Since an objective description is essential to determine infant’s postnatal condition and efficacy of interventions, two scores were suggested in the past but weren’t tested yet: The Specified-Apgar uses the 5 items of the conventional Apgar score; however describes the condition regardless of gestational age (GA) or resuscitative interventions. The Expanded-Apgar measures interventions needed to achieve this condition. We hypothesized that the combination of both (Combined-Apgar) describes postnatal condition of preterm infants better than either of the scores alone. Scores were assessed in preterm infants below 32 completed weeks of gestation. Data were prospectively collected in 20 NICU in 12 countries. Prediction of poor outcome (death, severe/moderate BPD, IVH, CPL and ROP) was used as a surrogate parameter to compare the scores. To compare predictive value the AUC for the ROC was calculated. Of 2150 eligible newborns, data on 1855 infants with a mean GA of 286/7 ± 23/7 weeks were analyzed. At 1 minute, the Combined-Apgar was significantly better in predicting poor outcome than the Specified- or Expanded-Apgar alone. Of infants with a very low score at 5 or 10 minutes 81% or 100% had a poor outcome, respectively. In these infants the relative risk (RR) for perinatal mortality was 24.93 (13.16-47.20) and 31.34 (15.91-61.71), respectively. The Combined-Apgar allows a more appropriate description of infant’s condition under conditions of modern neonatal care. It should be used as a tool for better comparison of group of infants and postnatal interventions. clinicaltrials.gov Protocol Registration System ( NCT00623038 ). Registered 14 February 2008.
Preterm infants who have respiratory distress syndrome have for many years been managed with a combination of early intubation and exogenous surfactant therapy. It is now recognized that applying continuous positive airway pressure (CPAP) in an extremely preterm infant is a reasonable alternative to early intubation after birth. Meta-analysis of large controlled trials comparing these two approaches suggests a benefit of CPAP, with a small reduction in the risk of the composite outcome of death or bronchopulmonary dysplasia. In the past decade, there has been an upsurge in the use of CPAP as primary therapy for preterm infants, bringing with it the dilemma of whether and how to give exogenous surfactant. In an effort to circumvent this problem, techniques of minimally invasive surfactant therapy have recently been investigated, aiming to administer surfactant to spontaneously breathing infants, allowing them to remain on CPAP in the critical first days after birth and, hopefully, beyond. These techniques have included administration of exogenous surfactant by brief tracheal catheterization, aerosolization, and laryngeal mask. Of these, the methods involving brief tracheal catheterization have been most extensively studied, with surfactant administered by using both a flexible feeding tube and a semi-rigid vascular catheter. In recent clinical trials (AMV [Avoidance of Mechanical Ventilation by Surfactant Administration] trial, Take Care study, and NINSAPP [Surfactant Application During Spontaneous Breathing With Continuous Positive Airway Pressure in Premature Infants <27 Weeks] trial), surfactant delivery via a feeding tube was found to reduce the need for subsequent intubation and ventilation and to improve short-term respiratory outcomes. Despite the relatively small numbers of infants in these trials, this technique has found its way into clinical practice in some centers. Further randomized controlled trials of surfactant administration via tracheal catheterization are underway or planned, and they will help clarify the place of this therapeutic approach. Additional studies will be needed to identify the best means of infant selection, refine the instillation technique, resolve the uncertainties regarding sedation, and determine the optimal surfactant dosage.
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.
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.
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.