Fetal Stress Index Research Articles

Surveillance fœtale : limites actuelles et nouvelles pistes basées sur l’analyse du système nerveux autonome fœtal

ObjectiveCurrently, fetal monitoring during labor is based on visual analysis of the fetal heart rate (FHR). This test is imperfect, with high intra- and inter-observer variability and a moderate to poor prediction of the occurrence of neonatal acidosis or anoxic-ischaemic encephalopathy. In situations where there is an intermediate risk of acidosis, it is possible to use second-line tests such as blood scalp sampling (with pH or lactate measurement) or ST segment analysis of the fetal ECG. However, these invasive tests have many limitations and their place is debated. Some authors suggest a more physiological approach to FHR assessment. The main actor in maintaining fetal homeostasis is the autonomic nervous system (ANS). Its activity can be assessed by analysing heart rate variability (HRV). The aim is to assess whether HRV can be used to identify situations at risk of acidosis. Materials and methodsOur team has developed an index, the Fetal Stress Index, to measure HRV. To test it in a situation of acidosis, we used a pregnant ewe model. We also developed in parallel a human fetal ECG recording system. ResultsIn our experimental model, we have shown that this index reflects variations in the parasympathetic system and correlates with the onset of acidosis. As its use in clinical practice requires the acquisition of a beat-to-beat FHR signal, we have also developed an abdominal patch that allows highly accurate analysis of the fetal ECG. ConclusionThe future is therefore to validate the FSI as a marker of acidosis in a prospective cohort using the signal obtained from our patch. This could be a new tool for fetal monitoring during labor.

Maternal–fetal stress and DNA methylation signatures in neonatal saliva: an epigenome-wide association study

BackgroundMaternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant’s neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA.ResultsA total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a ‘Fetal Stress Index’ (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn’s saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1, and two CpGs were located approximately lay at 50 kb from SSBP4 and SCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D.ConclusionsGenes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.

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.

Prenatal stress perturbs fetal iron homeostasis in a sex specific manner

The adverse effects of maternal prenatal stress (PS) on child’s neurodevelopment warrant the establishment of biomarkers that enable early interventional therapeutic strategies. We performed a prospective matched double cohort study screening 2000 pregnant women in third trimester with Cohen Perceived Stress Scale-10 (PSS-10) questionnaire; 164 participants were recruited and classified as stressed and control group (SG, CG). Fetal cord blood iron parameters of 107 patients were measured at birth. Transabdominal electrocardiograms-based Fetal Stress Index (FSI) was derived. We investigated sex contribution to group differences and conducted causal inference analyses to assess the total effect of PS exposure on iron homeostasis using a directed acyclic graph (DAG) approach. Differences are reported for p < 0.05 unless noted otherwise. Transferrin saturation was lower in male stressed neonates. The minimum adjustment set of the DAG to estimate the total effect of PS exposure on fetal ferritin iron biomarkers consisted of maternal age and socioeconomic status: SG revealed a 15% decrease in fetal ferritin compared with CG. Mean FSI was higher among SG than among CG. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.

Associations between fetal heart rate variability and umbilical cord occlusions-induced neural injury: An experimental study in a fetal sheep model.

This study evaluated the association between fetal heart rate variability (HRV) and the occurrence of hypoxic-ischemic encephalopathy in a fetal sheep model. The experimental protocol created a hypoxic condition with repeated cord occlusions in three phases (A, B, C) to achieve acidosis to pH <7.00. Hemodynamic, gasometric and HRV parameters were analyzed during the protocol, and the fetal brain, brainstem and spinal cord were assessed histopathologically 48h later. Associations between the various parameters and neural injury were compared between phases A, B and C using Spearman's rho test. Acute anoxic-ischemic brain lesions in all regions was present in 7/9 fetuses, and specific neural injury was observed in 3/9 fetuses. The number of brainstem lesions correlated significantly and inversely with the HRV fetal stress index (r=-0.784; p=0.021) in phase C and with HRV long-term variability (r=-0.677; p=0.045) and short-term variability (r=-0.837; p=0.005) in phase B. The number of neurological lesions did not correlate significantly with other markers of HRV. Neural injury caused by severe hypoxia was associated with HRV changes; in particular, brainstem damage was associated with changes in fetal-specific HRV markers.

