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18 juillet 2011 1 18 /07 /juillet /2011 22:04
Dr Roseline Péluchon (18/07/2011)


L'objectif du traitement de la colite ulcéreuse n'est plus seulement d'enrayer les signes cliniques, mais aussi d'assurer la cicatrisation muqueuse. Des marqueurs sont nécessaires pour le suivi de l'état muqueux et parmi ceux-ci, la lactoferrine fécale. Un essai récent compare les performances du dosage de la lactoferrine fécale, de la C Reactiv Protéine (CRP) et de l'indice d'activité endoscopique de Rachmilevitz, pour le diagnostic d'inflammation. La lactoferrine fécale offre une précision supérieure aux autres marqueurs, notamment à la CRP (72,6 % vs 64 %) pour le diagnostic d'inflammation de la muqueuse. Elle s'avère être un indicateur intéressant, non seulement dans le suivi thérapeutique, mais aussi dans le diagnostic différentiel entre colite ulcéreuse et syndrome de l'intestin irritable.
Langhorst J et coll. Fecal Lactoferrin As Biomarker for Monitoring the Mucosal Status in Patients with Ulcerative Colitis and Irritable Bowel Syndome. Digestive Disease Week 2011 (DDW) - 7-10 Mai 2011 - Chicago
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18 juillet 2011 1 18 /07 /juillet /2011 21:54
Le sénateur Gilbert Barbier (RDSE, Jura), membre de l’Office parlementaire d’évaluation des choix scientifiques et technologiques (Opecst) a remis le 12 juillet son rapport Les perturbateurs endocriniens, le temps de la précaution.

Dans ce rapport, le sénateur rappelle que les inquiétudes relatives aux perturbateurs endocriniens proviennent de « l’augmentation importante et non encore expliquée de maladies liées au système hormonal comme certains cancers ou des problèmes de fertilité. »  En France, l’incidence du cancer du sein a doublé depuis 1980. Ce serait également le cas du cancer du testicule dans les pays développés depuis 1970. En matière de fertilité, les chercheurs s’inquiètent d’une possible combinaison d’une baisse de moitié du nombre de spermatozoïdes et d’une augmentation des malformations génitales masculines.

Aussi, le rapport souligne-t-il que les données scientifiques disponibles envisagent un lien de causalité entre ces maladies et l’action de substances perturbant le système endocrinien ; l’impact avéré de certaines de ces substances sur les animaux sauvages, l’analogie avec des produits comme le Distilbène ou la chlordécone et plusieurs publications académiques allant dans ce sens. Toutefois, le sénateur souligne que les incertitudes restent nombreuses notamment quant aux mécanismes d’action à faible dose, en mélange ou à des moments précis de la vie, et quant aux différentes molécules impliquées. Mais les données disponibles sont suffisantes pour agir dès maintenant afin de protéger les populations les plus vulnérables, tout particulièrement les bébés et les femmes enceintes.

Dès lors, Gilbert Barbier propose de renforcer l’effort de recherche et d’améliorer sa coordination pour relever les défis scientifiques posés par ce problème émergent de santé publique. Il voudrait que des efforts soient faits au niveau européen pour aboutir d’ici à 2013 à la validation de tests internationaux permettant de détecter les perturbateurs endocriniens.

Il suggère également d’informer les consommateurs et d’apposer un pictogramme similaire à celui présent sur les bouteilles d’alcool pour indiquer aux femmes enceintes ou allaitantes qu’elles devraient éviter de s’exposer, elles et leurs jeunes enfants, à des produits contenant des perturbateurs endocriniens.

Enfin, le sénateur souhaite que soit affirmé, au niveau européen, l’objectif d’interdire la présence de perturbateurs endocriniens dans les produits spécifiquement destinés aux femmes enceintes et allaitantes et aux jeunes enfants car le moment d’exposition peut être plus important que la dose.
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18 juillet 2011 1 18 /07 /juillet /2011 18:36

En montrant que les sujets recevant du lithium au long cours pour des troubles dépressifs sont moins souvent atteints de démence sénile, certaines études ont déjà suggéré que les sels de lithium peuvent avoir un rôle protecteur vis-à-vis de la maladie d’Alzheimer (MA), contrairement à leur emploi à court terme qui n’a révélé « aucun bénéfice thérapeutique. »

Conduite à l’université de São Paulo et portant sur 24 patients de plus de 60 ans avec TCML (troubles cognitifs et mnésiques légers : amnestic mild cognitive impairment) et sur 21 sujets-contrôles recevant en double insu du lithium ou un placebo, une étude brésilienne évalue précisément l’intérêt du lithium administré pendant un an chez des patients avec TCML. Chez les sujets sous lithium, les auteurs constatent une « diminution significative » des concentrations des trois bio-marqueurs évocateurs de MA dans le liquide céphalo-rachidien : peptide bêta-amyloïde [1], protéine tau totale [2], et fraction phosphorylée de la protéine tau [2]. Ils observent aussi de meilleurs résultats aux tests psychométriques, notamment pour les performances cognitives et pour les tâches d’attention.

Quel est le mode d’action probable du lithium ? Les auteurs présument qu’il pourrait « entraver les mécanismes qui conduisent à la formation des plaques amyloïdes et des enchevêtrements neurofibrillaires. » En limitant ces processus neurotoxiques, les sels de lithium auraient donc un effet neuroprotecteur contre les atteintes neurologiques conduisant à la MA. Les chercheurs estiment que le lithium agit vraisemblablement en inhibant l’enzyme GSK3B [3], impliquée dans les processus neurodégénératifs (accumulation des plaques amyloïdes et de la protéine tau totale et phosphorylée). Bien que la petite taille de cette étude limite bien sûr sa portée, elle semble néanmoins baliser une nouvelle voie prometteuse et mérite en tout cas d’être reproduite sur une population plus vaste.

[1] http://fr.wikipedia.org/wiki/B%C3%AAta-amylo%C3%AFde
[2] http://fr.wikipedia.org/wiki/Prot%C3%A9ine_Tau
[3] Glycogène-synthase (ou synthétase)-kinase-3-bêta.



Dr Alain Cohen


Forlenza OV et coll. : Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry 2011-5 ; 198 : 351-356.

