Every year, new evidence emerges about how best to care for tiny babies with respiratory distress. We report the seventh version of "European Guidelines for the Management of RDS" by a panel of European neonatologists and an expert perinatal obstetrician based on available literature up to mid-2025. Optimising outcome involves close collaboration with obstetricians to predict risk of preterm delivery, consideration of transfer to perinatal centres, and perinatal optimisation including antenatal steroids. Delivery room protocols should include maintenance of normal body temperature while aiming to promote spontaneous breathing before clamping the umbilical cord, using non-invasive respiratory support (NRS) where possible, and considering early use of surfactant delivered by a thin catheter in an attempt to avoid intubation. Ongoing NRS and judicious use of surfactant using techniques that avoid intubation will help improve outcomes. If mechanical ventilation is needed, lung protective strategies should be employed and ventilation continued for the shortest time possible to reduce risk of bronchopulmonary dysplasia. Protocols for general supportive care are also reviewed, with an emphasis on good nutritional care, cardiovascular support and judicious use of antibiotics.

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of long-term cardiovascular complications, including elevated blood pressure, endothelial dysfunction, and arterial stiffness. Endothelial progenitor cells (EPCs), particularly endothelial colony-forming cells (ECFCs), play a critical role in maintaining vascular homeostasis. Previously, Simoncini et al. observed that in a rat model of IUGR, six-month-old males exhibited elevated systolic blood pressure (SBP) and microvascular rarefaction compared with control (CTRL) rats. These vascular alterations were accompanied by reduced numbers and impaired function of bone marrow-derived ECFCs, which were associated with oxidative stress and stress-induced premature senescence (SIPS). In contrast, IUGR females of the same age and from the same litter did not exhibit higher SBP or microvascular rarefaction, raising the question of whether ECFC dysfunction in IUGR female rats can be present without vascular alterations. So, we investigated ECFCs isolated from six-month-old female IUGR offspring (maternal 9% casein diet) and CTRL females (23% casein diet). To complete the vascular assessment, we performed in vivo and in vitro investigations. No alteration in pulse wave velocity (measured by echo-Doppler) was observed; however, IUGR females showed decreased aortic collagen and increased elastin content compared with CTRL. Regarding ECFCs, those from IUGR females maintained their endothelial identity (CD31+/CD146+ ratio among viable CD45− cells) but exhibited slight alterations in progenitor marker expression (CD34) compared with those of CTRL females. Functionally, IUGR-ECFCs displayed a delayed proliferation phase between 6 and 24 h, while their ability to form capillary-like structures remained unchanged, however their capacity to form capillary-like structures was preserved. Regarding the nitric oxide (NO) pathway, a biologically relevant trend toward reduced NO levels and decreased endothelial nitric oxide synthase expression was observed, whereas oxidative stress and SIPS markers remained unchanged. Overall, these findings indicate that ECFCs from six-month-old female IUGR rats exhibit only minor functional alterations, which may contribute to vascular protection against increase SBP, microvascular rarefaction, and arterial stiffness.

Individuals born after intrauterine growth restriction (IUGR) have a higher risk of developing metabolic syndrome (MetS) in adulthood. In a rat model, male IUGR offspring exhibit MetS features-including elevated systolic blood pressure, glucose intolerance, non-alcoholic fatty liver disease, and increased visceral adipose tissue (VAT)-by 6 months of age. Female offspring, however, do not. While higher VAT is associated with MetS, its role in IUGR-induced metabolic disorders remains unclear. The objective is to examine structural changes and mechanisms in VAT associated with metabolic disorders in IUGR rats. IUGR was induced via a maternal low-protein (9% casein) and compared to a control diet (23% casein). VAT was collected from 6-month-old offspring. Adipocyte hyperplasia and hypertrophy were analyzed using Ki-67 and hematoxylin/eosin (H/E) staining. Adipogenesis (PPAR-γ by Western blot; ZFP423 by RT-qPCR), inflammation (IL-6, TNF-α by RT-qPCR), macrophage markers (CD68, ITGAM, ITGAX by RT-qPCR), oxidative stress (superoxide anion via hydroethidine; Cu/Zn SOD, catalase by Western blot), and senescence (lipofuscin via autofluorescence, crown-like structures by H/E, p16INK4a, p21WAF1, Sirtuin-1 by Western blot) were evaluated. IUGR males showed increased adipocyte proliferation, hypertrophy, and upregulated adipogenic markers (PPAR-γ, ZFP423; P<.05, P<.001). Inflammatory and macrophage markers were elevated (P<.05), along with superoxide anion production, Cu/Zn SOD and catalase protein expression (P<.05). Senescence indicators-including lipofuscin, crown-like structures, p16INK4a, p21WAF1, and Sirtuin-1 were also upregulated (all P<.05). No significant changes were observed in females. VAT from male IUGR offspring exhibits increased adipogenesis, inflammation, oxidative stress, and premature senescence, suggesting a mechanistic link to their higher MetS susceptibility.

