexes and visual FHR analysis were poor predictors of neonatal acidosis. Including all indexes in a multivariate model increased the predictive ability.

How Does a Delay Between Temperate Running Exercise and Hot-Water Immersion Alter the Acute Thermoregulatory Response and Heat-Load?

Hot-water immersion following exercise in a temperate environment can elicit heat acclimation in endurance-trained individuals. However, a delay between exercise cessation and immersion is likely a common occurrence in practice. Precisely how such a delay potentially alters hot-water immersion mediated acute physiological responses (e.g., total heat-load) remains unexplored. Such data would aid in optimizing prescription of post-exercise hot-water immersion in cool environments, relative to heat acclimation goals. Twelve male recreational runners (mean ± SD; age: 38 ± 13 years, height: 180 ± 7 cm, body mass: 81 ± 13.7 kg, body fat: 13.9 ± 3.5%) completed three separate 40-min treadmill runs (18°C), followed by either a 10 min (10M), 1 h (1H), or 8 h (8H) delay, prior to a 30-min hot-water immersion (39°C), with a randomized crossover design. Core and skin temperatures, heart rate, sweat, and perceptual responses were measured across the trials. Mean core temperature during immersion was significantly lower in 1H (37.39 ± 0.30°C) compared to 10M (37.83 ± 0.24°C; p = 0.0032) and 8H (37.74 ± 0.19°C; p = 0.0140). Mean skin temperature was significantly higher in 8H (32.70 ± 0.41°C) compared to 10M (31.93 ± 0.60°C; p = 0.0042) at the end of the hot-water immersion. Mean and maximal heart rates were also higher during immersion in 10M compared to 1H and 8H (p < 0.05), despite no significant differences in the sweat or perceptual responses. The shortest delay between exercise and immersion (10M) provoked the greatest heat-load during immersion. However, performing the hot-water immersion in the afternoon (8H), which coincided with peak circadian body temperature, provided a larger heat-load stimulus than the 1 h delay (1H).

Influence of averaged fetal heart rate in heart rate variability analysis.

In high-income countries, fetal hypoxia affects 3 to 8 newborns per 1000 live births with subsequent moderate or severe Hypoxic-Ischemic Encephalopathy (HIE) in 0.5 to 1 per 1000 live births. Visual interpretation of FHR signal issued from a Doppler ultrasound cardiotocography is the gold standard to monitor fetal condition. Unfortunately, its analysis presents a high rate of inter-observer variability and a low specificity to predict poor neonatal outcomes. Under hypoxia, the fetus develops several adaptive mechanisms regulated by the autonomic nervous system inducing changes in the fetal heart rate variability. Though fetal heart rate variability methods demonstrated abilities to predict perinatal asphyxia, most of the Doppler ultrasound technologies used in clinical practice do not provide sufficiently accurate fetal heart rate signals for heart rate variability analysis. Indeed, Doppler ultrasound cardiotocography usually provides fetal heart rate values averaged over 2 or 3 beats which can constitute a limitation for spectral analysis. We developed a fetal heart rate variability analysis method: the Fetal Stress Index (FSI). The objective of this study was to investigate the influence of averaged fetal heart rate on this new index in order to check the feasibility of computing the FSI from the signal issued from Doppler ultrasound cardiotocography.

Effect of two-weeks endurance training wearing additional clothing in a temperate outdoor environment on performance and physiology in the heat.

This investigation assessed performance, physiological and perceptual responses to wearing additional clothing during endurance training for two-weeks in temperate environments, to determine if this approach could be used as a practical, alternative, heat acclimation strategy for athletes. Fifteen trained male triathletes assigned to performance-matched groups completed a two-week unsupervised endurance cycling and running program in either (i) shorts and a short sleeve top (CON; n = 8) or (ii) additional clothing of full-length pants, a "winter" jacket and gloves made from nylon, polyurethane and polyester (AC; n = 7). Participants completed three separate (i.e. familiarisation, pre-program and post-program), identical, pre-loaded cycling time-trials (20 min at 180 W followed by a 40 min self-paced time trial) in 32.5 ± 0.1°C and 55 ± 6% RH. Core and skin temperatures, heart rate, sweat rate, perceived exertion, thermal sensation and thermal comfort were measured across the pre-loaded time trials, and heart rate and thermal sensation were measured across the training program. All of the participants recorded in their diaries that they completed all of the programmed training sessions in the required attire. Mean thermal sensation was most likely hotter in AC (5.5 ± 0.4 AU) compared to CON (4.4 ± 0.4 AU; ES = 1.61, ± 0.68) during the training sessions. However, follow up tests revealed no physiological or perceptual signs of heat acclimation, and the change in time-trial performance from pre-post between groups was trivial (CON: -3.5 ± 12.0 W, AC: -4.1 ± 9.6 W; difference = -0.7%, ± 5.4%). Training in additional clothing for two-weeks in a temperate environment was not an effective heat acclimation strategy for triathletes.