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18 juillet 2011 1 18 /07 /juillet /2011 18:34

La trophicité de la muqueuse de l’intestin grêle dépend de l’alimentation, en particulier de l’apport en glutamine. Elle se traduit par une diminution de la perméabilité intestinale après la naissance. A cet égard, on peut se demander si des grands prématurés, à la tolérance digestive limitée, ne tireraient pas profit d’un supplément oral de glutamine ?

L’hypothèse a été testée dans un essai contrôlé et randomisé en double insu qui incluait 101 prématurés de moins de 34 semaines de terme et de 2 kg de poids de naissance [PN].

Les sujets étaient en nutrition parentérale partielle, alimentés avec un lait pour prématurés. De J3 à J30, 51 d’entre eux (PN=1,32 kg, terme=31 sem. en moyenne) ont reçu un supplément oral de glutamine de 0,3 g/kg/jour, et les 50 autres (PN=1,28 kg, terme=30 sem. en moyenne) un supplément oral de dextrine-maltose en guise de placebo.

La perméabilité intestinale a été appréciée en dosant le lactulose et le mannitol dans les urines pendant les six heures suivant l’ingestion d’une quantité donnée de ces deux sucres au 2e jour de vie (avant supplémentation en glutamine), à J7 et à J30. En effet le lactulose ne peut passer que par les « jonctions serrées » et, après absorption, les deux sucres sont excrétés tels quels dans les urines, ce qui fait que leur excrétion équivaut à leur absorption.

Sous glutamine, la perméabilité intestinale a diminué rapidement au cours du 1er mois de vie :

- de façon séquentielle, chez les enfants traités par glutamine, la fraction de lactulose absorbée était plus basse à J7 et à J30 qu’au 2e jour (p <0,005 pour les deux), et le rapport lactulose/ mannitol dans les urines plus bas à J7 (p <0,005) qu’au 2e jour. Chez les témoins, il n’y avait pas de modification autre qu’une baisse de l’absorption du mannitol à J7.

- de façon comparative, la fraction de lactulose absorbée et le rapport lactulose/ mannitol dans les urines étaient moindres chez les enfants traités par glutamine que chez les témoins à J7 (p <0,05) et plus nettement encore à J30 (p <0,005). La fraction de mannitol absorbée était aussi moindre à J30 (p <0,05).

L’incidence des entérocolites ulcéro-nécrosantes (définies par un stade de Bell >2) et celle des septicémies étaient significativement plus faibles chez les enfants traités par glutamine que chez les témoins aux pointages faits à J7 et à J30 (p <0,005 pour les entérocolites ; p <0,05 pour les septicémies).

Au total, la glutamine a fait diminuer la perméabilité intestinale de prématurés en nutrition parentérale partielle, et elle les a protégés contre les entérocolites et les septicémies (par translocation bactérienne ?). Cependant, il serait hâtif de donner un supplément de glutamine per os aux grands prématurés jusqu’à alimentation totale. L’essai ne démontre ni que l’effet protecteur est dû à la maturation des jonctions serrées ni que la voie orale est nécessaire, les entérocytes utilisant aussi la glutamine IV.



Dr Jean-Marc Retbi


Sevastiadou S et coll. : The impact of oral glutamine supplementation on the intestinal permeability and incidence of necrotizing enterocolitis/ septicemia in prematures neonates. J Maternal-Fetal Neonat Med 2011; publication avancée en ligne le 4 avril.

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18 juillet 2011 1 18 /07 /juillet /2011 18:32

C’est une première en France : un hôpital public, en l’occurrence celui de Rambouillet (Yvelines) va remplacer divers matériels de ses services de réanimation et de pédiatrie, comme poignées de portes, mains courantes, robinets et autres barres de lits, par d’autres en cuivre ou enrichis en alliages correspondants. Le but ? Profiter des propriétés anti bactériennes du cuivre, qui serait capable de détruire de nombreuses bactéries, résistantes ou non aux antibiotiques. Une étude d’impact sera menée dans la foulée (les résultats en sont attendus dans un an), et il y a fort à parier que la pratique sera suivie par d’autres établissements si le nombre des infections contractées dans les deux services baisse…

Le cuivre, véritablement anti bactérien ? La démonstration, en réalité, n’est pas nouvelle même si ses applications semblent prendre aujourd’hui une nouvelle ampleur. Plusieurs expériences, réalisées sur sites ces dernières années, avaient déjà montré que les surfaces de cuivre éradiquent naturellement la presque totalité des staphylocoques, résistants ou non à la méticilline, qui avaient eu la mauvaise idée de s’y déposer. Le phénomène vient encore d’être confirmé par une nouvelle étude, réalisée par un trio US comprenant le Memorial Sloan Kettering Cancer Center de New York, la Medical University of South California et le Ralph H. Johnson VA Medical Center de Charleston  et présentée à l’ICPIC (conférence sur le contrôle et la prévention des infections) de Genève : le but était, ici encore, de déterminer l’intérêt  pratique du cuivre en en recouvrant les éléments à portée de main des malades, poignées de porte, sonnettes d’appel, surfaces diverses etc. Avec un succès certain puisque, selon les auteurs américains, la destruction des bactéries pathogènes serait suffisamment efficace pour empêcher leur transmission par les soignants et diminuer les taux d’infections nosocomiales. L’élimination rapide des bactéries empêcherait que de nouvelles mutations de résistance n’apparaissent et diminuerait les échanges de gènes de résistance bactériens. Pour eux, pas de doute, la démonstration de l’intérêt du cuivre est faite, tant du point de vue théorique que pratique, dans la vraie vie…

En Arizona aussi on s’est intéressé aux propriétés anti bactériennes du cuivre. Une revue publiée ce mois ci dans un journal de référence rappelle encore une fois que les données sur le sujet commencent à s’accumuler, avec une bonne concordance : à l’instar des staphylocoques, il a été prouvé que le cuivre serait rapidement bactéricide pour les salmonelles, agents majeurs des TIAC, pour le désormais célèbre E coli O157H7, pour Clostridium difficile responsable de la colite pseudo membraneuse ou pour diverses espèces de champignons. Voilà qui permet d’augurer d’une utilisation de plus en plus large du cuivre et, peut être, de quelques inconvénients inattendus : pour J Elguindi et coll, « les consommateurs peuvent craindre que les alliages cuivreux utilisés en surfaces anti microbiennes par l’industrie alimentaire ne conduisent à une toxicité chez l’homme » ; sans compter d’éventuelles nuisances (locales) par saturation de l’environnement en métaux toxiques (exploitations de surfaces, dépôts divers etc).