The global incidence and prevalence of cardiometabolic disorders have risen significantly in recent years. Although lifestyle choices in adulthood play a crucial role in the development of these conditions, it is well established that events occurring early in life can have an important effect. Recent research on cardiometabolic diseases has highlighted the influence of sexual dimorphism on risk factors, underlying mechanisms, and response to therapies. In this narrative review, we summarize the current understanding of sexual dimorphism in cardiovascular and metabolic diseases in the general population and within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. We explore key risk factors and mechanisms, including the influence of genetic and epigenetic factors, placental and embryonic development, maternal nutrition, sex hormones, energy metabolism, microbiota, oxidative stress, cell death, inflammation, endothelial dysfunction, circadian rhythm, and lifestyle factors. Finally, we discuss some of the main therapeutic approaches, responses to which may be influenced by sexual dimorphism, such as antihypertensive and cardiovascular treatments, oxidative stress management, nutrition, cell therapies, and hormone replacement therapy.

In Europe, organic food must comply with specific regulations which do not include nutritional criteria. The ability of organic food to meet the nutritional needs of children is not assessed. This narrative review discusses the nutritional composition (macronutrients, micronutrients) of organic food compared with conventional products and its clinical relevance with a paediatric focus, as well as the health impact of these differences and of contaminants which interfere with metabolism. Other potential differences, particularly regarding the direct/indirect exposure to other contaminants in conventional food, are not addressed in this review. The composition of some organic food may differ from conventional food. Protein content was lower in cereals and eggs. A lower n-6:n-3 polyunsaturated fat (PUFA) ratio was observed in milk, meat and eggs. Long-chain PUFA and vitamin E may be higher in milk, meat and fish, as well as some minerals and antioxidants (phenolic compounds, vitamin C) in fruits, vegetables and starchy food and carotenoids in fruits and vegetables. Epidemiological studies suggest an association between organic diets and lower prevalence of childhood obesity, type 2 diabetes and metabolic syndrome, whereas the protective effect on allergy and cancer is controversial. Some organic food may be of greater nutritional interest for children's diet than conventional food. Standardised studies comparing food composition and diet in children are needed. Considering the lower toxicologic risk and the sustainability of organic food, the Committee on Nutrition encourages the use of organic food, provided that such food is affordable, alongside specific baby food which is subject to strict specific European Union regulations.

OBJECTIVES:Heart disease is a leading cause of death worldwide, with its prevalence exacerbated by inadequate nutritional intake. Particularly concerning is the elevated risk induced by imbalanced nutrition during development, which can impact lifelong heart health. Recent research has underscored mitochondrial dysregulation as a pivotal mechanism driving the enduring consequences of nutritional excess. Building upon previous findings wherein a maternal high-fat diet (HFD) led to cardiac hypertrophy and fibrosis, our current study aimed to evaluate the impact of such a challenge on myocardial mitochondrial function. METHODS:Female rats were fed a chow diet or HFD during gestation and lactation. The hearts of male offspring were analyzed at adulthood. Mitochondrial DNA abundance was evaluated by quantitative polymerase chain reaction. Proteins involved in mitochondrial biogenesis, fusion, fission, damage to the electron transport chain, metabolism, cell death, proliferation, and inflammation were measured by western blot. Mitochondrial clearance was evaluated by the measurement of mitophagy markers on isolated mitochondria. Lipids were visualized by histologic approaches. RESULTS:We detected decreased cardiac mitochondrial fission factor and mitochondrial adenosine triphosphate synthase beta subunit and increased Parkin, pro-tumor necrosis factor alpha, and pro-interleukin 1 beta protein levels associated with decreased microtubule-associated protein 1A/1B light chain 3B levels in cardiac mitochondrial fraction, with a tendency for increased Oil Red O staining in the adult hearts of male offspring exposed to HFD. CONCLUSIONS:Maternal exposure to HFD enhanced mitochondrial damage and impaired fission and clearance in offspring hearts at adulthood. These alterations were associated with altered expression of proteins involved in the mitochondrial electron transport chain coupled with a propensity for increased fatty acid accumulation and elevated proinflammatory markers.

