Caractéristiques cliniques et prise en charge des hémorragies pulmonaires chez les prématurés <32 SA (étude menée au CHU d'Amiens en réanimation néonatale entre janvier 2006-décembre 2010)

INTRODUCTION ; L hémorragie pulmonaire (HP) est caractérisée par l émission de sang frais dans les voies aériennes ; elle touche essentiellement le prématuré de faible poids de naissance. Sa faible incidence et son évolution rapide et habituellement fatale en font une pathologie peu étudiée. Bien que le métabolisme de l eau et les interactions pression capillaire-pression interstitielle soient les principaux mécanismes étio-pathogéniques soupçonnés, HP survient toujours dans un contexte multifactoriel qui ne permet pas de la rattacher à une cause unique. La prise en charge de l hémorragie pulmonaire n est pas encore bien codifiée et n est pas consensuelle.MATERIEL ET METHODE ; Type d étude: étude rétrospective cas/témoins réalisée entre janvier 2006 et décembre 2010 en réanimation néonatale au CHU d Amiens. Critères inclusion : chaque prématuré de < 32 SA ayant présenté une HP (groupe HP) a été apparié pour le terme et la période de naissance, à un autre prématuré indemne de HP (groupe témoin, T). Nous avons ensuite relevé les caractéristiques des patients à l admission, les variables autour de l hémorragie (chez les enfants du groupe T), puis la prise en charge de l HP et l évolution clinique jusqu à la fin de l hospitalisation. Afin de rendre la comparaison possible, nous avons relevé les mêmes variables au 3ème jour de vie chez les patients du groupe témoin. RESULTATS ; 2,5% (n=27) prématurés < 32 SA ont présenté une HP à 2,9 j (1,6 ; 3,4). Ces enfants étaient nés à 27,3 SA (26 ; 28,7) et avaient un poids de naissance de 819 g (680 ; 960), plus faible que dans le groupe témoin. Les 2 groupes HP et T n était pas différent pour score CRIB. En analyse univariée l hémorragie pulmonaire était associée au RCIU, à une forte ventilation , aux échanges pulmonaires altérés, à une altération de l hémostase (TP bas,et de l hémogramme (hématocrite bas, thrombopénie) et à des troubles hémodynamiques En analyse multivariée, après ajustement sur le poids de naissance et le genre (M/F), 3 facteurs de risque restaient associés à HP : la notion de CA significatif (HP=96 %), une pression artérielle basse (HP=78%) et le pH plasmatique bas. La proportion d HIV de grade 3-4 (HP=48 % vs T=15 %) étaient plus élevée chez les patients du groupe HP qui par ailleurs avait aussi un taux de décès très élevé (HP=88%). DISCUSSION ET CONCLUSION : L hémorragie pulmonaire survient le plus souvent, dès les premiers jours de vie et touche essentiellement le grand prématuré. Le fait que son mécanisme est multifactoriel et que les traitements n influence pas l évolution de l HP déjà installée, doit inciter à agir en amont en privilégiant l utilisation des apports hydriques adéquats, le recours préférentiel à un mode de ventilation non invasif (CPAP) pour la prévention des traumatismes pulmonaires, la correction des troubles ventilatoires, des troubles de l hémostase, des troubles hémodynamiques, en particulier le diagnostic précoce et la prise en charge du CA.INTRODUCTION; pulmonary hemorrhage (PH) is characterized by the emission of fresh blood in the airways, affecting mainly premature low birth weight. Its low incidence and its rapid and usually fatal disease are poorly studied. Although the water metabolism and interactions capillary pressure-pore pressure are the main etio-pathogenic mechanisms suspected, HP always occurs in a multifactorial does not link it to a single cause. The management of pulmonary hemorrhage is not well codified and is not consensual. Materials and Methods; Design: retrospective case / control study between January 2006 and December 2010 in neonatal resuscitation at the University Hospital of Amiens. Inclusion criteria: every premature <32 weeks who have had an HP (HP group) was matched to the term and period of birth to another premature free HP (control group, T). We then identified the characteristics of the patients on admission, the variables around the bleeding (in children of the group T), and support of HP and clinical course until the end of the hospitalization. To make the comparison possible, we identified the same variables in the third day of life for patients in the control group. RESULTS, 2.5% (n = 27) premature infants <32 weeks showed a 2.9 Hp d (1.6, 3.4). These children were born in SA 27.3 (26, 28.7) and had a birth weight of 819 g (680, 960), lower than in the control group. The HP and T 2 groups was not different for CRIB score. In univariate analysis pulmonary hemorrhage was associated with IUGR, high ventilation, altered lung trade, alteration of haemostasis (TP low, and the blood count (low hematocrit, thrombocytopenia) and hemodynamic disorders in multivariate analysis, after adjustment for birth weight and gender (M / F), three risk factors remained associated with HP, the notion of significant CA (HP = 96%), low blood pressure (HP = 78%) and plasma pH down. The proportion of HIV-grade 3-4 (HP = 48% vs. T = 15%) were higher among patients in the HP also was also a death rate very high (HP = 88%). DISCUSSION AND CONCLUSION: The pulmonary hemorrhage occurs most often in the first days of life and affects mainly the large premature. The fact that the mechanism is multifactorial and that treatments did not influence the evolution of the HP installed, should prompt to act upstream by focusing the use of adequate fluid intake, use of a preferential mode of ventilation not invasive (CPAP) for the prevention of lung injury, correction of ventilation problems, disorders of hemostasis, hemodynamic disturbances, especially early diagnosis and management of CA.lAMIENS-BU Santé (800212102) / SudocSudocFranceF