De nouveaux problèmes auxquels il faudra trouver des solutions. Décidément, rien n’est jamais aussi simple qu’il y paraît.



Dr Jack Breuil


Elguindi J et al. : Advantages and challenges of increased antimicrobial copper use and copper mining. Appl Microbiol Biotechnol., 2011 ; 91 : 237-249.

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18 juillet 2011 1 18 /07 /juillet /2011 15:57

Neuropsychopharmacology 36, 1792-1800 (August 2011) | doi:10.1038/npp.2011.53

The Effects of Nicotine Replacement on Cognitive Brain Activity During Smoking Withdrawal Studied with Simultaneous fMRI/EEG

John D BeaverChristopher J LongDavid M ColeMichael J DurcanLinda C BannonRajesh G Mishra and Paul M Matthews

Abstract

Impaired attention (‘difficulty concentrating’) is a cognitive symptom of nicotine withdrawal that may be an important contributor to smoking relapse. However, the neurobiological basis of this effect and the potentially beneficial effects of nicotine replacement therapy both remain unclear. We used functional MRI with simultaneous electroencephalogram (EEG) recording to define brain activity correlates of cognitive impairment with short-term smoking cessation in habitual smokers and the effects of nicotine replacement. We found that irrespective of treatment (ie nicotine or placebo) EEG α power was negatively correlated with increased activation during performance of a rapid visual information processing (RVIP) task in dorsolateral prefrontal, dorsal anterior cingulate, parietal, and insular cortices, as well as, caudate, and thalamus. Relative to placebo, nicotine replacement further increased the α-correlated activation across these regions. We also found that EEG α power was negatively correlated with RVIP-induced deactivation in regions comprising the ‘default mode’ network (ie angular gyrus, cuneus, precuneus, posterior cingulate, and ventromedial prefrontal cortex). These α-correlated deactivations were further reduced by nicotine. These findings confirm that effects of nicotine on cognition during short-term smoking cessation occur with modulation of neuronal sources common to the generation of both the blood oxygen-level-dependent and α EEG signals. Our observations thus demonstrate that nicotine replacement in smokers has direct pharmacological effects on brain neuronal activity modulating cognitive networks
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18 juillet 2011 1 18 /07 /juillet /2011 15:55

Neuropsychopharmacology (2011) 36, 1886–1893; doi:10.1038/npp.2011.74; published online 11 May 2011

Plasma Oxytocin Concentration during Pregnancy is associated with Development of Postpartum Depression

Marta Skrundz1, Margarete Bolten1,2, Irina Nast1, Dirk H Hellhammer3 and Gunther Meinlschmidt1,4

  1.  1Sesam—Swiss Etiological Study of Adjustment and Mental Health—National Centre of Competence in Research, Faculty of Psychology, University of Basel, Basel, Switzerland
  2.  2Child and Adolescents Psychiatric Clinic, Department of Developmental Psychopathology, University of Basel, Basel, Switzerland
  3.  3Division of Theoretical and Clinical Psychobiology, University of Trier, Trier, Germany
  4.  4Department of Clinical Psychology and Epidemiology, Faculty of Psychology, University of Basel, Basel, Switzerland

Correspondence: Dr G Meinlschmidt, Sesam—Swiss Etiological Study of Adjustment and Mental Health, Institute of Psychology, University of Basel, Missionsstrasse 60–62, Basel CH-4055, Switzerland, Tel: +41 61 267 0275, Fax: +41 61 267 0659, E-mail: gunther.meinlschmidt@unibas.ch

Received 5 December 2010; Revised 24 February 2011; Accepted 21 March 2011; Published online 11 May 2011.

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Abstract

Postpartum depression (PPD) affects up to 19% of all women after parturition. The non-apeptide oxytocin (OXT) is involved in adjustment to pregnancy, maternal behavior, and bonding. Our aim was to examine the possible association between plasma OXT during pregnancy and the development of PPD symptoms. A total of 74 healthy, pregnant women were included in this prospective study. During the third trimester of pregnancy and within 2 weeks after parturition, PPD symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Blood samples for plasma OXT assessment were collected in the third trimester. Following the literature, participants with postpartum EPDS scores of 10 or more were regarded as being at risk for PPD development (rPPD group). In a logistic regression analysis, plasma OXT was included as a potential predictor for being at risk for PPD. Results were controlled for prepartal EPDS score, sociodemographic and birth-outcome variables. Plasma OXT concentration in mid-pregnancy significantly predicted PPD symptoms at 2 weeks postpartum. Compared with the no-risk-for-PPD group, the rPPD group was characterized by lower plasma OXT concentrations. To our knowledge, this is the first study to show an association between prepartal plasma OXT concentration and postpartal symptoms of PPD in humans. Assuming a causal relationship, enhancing OXT release during pregnancy could serve as a potential target in prepartum PPD prevention, and help to minimize adverse effects of PPD on the mother–child relationship.

Keywords: postpartum depression; oxytocin; pregnancy; EPDS; adaptation to motherhood

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INTRODUCTION

Postpartum depression (PPD) affects up to 19% of all mothers and adversely influences maternal adaptation to motherhood (Gavin et al, 2005) with negative effects on child development, as children of depressive mothers are more vulnerable to develop mental disorders in later life (Grace et al, 2003).

