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International audience; Human milk odour has for long elicited research interest with regard to its function in breastfeeding initiation. The present review aims to provide an overview of the behavioural effects of human milk odour in the human neonate, considering different types of response measures in a feeding or non-feeding context. Further, an overview of the current knowledge of odorant composition and factors influencing milk odour is provided by summarizing results from analytical studies using olfactometry, and addressing changes in milk odour due to storage, lactational stage, and maternal dietary intake of odorous substances. We finally highlight some issues for future research.

National audience

International audience; In their native state, milk lipids are present in the form of dispersed droplets called Milk Fat Globules (MFG, diameter 0.1-20 μm, average = 4 μm in bovine milk). The native MFG is constituted by a triglyceride core covered with an external trilayered membrane inherited from its secretory past. This membrane is mainly based on polar lipids (glycerophospholipids, sphingolipids and glycosphingolipids), proteins (25 % of total membrane with high proportion of glycoproteins and enzymes), neutral lipids and minor components. The major biological function of the MFG is to deliver energy to the mammal newborn, for that, the MFG has to be hydrolyzed in the gastro-intestinal tract by lipases, in successive steps. The lipases should interact with the MFG membrane and diffuse in the supramolecular object. The aim of this work is to determine the mechanism involved in the enzymatic hydrolysis along the digestive process. Indeed, we used millifluidic cells designed to bloc MFG and injected successively each lipase involved in the digestion process. Thank to the UV-microscope developed on the DISCO beamline, the autofluorescence of tryptophan (and tyrosine) present in the lipase amino-acid sequences had allowed the protein observation without external labeling. The gastric and intestinal neonatal disintegration of milk fat globules has been approached through transmission images recording and analysis of the number of globules and their state of aggregation/coalescence during digestion (approached via diameter, size, mode and specific surface evolution against time). In this presentation, the first results of these experiments will be showed. Mainly, in the stomach, the gastric lipases bind the MFG surface. Then, the MFG decreased in size in the intestinal phase releasing the intact lipid membrane suggesting that the core is hydrolyzed through the external membrane.

Impact des procédés de transformation sur la digestion du lait maternel et des formules infantiles chez le nouveau-né. CIAG : Carrefour de l'innovation agronomique- alimentation 2018

Advances in neonatal nutrition: a step forward infant formula biomimetic of human milk structure and digestive behaviour. Conférence PPGAN UNIRIO

The biological membrane surrounding fat globules in milk, the MFGM, is poorly known despite its importance in the functional properties of many dairy products and in the mechanisms of milk lipids digestion occurring in the gastrointestinal tract of mammal newborns. Studies recently revealed the formation of lipid domains in the MFGM that have been interpreted as the lateral segregation of high phase transition temperature (Tm) lipids, mainly milk sphingomyelin (MSM; Tm 34°C) [1]. The role played by these MSM-rich domains in the MFGM is currently unknown and needs further investigation. In this context, the aim of this study was to investigate the role of temperature and cholesterol in the morphology and nanomechanical properties of the MFGM. Accessing the biophysical properties of biological membranes at nanoscale is possible using Atomic Force Microscopy (AFM). In the complex biomimetic membranes formed using a MFGM lipid extract, topographical AFM images revealed for T < 35°C the formation of µm-large domains that protruded above the continuous phase by ~1 nm [2]. The resistance of the MSM-rich gel phase domains to rupture was significantly higher than that of the liquid disordered continuous phase, i.e. breakthrough force FB of 23 nN vs. 6 nN at 25°C, respectively. The key role played by cholesterol in the lateral segregation of high Tm lipids, by decreasing the size of the lipid domains, their height and by fluidizing the MFGM has been demonstrated [3]. Such work on the heterogeneous distribution of polar lipids in the MFGM may open perspectives in dairy technology and infant nutrition, e.g. optimisation of the interface of processed lipid droplets in infant milk formulas to mimick the biological MFGM in breast milk.

Introduction : les maladies du tube digestif du nouveau-nés sont difficiles à prendre en charge. Une des principales complications est la résection chirurgicale d’une partie de l’intestin qui peut être responsable d’une insuffisance intestinale pouvant retentir sur la croissance et l’état nutritionnel. La citrulline est un acide aminé synthétisé par les entérocytes qui peut être un marqueur de la masse fonctionnelle intestinale et permettre de moduler le support nutritionnel. L’objectif principal était de chercher une corrélation entre la longueur d’intestin grêle post-chirurgicale et le taux de citrulline chez des nouveau-nés porteurs de pathologies digestives traitées chirurgicalement. Matériel et méthode : la citrulline plasmatique était dosée à plusieurs reprises chez des nouveau-nés porteurs de dérivation intestinale. La longueur de grêle était évaluée en peropératoire. Les éléments nutritionnels étaient relevés à partir du dossier du patient. Résultat : 15 nouveau-nés de 33,3 ± 5,9 [25-41] SA ont été inclus. Le taux de citrulline semble corrélé positivement à la longueur de grêle sans significativité statistique. La durée de nutrition parentérale est inversement proportionnelle à la longueur du grêle restant (p=0,01). Il existe un lien entre le taux de citrulline et la progression de la nutrition entérale permettant le sevrage de la nutrition parentérale. Conclusion : notre travail a permis de montrer que la citrulline pourrait être un marqueur biologique de la masse fonctionnelle intestinale chez des nouveau-nés porteurs de dérivation intestinale et ou de résection du grêle. Elle pourrait aider à monitorer la nutrition qui joue un rôle primordial dans le devenir de ces enfants.

