Infecciones relacionadas con la asistencia sanitaria en neonatología / Health care-associated infections in neonatology

Las infecciones relacionadas con la asistencia sanitaria (IRAS) son frecuentes en neonatología, pero no existe un consenso en sus definiciones. Esto dificulta la comparación de incidencias entre distintas unidades o la valoración de la eficacia de los paquetes de prevención. Por ello, es que consideramos muy importante lograr un acuerdo en las definiciones y diagnóstico de una de las morbilidades más recurrentes de los neonatos hospitalizados. El presente documento pretende unificar estas definiciones en relación con las infecciones más comunes como son la bacteriemia relacionada con el catéter (BRC), la neumonía vinculada a la ventilación mecánica (NAV) y la infección de la herida quirúrgica (IHQ), así como su abordaje diagnóstico-terapéutico.(AU)

Health care-associated infections are common in neonatology, but there is no consensus on their definitions. This makes it difficult to compare their incidence or assess the effectiveness of prevention bundles. This is why we think it is very important to achieve a consensus on the definitions and diagnostic criteria for one of the most frequent causes of morbidity in hospitalised neonates. This document aims to standardise the definitions for the most frequent health care-associated infections, such as catheter-associated bloodstream infection, ventilator-associated pneumonia and surgical wound infection, as well as the approach to their diagnosis and treatment.(AU)

Health care-associated infections in neonatology.

Health care-associated infections are common in neonatology, but there is no consensus on their definitions. This makes it difficult to compare their incidence or assess the effectiveness of prevention bundles. This is why we think it is very important to achieve a consensus on the definitions and diagnostic criteria for one of the most frequent causes of morbidity in hospitalised neonates. This document aims to standardise the definitions for the most frequent health care-associated infections, such as catheter-associated bloodstream infection, ventilator-associated pneumonia and surgical wound infection, as well as the approach to their diagnosis and treatment.

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.

Niveles asistenciales en las unidades neonatales en España: Una visión actualizada para una nueva realidad / Care levels in neonatal units in Spain: An updated vision for a new reality

La Sociedad Española de Neonatología estableció en el año 2013 los niveles asistenciales de las unidades neonatales en España. Desde entonces, la natalidad en nuestro país, así como la universalización del conocimiento, de las técnicas y de los dispositivos de tratamiento de los pacientes ha evolucionado significativamente. Esta situación obliga a una redefinición de los actuales niveles asistenciales basándose en criterios de calidad que permitan una mejor comparabilidad entre las unidades y supongan un impulso para la mejora en la atención de nuestros recién nacidos. (AU)

The Spanish Society of Neonatology established in 2013 the care levels of the neonatal units in Spain. Since then, the birth rate in our country, as well as the universalization of knowledge, techniques and patient treatment devices, has evolved significantly. This situation forces a redefinition of the current levels of care based on quality criteria that allow better comparability between the units and represents a challenge to improve the care of our newborns. (AU)

Care levels in neonatal units in Spain: an updated vision for a new reality.

The Spanish Society of Neonatology established the care levels of the Neonatal Units in Spain in 2013. Since then, the birth rate in our country, as well as the universalization of knowledge, techniques and patient treatment devices, has evolved significantly. This situation forces a redefinition of the current levels of care based on quality criteria that allow better comparability between the Units and represents a challenge to improve the care of our newborns.

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.

Recomendaciones para la transfusión de hemoderivados en neonatología / Recommendations for transfusion of blood products in neonatology

La escasa evidencia sobre el uso de las transfusiones en neonatología explica las limitaciones de las guías clínicas actuales. A pesar de ello, en este documento analizamos la evidencia más reciente para hacer unas recomendaciones para la práctica clínica. La prevención de la anemia de la prematuridad, el uso de protocolos y las indicaciones restrictivas de transfusión, componen la mejor estrategia para nuestros clínicos. En las transfusiones de plaquetas, es preciso valorar el riesgo de sangrado, integrando la situación clínica y analítica. Por último, el plasma fresco congelado está recomendado en neonatos con coagulopatía y sangrado activo, en déficits congénitos de factores sin tratamiento específico y en situaciones de coagulación intravascular diseminada. Todos los hemoderivados presentan efectos adversos que deben hacernos evaluar individual y minuciosamente la necesidad de una transfusión. (AU)

