Neurodevelopmental Outcome in Very Low Birth Weight Preterm Newborns: The Role of Neonatal Sepsis

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Fetal oxygenation in the last weeks of pregnancy evaluated through the umbilical cord blood gas analysis

IntroductionEmbryo and fetus grow and mature over the first trimester of pregnancy in a dynamic hypoxic environment, where placenta development assures an increased oxygen availability. However, it is unclear whether and how oxygenation changes in the later trimesters and, more specifically, in the last weeks of pregnancy.MethodsObservational study that evaluated the gas analysis of the umbilical cord blood collected from a cohort of healthy newborns with gestational age >= 37 weeks. Umbilical venous and arterial oxygen levels as well as fetal oxygen extraction were calculated to establish whether oxygenation level changes over the last weeks of pregnancy. In addition, fetal lactate, and carbon dioxide production were analyzed to establish whether oxygen oscillations may induce metabolic effects in utero.ResultsThis study demonstrates a progressive increase in fetal oxygenation levels from the 37th to the 41st weeks of gestation (mean venous PaO2 approximately from 20 to 25 mmHg; p < 0.001). This increase is largely attributable to growing umbilical venous PaO2, regardless of delivery modalities. In neonates born by vaginal delivery, the increased oxygen availability is associated with a modest increase in oxygen extraction, while in neonates born by cesarean section, it is associated with reduced lactate production. Independently from the type of delivery, carbon dioxide production moderately increased. These findings suggest a progressive shift from a prevalent anaerobic metabolism (Warburg effect) towards a growing aerobic metabolism.ConclusionThis study confirms that fetuses grow in a hypoxic environment that becomes progressively less hypoxic in the last weeks of gestation. The increased oxygen availability seems to favor aerobic metabolic shift during the last weeks of intrauterine life; we hypothesize that this environmental change may have implications for fetal maturation during intrauterine life

catheter and laryngeal mask endotracheal surfactant therapy the calmest approach as a novel mist technique

AbstractPurpose: Neonatal respiratory distress syndrome (RDS) is a major cause of mortality and morbidity among preterm infants. Although the INSURE (INtubation, SURfactant administration, Estubation) technique for surfactant replacement therapy is so far the gold standard method, over the last years new approaches have been studied, i.e. less invasive surfactant administration (LISA) or minimally invasive surfactant therapy (MIST). Here we propose an originally modified MIST, called CALMEST (Catheter And Laryngeal Mask Endotracheal Surfactant Therapy), using a particular laryngeal mask as a guide for a thin catheter to deliver surfactant directly in the trachea.Materials and methods: We performed a preliminary study on a mannequin and a subsequent in vivo pilot trial.Results and conclusions: This novel procedure is quick, effective and well tolerated and might represent an improvement in reducing neonatal stress. Ultimately, CALMEST offers an alternative approach that could be extremely useful for medica..

The genetic variant SLC2A1-rs1105297 is associated with the differential analgesic response to a glucose-based treatment in newborns

Neonatal pain is a critical issue in clinical practice. The oral administration of glucose-based solutions is currently one of the most common and effective nonpharmacologic strategies for neonatal pain relief in daily minor procedures. However, a varying degree of analgesic efficacy has been reported for this treatment. Environmental, maternal, and genetic factors may explain this variability and potentially allow for a personalized analgesic approach, maximizing therapeutic efficacy and preventing side effects. We investigated the exposome (ie, the set of clinical and anthropometric variables potentially affecting the response to the therapy) and the genetic variability of the noradrenaline transporter gene (solute carrier family 6 member 2 [SLC6A2]) and 2 glucose transporter genes (solute carrier family 2 member 1 [SLC2A1] and 2 [SLC2A2]) in relation to the neonatal analgesic efficacy of a 33% glucose solution. The study population consisted in a homogeneous sample of more than 1400 healthy term newborns. No association for the exposome was observed, whereas a statistically significant association between the G allele of SLC2A1-rs1105297 and a fourfold decreased probability of responding to the therapy was identified after multiple-testing correction (odds ratio of 3.98, 95% confidence interval 1.95-9.17; P = 4.05 × 10-4). This allele decreases the expression of SLC2A1-AS1, causing the upregulation of SLC2A1 in the dorsal striatum, which has been suggested to be involved in reward-related processes through the binding of opioids to the striatal mu-opioid receptors. Altogether, these results suggest the involvement of SLC2A1 in the analgesic process and highlight the importance of host genetics for defining personalized analgesic treatments

Treating infants with 0.2% propranolol eye micro-drops drastically reduced the progression of retinopathy of prematurity

Brief repor

Procalcitonin levels in preterm newborns: Reference ranges during the first three days of life

BackgroundSepsis is one of the most important causes of morbidity and mortality in the neonatal period, especially in preterms. Diagnosis is difficult because of specific signs and symptoms. The diagnostic gold standard is blood culture, but its sensibility is low. Much effort has been made to identify early, sensitive, and specific diagnostic markers; among these markers particular attention was paid to procalcitonin. However, reference ranges of serum procalcitonin (PCT) shortly after birth have not been sufficiently studied in healthy preterms, and literature is still contradictory. ObjectivesThe aim of the study is to define PCT age-specific reference ranges in the first 72 h of life in uninfected VLBW preterms. MethodsSerum levels of PCT were assessed for each newborn at birth and every 24 h until the 3rd day of life. The eligible patients were classified into two groups according to their sepsis status. ResultsApproximately 343 patients were enrolled; 28 were septic and 315 non-septic. In non-septic infants, 1,015 determinations of PCT values were performed. Our data showed a trend in average value of PCT to increase after birth up to a peak between 24 and 48 h of life and, subsequently, to fall. The average peak value was 15.12 ng/ml achieved at nearly 36 h of life. ConclusionOur study shows a PCT nomogram of healthy preterms, which is different from the one of term newborns. Data agree with what is reported in literature on the reference ranges and trends of PCT in non-septic preterms shortly after birth