Studying food digestion in humans through clinical trials is difficult for economical, ethical and technical reasons. In vitro alternatives are thus used for screening different foods and for a better understanding of the mechanisms of the digestive process. To date, there are only few models for simulating infant digestion and most of them lack of physiological relevance. Thanks to an extensive literature review of the in vivo infant digestive conditions, a gastrointestinal static in vitro model was developed for infants born at term and aged of 28 days. The oral phase was omitted due to the liquid nature of infant formula but also because carbohydrate digestion was not monitored here. The following parameters were determined: pH, ratio of meal to secretions, enzyme units of pepsin and gastric lipase (added as rabbit gastric extract) and of pancreatin (porcine source), and biliary salt molarity. Gastric and intestinal phases lasted 60 min each. The model was applied to the digestion of a commercial infant formula. Kinetics of digestion and end-points were compared with those obtained while submitting the same formula to the adult standardised protocol of in vitro static digestion1.Gastric and intestinal digesta were sampled regularly. Proteolysis kinetics were followed by SDS-PAGE and NMR and lipolysis kinetics by thin layer and gas chromatography. The structure evolution during the gastric phase was evaluated by confocal laser scanning microscopy and laser light scattering. As a result, the kinetics of proteolysis and lipolysis differed according to the physiological stage likely due to the reduced level of enzymes in the infant model and the higher gastric pH at the infant stage. This model is of interest for scientists or companies studying the digestion of infant food.

The aim is to compare the prevalence of maternal deficiencies in micronutrients, the obstetrical and neonatal complications after bariatric surgery according to surgical techniques, the time between surgery and conception, and BMI at the onset of pregnancy. A retrospective cohort study concerned 57 singleton pregnancies between 2011 and 2016 of 48 adult women who have undergone bariatric surgery. Small-for-gestational-age neonates were identified in 36.0% of pregnancies. With supplements intake (periconceptional period: 56.8%, trimester 1 (T1): 77.8%, T2: 96.3%, and T3: 100.0%), nutritional deficiencies involved vitamins A (T1: 36.4%, T2: 21.1%, and T3: 40.0%), D (T1: 33.3%, T2: 26.3%, and T3: 8.3%), C (T1: 66.7%, T2: 41.2%, and T3: 83.3%), B1 (T1: 45.5%, T2: 15.4%, and T3: 20.0%), and B9 (T1: 14.3%, T2: 0%, and T3: 9.1%) and selenium (T1: 77.8%, T2: 22.2%, and T3: 50.0%). There was no significant difference in the prevalence of nutritional deficiencies and complications according to surgery procedures and in the prevalence of pregnancy issues according to BMI at the beginning of the pregnancy and time between surgery and pregnancy. Prevalence of micronutritional deficiencies and small-for-gestational-age neonates is high in pregnant women following bariatric surgery. Specific nutritional programmes should be recommended for these women.

International audience; The authors have previously shown that neonatal hyperoxic stress leads to high blood pressure, impaired endothelium-mediated vasodilatation, and increased vascular production of superoxide anion by NAD(P)H oxidase in adulthood. However, it is unknown whether changes in nitric oxide (NO) production and/or bioinactivation prevail and whether NO synthase (NOS) is also a source of superoxide. The purpose of this study was to evaluate whether adult animals exposed to neonatal hyperoxic stress have impaired vascular NO production associated with NOS uncoupling participating to vascular superoxide production and vascular dysfunction. In adult male rats exposed to 80% oxygen from day 3 to 10 of life (H, n = 6) versus room air controls (CTRL, n = 6), vascular (aorta) NO production is decreased at baseline (CTRL: 21 +/- 1 vs. H: 16 +/- 2 4,5-diaminofluorescein diacetate fluorescence intensity arbitrary units; P < 0.05) and after carbachol stimulation (acetylcholine analog; CTRL: 26 +/- 2 vs. H: 18 +/- 2; P < 0.05). Pretreatment with L-arginine (CTRL: 32 +/- 4 vs. H: 31 +/- 5) and L-sepiapterine [analog of key NOS cofactor tetrahydro-L-biopterin (BH4)] (CTRL: 30 +/- 3 vs. H: 29 +/- 3) normalizes NO production after carbachol. L-Sepiapterine also normalizes impaired vasodilatation to carbachol. Vascular endothelial NO synthase (eNOS) immunostaining is reduced, whereas total eNOS protein expression is increased in H (CTRL: 0.76 +/- 0.08 vs. H: 1.76 +/- 0.21; P < 0.01). The significantly higher superoxide generation (CTRL: 20 +/- 2 vs. H: 28 +/- 3 hydroethidine fluorescence intensity arbitrary units; P < 0.05) is prevented by pretreatment with the eNOS inhibitor N-nitro-L-arginine methyl ester (CTRL: 21 +/- 4 vs. H: 22 +/- 4). Taken together, the current data indicate a role for eNOS uncoupling in enhanced vascular superoxide, impaired endothelium-mediated vasodilatation, and decreased NO production in adult animals with programmed elevated blood pressure after a brief neonatal oxygen exposure.