Obesity in pregnancy has significant short- and long-term consequences for both women and their neonates as well for long-life metabolic disorders. Myo-Inositol (MI) has a pivotal role in Insulin/glucose metabolism interacting with Inositol 3 phosphate receptor 1 (ITPR1) in endoplasmic reticulum. This pathway influences also cellular functions. The objective was to investigate potential changes of MI pathway in placental tissue of obese women, investigating its role in cellular proliferation. In a non-randomized experimental study, placental explants were collected from uncomplicated obese (OB) and normal weight (CTRL) women undergoing elective cesarean section, at term. Tissues were snap frozen in liquid nitrogen. Critical proteins involved in Ins regulation and pathway including SMIT1, SMIT2, ISYNA1, MIOX, ITPR1 and CN were analyzed. Total proteins were extracted with RIPA buffer, their concentrations measured with BCA assay and quantified by Western Blot (WB). To investigate the effect of MI treatment on placental cells, a trophoblast human cell line (HTR8/SVneo) was used for proliferation assay study (Immunological science). Student’s t test was used for single comparison analysis and ANOVA for multiple comparisons. Data were significant if p< 0.05. Thirty-four placenta samples (18 OB vs 16 CTRLs) were analyzed by WB. Data were normalized on GAPDH protein level. ITPR1 was upregulated in OB group (p=0.002) compared to CTRLs, as well as the active cleaved form of calcineurin (CN) (p=0.004). We did not observed alteration in SMITs, MIOX and ISYNA1 protein levels. “In vitro” MI treatment, in a dose-dependent way, decreased proliferation of trophoblast cells (Fig). An alteration of the MI pathway within placenta tissue of OB women was demonstrated as revealed by significant increase in ITPR1 protein level and active CN. No changes instead occurred in MI cellular intake, synthesis and catabolism. MI inhibited trophoblast cell proliferation. In women with pre-pregnancy obesity up-regulation of placental MI activity could affect placenta development.

Identifying the micro and macro plastic sources, transport vectors and the plastic litter path to the sea is currently a difficult and crucial issue, given the coexistence of multiple variables. With this preliminary study, we intend to develop a methodology that can be applied on a large scale in future studies. For each of the four types of main urbanized scenarios (industrial/harbour/fluvial/remote area), a series of variables have been identified, integrated with a weighted approach (assigning a different weight to each variable), highlighting the specific site characteristics. This methodology will allow the creation of predictive maps of vulnerability in future selected Mediterranean test sites.

Obesity during pregnancy has a critical impact not only on women's health and fetal growth, but also later on by increasing the risk of obesity and metabolic diseases in adulthood. Inositols (INOs) regulate glycogen storage, insulin-glucose and calcium pathways. Through their interaction with Inositol 3 phosphate receptor 1 (ITPR1), they mediate the efflux of calcium ions from the endoplasmic reticulum into the cytoplasm, modulating cellular functions and gene expression. The objective of the study was to evaluate alterations in INOs pathway in placental trophoblast cells. In this experimental study, placentas were obtained from Obese (OB) and Normal weight (CTRL) women, undergoing elective cesarean section (breech presentation), at term (Figure). None of them reported comorbidities. Trophoblasts cells were isolated based on enzyme digestion and Density gradient separation. Expression of critical genes involved in inositol regulation and pathway including SMIT1, SMIT2, IMPA1, ISYNA1 and ITPR1 were evaluated in isolated trophoblast cells. Total mRNA was extracted using column-based purification.mRNAs were reversed transcribed into cDNA and it was analysed through quantitative PCR using taqman reagent (Life Technologies) and primers.The relative expression levels of mRNAs were calculated using the comparative ΔΔCt method. Seven placentas (3 CTR vs 4 OB) were analysed. Diluted mRNA was used for qPCR analysis. Data were normalized on gapdh mRNA levels. ITPR1 mRNA level expression was downregulated in OB group (p < 0.03) compared to lean healthy women. We did not detect significant modifications in SMIT1, SMIT2, IMPA1 and ISYNA1 expression. With our data, we demonstrate an alteration in the INOs pathway in trophoblast cells induced by maternal obesity, as revealed by the significant decrease in ITPR1 expression. The identification of ITPR1 downregulation is a first step to identify potential targets and develop novel therapeutic approaches and personalized therapies to ameliorate obesity related conditions in pregnancy.