High-fidelity simulation in Neonatology and the Italian experience of Nina

The modern methodology of simulation was born in the aeronautical field. In medicine, anesthetists showed great attention for technological advances and simulation, closely followed by surgeons with minimally invasive surgery. In Neonatology training in simulation is actually useful in order to face unexpected dramatic events, to minimize clinical risk preventing errors and to optimize team work. Critical issues in simulation are: teachers-learners relationship, focus on technical and non-technical skills, training coordination, adequate scenarios, effective debriefing. Therefore, the quality of a simulation training center is multi-factorial and is not only related to the mannequin equipment. High-fidelity simulation is the most effective method in education. In Italy simulation for education in Medicine has been used for a few years only. In Pisa we founded Nina (that is the acronymous for the Italian name of the Center, CeNtro di FormazIone e SimulazioNe NeonAtale), the first neonatal simulation center dedicated but integrated within a Hospital Unit in Italy. This paper describes how we manage education in Nina Center, in order to offer a model for other similar experiences

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression

Despite the evident progress in neonatal medicine, retinopathy of prematurity (ROP) remains a serious threat to the vision of premature infants, due to a still partial understanding of the mechanisms underlying the development of this disease and the lack of drugs capable of arresting its progression. Although ROP is a multifactorial disease, retinal vascularization is strictly dependent on oxygen concentration. The exposition of the retina of a preterm newborn, still incompletely vascularized, to an atmosphere relatively hyperoxic, as the extrauterine environment, induces the downregulation of proangiogenic factors and therefore the interruption of vascularization (first ischemic phase of ROP). However, over the following weeks, the growing metabolic requirement of this ischemic retina produces a progressive hypoxia that specularly promotes the surge of proangiogenic factors, finally leading to proliferative retinopathy (second proliferative phase of ROP). The demonstration that the noradrenergic system is actively involved in the coupling between hypoxia and the induction of vasculogenesis paved the way for a pharmacologic intervention aimed at counteracting the interaction of noradrenaline with specific receptors and consequently the progression of ROP. A similar trend has been observed in infantile hemangiomas, the most common vascular lesion of childhood induced by pre-existing hypoxia, which shares similar characteristics with ROP. The fact that propranolol, an unselective antagonist of beta 1/2 adrenoceptors, counteracts the growth of infantile hemangiomas, suggested the idea of testing the efficacy of propranolol in infants with ROP. From preclinical studies, ongoing clinical trials demonstrated that topical administration of propranolol likely represents the optimal approach to reconcile its efficacy and maximum safety. Given the strict relationship between vessels and neurons, recovering retinal vascularization with propranolol may add further efficacy to prevent retinal dysfunction. In conclusion, the strategy of contrasting precociously the progression of the disease appears to be more advantageous than the current wait-and-see therapeutic approach, which instead is mainly focused on avoiding retinal detachment

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

Retinopathy of prematurity (ROP) is an evolutive and potentially blinding eye disease that affects preterm newborns. Unfortunately, until now no conservative therapy of active ROP with proven efficacy is available. Although ROP is a multifactorial disease, premature exposition to oxygen concentrations higher than those intrauterine, represents the initial pathogenetic trigger. The increase of oxygenation in a retina still incompletely vascularized promotes the downregulation of proangiogenic factors and finally the interruption of vascularization (ischemic phase). However, the increasing metabolic requirement of the ischemic retina induces, over the following weeks, a progressive hypoxia that specularly increases the levels of proangiogenic factors finally leading to proliferative retinopathy (proliferative phase). Considering non-modifiable the coupling between oxygen levels and vascularization, so far, neonatologists and ophthalmologists have "played defense", meticulously searching the minimum necessary concentration of oxygen for individual newborns, refining their diagnostic ability, adopting a careful monitoring policy, ready to decisively intervene only in a very advanced stage of disease progression. However, recent advances have demonstrated the possibility to pharmacologically modulate the relationship between oxygen and vascularization, opening thus the perspective for new therapeutic or preventive opportunities. The perspective of a shift from a defensive towards an attack strategy is now at hand

Can an Ozone System Generator reduce indoor triggers in asthmatic patient?

Objective: During the last decades, an increase in the prevalence of asthma and other allergic diseases has been recorded, together with modifications in the living environment and consequent changes in the quality of indoor air. Indoor environment is favorable to the proliferation of allergens such as: house dust mites, fungal spores and cockroaches. The primary action to be undertaken for an effective eradication of infectious agents constitutes in modifying the house environmental conditions, which make it favorable to infestations. Ozone can play a sanitize role, but at the same time it can cause inflammation, especially in the lung. The aim of this study was to verify the role and safety of ozone in the sanitation of the bedroom of a subject suffering from asthma. Methods: A daily ozone treatment was carried during a 14-day time period in the bedroom of an asthmatic patient. Aerobiological sampling in indoor air, microbiological sampling and detection of ATP bioluminescence on the surface were performed before and after treatment at the first day, as well as after treatment at the 7th and 14th day of the study. An aerobiological measurement was also performed outdoor of the patient\u2019s bedroom only for the first day. Results: Our analysis confirms that low ozone levels induced a marked reduction of indoor air microbiological pollution without adverse effects on lung functionality of the asthmatic patient we considered. Conclusion: Our observations warrant further investigation on the role that ozone-based sterilization might have in controlling asthmatic symptom