[Pulmonary lipofibroblasts in adults and alveolar regeneration in emphysema]. / Lipofibroblastes pulmonaires chez l'adulte et régénération alvéolaire au cours de l'emphysème.

Lipofibroblasts form a sub-population of fibroblasts located in the mesenchymal alveolar stem cell niche. They show close proximity with alveolar epithelial type 2 cells and play a key role in alveolar development and lung homeostasis. Their role in various diseases such as acute respiratory distress syndrome, pulmonary fibrosis and emphysema is progressively better understood. Through the activation of signaling pathways such as PPARg lipofibroblasts may help to induce endogenous alveolar regeneration.

Mortality and morbidity of preterm neonates weighing less than 750g: A 2-year retrospective cohort study.

BACKGROUND: The rate of premature births in France is 6% and is increasing, as is the rate of extremely premature births. Morbidity and mortality rates in this population remain high despite significant medical progress. We aimed to evaluate the morbidity and mortality rate in preterm neonates weighing<750g and to evaluate their outcome at 2 years' corrected age (CA). METHODS: This was a retrospective monocentric study including babies born between May 2011 and April 2013 who were preterm and weighed<750g. We evaluated mortality and morbidity in the neonatal period. At 2 years' CA, we focused on developmental quotient (DQ) with the Brunet-Lézine test, on neurosensory assessment (sleeping/behavior), and growth evaluation. RESULTS: Among the 107 infants included, 29 (27%) died in the neonatal period. Mean gestational age was 25.6 weeks' gestation. Female sex and higher birth weight were independent predictors of survival. A total of 61 (78.2%) infants showed extra-uterine growth retardation at 36 weeks' postmenstrual age. At 2 years' CA, 57 children were followed up; 38 were evaluated using the Brunet-Lézine test, 20 (52.6%) had a DQc<85, and none had a severe developmental delay (DQc<50). Six (10%) children had cerebral palsy and 22 of 56 (39.2%) showed language delay. Growth retardation persisted in 15 of 52 (28.8%) children. CONCLUSION: Our results confirm the acute fragility of extremely low-birth-weight babies with a high rate of morbidity and mortality. At 2 years' CA, this population still shows a considerable rate of mild difficulties, whose long-term evolution needs to be followed.

Recommendation for hygiene and topical in neonatology from the French Neonatal Society.

We sought to establish guidelines for hygiene care in newborns based on a systematic review of the literature and grading of evidence using the Groupe de Réflexion et d'Evaluation de l'Environement des Nouveau-nés (GREEN) methodology. We examined 45 articles and 4 reports from safety agencies. These studies recommend a tub bath (rather than a sponge bath) for full-term infants and a swaddle bath for preterm newborns. They also recommend against daily cleansing of preterm infants. The literature emphasized that hygiene care must consider the clinical state of the newborn, including the level of awareness and behavioral responses. Hospitalized newborns treated with topical agents may also experience high exposure to potentially harmful excipients of interest. Caregivers should therefore be aware of the excipients present in the different products they use. In high-resource countries, the available data do not support the use of protective topical agents for preterm infants.Conclusions: We recommend individualization of hygiene care for newborns. There is increasing concern regarding the safety of excipients in topical agents that are used in neonatology. A multidisciplinary approach should be used to identify an approach that requires lower levels of excipients and alternative excipients. What is known: • Hygiene care is one of the most basic and widespread types of care received by healthy and sick newborns worldwide. • There is no current guideline on hygiene for preterm or hospitalized term newborn. What is new: • The French Group of Reflection and Evaluation of the environment of Newborns (GREEN) provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' behavioral responses to hygiene care, exposition to excipients of interest, and the potential risk of protective topical agents in a preterm infant. provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' possible behavioral responses to hygiene care, exposition to excipients of interest and the potential risk of protective topical agents in a preterm infant.

Impaired alveolarization and intra-uterine growth restriction in rats: a postnatal genome-wide analysis.

Intra-uterine growth restriction (IUGR) dramatically increases the risk of bronchopulmonary dysplasia in preterm babies, a disease characterized by arrested alveolarization and abnormal microvascular angiogenesis. We have previously described a rodent low protein diet (LPD) model of IUGR inducing impaired alveolarization, but failed to demonstrate any modification of the classical factors involved in lung development. We performed a genome-wide microarray analysis in 120 rat pups with LPD-induced IUGR and their controls, at three key time points of the alveolarization process: postnatal day 4 (P4): start of alveolarization; P10: peak of the alveolarization process and P21: end of the alveolarization process. Results were analysed using Arraymining, DAVID and KEGG software and validated by qRT-PCR and western blots. Considering a cut-off of 2:1 as significant, 67 transcripts at P4, 102 transcripts at P10 and 451 transcripts at P21 were up-regulated, and 89 transcripts at P4, 25 transcripts at P10 and 585 transcripts at P21 were down-regulated. Automatic functional classification identified three main modified pathways, 'cell adhesion molecules', 'cardiac muscle contraction' and 'peroxisome proliferator-activated receptor' (PPAR). Protein analysis confirmed involvement of the PPAR pathway, with an increase of FABP4, an activator of this pathway, at P4 and an increase of adiponectin at P21. Other data also suggest involvement of the PPAR pathway in impaired alveolarization. Our results show that deregulation of the PPAR pathway may be an important component of the mechanism inducing impaired alveolarization observed in IUGR. The complete dataset is available as GEO profiles on the Gene Expression Omnibus (GEO) database ( www.ncbi.nih.gov/geo/, GEO Accession No. GSE56956).

[Basic aspects of the potential toxicity of anesthetic drugs]. / Aspects fondamentaux de la toxicite éventuelle des drogues anesthésiques.

Brain development is a complex phenomenon in which several stages of production, maturation, and organization of neural cells in a network succeed each other. Various environmental factors can disrupt these stages. During the last decade, numerous in vitro and in vivo experimental studies in newborn animal models have established the neurotoxic effects of most anesthetic and sedative drugs used in pediatrics. These effects are essentially responsible for neuronal apoptosis and have been associated with learning disorders in adulthood. This neurotoxicity is time-varying: there is a vulnerability period during synaptogenesis. These toxic effects were attributed to agonist properties on GABA receptors or antagonist properties on NMDA receptors, which are characteristics of all implicated anesthetics. Excessive activation of the GABA pathway and/or excessive inhibition of the NMDA pathway activate cellular mechanisms leading to apoptosis. The intensity of neurotoxic effects is dose- and time-exposure-dependent. These numerous experimental data must be interpreted with caution with regard to their validity in humans, mainly because of interspecies differences as well as differences between experimental conditions and clinical practice. Today, these data are insufficient to change our practices, taking into account the indisputable benefits of the use of anesthetics and sedative drugs. However, progress in experimental research will help us identify the safest therapeutic strategies and neuroprotective treatments.

[Intrauterine growth retardation and lung development]. / Retard de croissance intra-utérin et développement pulmonaire : approche expérimentale et clinique.

Epidemiological studies have shown that intrauterine growth restriction is associated with increased respiratory morbidity in the neonatal period with an increased risk of bronchopulmonary dysplasia. Respiratory consequences of environmental intrauterine changes extend into childhood and adulthood with abnormal lung function tests. In animal models, changes in surfactant and alveolarization disorders vary from one study to another. Moreover, the molecular mechanisms involved are poorly understood. Fetal adaptations to intrauterine malnutrition result in permanent changes in lung structure, raising the question of lung "programming".