Do Lower Levels of Fetal Hemoglobin in Preterm Infants Relate to Oxidative Stress?

Fetal hemoglobin (HbF) has a higher affinity to oxygen than adult hemoglobin, allowing for a slower oxygen transfer to peripheral tissue, creating a microenvironment conducive to adequate fetal development in utero. However, most preterm infants receive packed red blood cell transfusions from adult donors leading to a drastic nonphysiological descent of circulating HbF. We hypothesized that this drop could enhance oxygen delivery to peripheral tissues generating a hyperoxic pro-oxidant environment. To investigate this, we assessed differences in oxidative stress biomarkers determined in urine samples in a cohort of 56 preterm infants born <32 weeks' gestation. Median oxidative stress biomarkers were compared between patients with circulating HbF above or below median HbF levels using Wilcoxon rank sum test. Oxidative stress biomarkers were significantly higher in the group of patients with lower levels of HbF. This study provides the initial evidence indicating elevated levels of oxidative stress biomarkers in preterm neonates with lower HbF levels. Based on the results, we hypothesize that HbF may contribute to preventing free radical-associated conditions during the newborn period. Antioxid. Redox Signal. 40, 453-459.

Effect of autologous umbilical cord blood transfusion in the development of retinopathy of prematurity: randomized clinical trial - study protocol.

Background: Currently, the treatment of anemia in preterm infants is based on packed red blood cell (RBC) transfusions from adult donors. Oxygen (O2) is mainly transported to the tissues bound to hemoglobin (Hb). In extremely low gestational age neonates (ELGANs), fetal hemoglobin (HbF), which has a higher affinity for O2, represents up to 95% of circulating hemoglobin. During the first month of life, the majority of ELGANs will require an adult-donor RBC transfusion causing HbF levels to rapidly drop. HbA releases 50% more oxygen in peripheral tissues than HbF. Increased release of O2 in the retina is one of the main factors related to the development of retinopathy of prematurity (ROP). Collecting umbilical cord blood and using autologous umbilical cord whole blood (UCB) transfusions would contribute to maintaining physiological HbF concentrations in newborns and avoid oxygen-in-excess derived damage. Methods: This is a randomized, double-blinded, multicenter clinical trial. ELGANs ≤28 weeks of gestational age will be randomized 1:1 to receive an autologous umbilical cord blood transfusion (intervention arm) or standard transfusion of packed RBC from an adult donor (control arm) to assess ROP development. Assuming a 50% reduction in ROP incidence, 134 patients (67 per group) will be recruited. When blood transfusion is indicated, the Blook Bank will supply UCB or RCB according to the patient's group. The primary endpoint is the incidence of any ROP. Secondary endpoints are assessessment of treatment safety, results of biomarkers related to ROP and its chronology, and urine oxidative stress markers. In addition, the cellular composition of umbilical cord blood and its relationship with prematurity-related pathologies will be analyzed. All patients will be followed-up to 24 months of corrected age to evaluate their neurodevelopment. Discussion: ROP is a major cause of irreversible blindness in preterm newborns. Transfusions with adult donor blood can lead to complications, including ROP. UCB transfusions offer advantages by maintaining physiological HbF levels and potentially optimizing postnatal development. Moreover, autologous UCB transfusion could reduce risks associated with heterologous blood products, although volume collection remains challenging. UCB contains growth factors and progenitor cells that may impact ROP.

Analysis of Fractional Cerebral Oxygen Extraction in Preterm Infants during the Kangaroo Care.

INTRODUCTION: We aimed to investigate the cerebral fractional tissue oxygen extraction (FtOE) during kangaroo care (KC) in premature infants and compare cardiorespiratory stability and hypoxic or bradycardic events between KC and incubator care. METHODS: A single-center prospective observational study was carried out at the NICU of a level 3 perinatal center. Preterm infants <32 weeks gestational age were subjected to KC. Patients were subjected to continuous monitoring of regional cerebral oxygen saturation (rScO2), peripheral oxygen saturation (SpO2), and heart rate (HR) during KC, before KC (pre-KC), and after KC (post-KC). The monitoring data were stored and exported to MATLAB for synchronization and signal analysis including the calculation of the FtOE and events analysis (i.e., desaturations and bradycardias counts and anormal values). Furthermore, the event counts and the mean SpO2, HR, rScO2, and FtOE were compared between studied periods employing the Wilcoxon rank-sum test and the Friedman test, respectively. RESULTS: A total of forty-three KC sessions with their corresponding pre-KC and post-KC segments were analyzed. The distributions of the SpO2, HR, rScO2, and FtOE showed different patterns according to the respiratory support, but not differences between the studied periods were detected. Accordingly, no significant differences in monitoring events were evidenced. However, cerebral metabolic demand (FtOE) was significantly lower during KC compared with post-KC (p = 0.019). CONCLUSION: Premature infants remain clinically stable during KC. Moreover, cerebral oxygenation is significantly higher and cerebral tissular oxygen extraction is significantly lower during KC compared with incubator care in post-KC. No differences in HR and SpO2 were shown. This novel data analysis methodology could be expanded to other clinical situations.