Introduction et but de l’étude : Assurer une croissance et un développement optimal chez les nouveau-nés prématurés est une priorité (WHO, 2015). Contrairement aux formules infantiles, le lait maternel permet de limiter les entérocolites nécrosantes, mais doit être supplémenté pour répondre aux besoins nutritionnels du prématuré. Cette stratégie est largement débattue. Une alternative pourrait être l’homogénéisation du lait maternel pasteurisé afin d’augmenter sa digestibilité lipidique (Thomaz, Goncalves, & Martinez, 1999). L’homogénéisation, qui fragmente les globules gras en gouttelettes, conduit à l’augmentation de la surface disponible pour les lipases (Bourlieu et al., 2015). L’objectif était d’évaluer l’impact de l’homogénéisation de lait pasteurisé sur ses cinétiques d’hydrolyse gastrique et sa déconstruction en phase gastrique chez le prématuré. Matériel et méthodes : 8 enfants prématurés hospitalisés nourris par sonde gastrique ont participé à cette étude randomisée (NCT02112331). Sur 6 jours consécutifs, chaque enfant recevait chaque jour du lait maternel pasteurisé (LMP) et pasteurisé homogénéisé (LMP+H). Les effluents gastriques étaient collectés à jeun puis à 35, 60 ou 90 min, chaque temps étant collecté en double. Après mesure du volume et pH, les effluents étaient analysés par granulométrie laser et microscopie confocale, puis par électrophorèse (SDS-PAGE) pour le suivi des protéines et par chromatographie pour le suivi lipidique. Concernant les statistiques (logiciel R), un modèle linéaire mixte était utilisé avec comme facteurs : temps, repas, sujet et sujet x repas, et éventuellement après sélection de modèle : jour de prélèvement ou poids de l’enfant, teneur en lipides ou protéines. Résultats et Analyse statistique : L’homogénéisation du lait maternel pasteurisé a conduit à une réduction significative de taille des particules d’un facteur 10 [mode de la distribution (moy ± ET) : 7.0 ± 0.9 (LMP) vs. 0.8 ± 0.3 – 0.16 ± 0 µm (LMP+H)] et une augmentation significative de la surface spécifique d’un facteur 6 [4.1 ± 1.2 (LMP) vs 25.5 ± 3.8 m²/g de lipide (LMP+H)]. L’homogénéisation accélérait significativement la lipolyse instantanée (LMP+H : 10.9 ± 1.8, 12.7 ± 2.3 et 15.0 ± 7.1 % ; LMP : 8.5 ± 2.7, 9.6 ± 2.6 et 13.8 ± 5.2 % à 35, 60 et 90 min, respectivement) mais n’avait pas d’impact sur la protéolyse. Un ralentissement significatif de la vidange gastrique du repas était observé pour LMP+H avec un temps de demi-vidange de 38 min contre 30 min pour LMP. Il n’y avait pas de différence significative d’acidification gastrique entre LMP et LMP+H. Conclusion : L’impact de l’homogénéisation du lait maternel pasteurisé sur l’augmentation du degré de lipolyse gastrique a été démontré in vivo, en parallèle d’un ralentissement de la vidange gastrique. L’impact global sur la croissance du prématuré reste à évaluer dans une étude clinique randomisée plus large.

Introduction The anatomy and embryology of the nail are well known, and nail abnormalities are a feature of many genodermatoses. However, the physiological aspect is not well described. We aimed to analyse the physiological features of nails in healthy newborns. Methods We performed an observational, prospective study at University Hospital Center of Tours between July and October 2015. Newborns were included by a dermatologist assistant during the systematic examination on release of the mother from the hospital. The medical history of the mother and infant were recorded by using a standardized questionnaire. Finger- and toenails were systematically photographed for a second interpretation by a dermatologist with blinding to the first photograph. Results Fifty-eight patients were eligible, and 52 were included. Half of the newborns were males, and the mean age at inclusion was 3.6 ± 1.2 days. Fingernails had an oval shape (71.1%) or a flat curvature (63.5%), and half had a lunula. Toenails showed an apparent hypertrophy of the proximal nail fold (38.4%) and lateral nail fold (73.1%). The shape of the nails was triangular (50.0%) or round (21.1%). We noted koilonychia in 32.7% of infants and lunula in 7.7%. Distal parts showed onychoschizia (28.8%) and onycholysis (26.9%). Conclusion Koilonychia, onychoschizia of toenails or absence of lunula are physiological features of nails in newborns.

Au Burkina Faso, la naissance de jumeaux contraint leurs mères à un rite de présentation des enfants, lors duquel elles reçoivent des offrandes. Cet article a pour objectif d'interroger l'évolution de cette pratique en une forme de mendicité des mères de jumeaux autour des mosquées en contexte urbain. Ouagadougou a constitué le terrain d'observation des lieux de mendicité. Les résultats font apparaître les mosquées comme lieux privilégiés de convergence de mobilités féminines en lien avec une mendicité pourtant non dépendante des pratiques religieuses islamiques et une mutation de l'économie morale du don au niveau local.

In mammals, hepatic lipid catabolism is essential for the newborns to efficiently use milk fat as an energy source. However, it is unclear how this critical trait is acquired and regulated. We demonstrate that under the control of PPARα, the genes required for lipid catabolism are transcribed before birth so that the neonatal liver has a prompt capacity to extract energy from milk upon suckling. The mechanism involves a fetal glucocorticoid receptor (GR)-PPARα axis in which GR directly regulates the transcriptional activation of PPARα by binding to its promoter. Certain PPARα target genes such as Fgf21 remain repressed in the fetal liver and become PPARα responsive after birth following an epigenetic switch triggered by β-hydroxybutyrate-mediated inhibition of HDAC3. This study identifies an endocrine developmental axis in which fetal GR primes the activity of PPARα in anticipation of the sudden shifts in postnatal nutrient source and metabolic demands. DOI: http://dx.doi.org/10.7554/eLife.11853.001, eLife digest Birth is a highly stressful and critical event. In the womb, babies rely on the supply of oxygen and nutrients provided by the placenta. However, once they are born they need to breathe for themselves and gain all their nutrients from suckling milk. The placenta provides a sugar-rich diet, while milk is richer in fat. Failing to cope with this change in diet leads to serious complications and sometimes death. Therefore, a better understanding of how the body adapts to these changes may shed light on pathways that are important for good health in later life. The liver plays a central role in processing the nutrients absorbed by the gut. It uses fats to produce molecules called ketone bodies, such as β-hydroxybutyrate, which are then used as fuel by other tissues and organs including the heart, muscle and the brain. A protein called PPARα controls the production of ketone bodies primarily by regulating genes that are involved in the uptake and breakdown of fat in the liver. However, little is known about how this protein affects the development of the liver. Here, Rando, Tan et al. report that mice start to produce more PPARα in the liver shortly before birth. This ultimately activates several genes that encode enzymes that break down fats. The experiments show that during labor, stress hormones called glucocorticoids directly stimulate the production of PPARα in the liver of the fetus to prepare newborn mice for harnessing energy from fat-rich milk. In the absence of PPARα, mouse liver cells are less able to break down fats after birth and so start to accumulate fat, resulting in fewer ketone bodies being produced. Rando, Tan et al. show that β-hydroxybutyrate regulates some PPARα target genes, including one called Fgf21. The activity of this gene increases only after milk suckling starts and it encodes a protein that enhances the breakdown of fats in the liver. Without PPARα, the expression levels of its target genes, including Fgf21, do not increase after birth, which promotes the build up of fats in liver cells, a condition known as liver steatosis. Overall, the results reported by Rando, Tan et al. highlight how stress during labor plays an important role in priming the body to cope with a fat-rich diet after birth. Future studies will need to determine if stress hormones and ketone bodies could be used as therapies for babies born by caesarean section with liver steatosis. DOI: http://dx.doi.org/10.7554/eLife.11853.002