When should foetal pH measurements be performed after a prolonged deceleration? An experimental study in a fetal sheep model.

OBJECTIVE: The aim of fetal heart rate monitoring during labour is to identify and prevent foetal distress, but its evaluation is not perfect. Fetal scalp blood sampling for pH measurement is one of the second-line methods of monitoring when fetal heart rate is classified as suspicious. This study aims to determine when pH testing should be performed after a prolonged deceleration. STUDY DESIGN: This was an experimental study in a fetal sheep model. A partial umbilical cord occlusion was performed for seven minutes followed by a recuperation period of 30 min. Hemodynamic parameters (heart rate, mean blood pressure and intra-amniotic pressure) and blood gases were recorded before occlusion (T0), during occlusion (T4), just after the end of occlusion (T7), and then 10, 20 and 30 min after occlusion (T17, T27 and T37 respectively). RESULTS: Ten experiments were carried out. During partial cord occlusion, the fetal pH decreased significantly to acidosis. After a prolonged deceleration with fetal acidosis, the pH recovered to a normal value, defined by a pH greater than or equal to 7.25, after 20 min of recuperation. CONCLUSION: After a prolonged deceleration, fetal pH normalizes between 20 and 30 min thereafter. Thus, if a foetal blood sample is indicated, this delay must be respected in order to avoid inducing an unnecessary intervention decision.

Exploring fetal response to acidosis in ewes: Choosing an adequate experimental model.

INTRODUCTION: Knowledge of fetal physiology during labor has been largely generated from animal models. Our team recently developed a new index to assess parasympathetic activity using different experimental protocols to obtain acidosis. The objective of the present study was to discuss the different protocols and to review other models proposed in the literature. MATERIAL AND METHODS: Pregnant ewes underwent a surgical procedure at the 123±2 days gestational age (term=145 days). Three experimental protocols were used: protocol A consisted of 25%, 50% and 75% umbilical cord occlusion (UCO) for 20min. Protocol B consisted of partial 75% UCO until reaching a pH<7.10. Protocol C consisted of brief, repetitive complete occlusion until severe acidosis occurred. Hemodynamic and blood gas parameters were compared to those of the stability period before UCO. RESULTS: Protocol A led to a progressive response depending on the degree of occlusion (decrease in fetal heart rate, arterial hypertension and pH). Protocol B led to severe acidosis, although the duration of UCO varied per animal. Protocol C also progressively led to acidosis. We observed high inter individual variability in the acidosis response. CONCLUSION: Pregnant ewes are a relevant model for exploring fetal response to acidosis. The frequency of UCO and partial or complete occlusion should be adapted to the expected effects. Knowledge of these protocols is important to respect ethical guidelines and to reduce the required number of animals. Moreover, it is important to consider the high individual variability of the acidosis response in the interpretation of the results.

Correlation of a new index reflecting the fluctuation of parasympathetic tone and fetal acidosis in an experimental study in a sheep model.