Detection of maternal and fetal stress from the electrocardiogram with self-supervised representation learning

In the pregnant mother and her fetus, chronic prenatal stress results in entrainment of the fetal heartbeat by the maternal heartbeat, quantified by the fetal stress index (FSI). Deep learning (DL) is capable of pattern detection in complex medical data with high accuracy in noisy real-life environments, but little is known about DL’s utility in non-invasive biometric monitoring during pregnancy. A recently established self-supervised learning (SSL) approach to DL provides emotional recognition from electrocardiogram (ECG). We hypothesized that SSL will identify chronically stressed mother-fetus dyads from the raw maternal abdominal electrocardiograms (aECG), containing fetal and maternal ECG. Chronically stressed mothers and controls matched at enrolment at 32 weeks of gestation were studied. We validated the chronic stress exposure by psychological inventory, maternal hair cortisol and FSI. We tested two variants of SSL architecture, one trained on the generic ECG features for emotional recognition obtained from public datasets and another transfer-learned on a subset of our data. Our DL models accurately detect the chronic stress exposure group (AUROC = 0.982 ± 0.002), the individual psychological stress score (R2 = 0.943 ± 0.009) and FSI at 34 weeks of gestation (R2 = 0.946 ± 0.013), as well as the maternal hair cortisol at birth reflecting chronic stress exposure (0.931 ± 0.006). The best performance was achieved with the DL model trained on the public dataset and using maternal ECG alone. The present DL approach provides a novel source of physiological insights into complex multi-modal relationships between different regulatory systems exposed to chronic stress. The final DL model can be deployed in low-cost regular ECG biosensors as a simple, ubiquitous early stress detection and monitoring tool during pregnancy. This discovery should enable early behavioral interventions.

Opioid effect on the autonomic nervous system in a fetal sheep model.

Opioid use during labour can interfere with cardiotocography patterns. Heart rate variability indirectly reflects a fluctuation in the autonomic nervous system and can be monitored through time and spectral analyses. This experimental study aimed to evaluate the impact of nalbuphine administration on the gasometric, cardiovascular, and autonomic nervous system responses in fetal sheep. This was an experimental study on chronically instrumented sheep fetuses (surgery at 128 ± 2days of gestational age, term = 145days). The model was based on a maternal intravenous bolus injection of nalbuphine, a semisynthetic opioid used as an analgesic during delivery. Fetal gasometric parameters (pH, pO2, pCO2, and lactates), hemodynamic parameters (fetal heart rate and mean arterial pressure), and autonomic nervous system tone (short-term and long-term variation, low-frequency domain, high-frequency domain, and fetal stress index) were recorded. Data obtained at 30-60min after nalbuphine injection were compared to those recorded at baseline. Eleven experiments were performed. Fetal heart rate, mean arterial pressure, and activities at low and high frequencies were stable after injection. Short-term variation decreased at T30 min (P = 0.02), and long-term variation decreased at T60 min (P = 0.02). Fetal stress index gradually increased and reached significance at T60 min (P = 0.02). Fetal gasometric parameters and lactate levels remained stable. Maternal nalbuphine use during labour may lead to fetal heart changes that are caused by the effect of opioid on the autonomic nervous system; these fluctuations do not reflect acidosis.

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 90min 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.

Autonomic response to fetal acidosis using an experimental sheep model

BackgroundThe autonomic nervous system has a major role in fetal adaptation to hypoxia. Its activity might be assessed using heart rate variability and heart rate deceleration analyses. ObjectiveTo evaluate the ability of different heart rate variability and morphological deceleration analyses to predict fetal acidosis during labor in an experimental fetal sheep model. Study DesignRepeated 1-minute total umbilical cord occlusions were performed at mild (1minute every 5 min), moderate (1 min every 3 min), and severe (1 min every 2 min) umbilical cord occlusion periodicities until arterial pH reached 7.10. Hemodynamic,blood gas analysis, morphological analysis of decelerations (magnitude, slope, and area ofdecelerations), and heart rate variability parameters were recorded throughout the experiment.Heart rate variability analysis included temporal analysis (root mean square of successivedifferences between adjacent RR intervals, standard deviation of normal to normal RR intervals, short term variability), spectral analysis (low frequencies, high frequencies,normalized high frequencies), and a new index developed by our team, the Fetal Stress Index.We defined and compared three pH groups: >7.20, 7.10–7.20, and <7.10. ResultsEleven experiments were performed. Repetitive umbilical cord occlusions resulted in progressive fetal acidosis. Fetal Stress Index was correlated with pH and lactate (p < 0.05) and increased with acidosis. There were no significant correlations between pH, lactate, and other indices (spectral analysis, temporal analysis, or morphological analysis of decelerations). ConclusionThis protocol allowed us to identify the progressive onset of fetal acidosis in an experimental model close to labor. Fetal Stress Index is a heart rate variability method that varies with acidosis and indicates an increase in parasympathetic nervous system activity in response to fetal acidosis.