Linseed oil, being rich in 18 : 3n-3, represents an alternative source ofn-3 PUFA in the maternal diet. However, little is known about the effect of this oil on the long chainn-3 PUFA composition of offspring, which are required for normal growth and maturation of numerous organs. The main objective of the experiment was therefore to investigate fatty acid composition of tissues from sows at the end of gestation and from piglets during the first week of postnatal life in response to maternal dietary linseed oil intake. Sows received either a lard (LAR)-based diet or a linseed oil (LSO)-based diet during gestation and lactation. Fatty acid composition was evaluated in sow plasma, placenta and milk, and in different tissues of piglets on days 0, 3, 7, 21 and 32. The LSO diet increased the proportions ofn-3PUFA and especially 22 : 6n-3 in the placenta. The carcass of LSO piglets at birth contained greater proportions of 20 : 5n-3, 22 : 5n-3 and 22 : 6n-3. The LSO sow milk exhibited greater proportions of 18 : 3n-3compared with the LAR sow milk. The piglets suckling LSO sows had greater proportions of 18 : 3n-3, 20 : 5n-3 and 22 : 5n-3 in plasma and carcass. The proportions of 22 : 5n-3 and 22 : 6n-3 were greater in the brain of LSO piglets than in that of LAR piglets during the suckling period. In conclusion, LSO in the maternal diet during gestation and lactation increases 22 : 6n-3 concentrations in the placenta and in the foetus carcass, and it maintains 22 : 6n-3 concentrations in the brain during the first week of postnatal life.

Introduction et But de l’étude Une meilleure compréhension de la digestion du lait maternel chez le nouveau-né est nécessaire pour améliorer les formules infantiles et les rendre plus biomimétiques. Pour des raisons éthiques, il est difficile de conduire de telles études chez le nouveau-né. Il est donc nécessaire de développer des modèles pertinents de digestion in vitro. L’objectif de notre étude était de comparer un modèle de digestion dynamique in vitro avec des données obtenues chez le nouveau-né.Matériel et Méthodes Un digesteur in vitro dynamique (i.e. avec, en continu, une régulation du pH, une sécrétion enzymatique et une vidange) comportant une phase gastrique et une phase intestinale (DIDGI®, INRA) a été utiliséa. Les paramètres du modèle de digestion au stade nouveau-né prématuré ont été fixés grâce à une revue exhaustive de la littératureb en termes de types et quantités d’enzymes, de flux de sécrétions, de descente en pH et de vitesse de vidange. Un pool de lait maternel cru ou pasteurisé (62,5°C, 30 min) issu de mères d’enfants prématurés (n = 5) a été digéré in vitro. Les digestas gastriques étaient prélevés à intervalle régulier. En parallèle, la digestion de lait maternel cru ou pasteurisé a été suivie chez des nouveau-nés prématurés au Centre Hospitalo-Universitaire de Rennes (NCT02112331, n=12). Des prélèvements postprandiaux étaient réalisés à 35, 60 ou 90 minutes après le début du repas par la sonde d’alimentation de ces enfants. La structure des digestas (in vitro et in vivo) a été analysée par granulométrie laser et microscopie confocale, la protéolyse par électrophorèse (SDS-PAGE) et la lipolyse par chromatographies en couche mince et gazeuse. Le pH et les volumes des digestas étaient également suivis.Résultats et Analyse statistique Au cours des digestions in vitro et in vivo, une hydrolyse rapide des caséines et une résistance de l’alpha-lactalbumine ont été observées. Un faible degré de lipolyse gastrique (7-19% à 90 min) a été confirmé in vitro et in vivo. Dans les deux types de digestion, la pasteurisation n’affectait pas les cinétiques ni le degré final de lipolyse et protéolyse, mais impactait l’évolution structurale des digestas, en particulier la désintégration de l’émulsion et l’agrégation protéique. Les données de descente en pH et de vidange gastrique paramétrées dans le digesteur sont à améliorer pour s’approcher au mieux de la physiologie du nouveau-né prématuré.ConclusionNotre étude a permis de mettre en évidence des conclusions similaires in vitro et in vivo quant à l’impact de la pasteurisation sur la digestion du lait maternel, en termes d’hydrolyse digestive mais aussi en termes d’évolution structurale. Les données in vivo vont permettre d’ajuster au plus près les paramétrages concernant la descente en pH et la vidange gastrique. Notre modèle sera utile à la fois pour la communauté scientifique et pour les industriels qui s’intéressent à la digestion néonatale et l’optimisation de formules infantiles.Références:a Bourlieu C., et al. (2015). Crit Rev Food Sci Nutr, 54(11), 1427-57.b Ménard O., et al. (2014). Food Chem, 145, 1039-45.