Epigenetics brings together a set of molecular mechanisms capable of modifying the level of gene activity under the influence, generally, of stimuli from the environment. It thus contributes to the expression of genes involved in cell differentiation and ultimately the development of the individual. As such, the epigenetic imprints acquired early, from the preconception period, during fetal development and in childhood, can condition health trajectories extended to the entire life course, or even be transmitted despite their acquired trait character over several generations. As a result, the early effects of environmental factors such as nutrition, parental lifestyles, relational context, stress, exposure to different types of toxicants can influence health and the risk of chronic, non-communicable diseases such as metabolic and cardiovascular diseases in adulthood. These developmental, health programming mechanisms offer an exceptional opportunity to promote health, both at the individual and population levels, through primary and early prevention.

La diversification alimentaire menée par l’enfant (DME), proposée comme une nouvelle méthode de diversification alimentaire, s’est imposée comme un véritable phénomène à la mode dans les médias. Les bébés sont assis à la table familiale dès l’âge de 6 mois, face aux aliments qu’ils attrapent et portent à leur bouche : ils décident des aliments qu’ils veulent manger et de leur quantité. La consommation d’aliments en purée et l’utilisation d’une cuillère y sont déconseillées. L’objectif de cet article est d’évaluer les avantages et les risques de la DME à travers l’analyse critique de la bibliographie entre 2000 et 2022. Parmi 423 articles identifiés, 38 ont été sélectionnés. Parmi les études cliniques retenues, 11 sont observationnelles transversales et 2 contrôlées randomisées. La DME favorise l’allaitement maternel, l’introduction précoce des morceaux, l’utilisation d’aliments non transformés, le choix du « fait maison » et la convivialité. Ces bénéfices peuvent néanmoins être atteints avec la diversification alimentaire standard (DS) selon les recommandations actuelles. D’autres bénéfices sont revendiqués mais sans preuves scientifiques comme le respect de l’appétit de l’enfant et son autonomisation, une réalisation plus facile de la diversification alimentaire et une croissance optimale avec prévention de l’excès de poids. La DME a comme inconvénients une insuffisance d’apport en énergie, fer, zinc, vitamines et autres nutriments, un excès en protéines, graisses saturées, sel et sucre. Le risque d’étouffement, qu’il faut distinguer du réflexe physiologique de haut-le-cœur, est régulièrement évoqué mais les études scientifiques n’ont pas pu apporter de réponse claire. Actuellement, le Comité de nutrition de la Société Française de Pédiatrie considère que les données publiées à ce jour en termes de bénéfices et de risques de la DME ne permettent pas de préférer cette pratique à la DS réalisée selon les recommandations actuelles.

Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of “European Guidelines for the Management of RDS” by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12, 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS).

The role of nutritional interventions for the primary prevention of cow's milk allergy (CMA) remains debated as well as the role of early introduction of allergenic foods, which is largely encouraged from the beginning of complementary feeding. Considering the introduction of cow's milk protein (CMP), current recommendations suggest avoidance of any cow's milk formula (CMF) supplements in breastfed infants in the maternity ward. By contrast, based on poor evidence, some authors support systematic supplements of CMP in breastfed children at risk of allergy from the first week of life. The Committee on Nutrition of the French Society of Pediatrics considers that such a proposal requires more clinical studies and mainly randomized and placebo-controlled clinical trials before becoming a recommendation.