The autonomic nervous system plays a leading role in the control of fetal homeostasis. Fetal heart rate variability (HRV) analysis is a reflection of its activity. We developed a new index (the Fetal Stress Index, FSI) reflecting parasympathetic tone. The objective of this study was to evaluate this index as a predictor of fetal acid-base status. This was an experimental study on chronically instrumented fetal lambs (n = 11, surgery at 128 +/- 2 days gestational age, term = 145 days). The model was based on 75% occlusion of the umbilical cord for a maximum of 120 minutes or until an arterial pH ≤ 7.20 was reached. Hemodynamic, gasometric and FSI parameters were recorded throughout the experimentation. We studied the FSI during the 10 minutes prior to pH samplings and compared values for pH>7.20 and pH≤ 7.20. In order to analyze the FSI evolution during the 10 minutes periods, we analyzed the minimum, maximum and mean values of the FSI (respectively FSImin, FSImax and FSImean) over the periods. 11 experimentations were performed. During occlusion, the heart rate dropped with an increase in blood pressure (respectively 160(155-182) vs 106(101-120) bpm and 42(41-45) vs 58(55-62) mmHg after occlusion). The FSImin was 38.6 (35.2-43.3) in the group pH>7.20 and was higher in the group pH less than 7.20 (46.5 (43.3-52.0), p = 0.012). The correlation of FSImin was significant for arterial pH (coefficient of -0.671; p = 0.004) and for base excess (coefficient of -0.632; p = 0.009). The correlations were not significant for the other parameters. In conclusion, our new index seems well correlated with the fetal acid-base status. Other studies must be carried out in a situation close to the physiology of labor by sequential occlusion of the cord.

Review shows that implementing a nationwide protocol for congenital diaphragmatic hernia was a key factor in reducing mortality and morbidity.

The French Rare Disease Reference Center for congenital diaphragmatic hernia (CDH) was created in 2008, to implement a national protocol for foetuses and children with this serious condition. Neonatal mortality from CDH is 30-40%, mainly due to pulmonary hypoplasia and persistent pulmonary hypertension, and half of those who live have high respiratory, nutritional and digestive morbidity. CDH management requires long-term and specialised multidisciplinary care. It has been well established that a standardised management protocol improves the prognosis of children with CDH. CONCLUSION: Organising health care and implementing a nationwide French protocol were key factors for reducing mortality and morbidity from CDH.

Passive Heating: Reviewing Practical Heat Acclimation Strategies for Endurance Athletes.

Heat acclimation protocols-both active and passive-have been employed by athletes in an effort to attenuate the detrimental effects of heat stress on physical capacities and sports performance. Active strategies have been extensively reviewed, but have various practical and economic limitations. The purpose of this review was therefore to provide an overview of the passive strategies that have received less attention, yet may be more practical or economically viable; recommendations for athletes are also provided. With a systematic search of the relevant databases ending in June 2018, 16 articles on passive heat acclimation that met the inclusion criteria were included in the review. The review highlighted that passive heat acclimation strategies can successfully induce heat adaptations, evident by reports of improved exercise performance, thermoregulatory, cardiovascular, and perceptual responses accompanying such interventions. Based on the review it is apparent that the use of sauna, hot-water immersion and environmental chambers may be used to provide heat stress under passive conditions, for the purpose of acclimation. To maximize the thermoregulatory-adaptive responses, exercise bouts should be employed prior to passive heat stress, rather than passive heating alone, with a minimal delay between exercise and the application of heat stress. Heating bouts should have a minimum duration of 30 min per session and be employed on consecutive days, when possible, with a minimum of 6-7 exposures to induce adaptation. This review identified that information regarding the magnitude of performance changes that can occur, as well as the perceptual responses to passive heating protocols is limited. Future research should investigate the use of passive heat exposures before and/or after repeated heat training sessions, to assess if a further boost to heat adaptation can be achieved with this strategy.

Review shows that using surfactant a number of times or as a vehicle for budesonide may reduce the risk of bronchopulmonary dysplasia.

AIM: Bronchopulmonary dysplasia (BPD) remains the most common respiratory morbidity in immature infants. This review describes the diagnosis of BPD has evolved and summarises the therapeutic approaches that have made it possible to limit the incidence of BPD. METHOD: We reviewed the literature from the first definition of BPD by Northway in 1967 to the surfactant treatment policies that are currently in use, drawing on more than 50 papers up to 2017. RESULTS: Our review showed that improvements in neonatal survival have been associated with an increased risk of severe BPD, significant levels of long-term morbidity and the increased use of healthcare resources. These issues have encouraged researchers to explore potential new treatments that limit the incidence of BPD. Repeated surfactant instillation and the use of surfactant as a vehicle for budesonide are promising strategies for alleviating the burden of chronic lung disease. Ongoing research on surfactant or stem cell therapy may further improve the respiratory prognosis for prematurely born children. CONCLUSION: Considerable research has been carried out into the increase in BPD, which has resulted from improvements in neonatal survival. Key areas of research include repeated surfactant administration, using surfactant as a vehicle for budesonide and stem cell therapy.