International audience; The enzymatic lipolysis of complex natural lipoproteic assemblies such as milk fat globules is central in neonatal digestion. This process first requires the rapid adsorption of a lipolytic enzyme, gastric lipase, onto the membrane enveloping the triglyceride substrate before the onset of catalytic activity. The interactions governing lipase adsorption onto this complex lipid/water interface are not fully elucidated. This study was designed to unravel the interactions of recombinant dog gastric lipase (rDGL) with model monolayers presenting liquid-liquid phase coexistence and mimicking the outer leaflet of the milk fat globule membrane. Combining biophysical tools (ellipsometry, tensiometry and atomic force microscopy), it was evidenced that rDGL partitions toward liquid expanded phase and at phase boundaries. rDGL gets adsorbed at several levels of insertion suggesting molecular cooperation that may favor insertion and strongly impacts on the lipid phase lateral organization. The addition of phosphatidylserine, negatively charged, reinforced adsorption; hence besides hydrophobic interactions and as further investigated through surface potential modeling, rDGL adsorption is favored by electrostatic interactions

Respiratory syncytial virus (RSV) causes severe bronchiolitis in infants worldwide. The immunological factors responsible for RSV susceptibility in infants are poorly understood. Here, we used the BALB/c mouse model of neonatal RSV infection to study the mechanisms leading to severe disease upon reexposure to the virus when adults. Two major deficiencies in neonatal lung innate responses were found: a poor DCs mobilization, and a weak engagement of the IFNI pathway. The administration of Flt3 ligand (Flt3-L), a growth factor that stimulates the proliferation of hematopoietic cells, to neonates before RSV-infection, resulted in increased lung DC number, and reconditioned the IFNI pathway upon RSV neonatal infection. Besides, neonates treated with Flt3-L were protected against exacerbated airway disease upon adult reexposure to RSV. This was associated with a reorientation of RSV-specific responses toward Th1-mediated immunity. Thus, the poor lung DCs and IFNI responses to RSV in neonates may be partly responsible for the deleterious long-term consequences revealed upon adult reexposure to RSV, which could be prevented by Flt3-L treatment. These results open new perspectives for developing neonatal immuno-modulating strategies to reduce the burden of bronchiolitis.

Bien qu'une augmentation de l'incidence et de la severite des infections invasives au streptocoque du groupe A (SGA) durant ces dernieres decades ait ete constatee par plusieurs auteurs, les meningites dues a cette bacterie restent exceptionnelles chez le nouveau ne et leur physiopathologie est encore mal connue. A travers ce travail nous allons rapporter le cas d'une meningite neonatale a SGA diagnostiquee au sein de notre formation, avec revue de la litterature s'interessant a ces meningites.

Les érythrodermies du nouveau-né sont des tableaux rares, d’évolution chronique et potentiellement mortelles. Leurs étiologies sont diverses et variées dominées par les ichtyoses, le déficit immunitaire primaire, ou plus exceptionnellement le psoriasis sévère, les maladies métaboliques, la dermatite atopique ou une cause infectieuse. La détermination rapide de la cause sous-jacente est cruciale pour une meilleure prise en charge. Cependant, le diagnostic constitue un défi pour le clinicien et est souvent retardé en raison de la nature non spécifique des signes cliniques et histopathologiques. L'objectif de notre travail est de rappeler aux praticiens une étiologie grave de l’érythrodermie néonatale: le déficit immunitaire ceci à travers l'observation d'un nourrisson suivi pour une érythrodermie évoluant depuis la naissance, hospitalisé pour une fièvre prolongée, et chez qui un interrogatoire minutieux, un examen clinique soigneux, ainsi que l’évolution ont pu redresser le diagnostic vers un déficit immunitaire.

Les érythrodermies du nouveau-né sont des tableaux rares, d'évolutions chroniques et potentiellement mortelles. Leurs étiologies sont diverses et variées dominées par les ichtyoses, le déficit immunitaire primaire, ou plus exceptionnellement le psoriasis sévère, les maladies métaboliques, la dermatite atopique ou une cause infectieuse. La détermination rapide de la cause sous-jacente est cruciale pour une meilleure prise en charge. Cependant, le diagnostic constitue un défi pour le clinicien et est souvent retardé en raison de la nature non spécifique des signes cliniques et histopathologiques. L'objectif de notre travail est de rappeler aux praticiens une étiologie grave de l'érythrodermie néonatale: le déficit immunitaire ceci à travers l'observation d'un nourrisson suivi pour une érythrodermie évoluant depuis la naissance, hospitalisé pour une fièvre prolongée, et chez qui un interrogatoire minutieux, un examen clinique soigneux, ainsi que l'évolution ont pu redresser le diagnostic vers un déficit immunitaire.

Background Individuals may be homozygous (SS) or heterozygous (AS) sickle cell gene carriers or have normal adult haemoglobin (AA). Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known. Methods We followed two cohorts of children. The first was enrolled at birth (156 newborn babies) and the second at 24‐36 months old (84 children). Both cohorts were followed for 30 months; monthly for parasitological data and half yearly for immunological data. Results In the first cohort, 22%, and in the second 13% of children were AS. Whatever their age parasite prevalence rates were similar in AA and AS individuals. Mean parasite densities increased less rapidly with age in AS than in AA children, and were significantly lower in AS than in AA children .48 months old. The AA children tended to be more often admitted to hospital than AS children (22% versus 11%, NS). Both anti-Plasmodium falciparum and anti-Pf155/RESA antibody rates increased more rapidly in AA than in AS children. Conversely, the prevalence rate of cellular responders to the Pf155/RESA antigen was similar in AA and AS children during the first 2 years of life, then it was higher in AS than in AA children. Conclusions Sickle cell trait related antimalarial protection varies with age. The role of the modifications of the specific immune response to P. falciparum in explaining the protection of AS children against malaria is discussed.