The etiology of PPD is closely related to psychological determinants and experiences during pregnancy (O’Hara and Swain, 1996). Identification of psychological risk factors for PPD has been an important issue in the recent years. Major identified risk factors are a history of previous PPD or affective disorders in general, stressful life events, lack of social support, and low self-esteem (Beck, 2006; Robertson et al, 2004). Additionally, the early postpartum period is seen as a time of increased emotional vulnerability, partly caused by dysregulations of the endocrinological homeostasis (Wisner and Stowe, 1997). Because of the challenging reorganization of physiological processes that comes along with pregnancy and parturition, research started to address endocrine factors as potential determinants in the etiology of PPD. From animal models of PPD, we know that withdrawal from high doses of estradiol and progesterone, comparable to the respective amounts available during pregnancy, is followed by depression-like symptoms (Green et al, 2009). Addtionally, the regulation of the hypothalamic–pituitary–adrenal (HPA) axis seems to be disturbed in women with PPD (Brummelte and Galea, 2010) or short periods of Postpartum Blues (Ehlert et al, 1990). However, existing findings are not consistent (Bloch et al, 2003). One biological parameter that has not yet been considered in PPD etiology, is the non-apeptide oxytocin (OXT). OXT is synthesized in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus and released peripherally into the blood and centrally into different brain regions (Gimpl and Fahrenholz, 2001). In context of pregnancy, OXT is known for its involvement in the process of delivery (Russell et al, 2003) and its physiological role in the onset and maintenance of lactation (Sala and Althabe, 1968).

Beyond its physiological functions in the periphery, animal studies provide evidence for a major role of OXT in behavioral adaptation to pregnancy and motherhood. Characteristic maternal behaviors (pup-grooming, hover over offspring and respond latency) are impaired, if OXT availability is diminished (Higuchi and Kaba, 1997; Olazabal and Young, 2005; Pedersen et al, 2006). Furthermore, maternal OXT functioning influences reciprocal affective behaviors between mother and offspring in mammalian species (Nelson and Panksepp, 1998). Recently, this association was also shown in humans. Parents showing more affectionate and stimulatory behaviors in interactions with their children were characterized by higher plasma OXT concentrations (Gordon et al, 2010). Further, Feldman et al. (2007) reported associations between prepartum-assessed OXT concentrations and postpartum maternal adaptation. The maternal plasma OXT level, measured during early and late pregnancy, as well as in the first month postpartum, predicted maternal behavior (mother's gaze at infant, motherese vocalizations and affectionate touch) in interaction with the child. A study assessing plasma OXT twice during pregnancy showed higher postpartum maternal–fetal attachment-scores in women with a OXT rise between the first and third trimester compared with women with stable or decreasing patterns of OXT (Levine et al, 2007). In non-pregnant women, OXT is known to promote interpersonal relationships and enhance feelings of love and trust (Heinrichs and Domes, 2008).

On the basis of current evidence, lower OXT levels in pregnancy could result in impaired emotional adaptation to motherhood, which is a major risk factor for PPD development and subsequently affects the quality of maternal behavior (Murray et al, 1993; Stein et al, 2010). Therefore, the aim of this study was to assess a potential association between OXT during pregnancy and postpartum PPD symptoms in a sample of healthy pregnant women. We expected, that lower plasma OXT levels during the third trimester of pregnancy would result in an increased risk for PPD, as assessed postpartum. Results could help to elucidate the etiopathology of PPD and provide new targets for prepartal prevention of PPD.

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METHODS

Subjects

Data were collected within a larger longitudinal study conducted with 100 pregnant women in the area of Basel, Switzerland. All participants were recruited between their 21st and 32nd week of gestation. Recruitment methods included local newspaper announcements, promotion of the study at local hospitals and a call for participants on local TV. A detailed study description was given to all interested women and, if any arised, questions were answered. All participants were screened for the following inclusion criteria: (a) no current mental illness, (b) no severe medical complications (acute or chronic physical diseases, such as gestational diabetes, metabolic diseases, hypertension and thyroid dysfunction), (c) no signs of fetal malformation, (d) a pre-pregnancy BMI below 32, (e) no smoking beyond the 10th week of gestation and (f) good knowledge of German language. Data for analyses of the present paper were available for 73 participants, of which 16 were characterized by at least one lifetime depressive episode. All lifetime episodes of depression occured more than 2 years before participation in the study. A flowchart of study participants is displayed in Figure 1. Comparisons between the 73 women providing complete data and the 27 excluded women indicated no significant differences on age, parity, socioeconomic status and PPD symptoms.

 

Figure 1. 

Flowchart of study participants.

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Informed written consent was obtained from all participants. The study protocol was approved by the local ethics committee and is consistent with the revised Helsinki Declaration of 1975.

Blood Sampling and OXT Measurement

All blood samples were obtained between the 30th and 34th week of gestation. Participants visited the study centre for an experimental session, which included blood sampling and other physiological assessments. The samples for the OXT assessment were collected at the beginning of the session, starting between 1300 hours and 1500 hours. Participants were seated on a examination couch and a study nurse sampled 2.7 ml of blood into vacutainer tubes containing lithium heparin and 108 μl of Aprotinin (BioChemica, Germany). Tubes were kept on ice and centrifuged within 10 min at 6 °C at 3000 g for 10 min. Supernatants were pipetted into safe-lock devices and stored at −80 °C until analysis.

Samples were analyzed at the Department of Behavioural Neuroendocrinology, Max Plank Institute of Psychiatry, Munich, Germany, using a radioimmunoassay, as described elsewhere (Landgraf et al, 1995). This assay was reported to have an antiserum cross-reactivity of less than 0.7%, with a detection limit of 0.1 pg per sample. All samples were analyzed in duplicates. The intra-assay and inter-assay coefficients of variability were 6–8 and 8–10%, respectively.

Assessment of Demographic and Psychological Characteristics

After inclusion, participants were interviewed for assessing possible present, recent or life-time depression and anxiety disorders using the German translation of corresponding sections of the Computer Assisted Personal Interview (CAPI) version of the Composite International Diagnostic Interview (Wittchen et al, 1998; Wittchen and Pfister, 1997; World Health Organization, 1990) and general socioeconomic data.

Depressive symptoms were assessed within 2 weeks after delivery using the Edinburgh Postnatal Depression Scale (EPDS), a scale originally developed as a screening measure for depression, showing good reliability (split-half: 0.82; standardized α=0.81) (Bergant et al, 1998). A total of 10 items, dealing with typical PPD symptoms are answered on a 4-point scale. As a control variable, the prepartal EPDS score was assessed between the 32nd and 34th week of gestation.

Information on length of gestation and birth outcome were collected from medical records.