Intérêt de l'analyse des variables cardio-respiratoires pour la caractérisation du canal artériel du prématuré (argumentation en faveur d'un rôle de la régulation autonome)

La persistance du canal artériel (CAP) est caractérisée par un shunt aorto-pulmonaire responsable d une surcharge vasculaire pulmonaire et d un bas débit systémique à l origine de complications. Objectifs : (1) mettre en évidence, par l étude des variables cardio-respiratoires, des éléments en faveur d un rôle de la régulation autonome dans les adaptations hémodynamiques au cours du CAP, (2) évaluer les inhomogénéités dans la redistribution de la perfusion en cas de CAP par la méthode de calcul de la différence des phases des pouls (PPD). Résultats : les enfants avec CAP avaient une prédominance de la stimulation parasympathique (par étude HRV) et une baisse des propriétés fractales (DFA). L analyse par entropie de transfert a détecté des différences dans les couplages cardio-respiratoires autonomes : SaO2 se comportait comme une source dominante par rapport aux signaux de fréquence cardiaque et respiratoire en cas de CAP et comme une variable dominée en cas de canal fermé. La détermination de PPD entre main droite et pied gauche a conclu à une accentuation des inhomogénéités circulatoires en cas de CAP. Ces observations étaient corroborées par les résultats de la simulation de la circulation néonatale réalisée par ordinateur sur modèle analogue électrique. Conclusions : nos résultats suggèrent l implication des réflexes autonomes au cours du CAP. D autres études sont nécessaires pour appliquer notre méthode PPD pour l évaluation du CAP en routine clinique. Certains aspects discutés dans ce travail pourraient servir de base pour étudier l intérêt des vagolytiques pour le traitement de l hypotension réfractaire considérée dans ce cas comme un baroréflexe inapproprié du CAP.Patent ductus arteriosus (PDA) is characterized by an aorto-pulmonary shunt that evokes a blood overload in the pulmonary vascular bed and the decrease in systemic perfusion, at the origin of associated complications. Objectives: (1) To emphasize arguments for autonomic mechanisms participating in hemodynamic adjustments in infants with PDA, from the analysis of cardiorespiratory recordings, (2) To develop methods with détermination of pulse phase difference to evaluate inhomogeneities in blood redistribution during PDA. Results: Infants with PDA had a predominant parasympathetic stimulation (Spectral analysis of heart rhythm) and a loss of fractal properties (DFA). The analysis by transfer entropy method showed major differences in the autonomic cardio-respiratory coupling: compared to heart and breathing rates s signals, the oxygen saturation (SaO2) behaved as a driving source when ductus was open and as a driven variable after ductus closure.The analysis of arterial pulse phase difference between right hand and left foot concluded to an accentuation of inhomogeneities in the distribution of blood perfusion when ductus was open. These findings were corroborated by results of computer simulation using an analog electrical model. Conclusions: Our results suggest significant involvement of autonomic mechanisms in PDA; further researches are needed for the application of the method of pulse phase analysis for the assessment of PDA. Some issues addressed in this work could serve as a basis for further research to verify the interest of vagolytic medications in the treatment of refractory hypotension, considered as an inappropriate cardiovascular baroreflex.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Neurovascular coupling in the developing neonatal brain at rest