592: Autonomic and cerebral response to umbilical cord occlusions with worsening acidosis in the fetal sheep

Labor is a situation at risk of fetal hypoxia due to uterine contractions and/or compression of the umbilical. It could lead to fetal brain injury and hypoxic-ischemic encephalopathy (HIE). The autonomic nervous system (ANS) is a key mediator of fetal homeostasis, and its activity can be measured with heart rate variability (HRV) analysis. The objective of this experimental study in a fetal sheep model, was to evaluate HRV variation and cerebral injury. Repeated 1-minute umbilical cord occlusions (UCO) were performed at a mild (phase A, 1UCO/5mn)), moderate (phase B, 1 UCO/3mn), and severe (phase C, 1UCO/2mn) period until arterial pH reached 6.90. Hemodynamic, blood gas analysis, S100B and Troponin T assessment, and HRVwere recorded at specific time points. S100B is a protein linked with cerebral injury. ANS activity was evaluated though a new index developed by our team, the Fetal Stress Index (FSI), which was correlated in previous studies with parasympathetic activity and acidosis. Ten experiments were performed. UCOs resulted in progressive severe fetal acidosis with pH dropping to 6.99 0.13. FSI increased with acidosis: 57.7 8.6 during phase A vs 71.9 11.4 during phase C (p=0.032). Fetal S100B also increased throughout UCO series with a rise of 7% 4 during phase A compared to initial value, and 24% 8 during phase C (p< 0.001). FSI was correlated with pH (r=-0.529, p=0.003) and fetal S100B variation (r=0.583, p= 0.002). The main objective of fetal monitoring during labor is to prevent HIE. In this study, we observed that HRV analysis could predict cerebral injury and be a future marker of fetal well-being during labor.

Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG.

Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR. Prospective case-control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2-3months, was measured at birth. 538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother-child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg (p = 0.029). At 36 + 5weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18-0.85) versus 0.00 (- 0.49-0.18), p < 0.001]. Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied. Clinical trial registration: NCT03389178.

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.

Parasympathetic nervous system response to acidosis: Evaluation in an experimental fetal sheep model.

Heart rate variability and fetal heart rate decelerations are impacted by parasympathetic function and reflect acid-base status. Our team developed a new heart rate variability index, the fetal stress index (FSI), which has lower interindividual variability and higher sensitivity for detecting fluctuations in parasympathetic nervous system activity. The aim of this study was to explore the ability of the FSI to predict fetal acidosis in a fetal sheep model. Repeated 1-minute total umbilical cord occlusions (UCOs) were performed every 2.5minutes over 3hours to generate fetal acidosis mimicking that which occurs during labor and contractions. Fetal hemodynamic parameters, blood gas, the FSI and the magnitude (from the beginning to the nadir) of the fetal heart rate deceleration were recorded at regular intervals. The data were analyzed over three time intervals because of variation in the duration of the experiments: period A (first 12 UCOs), period B (middle 12 UCOs) and period C (last 12 UCOs). Nine experiments were performed. Acidosis was progressive with a significant difference between the pH, lactate levels and base deficit values for the three periods of occlusion (P<0.05). Both FSI and the magnitude of fetal heart rate decelerations gradually increased during the UCOs and both differed significantly between periods A and C (P=0.0008 for FSI and P=0.003 for deceleration). This experimental protocol allowed the development of progressive acidosis in a good model of the physiology of labor. Parasympathetic nervous system activity increased during acidosis and could be measured using our index, the FSI, and the magnitude of fetal heart rate decelerations.