Data Analyses

All variables were checked for normal distribution, missing data and outliers (defined as more than two standard deviations below or above the mean) by the Kolmogorov–Smirnof test and visual inspection. Outliers were checked for validity and excluded if reasonable. If necessary, variables were subjected to transformation by natural logarithm before further analyses. Differences on demographic, biological and psychological characteristics between included and excluded study participants were tested by t and χ2 tests. Participants were divided into a risk-for PPD group (rPPD) and a no-risk-for PPD group (nPPD), according to the respective postpartum EPDS score. On the basis of the proposals of Bergant et al. (1998) and Jardri et al. (2006), the chosen cut-off score for being at risk for PPD was 10 or more within the first 2 weeks postpartum. T and χ2 tests were computed between the groups, to identify possible confounders among the demographical and medical variables. Descriptive statistics of EPDS scores and OXT values are reported. The postpartal EPDS scores of nursing and not nursing mothers were compared using the t-test. The bivariate correlation was computed between the pre- and postpartal EPDS score. The association between OXT and PPD symptoms was tested by conducting a binary logistic regression analysis with the group variable as outcome variable and OXT concentration as the potential predictor in the first run. In a second run the prepartal EPDS score was added, to control for potential confounding by previous depressive symptoms. Further analyses were computed including OXT concentration as the first predictor and other potential predictors, identified through previous group comparisons. Because of the expected, unequal group sizes, every logistic regression analysis was conducted with not more than two predictors, of which the first one was always OXT concentration. Because accurate classification of participants is difficult when groups are not evenly split, primary emphasis was placed on prediction rather than classification of being at risk for PPD. Data were analyzed using SPSS 16.0.2 for Mac OS X. The level of significance for all analyses was set at α=0.05.

 

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RESULTS

Sample and Group Characteristics

Demographic and pregnancy-related sample and group characteristics are displayed in Table 1. A group variable was introduced according to the postpartum EPDS score. In all, 14 participants were identified as having a postpartum EPDS score of 10 or more and were assigned to the rPPD group, representing a higher risk for the development of PPD. The remaining 59 participants were assigned to the nPPD group. Groups were tested for significant differences regarding sociodemographic and birth characteristics. Groups differed only in length of gestation. Participants in the rPPD group had a significantly shorter length of gestation (M=39.02 weeks) compared with participants in the nPPD group (M=39.73 weeks) (T (71)=2.049; P<0.05). Therefore length of gestation was included as a potential mediator in further analysis of the relationship between OXT and PPD symptoms.

 

Table 1 - Sample and Group Characteristics and Tests for Group Differences. 

Full table 

Pre and Postpartal EPDS Scores

Postpartal EPDS scores did not differ between nursing and not nursing mothers (T (69)=0.025; P=0.98). Prepartal EPDS scores (Range 0–17) were significantly correlated with postpartal EDPS scores (Range 0–22) (r=0.232; p=0.048). Mean prepartal and postpartal total EPDS scores were 4.77 and 5.85 respectively.

Plasma OXT Concentrations

Plasma OXT concentrations had a range of 14.39–245.71 pg/ml and mean OXT concentration for the overall sample was 80.81 pg/ml (SD=48.81 pg/ml). Three outliers with OXT values above 200 pg/ml were identified. Information on these three subjects did not provide a clear reason for exclusion of these cases or any indication for invalidity of assessments. Therefore, they were retained in the analyses. All further analyses were conducted with the log-transformed OXT concentrations to assure normal distribution. The bivariate correlation between prepartal EPDS scores and OXT concentrations was not significant (r=−0.086; p=0.467).

The Association between OXT Concentration in Pregnancy and Postpartum PPD Symptoms

The test statistics of the logistic regression analyses, with OXT predicting PPD symptoms are displayed in Table 2. Plasma OXT level significantly predicted PPD symptoms (Exp (b)=0.290; p<0.05). The coefficient of association between OXT concentration and PPD was below one, indicating lower OXT levels in the rPPD group and higher OXT levels in the nPPD group. The addition of the prepartal EPDS score as a further covariate in a second analysis did not improve the model fit (Δχ2 (1)=0.302; P>0.05). According to the results of descriptive statistics, length of gestation was tested as a potential mediator in a third analysis. Length of gestation did not predict PPD symptoms (Exp (b)=0.931; p>0.05) and the model fit did not improve either (Δχ2 (1)=3.507; P>0.05).

Table 2 - Binary Logistic Regression Analysis Fort he Prediction of Being at Risk for Postpartal Depression.

Full table

With OXT as predictor of PPD symptoms, 83.6% of the sample was classified correctly into the nPPD and rPPD group. To visualize the difference in OXT values between the groups, mean OXT concentrations are displayed in Figure 2.

Figure 2.

Graph shows individual oxytocin concentrations in the two groups and group means. Oxytocin values are shown on a logarithmic scale.

Full figure and legend (42K)

Download Power

 

Point slide (458 KB)

Repeating the analyses, excluding the three cases with outlying OXT concentrations, did not change the results.

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DISCUSSION

In line with our hypothesis, we could show that OXT during pregnancy was negatively associated with a positive screen on the EPDS at greater than or equal to 10, indicating a higher risk for the development of PPD. This suggests an increased occurrence of depressive symptoms in the first 2 weeks after delivery in individuals with low plasma OXT concentrations during pregnancy. The relationship persisted after controlling for prepartal EPDS scores.

Our findings are in agreement with the only human study addressing the link between plasma OXT during pregnancy and postpartal maternal behavior. Plasma OXT concentrations during pregnancy were found to be positively associated with a set of maternal bonding behaviors, such as positive affect and gaze in interactions, as well as cognitive attachment representations towards the newborn in the early postpartum period (Feldman et al, 2007). In women suffering from PPD the same behaviors are impaired, accompanied by feelings of overload and difficulties in emotional attachment development towards their child (Beck, 2006; Martins and Gaffan, 2000). Correspondingly studies with rodents report deficits in maternal behavior, such as less protective behavior and less pup-licking, and longer latencies in postpartal onset of maternal behavior in animals with decreased central OXT availability (Pedersen et al, 2006; van Leengoed et al, 1987). Non-human primate mothers show increased maternal affiliation towards offspring when central OXT is enhanced (Holman and Goy, 1995). The present findings are also in agreement with human studies reporting relationships between plasma OXT, assessed in the 2nd and 6th month postpartum and affectionate maternal behavior during mother–child interactions (Gordon et al, 2010). Again, mothers’ OXT concentrations were positively correlated with the behavioral indicators of attachment, such as motherese vocalization, affectionate touch and positive affect. As anxiety and excessive preoccupation are other important symptoms of PPD, our results also match reports of OXT acting as anxiolytic and enhancing positive emotional affiliation in non-pregnant humans (Uvnas-Moberg, 1998). There is also evidence for decreased plasma OXT concentrations in individuals suffering from major depression or reporting increased depressive symptoms (Frasch et al, 1995; Ozsoy et al, 2009; Scantamburlo et al, 2007).