Effects of Sepsis on Immune Response, Microbiome and Oxidative Metabolism in Preterm Infants.

This is a narrative review about the mechanisms involved in bacterial sepsis in preterm infants, which is an illness with a high incidence, morbidity, and mortality. The role of the innate immune response and its relationship with oxidative stress in the pathogenesis are described as well as their potential implementation as early biomarkers. Moreover, we address the impact that all the mechanisms triggered by sepsis have on the dysbiosis and the changes on neonatal microbiota.

Early molecular markers of ventilator-associated pneumonia in bronchoalveolar lavage in preterm infants.

INTRODUCTION: Ventilator-associated pneumonia (VAP) constitutes a serious nosocomial infection. Our aim was to evaluate the reliability of cytokines and oxidative stress/inflammation biomarkers in bronchoalveolar lavage fluid (BALF) and tracheal aspirates (TA) as early biomarkers of VAP in preterm infants. METHODS: Two cohorts were enrolled, one to select candidates and the other for validation. In both, we included preterms with suspected VAP, according to BALF culture, they were classified into confirmed VAP and no VAP. Concentration of 16 cytokines and 8 oxidative stress/inflammation biomarkers in BALF and TA was determined in all patients. RESULTS: In the first batch, IL-17A and TNF-α in BALF, and in the second one IL-10, IL-6, and TNF-α in BALF were significantly higher in VAP patients. BALF TNF-α AUC in both cohorts was 0.86 (sensitivity 0.83, specificity 0.88). No cytokine was shown to be predictive of VAP in TA. A statistically significant increase in the VAP group was found for glutathione sulfonamide (GSA) in BALF and TA. CONCLUSIONS: TNF-α in BALF and GSA in BALF and TA were associated with VAP in preterm newborns; thus, they could be used as early biomarkers of VAP. Further studies with an increased number of patients are needed to confirm these results. IMPACT: We found that TNF-α BALF and GSA in both BALF and TA are capable of discriminating preterm infants with VAP from those with pulmonary pathology without infection. This is the first study in preterm infants aiming to evaluate the reliability of cytokines and oxidative stress/inflammation biomarkers in BALF and TA as early diagnostic markers of VAP. We have validated these results in two independent cohorts of patients. Previously studies have focused on full-term neonates and toddlers and determined biomarkers mostly in TA, but none was exclusively conducted in preterm infants.

Venous sinus thrombosis in pediatrics. Case series of a tertiary hospital. / Trombosis de senos venosos en pediatría. Serie de casos de un hospital terciario.

INTRODUCTION: Venous sinus thrombosis (VST) is a rare entity in pediatrics, probably under-diagnosed and poten tially serious, described as a cause of stroke in childhood. OBJECTIVE: To describe the clinical presenta tion, risk factors, treatment, and evolution of pediatric patients with VST. PATIENTS AND METHOD: Re trospective study of patients admitted to a referral hospital, diagnosed with VST, aged between one month and seventeen years, from January 2011 to December 2019. The following data were re viewed: age at diagnosis, sex, signs and symptoms of presentation, predisposing mechanisms, study of thrombophilias, treatment and duration of treatment, follow-up protocol, long-term sequelae, and mortality. Due to their differences in clinical presentation, the sample was divided into two age groups: young children between 1 month and 5 years and older children and adolescents between 6 and 17 years. RESULTS: 17 patients were diagnosed with VST, 45% were women, with a median age of 4.5 years. The most frequent symptoms in older children (6-17 years old) were headache (80%) and diplopia (60%). In children under 5 years old, the most frequent clinical presentation was cerebellar ataxia (42%), asymptomatic (34%), and headache (25%). In 23.5% of the total, VST was a casual fin ding in neuroimaging. 13 patients presented relevant histories such as complicated otitis media with mastoiditis (53%), severe traumatic head injury (6%), and resection of a space-occupying lesion of the brain (6%). 23% of the cases were idiopathic and in 23% there were prothrombotic factors. The treatment of choice in all patients was low-molecular-weight heparin. During the short-term follow- up, 11.8% presented self-limited neurological symptoms. One patient presented long-term paresis of the sixth paired cranial nerve. There were no deaths or recurrences of the episode in our series. CONCLUSIONS: VST is a rare entity and it usually appears with signs and symptoms of intracranial hy pertension. It is a potentially serious condition and early diagnosis and treatment can help minimize long-term sequelae.

Selección del tratamiento antibiótico empírico en pielonefritis según el perfil del paciente / Selection of empirical antibiotic treatment in pyelonephritis according to the patient's profile

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