Deleterious functional consequences of perfluoroalkyl substances accumulation into the myelin sheath.

Exposure to persistent organic pollutants during the perinatal period is of particular concern because of the potential increased risk of neurological disorders in adulthood. Here we questioned whether exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) could alter myelin formation and regeneration. First, we show that PFOS, and to a lesser extent PFOA, accumulated into the myelin sheath of postnatal day 21 (p21) mice, whose mothers were exposed to either PFOA or PFOS (20 mg/L) via drinking water during late gestation and lactation, suggesting that accumulation of PFOS into the myelin could interfere with myelin formation and function. In fact, PFOS, but not PFOA, disrupted the generation of oligodendrocytes, the myelin-forming cells of the central nervous system, derived from neural stem cells localised in the subventricular zone of p21 exposed animals. Then, cerebellar slices were transiently demyelinated using lysophosphatidylcholine and remyelination was quantified in the presence of either PFOA or PFOS. Only PFOS impaired remyelination, a deleterious effect rescued by adding thyroid hormone (TH). Similarly to our observation in the mouse, we also showed that PFOS altered remyelination in Xenopus laevis using the Tg(Mbp:GFP-ntr) model of conditional demyelination and measuring, then, the number of oligodendrocytes. The functional consequences of PFOS-impaired remyelination were shown by its effects using a battery of behavioural tests. In sum, our data demonstrate that perinatal PFOS exposure disrupts oligodendrogenesis and myelin function through modulation of TH action. PFOS exposure may exacerbate genetic and environmental susceptibilities underlying myelin disorders, the most frequent being multiple sclerosis.

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.

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.

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.

Inter-observer reliability of 4 fetal heart rate classifications.

OBJECTIVE: Different classification of fetal heart rate (FHR) pattern have been proposed: FHR classified as either "reassuring" or "non-reassuring", the National Institute of Child Health and Human Development (NICHD) published in 2008 a 3-tier system, the French College of Gynecology and Obstetrics (CNGOF) recommended in 2013 a 5-tier system and recently in 2015, the Federation International of Gynecology and Obstetrics (FIGO) proposed a new classification based on a 3-tier system. Our objective was to assess the inter-observer reliability of these 4 existing classifications. STUDY DESIGN: Four observers reviewed 100 FHR without clinical information. FHR were obtained from term singleton pregnancies. Fetal heart rate patterns were classified by one 2-tier ("reassuring vs. non-reassuring"), two 3-tier (NICHD 2008 and FIGO 2015), and one 5-tier (CNGOF 2013) fetal heart classifications. RESULTS: The global agreement between observers was moderate for each classification: 0.58 (0.40-0.74) for the 2-tier, 0.48 (0.37-0.58) for the NICHD 2008, 0.58 (0.53-0.63) for the CNGOF 2013 and 0.59 (0.49-0.67) for the FIGO 2015 classification. When FHR was classified as reassuring, it was classified as normal in 85.5% for the NICHD 2008 and in 94.5% for the FIGO 2015. For the CNGOF 2013, 65.0% were classified as normal and 32.5% as quasi normal. There was strong concordance between FIGO category I and "reassuring" FHR (kappa=0.95). CONCLUSION: Inter-observer agreement of FHR interpretation is moderate whatever the classification used. To evaluate the superior interest of one classification, it will be interesting to compare their impact on need of second line techniques and on neonatal outcome.

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.

[Evaluation of the CNGOF foetal heart rate classification]. / Évaluation de la forme simplifiée de la classification du rythme cardiaque fœtal proposée dans le cadre des recommandations pour la pratique clinique « surveillance du travail ¼.

INTRODUCTION: The 2007 CNGOF guidelines for good practice on "Methods of foetal surveillance during labour" proposed a consensual definition of intra-partum foetal heart rate (FHR) patterns. In order to facilitate its application, Carbon et al. published in 2013 a simplified table of the classification with 5 types of tracing. OBJECTIVES: To evaluate the diagnosis value of this FHR classification to determine the risk of foetal acidosis. METHODS: Retrospective single-centre study including 252 single pregnancies beyond 34 weeks of gestation with a record of at least 60minutes before delivery. The primary endpoint was a pH at birth < 7.20. RESULTS: When pH was < 7.20, type 3 tracing was significantly more frequent during the first stage of labour while types 4 and 5 were more frequently found during active second stage. A pH<7.20 was significantly associated with more instrumental extractions, emergency caesarean section, Apgar score < 7 and neonatal respiratory distress. The areas under the curve were 0.63 for the analysis during the first stage of labour, 0.69 for second stage, and 0.68 when the two stages were combined. CONCLUSION: Our study found that the CNGOF classification improved the FHR interpretation but its diagnosis value to predict acidosis remained limited.