The herein observed prevalence of subjects above cutoff resembles to those of other studies using the same screening instrument. Here, we identified 19.18% of the sample having an EPDS score of 10 or more. Other comparable studies found a rate of 20% at 5 days postpartum (Bergant et al, 1998) and 16% at 2 months postpartum (Yim et al, 2009).

Group comparisons revealed a significantly shorter gestation among women within the rPPD group. In women with lower OXT availability in pregnancy, the oxytocinergic inhibition of the HPA axis could be decreased. Decreased HPA axis inhibition would enhance the exponential increase of placental corticotropin-releasing factor that promotes the onset of labor (Smith, 1998). However, the length of gestation variable did not reach significance in the following prediction of PPD symptoms. It remains to be elucidated whether length of gestation has a mediating role in the relationship between OXT and PPD in samples including premature deliveries.

The range of OXT concentrations found in the present sample, is in line with those of previous studies (Dawood et al, 1979; De Geest et al, 1985). One often-mentioned issue concerning OXT assessment in human samples is that central OXT release is not necessarily related to peripheral OXT release, and therefore associations between centrally regulated psychological variables and peripheral measured OXT should be handled with caution (Jones et al, 1983; Landgraf and Neumann, 2004). However, in animals, there are also studies accounting for joint control mechanisms of central and peripheral OXT release in context of fear-related stress responses (Wotjak et al, 1998), and for autostimulatory effects at the level of the hypothalamus, in terms of peripheral OXT release activation by centrally released OXT (McKenzie et al, 1995; Neumann et al, 1994). Given the current evidence from animal studies and the difficulties in the determination of central OXT release in humans, it seems justifiable to revert to peripheral OXT assessment. This is supported by several findings reporting relations between peripheral OXT in humans and various psychological constructs, all representing aspects of human affiliation and attachment (Feldman et al, 2007; Light et al, 2004; Tops et al, 2007; Wismer Fries et al, 2005).

The mechanisms behind the observed association between OXT and PPD symptoms remain to be elucidated. Although we cannot rule out residual confounding by unknown factors, the prospective design and the inclusion of pre-pregnancy EPDS scores as a covariate make a causal relationship imaginable. There already exists evidence that OXT concentrations are lower in mothers characterized by depressive symptoms and negative affect during pregnancy, when assessed postpartum (Light et al, 2004). Further, OXT is known to reduce psychological and physiological stress responses (Heinrichs et al, 2003) and to inhibit hyperactive fear-responses of the amygdala (Labuschagne et al, 2010). There is also evidence that the properties of endocrine systems during pregnancy have programming functions for the postpartal period (Meinlschmidt et al, 2010; Pop et al, 1993). In our study, an interplay between low OXT and effects on amygdala reactivity and the HPA axis in pregnancy could indicate an increased reactivity to stressful stimuli at that time and promote the development of depressive symptoms after birth, when mothers are challenged by a bulk of potentially stressful new conditions. Additionally, expectations of the social environment and the growing demands of the child may promote feelings of fear and insecurity. Notably, a study comparing the symptomatology of postpartum and non-postpartum depression found more anxious features among the investigated PPD group (Hendrick et al, 2000). As we know from animal studies, besides the general importance of OXT in the formation of social bonds in females (Insel, 1997), the positive feedback mechanism of the oxytocinergic system is supposed to provide long-lasting stimulation of maternal behaviors after parturition (DaCosta et al, 1996). It may be less efficient, if OXT availability is diminished. Adopted to human mothers, this would be reflected by the difficulties depressed mothers have in implementing maternal behaviors and forming a relationship with their child (Beck, 1995; Cooper and Murray, 1998). Considering the profound physiological challenge caused by endocrinological changes over the course of gestation and the following abrupt shift after parturition, it is not possible to form a biological model for PPD development, that accounts for all contributing factors yet. Future studies should try to experimentally modify OXT concentrations in mid-pregnancy, to verify, whether OXT during pregnancy contributes to the generation of depressive symptoms during the postpartum period.

There are some limitations of the study. First, our finding needs to be confirmed in future studies with more than one OXT assessment over the course of pregnancy to clarify, if the relationship is specific to OXT concentrations between the 30th and 34th week of gestation. Studies assessing OXT at different stages of gestation suggest individually different patterns of OXT fluctuations over time, indicating that there might be a functional difference between women with stable OXT levels and those with rising ones (Dawood et al, 1979; Levine et al, 2007). But high intra-individual stability of values has also been reported (Feldman et al, 2007; Leake et al, 1981; van der Post et al, 1997). From our point of view, the present results refer to plasma OXT levels between the 30th and 34th week of gestation only, as we did not assess potential alterations in peripheral OXT release over the course of gestation. Second, the sample consisted of women with mostly medium to high socioeconomic status. Consequently, results need to be replicated with more heterogenous samples. Third, PPD symptoms were assessed by questionnaire (EPDS), which should be complemented in future studies by structured or standardized interviews to verify the presence of a diagnosis of PPD. It should be noted that as yet, estimations of the sensitivity and specificity of the EPDS to detect PPD vary across studies, warranting further attention of this issue (Eberhard-Gran et al, 2001; Gaynes et al, 2005; Gibson et al, 2009). Nevertheless there are validation studies reporting good sensitivity and specificity values for the EPDS within comparable study designs and according to DSM-III and ICD-10 criteria (Harris et al, 1989; Jardri et al, 2006). Important to note, our use of the EPDS within a period of 2 weeks postpartum does not provide information on the diagnosis of PPD, which requires the presence of symptoms for at least 2 weeks. Moreover, heightened EPDS scores in this early postpartum period may still be picking up the tail end of postpartum blues, which itself is a risk factor for the development of PPD. Finally, future studies should clarify, if the association between prepartal OXT and depressive symptoms during the postpartum period remains stable beyond the first 2 weeks up to several months postpartum, and if this relationship holds true for individuals with diagnosed episodes of PPD, as not all women with increased depressive symptoms after delivery develop a full-blown affective disorder.