Influence of ECG sampling rate in fetal heart rate variability analysis.

Fetal hypoxia results in a fetal blood acidosis (pH<;7.10). In such a situation, the fetus develops several adaptation mechanisms regulated by the autonomic nervous system. Many studies demonstrated significant changes in heart rate variability in hypoxic fetuses. So, fetal heart rate variability analysis could be of precious help for fetal hypoxia prediction. Commonly used fetal heart rate variability analysis methods have been shown to be sensitive to the ECG signal sampling rate. Indeed, a low sampling rate could induce variability in the heart beat detection which will alter the heart rate variability estimation. In this paper, we introduce an original fetal heart rate variability analysis method. We hypothesize that this method will be less sensitive to ECG sampling frequency changes than common heart rate variability analysis methods. We then compared the results of this new heart rate variability analysis method with two different sampling frequencies (250-1000 Hz).

Impact of skin-to-skin contact on the autonomic nervous system in the preterm infant and his mother.

Before, during and after mother-newborn skin-to-skin contact (SSC), parasympathetic activity was evaluated by heart rate variability (HRV) analysis. SSC had a favorable impact on maternal and premature infant parasympathetic activities with a more pronounced response for neonates when the basal HRV values were lower, without modifications of EDIN scores, temperatures or oxygen saturation.

A new analysis of heart rate variability in the assessment of fetal parasympathetic activity: An experimental study in a fetal sheep model.

Analysis of heart rate variability (HRV) is a recognized tool in the assessment of autonomic nervous system (ANS) activity. Indeed, both time and spectral analysis techniques enable us to obtain indexes that are related to the way the ANS regulates the heart rate. However, these techniques are limited in terms of the lack of thresholds of the numerical indexes, which is primarily due to high inter-subject variability. We proposed a new fetal HRV analysis method related to the parasympathetic activity of the ANS. The aim of this study was to evaluate the performance of our method compared to commonly used HRV analysis, with regard to i) the ability to detect changes in ANS activity and ii) inter-subject variability. This study was performed in seven sheep fetuses. In order to evaluate the sensitivity and specificity of our index in evaluating parasympathetic activity, we directly administered 2.5 mg intravenous atropine, to inhibit parasympathetic tone, and 5 mg propranolol to block sympathetic activity. Our index, as well as time analysis (root mean square of the successive differences; RMSSD) and spectral analysis (high frequency (HF) and low frequency (LF) spectral components obtained via fast Fourier transform), were measured before and after injection. Inter-subject variability was estimated by the coefficient of variance (%CV). In order to evaluate the ability of HRV parameters to detect fetal parasympathetic decrease, we also estimated the effect size for each HRV parameter before and after injections. As expected, our index, the HF spectral component, and the RMSSD were reduced after the atropine injection. Moreover, our index presented a higher effect size. The %CV was far lower for our index than for RMSSD, HF, and LF. Although LF decreased after propranolol administration, fetal stress index, RMSSD, and HF were not significantly different, confirming the fact that those indexes are specific to the parasympathetic nervous system. In conclusion, our method appeared to be effective in detecting parasympathetic inhibition. Moreover, inter-subject variability was much lower, and effect size higher, with our method compared to other HRV analysis methods.

Safety and tolerability of subcutaneous treprostinil in newborns with congenital diaphragmatic hernia and life-threatening pulmonary hypertension.