International audienceThe neonatal brain is an extremely dynamic organization undergoing essential development in terms of connectivity and function. Several functional imaging investigations of the developing brain have found neurovascular coupling (NVC) patterns that contrast with those observed in adults. These discrepancies are partly due to that NVC is still developing in the neonatal brain. To characterize the vascular response to spontaneous neuronal activations, a multiscale multimodal noninvasive approach combining simultaneous electrical, hemodynamic, and metabolic recordings has been developed for preterm infants. Our results demonstrate that the immature vascular network does not adopt a unique strategy to respond to spontaneous cortical activations. NVC takes on different forms in the same preterm infant during the same recording session in response to very similar types of neural activation. This includes (a) positive stereotyped hemodynamic responses (increases in HbO, decreases in HbR together with increases in rCBF and rCMRO2), (b) negative hemodynamic responses (increases in HbR, decreases in HbO together with decreases in rCBF and rCMRO2), and (c) Increases and decreases in both HbO-HbR and rCMRO2 together with no changes in rCBF. Age-related NVC maturation is demonstrated in preterm infants, which can contribute to a better understanding/prevention of cerebral hemodynamic risks in these infants

Functional Maps at the Onset of Auditory Inputs in Very Early Preterm Human Neonates

International audienceDuring the last trimester of human gestation, neurons reach their final destination and establish long-and short-distance connections. Due to the difficulties obtaining functional data at this age, the characteristics of the functional architecture at the onset of sensory thalamocortical connectivity in humans remain largely unknown. In particular, it is unknown to what extent responses evoked by an external stimulus are general or already sensitive to certain stimuli. In the present study, we recorded high-density event-related potentials (ERPs) in 19 neonates, tested ten weeks before term (28-32 weeks gestational age (wGA), that is, at an average age of 30 wGA) by means of a syllable discrimination task (i.e., a phonetic change: ba vs. ga; and a voice change: male vs. female voice). We first observed that the syllables elicited 4 peaks with distinct topographies implying a progression of the sensory input along a processing hierarchy; second, repetition induced a decrease in the amplitude (repetition suppression) of these peaks, but their latencies and topographies remained stable; and third, a change of stimulus generated mismatch responses, which were more precisely time-locked to event onset in the case of a phonetic change than in the case of a voice change. A hierarchical and parallel functional architecture is therefore able to process environmental sounds in a timely precise fashion, well before term birth. This elaborate functional architecture at the onset of extrinsic neural activity suggests that specialized areas weakly dependent on the environment are present in the perisylvian region as part of the genetic endowment of the human species

Blood product transfusions are associated with an increase in serum (1-3)-beta-d-glucan in infants during the initial hospitalization in neonatal intensive care unit (NICU)

International audienceIntroduction: Serum (1-3)-beta-d-glucan (BDG) assay has been proposed as an adjunct for the rapid diagnosis of invasive fungal infection (IFI). However, false-positive results have been reported following transfusion of blood products in adults. Aims: To assess the relationship between blood product transfusion and elevated BDG in neonates. Method: Retrospective study including neonates 32 weeks, with no fungal colonization or infection, in whom BDG assay was performed for suspicion of IFI. Patients were classified in Transfusion (n=78) and No Transfusion (n=55) groups depending on whether or not they were transfused. Clinical, biochemical and microbiological characteristics were recorded. A BDG assay >80pg/mL was considered as positive. Statistical analyses: bivariate and multivariate logistic regression. Results (median, IQR): One hundred and thirty-three infants were included (gestational age 28.4 weeks, 26.9-30; birth weight 1000g, 847-1300). BDG was higher in the Transfusion group (170pg/mL, 65-317) than in the No Transfusion group (57pg/mL, 34-108; p<0.001). False-positive BDG assay results were associated with red blood cells (RBC) and fresh frozen plasma (FFP) transfusions. Conclusion: BDG is increased after RBC and FFP transfusions in neonates, leading to overdiagnosis of IFI. Fungal colonization status in peripheral sites and central cultures could help to reduce the risk of misdiagnosis

NEUROVASCULAR COUPLING IN PRETERM NEONATES WITH INTRAVENTRICULAR HEMORRHAGE: COMBINED HIGH DENSITY EEG-NIRS STUDY

27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, Vancouver, CANADA, JUN 27-30, 2015International audienc

Neurodevelopment and asymmetry of auditory-related responses to repetitive syllabic stimuli in preterm neonates based on frequency-domain analysis