In summary, our findings suggest that OXT is involved in the etiology of depressive symptoms during the postpartum period, and need to be further elaborated in studies assessing neuroendocrinological aspects of PPD. If replicated, the presented results will have important clinical relevance. Prepartal identification of subjects at risk for PPD could allow for early preventive interventions and minimize adverse effects for the physiological and psychological wellbeing of mother and child.

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Conflict of interest

The authors declare no conflict of interest.

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Neuropsychopharmacology (2011) 36, 1779–1780; doi:10.1038/npp.2011.83

Is there Evidence for Neurotoxicity in the Prodromal and Early Stages of Schizophrenia?

Adrienne C Lahti1 and Meredith A Reid1,2

  1.  1Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham, Birmingham, AL, USA
  2.  2Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence: Dr AC Lahti, Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham, 1530 3rd AVE S, Birmingham, AL 35294-0017, USA, Tel: +1 205 996 6776, Fax: +1 205 975 4879, E-mail: alahti@uab.edu

Received 19 April 2011; Accepted 19 April 2011

 

Retrospective and prospective studies in schizophrenia have identified a period of time, termed the prodromal period, that precedes the first episode of frank psychosis by a variable length of time (days–years) and is characterized by subthreshold psychotic symptoms. 

Importantly, both the prodromal phase and the early stages of the schizophrenia illness are associated with significant loss in social and intellectual abilities (Yung et al, 2005), as well as gray matter volume (Cahn et al, 2006; Pantelis et al, 2003).

Biol Psychiatry. 2009 Sep 15;66(6):533-9. Epub 2009 Jun 25.

Glutamate dysfunction in people with prodromal symptoms of psychosis: relationship to gray matter volume.

Stone JM, Day F, Tsagaraki H, Valli I, McLean MA, Lythgoe DJ, O'Gorman RL, Barker GJ, McGuire PK; OASIS.

Collaborators (8)

 

Source

Institute of Psychiatry, King's College London, University College London, United Kingdom. james.stone@iop.kcl.ac.uk

Abstract

BACKGROUND:

The glutamate model of schizophrenia proposes that altered glutamatergic neurotransmission is fundamental to the development of the disorder. In addition, its potential to mediate neurotoxicity raises the possibility that glutamate dysfunction could underlie neuroanatomic changes in schizophrenia. Here we determine whether changes in brain glutamate are present in subjects at ultra high risk of developing psychosis and whether these changes are related to reductions in cortical gray matter volume.

METHODS:

Twenty-seven individuals with an at-risk mental state and a group of 27 healthy volunteers underwent proton magnetic resonance spectroscopy and volumetric proton magnetic resonance imaging using a 3-Tesla scanner. Glutamate and glutamine levels were measured in anterior cingulate, left hippocampus, and left thalamus. These measures were then related to cortical gray matter volume.

RESULTS:

At-risk mental state (ARMS) subjects had significantly lower levels of glutamate than control subjects in the thalamus (p < .05) but higher glutamine in the anterior cingulate (p < .05). Within the ARMS group, the level of thalamic glutamate was directly correlated with gray matter volume in the medial temporal cortex and insula (p < .01).

CONCLUSIONS:

This study provides the first evidence that brain glutamate function is perturbed in people with prodromal signs of schizophrenia and that glutamatergic dysfunction is associated with a reduction in gray matter volume in brain regions thought to be critical to the pathogenesis of the disorder. These findings support the hypothesis that drugs affecting the glutamate system may be of benefit in the early stages of psychotic illness.

Comment in

  1. Biol Psychiatry. 2009 Sep 15;66(6):530-2.

PMID: 19559402 [PubMed - indexed for MEDLINE]