Les individus nés après une restriction de croissance intra-utérine (RCIU) sont à risque de développer des altérations cardio-métaboliques (hypertension artérielle, maladies coronariennes, diabète de type-2, stéatose hépatique non-alcoolique, etc) plus tard dans la vie. Le stress oxydant et la sénescence cellulaire sont associés à ces maladies dans la population générale. Cependant, l’implication de ces facteurs dans le développement des maladies cardio-métaboliques chez les individus nés après une RCIU n’est pas clairement établie. Durant toute la gestation, les rattes ont reçu un régime contrôle (caséine 23 %, CTRL) ou une diète faible en protéines (caséine 9 %, RCIU). Chez les animaux mâles et femelles à 6 mois de vie (n = 6 par groupe) : la pression artérielle systolique (PAS) (pléthysmographie), des échographies cardiaques, la graisse viscérale (CT-scan), la tolérance au glucose (injection intrapéritonéale de glucose), l’histologie hépatique et myocardique, les niveaux plasmatiques des transaminases ont été investigués. Le stress oxydant (anions superoxyde ; fluorescence), les défenses anti-oxydantes (western blot), la sénescence cellulaire (lipofuscine (histologie)) et l’expression de facteurs associés (western blot) ont été évalués dans le foie et le cœur (VG). Un test Mann-Whitney a été utilisé avec un seuil de significativité à p < 0,05. Les mâles RCIU présentent une élévation de la PAS et de la masse grasse viscérale, une intolérance au glucose, des altérations hépatiques (élévation des ASAT et ALAT, des triglycerides), une augmentation de la masse du VG sans altération de la fonction cardiaque. Au niveau du foie et du VG, une production accrue d’anions superoxides, une diminution de la Cu/Zn superoxide dismutase, une augmentation des dépôts de lipofuscine, de l’expression de p16ink4a et de p21waf, et une diminution de l’expression de sirtuin-1 ont été observées (p < 0,05 pour tous). Aucune altération significative n’a été observée chez les femelles. Nos résultats ont démontré un dimorphisme sexuel dans le développement de maladies cardio-métaboliques chez le rat suite à une RCIU, associé à un stress oxydant et une sénescence cellulaire prématurée.

Background:Type 2 diabetes (T2D) and obesity induce left ventricular (LV) dysfunction. The underlying pathophysiological mechanisms remain unclear, but myocardial triglyceride content (MTGC) could be involved.Objectives:This study aimed to determine which clinical and biological factors are associated with increased MTGC and to establish whether MTGC is associated with early changes in LV function.Methods:A retrospective study was conducted using five previous prospective cohorts, leading to 338 subjects studied, including 208 well-phenotyped healthy volunteers and 130 subjects living with T2D and/or obesity. All the subjects underwent proton magnetic resonance spectroscopy and feature tracking cardiac magnetic resonance imaging to measure myocardial strain.Results:MTGC content increased with age, body mass index (BMI), waist circumference, T2D, obesity, hypertension, and dyslipidemia, but the only independent correlate found in multivariate analysis was BMI (p=0.01; R²=0.20). MTGC was correlated to LV diastolic dysfunction, notably with the global peak early diastolic circumferential strain rate (r=-0.17, p=0.003), the global peak late diastolic circumferential strain rate (r=0.40, p<0.0001) and global peak late diastolic longitudinal strain rate (r=0.24, p<0.0001). MTGC was also correlated to systolic dysfunction via end-systolic volume index (r=-0.34, p<0.0001) and stroke volume index (r=-0.31, p<0.0001), but not with longitudinal strain (r=0.009, p=0.88). Interestingly, the associations between MTGC and strain measures did not persist in multivariate analysis. Furthermore, MTGC was independently associated with LV end-systolic volume index (p=0.01, R²=0.29), LV end-diastolic volume index (p=0.04, R²=0.46), and LV mass (p=0.002, R²=0.58).Conclusions:Predicting MTGC remains a challenge in routine clinical practice, as only BMI independently correlates with increased MTGC. MTGC may play a role in LV dysfunction but does not appear to be involved in the development of subclinical strain abnormalities.

Exposure to nutritional imbalance during early life can influence disease risk lifelong and across generations. In this long-term conditioning, epigenetics constitutes a key mechanism. They bridge environmental cues and the expression of genes involved in the setting of long-standing biological regulations in numerous organs and species. Epigenetic marks are proposed as innovative diagnostic biomarkers and potential targets in the prevention of diseases. However, a number of uncertainties make them difficult to use in clinical approaches in the context of early exposure to nutritional challenge. In conclusion, active investigations in this field are still needed before clinical applications are considered.