Chez les ruminants, le comportement maternel présente, immédiatement après la mise-bas, un certain nombre de traits communs comme la consommation des membranes et des liquides foetaux (les camélidés font exception), l’intérêt pour le nouveau-né et son léchage. Ces soins focalisent l’attention du nouveau-né vers le corps maternel et favorisent le succès des premières prises de colostrum. Après cette phase initiale qui dure quelques heures, les ruminants se subdivisent en deux groupes distincts : les espèces qui cachent leur nouveau-né pendant une durée variable (ex : cerf, chevreuil, caprins, bovins), et ceux dont le petit suit sa mère dès la naissance (ex : renne, ovins). La relation mère-jeune est, par ailleurs, caractérisée par une reconnaissance interindividuelle bien développée, base de la sélectivité maternelle : rapidement, la femelle n’accepte d’allaiter que son nouveau-né. La formation du lien mère-jeune s’effectue généralement sans problème. Toutefois, dans certaines conditions, le comportement maternel peut, par son absence ou sa sélectivité, devenir un facteur limitant la production., Between ruminant species a number similarities in maternal behaviour become evident immediately after parturition: consumption of foetal membranes and fluids (excepting camelidae), an interest in the neonate and care directed towards it. Maternal care focuses the new-born's attention towards the mother's body and favours the success of the first sucking bouts. After this initial phase lasting a few hours, ruminants can be divided into two categories according to the type of spatial association of mother and offspring: species that hide their young for a variable amount of time (e.g. red deer, roe deer, goat, cattle) and those where the young follows the mother soon after birth (e.g. reindeer, sheep). The mother young relationship is also characterised by a process of inter individual recognition that is well developed, Generally the establishment of the mother young relationship takes place without major problems, However, under certain conditions, by its absence or its selectivity, maternal behaviour can become a factor limiting production.

International audience; Background: Renal failure in neonates is associated with an increased risk of mortality and morbidity. But critical values are not known. Objective: To define critical values for serum creatinine levels by gestational age in preterm infants, as a predictive factor for mortality and morbidity. Study Design: This was a retrospective study of all preterm infants born before 33 weeks of gestational age, hospitalized in Nantes University Hospital NICU between 2003 and 2009, with serum creatinine levels measured between postnatal days 3 to 30. Children were retrospectively randomized into either training or validation set. Critical creatinine values were defined within the training set as the 90th percentile values of highest serum creatinine (HSCr) in infants with optimal neurodevelopmental at two years of age. The relationship between these critical creatinine values and neonatal mortality, and non-optimal neural development at two years, was then assessed in the validation set. Results and Conclusion: The analysis involved a total of 1,461 infants (gestational ages of 24-27 weeks (n=322), 28-29 weeks (n=336), and 30-32 weeks (803)), and 14,721 creatinine assessments. The critical values determined in the training set (n=485) were 1.6, 1.1 and 1.0 mg/dL for each gestational age group, respectively. In the validation set (n=976), a serum creatinine level above the critical value was significantly associated with neonatal mortality (Odds ratio: 8.55 (95% confidence interval: 4.23-17.28); p

L'infection néonatale invasive à entérovirus (EV) reste rare mais souvent fatale et devrait être prise dans le diagnostic différentiel chez les enfants septiques. Nous rapportons le cas d'un nouveau-né hospitalisé pour un sepsis grave à EV avec une méningite et une myocardite sévère d'évolution favorable après une corticothérapie. Nous présentons une discussion basée sur une revue de la littérature pour aider le clinicien à reconnaitre les facteurs de gravité et à apprécier les nouvelles stratégies diagnostiques telle la PCR (Polymerase Chain Reaction) et l'imagerie par résonance magnétique (IRM) cardiaque. Nous passons également en revue les nouvelles approches thérapeutiques telles les biothérapies, les antiviraux spécifiques et l'Oxygénation par Membrane Extra-Corporelle (ECMO).

Ouvrage issu d'un colloque, édité sous la direction de Benoist Schaal, Camille Ferdenzi et Olivier Wathelet. Publié par les Editions Universitaires de Dijon en avril 2013. Il présente les diverses méthodes et les concepts liés aux relations entre olfaction et affectivité.; Le nez a ses raisons que, dit-on, la raison ne connaîtrait pas. Ou ne connaît plus. L'affirmation est en effet courante selon laquelle l'odorat humain ne serait qu'une relique superflue d'un lointain passé simien. Un sens qui serait dépourvu de toute fonction, en particulier dans les mondes urbains et soi-disant aseptisés du 21ème siècle. Et pourtant, odeurs, parfums, arômes et fragrances sont des expédients très actuels et universels destinés à agrémenter les mets, parer les corps, enjoliver les lieux de vie, combattre le malodorant et le pestilentiel. Les émotions olfactives, souvent inconscientes, dirigent le regard et entérinent les décisions, parfois avant même qu'elles aient été articulées. Elles fabriquent aussi les souvenirs les plus persistants et les plus vivaces des "premières fois" de l'enfance ou de l'émoi amoureux. Aussi, quand l'odorat vient à manquer, le vécu des émotions s'érode et c'est progressivement le goût même de la vie qui se fane. Cet ouvrage offre un tableau synthétique des travaux actuels de psychologues, biologistes et neurobiologistes, anthropologues et philosophes à l'interface des odeurs et des émotions. Il illustre la diversité des méthodes et concepts qui permettent de penser les relations réciproques entre olfaction et affectivité. Ces liens odeurs-émotions suscitent actuellement un intérêt très vif auprès du grand public autant que pour différentes pratiques professionnelles.

The perception of some mixtures of odorants engages configural abilities, i.e. the perception of these mixtures as single odor objects. For instance, data in human adults demonstrated that a mixture of two odorants (AB), one smelling like strawberry and the other like caramel, generates the configural perception of the odor of pineapple (Le Berre et al., 2008; Barkat et al., 2012). Configural processing may be adaptive also for young organisms, to which rapid extraction of chemical information from the maternal environment, highly complex, is a prerequisite to survival. Thus, results in newborn rabbits suggest the perception of a unique odor in the AB mixture (smelling like configural pineapple in humans) and different from the odors of the elements (Coureaud et al., 2008, 2009a). To clearly demonstrate that the configural AB perception does not directly depend on A and B perception, we investigated here whether rabbit neonates recognize the AB mixture even in the absence of A and B recognition. To that goal, rabbit pups were conditioned to AB on day 1. On day 2, recall of A and recall of B were followed by intraperitoneal injection of either saline or a pharmacological amnesic agent (see Coureaud et al., 2009b, 2011). Testing for behavioral responsiveness to A, B and AB occurred on day 3. Control pups responded behaviorally to AB but also to A and B. As expected, the pups injected with the amnesic agent did not respond to A and to B. However, they responded to AB, indicating an AB perception independent of A and B representations. In summary, the present results confirm the perception by rabbit neonates of a configuration in the AB mixture, and demonstrate for the first time the neonatal ability to memorize odor mixtures as configurations independent of the memory of their elements.