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5 juillet 2011 2 05 /07 /juillet /2011 23:40
Tels sont les résultats dévoilés par une étude anglo-saxonne. L'organe qui présente ces conclusions condamnent les prescriptions abusives d'antidépresseurs. Au cours d'une vie, une femme sur trois aurait eu recours à des antidépresseurs. Ce constat inquiétant est révélé par des chercheurs britanniques de l'association féminine " Platform 51 " qui précisent, entre autres, que 48% des femmes qui utilisent ce traitement, l'ont suivi pendant au moins cinq ans, tandis que 24% en ont pris pendant plus de 10 ans.  Selon une enquête menée en Grande Bretagne, la question la plus sensible tient à la facilité de prescription. Les antidépresseurs seraient distribués a tours de bras, au grand dam des associations, qui luttent contre cette médication abusive. Selon Rebecca Gill, chargée de la communication de Plateform 51, cette facilité de prescription encourage les femmes à recourir aux antidépresseurs. " Nous ne nions pas le rôle de ce traitement, mais en travaillant de concert avec des femmes qui y ont eu recours, nous constatons que la prescription est un peu trop laxiste. Ils sont prescrits trop facilement et souvent présentés comme l'unique remède."   En effet, pour trois femmes sur cinq s'étant rendues à leur consultation médicale, aucune alternative à l'antidépresseur n'a été proposée.  Cette association féminine qui déclare une guerre ouverte à l'abus d'antidépresseurs, en rappelle également les dangers. Ainsi, selon une étude américaine, leur consommation durant la grossesse met en danger la santé de l'enfant à naître. Le foetus, en se développant, pourrait présenter des signes d'autisme. Cette pathologie a été détectée chez 6,7% des enfants exposés à l'antidépresseur de type ISRS, dit inhibiteurs sélectifs de la recapture de la sérotonine, contre seulement 3,3% des enfants dont le développement s'est effectué sans facteurs aggravants. Au delà des risques liés à la santé, les études dévoilées par l'association Platform 51 ont mis le doigt sur un point délicat. Rebecca Gill précise qu'il existe toujours aujourd'hui, une véritable stigmatisation des pathologies psychologiques. " Il est clair que les femmes [sous antidépresseurs, ndlr] ont peur d'être jugé quant à leur santé mentale, c'est pour cela qu'elles ne diront rien à leurs proches."  Lever ce tabou sera probablement, le premier engrenage d'une lutte efficace contre les prescriptions abusives d'antidépresseurs.
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Published by Chronimed - dans Concept
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5 juillet 2011 2 05 /07 /juillet /2011 23:17
Vaccin anti-rotavirus et invagination intestinale aiguë En 1998, un vaccin vivant atténué contre le rotavirus, le Rotashield, était autorisé et recommandé aux Etats-Unis pour la prévention des diarrhées à rotavirus chez le nourrisson. Malgré une efficacité démontrée, ce vaccin était retiré du marché américain dès 1999 en raison d’un effet secondaire inattendu, la survenue d’invaginations intestinales aiguës (IIA). Cet accident dont la fréquence était estimée à 1 enfant sur 10 000, survenait dans les 10 jours qui suivaient la vaccination. Cette chronologie semblait liée au pic intestinal de réplication virale après l’absorption du vaccin. Depuis ce retrait, deux autres vaccins vivant ont reçu des autorisations de mise sur la marché dans de très nombreux pays du monde (dont la France). Il s’agit du RotaTeq qui contient 5 virus réassortants et s’administre en 3 doses et le Rotarix qui est un vaccin monovalent entraînant une protection croisée contre les autres sérotypes, et qui nécessite 2 doses. Dans les deux cas, par précaution, en raison d’un risque observé d’IIA plus élevé après le 3ème mois avec le Rotashield, ces nouveaux vaccins doivent être débutés avant la 12ème semaine. Bien sûr, compte tenu des antécédents du Rotashield, les essais cliniques réalisés avec RotaTeq et Rotarix se sont attachés à rechercher un risque d’IIA en post vaccinal. Mais malgré plus de 130 000 enfants concernés, aucune majoration du nombre de cas d’IIA n’a été constatée. Il en a été de même lors de la surveillance post-commercialisation aux Etats-Unis où cette vaccination est recommandée pour tous les jeunes nourrissons. Cependant, les autorités sanitaires mexicaines et brésiliennes ainsi que les Centers for Disease Control d’Atlanta ont voulu aller plus loin et ont initié deux très vastes études cas témoins concernant le vaccin Rotarix sur une grande partie de la population des ces deux pays d’Amérique latine où 6 millions d’enfants naissent chaque année et où la vaccination est systématique (1). Un risque d’IIA accru dans la semaine suivant la primo-vaccination Deux cent quatre vingt-cinq cas d’IIA survenus avant l’âge de 35 semaines ont été inclus dans l’étude au Mexique et 330 au Brésil et appariés à respectivement 739 et 1 311 contrôles. Les résultats ont été différents dans les deux pays. Au Mexique, il est apparu que le risque d’IIA était multiplié par 5,3 à 5,8 dans les 7 jours suivant la première dose de vaccin (intervalle de confiance à 95 % [IC95] entre 2,6 et 13). Au Brésil, le risque n’était pas accru après la première dose mais dans la semaine suivant la seconde (multiplié par 1,9 à 2,6). Le calcul a montré que ce vaccin pourrait être responsable de 96 cas d’IIA au Mexique et au Brésil, avec 5 décès soit un risque d’IIA de 1 pour 51 000 au Mexique et de 1 pour 68 000 au Brésil. Ce risque d’événement exceptionnel, ne pouvait, comme toujours avec de nouveaux produits, être détecté lors des essais cliniques en raison de leur trop faible puissance. Risque au Mexique mais non au Brésil Les causes de la différence entre les deux pays ne sont pas pleinement élucidées. L’explication proposée la plus plausible est que le vaccin rotavirus étant administré en association avec le vaccin polio oral au Brésil (et non au Mexique, pays ou le vaccin polio injectable est utilisé), la multiplication intestinale du virus vaccinal poliomyélitique inhiberait celle du rotavirus vaccinal. Dans cette hypothèse, le pic d’IIA observé après la seconde dose de vaccin au Brésil serait dû au fait que lors de cette seconde vaccination, l’immunité anti-rotavirus serait incomplète tandis que la multiplication du virus polio vaccinal serait moindre (2).  Quoi qu’il en soit ces données nouvelles semblent corroborer des études post AMM conduites en Australie qui ont été publiées en 2011 dans Vaccine et qui montrent une multiplication du risque d’IIA par 3 à 5 dans les 7 jours qui suivent une vaccination contre le rotavirus avec l’un ou l’autre des vaccins disponibles. Un rapport risque-bénéfice toujours favorable Cette possibilité, qui semble maintenant établie, doit être mise en balance avec les bénéfices tirés de la vaccination. D’une part, il est possible, comme l’ont montré des études de tolérance conduite avec le Rotarix, que cette majoration immédiate de la fréquence des IIA soit suivie d’une diminution du risque dans les mois suivants (peut être en raison d’une réduction du nombre de cas d’IIA liés à une infection par le virus sauvage). D’autre part et surtout, ce danger d’IIA est infiniment moins important que le bénéfice attendu (et démontré) de la vaccination en particulier dans les pays en développement. Manish Patel et coll. qui signent cette étude dans le New England Journal of Medicine évaluent le nombre d’hospitalisations pour diarrhées à rotavirus évitées grâce au vaccin chaque année dans ces deux pays à 80 000 et le nombre de décès épargné à 1 300 soit plus de 200 fois plus que la mortalité due aux IIA induites par le vaccin. Sur ces bases, l’OMS et les autorités sanitaires mexicaines, brésiliennes et américaines ont décidé de façon unanime de maintenir leurs recommandations de vaccination systématique des enfants de moins de 3 mois.   Rappelons qu’en France, bien que les deux vaccins aient obtenu l’AMM, cette vaccination n’est pas intégrée aujourd’hui au calendrier vaccinal en raison des doutes émis par le Conseil supérieur d’hygiène publique sur leurs rapports coût-efficacité. Dr Laurence Terrasse 1) Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil. N Engl J Med 2011; 364: 2283-92. 2) Rotavirus vaccination and intussusception. Act two. N Engl J Med 2011; 364: 2354-55.
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Published by Chronimed - dans Infections froides
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