769: Fetal autonomic nervous system response to acidosis

The Autonomic Nervous System (ANS) is a major component of fetal adaptation to hypoxia. Different methods have been developed to study Heart Rate Variability (HRV), which reflects fluctuation of ANS. The aim of this study was to evaluate the different methods of ANS analysis on their abilities to reflect fetal acidosis during labor in an experimental model. Experimental study on a sheep model based on repetitive umbilical cord occlusions (UCOs) with mild (1/5 minutes), moderate (1/3 minutes) and severe (1/2 minutes) rhythm of UCOs until arterial pH reached 7.10. Hemodynamic, blood gas analysis, morphological analysis of decelerations and HRV parameters were recorded throughout the experimentation. Morphological analysis relied on depth, slope and the sum of total area of decelerations. HRV analysis included temporal analysis (RMSSD, SDNN, STV), spectral analysis (LF, HF, HF n.u.) and a new index developed by our team (Fetal Stress Index, FSI). We defined and compared 3 groups of pH: >7.20, 7.10-7.20 and <7.10. 11 experiments were performed, resulted in gradually fetal acidemia. FSI was correlated to arterial pH and lactates (p<0.05). FSI increased when fetal acidemia occurred. There was no significant relationship between RMSSD, STV LF, HF, HFn.u., total area of decelerations and pH or lactates. SDNN, baseline of fetal heart rate and slopes during decelerations increased while pH decreased, but not in a significative way. FSI seems a good HRV method to evaluate acidosis. It would be interesting to test the accuracy of a multiparametric model to predict fetal acidosis including FSI, SDNN, variation of the baseline of fetal heart rate and deceleration slopes.

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.

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.

Fetal Heart-Rate Variability: Validation of a New Continuous, Noninvasive Computerized Analysis

Objective: We developed a computerized heart-rate variability index related to the fetal parasympathetic activity: the Fetal Stress Index (FSI). The objective was to determine whether the FSI is related to the visual analysis of the fetal heart rate (FHR). Methods: Thirty tracings recorded at a labor ward were classified according to the NICHD categories: (I) normal FHR tracing, (II) intermediate risk of acidosis, and (III) high risk. FSI was calculated as minimum, maximum, and mean, and was evaluated before the onset of the FHR pattern, during the 10 min following, and between 10 and 20 min after that. Results: The FSI for categories II and III was similar to that of category I before the onset of the FHR pattern. FSI min was lower just after the onset of the abnormal FHR in category III, compared with that of category I (33 vs. 43, p < 0.001). Between 10 and 20 min after the onset of the abnormal FHR, we observed a significant reduction in FSI min in categories II and III (44 vs. 39 vs. 29.7, p < 0.0001). Conclusion: Although further studies are necessary for the sake of clinical validation, FSI could constitute an interesting method for the evaluation of fetal well-being.

Parasympathetic tone variations according to umbilical cord pH at birth: a computerized fetal heart rate variability analysis.

Non-reassuring fetal heart rate tracings reflect an imbalance between the parasympathetic and sympathetic nervous systems. In this situation, fetal asphyxia can be suspected and may be confirmed by metabolic measurements at birth like low pH or high base deficit values. The objective of this study was to determine whether fetal asphyxia during labor is related to parasympathetic nervous system activity. This is a retrospective study of a database collected in 5 centers. Two hundred and ninety-nine fetal heart rate tracings collected during labor were analyzed. Autonomic nervous system, especially the parasympathetic nervous system, was analyzed using an original index: the FSI (Fetal Stress Index). The FSI is a parasympathetic activity evaluation based on fetal heart rate variability analysis. Infants were grouped based on normal or low pH value at birth. FSI was measured during the last 30min of labor before birth and compared between groups. The minimum value of the FSI during the last 30min before delivery was significantly lower in the group with the lower umbilical cord arterial pH value. In this pilot study during labor, FSI was lower in the group of infants with low arterial pH at birth.

The quality of fetal arm movements as indicators of fetal stress

Background Although a number of studies have found that maternal stress affects the fetus, it is unclear whether jerky fetal movements observed on ultrasound scans are indicative of fetal stress, or whether they are part of normal development. Aims The present study was designed to examine the relationship between jerky fetal arm movements in relation to fetal age and stress. Methods Video recordings were made of routine ultrasound scans of 57 fetuses (age range 8 to 33 weeks) classified into three age groups: 1st trimester (8–12 weeks, N = 9), 2nd trimester (13–24 weeks, N = 38), and 3rd trimester (26–33 weeks, N = 10). Following previous research on stress behaviour in neonates, a fetal index of stress was derived from frequency of hiccup, back arch and rhythmical mouthing . Results Results indicated that while stress level was unrelated to fetal age, jerkiness of arm movements was significantly associated with the fetal stress index but not age. Conclusions Our findings suggest that jerky arm movements in fetuses are suggestive of fetal stress.

200: Intra-amniotic inflammation (IAI) is associated with a low fetal plasma cortisol / dehydroepi- androsterone sulfate ratio (fetal stress index)

200: Intra-amniotic inflammation (IAI) is associated with a low fetal plasma cortisol / dehydroepi- androsterone sulfate ratio (fetal stress index)