International audience; Cryptosporidium parvum is a zoonotic protozoan parasite found worldwide, that develops only in the gastrointestinal epithelium and causes profuse diarrhea. Using a mouse model of C. parvum infection, we demonstrated by conditional depletion of CD11c+ cells that these cells are essential for the control of the infection both in neonates and adults. Neonates are highly susceptible to C. parvum but the infection is self-limited, whereas adults are resistant unless immunocompromised. We investigated the contribution of DC to the age-dependent susceptibility to infection. We found that neonates presented a marked deficit in intestinal CD103+ DC during the first weeks of life, before weaning, due to weak production of chemokines by neonatal intestinal epithelial cells (IEC). Increasing the number of intestinal CD103+ DC in neonates by administering FLT3-L significantly reduced susceptibility to the infection. During infections in neonates, the clearance of the parasite was preceded by a rapid recruitment of CD103+ DC mediated by CXCR3-binding chemokines produced by IEC in response to IFN gamma. In addition to this key role in CD103+ DC recruitment, IFN gamma is known to inhibit intracellular parasite development. We demonstrated that during neonatal infection CD103+ DC produce IL-12 and IFN gamma in the lamina propria and the draining lymph nodes. Thus, CD103+ DC are key players in the innate immune control of C. parvum infection in the intestinal epithelium. The relative paucity of CD103+ DC in the neonatal intestine contributes to the high susceptibility to intestinal infection.

Le peptide apparenté à l’hormone parathyroïdienne (PTHrP) joue un rôle important dans la régulation de la croissance osseuse foetale et néonatale. Chez la femelle gestante et/ou allaitante, l’hormone sécrétée par les parathyroïdes foetales, les membranes placentaires et/ou la glande mammaire en lactation, stimule les transferts calciques placentaires, module la tonicité utérine en fonction de la taille du (ou des) foetus, contrôle le débit artériel mammaire et la teneur du lait en calcium et en phosphore. Chez le nouveau-né, le PTHrP apporté par le lait pourrait intervenir dans la régulation de la motricité intestinale et de l’absorption intestinale du calcium et du phosphore., Parathyroid hormone-related peptide (PTHrP) plays a major role in the regulation of bone growth in the fetus and the neonate. In pregnant and/or lactating ruminant animals, the PTHrP secreted by fetal parathyroid glands and placental membranes stimulates calcium placental transfer from the dam to the fetus. PTHrP also modulates myometrial uterine activity. The expression of the PTHrP gene in pregnant uterus is under the control of mechanical stretch induced by uterine distension following fetal growth. Thus PTHrP controls the rhytmicity and/or force of myometrial contractions during pregnancy Since uterine contractions severely depress blood flow, another possibility is that PTHrP might act to dilate uterine (and placental) blood vessels and assure adequate blood flow to the uterus and feto-placental unit. Conversely, in ewes and goats, the PTHrP released by the lactating mammary gland regulates mammary blood flow and calcium and phosphorus mammary secretion. In neonates, milk PTHrP might control gut motility and calcium and phosphorus intestinal absorption. Thus, by controling calcium placental transfer, myometrial uterine activity, placental and mammary blood flow, milk calcium and phosphorus concentration, and, possibly, calcium and phosphorus intestinal absorption in the newborn, PTHrP regulates skeletal growth during fetal and postnatal periods.

International audience

The AVCnn study is a French multicentre cohort of 100 term newborns with symptomatic arterial ischemic stroke. The homogeneity of the population, the number of patients included, the amount of collected data and their comparison with control groups and duration of follow-up allow to make the cohort AVCnn unique in the literature. Initial data confirm that many obstetrical and perinatal factors are risk determinants (principal objective of the study). Conversely, other suspected risk factors (such as dysgravidia or mutations of coagulation factors II and V) were not confirmed, probably due to the selectivity of the inclusion criteria: previous studies have in fact included children with various types of perinatal stroke. The cause of the accident has been formally established (secondary objective) in only two cases. Nevertheless, birth weight and gender may be biomarkers of two populations of neonates with different pathological mechanisms. Prediction of motor outcomes (secondary objective) can be obtained from early imaging data (, Histoire et suivi d'une cohorte multicentrique de 100 nouveau-nés à terme ayant eu un infarctus cérébral artériel (cohorte AVCnn). L’homogénéité de la population, le nombre d’inclus, la somme des données collectées et leur comparaison à des groupes témoins puis désormais la durée du suivi font de la cohorte AVCnn un outil de travail unique dans la littérature. Les premiers résultats ont permis de définir un profil obstétrico-néonatal clinique et biologique à risque (objectif principal de l'étude). Inversement d'autres facteurs de risque suspectés (comme les dysgravidies ou les mutations des facteurs II et V de la coagulation) n'ont pu être confirmés, probablement du fait de la sélectivité des critères d'inclusion; les études antérieures ayant en effet inclus des enfants avec divers types d'AVC périnatals. La cause de l'accident n'a été établie (objectif secondaire) que pour une minorité d'enfants. Il semble exister plusieurs mécanismes pathologiques, dont le poids de naissance et le sexe seraient des biomarqueurs. Des facteurs pronostiques (objectif secondaire) de l'évolution motrice, accessibles dès les premiers jours de vie à l'lRM, ont également été déterminés alors que les symptômes n'apparaîtront que plusieurs mois après. Ceci permet d'envisager qu'une prise en charge précoce et ciblée sur ces nouveau-nés serait d'autant plus efficace que l'enfant n'a pas encore de symptômes. L'évaluation de la qualité de vie et de l'autonomie à l'âge de 3,5 ans est terminée. L'évaluation développementale (profil moteur, neuropsychologique, langagier, comportemental, épileptique et réussite scolaire) et de la réorganisation fonctionnelle cérébrale par IRM à 7 ans viennent de débuter