International audienceSensory development of the human brain begins prenatally, allowing cortical auditory responses to be recorded at an early age in preterm infants. Despite several studies focusing on the temporal characteristics of preterm infants' cortical responses, few have been conducted on frequency analysis of these responses. In this study, we performed frequency and coherence analysis of preterm infants' auditory responses to series of syllables and also investigated the functional brain asymmetry of preterm infants for the detection of the regularity of auditory stimuli. Cortical auditory evoked potentials (CAEPs) were recorded in 16 preterm infants with a mean recording age of 31.48 weeks gestational age (29.57-34.14 wGA) in response to a repetitive syllabic stimulus. Peak amplitudes of the frequency response at the target frequency and the first harmonic, as well as the phase coherence (PC) at the target frequency were extracted as age-dependent variables. A functional asymmetry coefficient was defined as a lateralization index for the amplitude of the target frequency at each electrode site. While the findings revealed a significant positive correlation between the mean amplitude at the target frequency vs. age (R2 = 0.263, p = 0.042), no significant correlation was observed for age-related changes of the mean amplitude at the first harmonic. A significant correlation was also observed between the mean PC and age (R2 = 0.318, p = 0.023). A right hemisphere lateralization over many channels was also generally observed. The results demonstrate that rightward lateralization for slow rate modulation, previously observed in adults, children and newborns, appears to be in place at a very young age, even in preterm infants. Development of the auditory system is an intricate process beginning early in gestation 1. Major structures of the ear, including the cochlea, develop between 23 and 25 weeks gestational age (wGA) 1-3 and the capacity of the foetus to perceive and react to auditory inputs, related to brainstem network activation, emerges around 26 weeks of foetal life 4. After 28 wGA, the thalamocortical auditory system is sufficiently mature to perceive complex sounds and discriminate between different speech phonemes 5-9 , corresponding to the beginning of language and speech development 10. A critical period for neurosensory development of the auditory system starts around 25 wGA. During this period, the hair cells of the cochlea, the axons of the auditory nerve and the neurons of the temporal lobe in the auditory cortex are tuned to receive signals of specific frequencies and intensities 11. Cortical brain development can also be studied in preterm infants, who, as a result of intensive care, can survive when born after 28 wGA, and even 23 wGA 5. Arousal behaviour confirms that the auditory system i

Consequence of intraventricular hemorrhage on neurovascular coupling evoked by speech syllables in preterm neonates

International audienceIntraventricular Hemorrhage (IVH) is the leading cause of neurological and cognitive impairment in preterm neonates with an incidence that increases with increasing prematurity. In the present study, we tested how preterm neonates with IVH react to external stimulation (i.e. speech syllables). We compared their neural responses measured by electroencephalography (EEG), and hemodynamic responses measured by functional near-infrared spectroscopy (fNIRS), with those of healthy preterms. A neural response to syllables was observed in these infants, but did not induce a vascular response in contrast with healthy neonates. These results clearly demonstrate that the cerebral vascular network in IVH preterm neonates was unable to compensate for the increased metabolism resulting from neuronal activation in response to external stimulation. Optical imaging is thus a sensitive tool to identify altered cerebral hemodynamic in critically ill preterms before behavioral changes are manifested or when only minor abnormalities on other functional monitoring techniques such as EEG are visible. We propose that a multi-modal approach provides unique opportunities for early monitoring of cognitive functions and opens up new possibilities for clinical care and recommended practices by studying the difficulties of the premature brain to adapt to its environment

Evaluation of the (1,3)-beta-D-glucan assay for the diagnosis of neonatal invasive yeast infections

International audienceMost newborns in the neonatal intensive care unit (NICU) are premature and at risk of invasive fungal infections (IFIs). Invasive yeast infections (IYIs) are the most common fungal infections in this population. These infections are difficult to diagnose because symptoms are nonspecific, and the sensitivity of blood cultures is low. The serum (1,3)-beta-D-glucan (BDG) assay provides a reliable marker for the diagnosis of IFIs in adults with haematological malignancies. We assessed the diagnostic performance of this test in neonatal IYIs and its contribution to the monitoring of antifungal treatment. A retrospective study was performed in the NICU of the French University Hospital of Amiens from February 2012 to February 2014. Forty-seven neonates (33 males, 14 females) with a median gestational age of 30 weeks (IQR: 27-31) and median birth weight of 1200 g (IQR: 968-1700) were included and divided into three groups: 21 control neonates (CTRL), 20 neonates with probable IYI (PB), and six with proven IYI (PV). Median BDG levels were significantly higher in the global IYI group (PB + PV): 149 pg/ml (IQR: 85-364) vs. CTRL group: 39 pg/ml (IQR: 20-94) (P < .001). The optimal cut-off was 106 pg/ml (sensitivity 61.5%; specificity 81%). BDG levels decreased with antifungal treatment. BDG was detectable in cerebrospinal fluid, but the interest of this for diagnostic purposes remains unclear. Our results suggest that the BDG assay may be useful for the early identification of IYIs in neonates and for monitoring antifungal therapy efficacy