BACKGROUND: Prolonged pulmonary hypertension (PH) is highly predictive for pulmonary morbidity and death in infants with congenital diaphragmatic hernia (CDH). OBJECTIVES: To report the effects and tolerability of subcutaneous treprostinil in newborns with severe CDH and late life-threatening PH. METHODS: We recorded clinical and echocardiography data before and after starting subcutaneous treprostinil, on patients with severe CDH and late PH, refractory to inhaled nitric oxide and oral sildenafil. RESULTS: 14 patients were treated with treprostinil (gestational age: 39.1±2.0weeks; birth weight: 3200±600g). Prior to treatment, the pre- and post-ductal SpO2 difference (Δ SpO2) was 14±10%. Treprostinil was initiated at a median age of 12days [5-157]. After starting treprostinil, ΔSpO2 decreased to 3% at day 7 (p<0.05), and the mean blood flow velocities in the right pulmonary arteries increased by 110% (p<0.05). 2 of the 14 patients died. At the age of follow up (12months to 3years), the 12 surviving infants were all weaned from respiratory support and discharged home. CONCLUSION: The subcutaneous treprostinil improves pulmonary hemodynamics and outcomes in infants with CDH and life-threatening PH. We suggest that the treatment should be considered in infants with severe CDH and late PH. TYPE OF STUDY: Case series with no comparison group. LEVEL OF EVIDENCE: Level IV.

Understanding fetal physiology and second line monitoring during labor.

Cardiotocography (CTG) is a technique used to monitor intrapartum fetal condition and is one of the most common obstetric procedures. Second line methods of fetal monitoring have been developed in an attempt to reduce unnecessary interventions due to continuous cardiotocography and to better identify fetuses at risk of intrapartum asphyxia. The acid-base balance of the fetus is evaluated by fetal blood scalp samples, the modification of the myocardial oxygenation by the fetal ECG ST-segment analysis (STAN) and the autonomic nervous system by the power spectral analysis of the fetal heart variability. To correctly interpret the features observed on CTG traces or second line methods, it seems important to understand normal physiology during labor and the compensatory mechanisms of the fetus in case of hypoxemia. Therefore, the aim of this review is first to describe fetal physiology during labor and then to explain the modification of the second line monitoring during labor.

Is trial of labor harmful in breech delivery? A cohort comparison for breech and vertex presentations.

INTRODUCTION: Planned vaginal delivery in breech presentation is accompanied by an excess neonatal risk that has, however, rarely been compared to that of delivery in vertex presentation. Because of the severity of complications that can occur in long-term follow-up, the risk of asphyxia is of particular concern. MATERIAL AND METHODS: To assess immediate neonatal status after a planned vaginal delivery of fetuses in breech compared with vertex presentation, we planned a retrospective hospital cohort study of singleton term deliveries from 2000 to 2011. The indicators used to assess neonatal status were: 5-min Apgar score<7, acidosis, both moderate (pH<7.15) and severe (pH<7.0), asphyxia (pH<7.0 and base deficit≥12.0mmol/L), transfer to the neonatal intensive care unit (NICU), and in-hospital neonatal death. RESULTS: Compared with 43,595 trials of vaginal delivery in vertex presentation at term during the 12-year study period (93.8% of all vertex presentations), the 665 breech deliveries for which planned vaginal delivery was planned (43.2% of all breech presentations) had a quadrupled risk of severe acidosis (ORa 4.3 [2.2-7.5]), but no increase in the risk of asphyxia (ORa 0.7 [0.1-3.0]), NICU transfer (ORa 0.8 [0.4-1.3]) or in-hospital death (ORa 1.3 [0.1-6.0]). Moreover, compared with the 876 planned cesareans, the risk of severe acidosis in the 665 trials of vaginal delivery in breech presentation was four times higher (OR 4.3 [2.3-4.7]), but we observed no increase in neither asphyxia nor other risks studied. CONCLUSION: In our hospital, planned vaginal delivery is safe for breech presentations because it is associated with an increase of severe acidosis but not asphyxia.

[Organization of collaborative deliberation for limiting or withholding treatments in children]. / Comment organiser la délibération collégiale pour limiter ou arrêter les traitements en pédiatrie?

In 2005, the French law on patients' rights at the end of life required that decisions to withdraw or withhold life-sustaining treatments be made and carried out by the physician in charge of the patient, after obtaining advice from an independent consulting colleague and the caregiving team. The purpose of this study was to identify theoretical and practical obstacles to this collaborative deliberation and to propose practical guidelines to organize it.