National audience; There is still no licensed vaccine against human respiratory syncytial virus (RSV) which causes severe bronchiolitis in yound children. The nucleoprotein N, a major component of the RSV nucleocapsid, is remarkably conserved among RSV subtypes and is recognized as a target of protective T cell responses. We reported a method to produce recombinant N assembling in homogenous rings composed of 10-11 N subunits.Intranasal vaccination of adult BALB/c mice with N-rings and detoxified E.coli enterotoxin LT(R192G) as adjuvant (provided by J. Clements, USA), proved protective against an RSV challenge, without causing significant lung inflammatory reactions. In the present study, we evaluated the vaccine potential of N-rings in 5 to 7 day-old BALB/c pups: a single intranasal administration of N-rings with LT(R192G) provided a significant reduction of the viral load after an RSV challenge at five weeks of age. However, neonatal vaccination also generated an enhanced lung infiltration by eosinophils following the RSV challenge. Analysis of antibody subclasses and cytokines produced after an RSV challenge or a boost administration of the vaccine suggested that neonatal vaccination induced a long lasting Th2 biased local immune memory. This early Th2 bias could be prevented by adding CpG-ODN to the vaccine formulation, but then the protection against virus replication was also reduced. In conclusion, protective vaccination against RSV can be achieve in neonates but requires an appropriate combinations of adjuvant.

Flash visual evoked potentials: maturation from birth to 15 years of age. annual meeting of the association-for-research-in-vision-and-ophthalmology (ARVO)

Soutenue le 16 mars 2011 Diplôme : Dr. Ing.; The main objective of our study was to evaluate the effect of maternal ALA supplementation on postnatal development of the nervous regulation of intestinal permeability in newborn piglets. The experimental strategy was conducted in 3 steps. The first step consisted in evaluate the n-3 polyunsaturated fatty acid (PUFA) composition of newborn tissue in response to different maternal ALA supplementation. We observed that ALA supplementation in the maternal diet during gestation and lactation increased long chain n-3PUFA concentrations in the piglet tissue and maintained DHA concentrations in the brain during the first weeks of postnatal life. In the second step, we demonstrated that supplementation of the maternal diet with ALA increased the intestinal paracellular permeability at birth and at postnatal day (PND) 21 and 28. Modifications in permeability at PND21 and 28 were linked to modification in the development of the enteric nervous system (ENS) and in the nervous regulation of intestinal permeability, with the induction of a cholinergic tonus. In addition, in primary culture of ENS, we showed that long chain n-3PUFA but not ALA induced modification in phenotype of enteric neurons. Finally, in the third step, we showed that higher intestinal permeability induced by maternal diet was not associated with modification in intestinal immune status of newborn piglet. The acquisition of oral tolerance to ovalbumin was not different between the dietary groups. However, the intestinal immune cells isolated at PND52 from piglets with a high maternal ALA intake displayed a higher proliferation response to inflammatory stimulation (LPS) than those from piglets with a low maternal ALA intake. In conclusion, maternal ALA supplementation increased n-3PUFA concentrations in piglet tissue and induced increasing intestinal permeability at birth and at PND21 and 28 by modifying the nervous regulation of intestinal barrier function. Moreover, these modifications were not associated with immediate consequences on newborn intestinal immunity. However, this maternal diet seems to modify, in long term, the intestinal immune response of newborn piglet.; Dans le but de diversifier les sources en AGPIn-3 dans notre alimentation, nous nous sommes intéressés à l’impact de l’incorporation dans l’alimentation maternelle d’acide alpha-linolénique (ALA), précurseur des AGPIn-3 à longue chaîne, sur la mise en place de la régulation nerveuse de la barrière intestinale du porcelet nouveau-né. Pour répondre à cet objectif, nous avons mis en place un plan expérimental en 3 étapes. La première étape consistait à examiner la composition en AGPIn-3 des tissus du nouveau-né en réponse à une alimentation maternelle plus ou moins riche en ALA. L’incorporation d’ALA dans le régime maternel a enrichi l’ensemble des tissus du porcelet en AGPIn-3 à longue chaîne à la naissance. De plus, ce régime a permis de maintenir un niveau d’acide docosahexaenoique (DHA) constant dans le cerveau dans les premières semaines de vie. Dans une deuxième étape nous avons montré qu’un régime maternel enrichi en ALA induit une perméabilité paracellulaire du jéjunum plus élevée à la naissance et à 21-28 jours d’âge chez les porcelets. Cette augmentation de perméabilité était liée à 21-28 jours à des modifications du phénotype du SNE résultant en un tonus cholinergique stimulateur du SNE. Une étude in vitro a permis de préciser que seuls les AGPIn-3 à longue chaine pouvaient modifier le phénotype des neurones entériques. Enfin, dans une troisième étape, nous avons montré que les animaux dont les mères avaient reçu le régime enrichi en ALA ne présentaient pas de passage accru d’immunoglobulines dans les premières heures de vie ni de sensibilité à l’inflammation excessive à 28 jours de vie malgré l’augmentation de perméabilité observée. L’acquisition de la tolérance orale ne semblait pas non plus altérée. Cependant, à plus long terme (24 jours après la fin de la phase d’allaitement), la réponse des cellules immunitaires intestinales des porcelets allaités par les truies ayant consommé le régime riche en ALA à un stimulus pro-inflammatoire (LPS) était augmentée par rapport à celle des témoins. En conclusion, un régime maternel riche en ALA permet d’enrichir les tissus du nouveau-né en AGPIn-3 à longue chaine nécessaires à son développement et induit des augmentations de perméabilité intestinale à la naissance et en fin de phase d’allaitement liées à des modifications de la régulation nerveuse de cette fonction barrière mais sans conséquence immédiate en terme d’immunité intestinale. Cependant, à plus long terme, il semblerait que ce régime induise des modifications de la fonction immunitaire intestinale du nouveau-né.