The scant evidence on the use of transfusions in neonatal care explains the limitations of current clinical guidelines. Despite this, in this document we explore the most recent evidence to make recommendations for the clinical practice. The prevention of anaemia of prematurity, the use of protocols and restrictive transfusion strategies constitute the best approach for clinicians in this field. In the case of platelet transfusions, the risk of bleeding must be assessed, combining clinical and laboratory features. Lastly, fresh frozen plasma is recommended in neonates with coagulopathy and active bleeding, with congenital factor deficiencies for which there is no specific treatment or with disseminated intravascular coagulation. All blood products have adverse effects that warrant a personalised and thorough assessment of the need for transfusion. (AU)

Recommendations for transfusion of blood products in neonatology.

The scant evidence on the use of transfusions in neonatal care explains the limitations of current clinical guidelines. Despite this, in this document we explore the most recent evidence to make recommendations for the clinical practice. The prevention of anaemia of prematurity, the use of protocols and restrictive transfusion strategies constitute the best approach for clinicians in this field. In the case of platelet transfusions, the risk of bleeding must be assessed, combining clinical and laboratory features. Lastly, fresh frozen plasma is recommended in neonates with coagulopathy and active bleeding, with congenital factor deficiencies for which there is no specific treatment or with disseminated intravascular coagulation. All blood products have adverse effects that warrant a personalised and thorough assessment of the need for transfusion.

Perinatal palliative care.

Perinatal Palliative Care is a model of care designed to prevent and treat the physical, spiritual, emotional, and social needs of fetuses and newborn infants with life-threatening or life-limiting conditions. The care extends to the infant's family. It is delivered by an interdisciplinary team to improve the quality of life from the time of diagnosis (possibly in utero) into death and bereavement (days, months or years later). To guarantee the access of this vulnerable population to high quality palliative care, structured programs and protocols need to be further developed in tertiary hospitals that treat highly complex obstetric and neonatal pathologies. Basic training is required for all the professionals involved.

Cuidados paliativos perinatales / Perinatal palliative care

Los cuidados paliativos perinatales son una forma de atención clínica diseñada para anticipar, prevenir y tratar el sufrimiento físico, psicológico, social y espiritual de los fetos y recién nacidos con enfermedades limitantes o amenazantes de la vida, que se extiende a sus familias. Se trata de una atención interdisciplinaria y coordinada que busca ofrecer la mejor calidad de vida posible, desde el diagnóstico (muchas veces intraútero) hasta el fallecimiento y el duelo (días, meses o años después). Los cuidados paliativos perinatales constituyen una prestación de salud básica dirigida a una población particularmente vulnerable. Para garantizar el acceso a una atención de calidad es esencial desarrollar programas estructurados y protocolos clínicos en todos los hospitales terciarios que atienden patología obstétrica y neonatal de alta complejidad. Se requiere también una formación básica de todos los profesionales implicados.(AU)

Perinatal palliative care is a model of care designed to prevent and treat the physical, spiritual, emotional, and social needs of fetuses and newborn infants with life-threatening or life-limiting conditions. The care extends to the infant's family. It is delivered by an interdisciplinary team to improve the quality of life from the time of diagnosis (possibly in utero) into death and bereavement (days, months, or years later). To guarantee the access of this vulnerable population to high quality palliative care, structured programs and protocols need to be further developed in tertiary hospitals that treat highly complex obstetric and neonatal pathologies. Basic training is required for all the professionals involved.(AU)

Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates.

BACKGROUND: Genome-wide expression profiles have been previously employed as clinical research diagnostic tools for newborn sepsis. We aimed to determine if transcriptomic profiles could discriminate between Gram-positive and Gram-negative bacterial sepsis in preterm infants. METHODS: Prospective, observational, double-cohort study was conducted in very low birth weight infants with clinical signs and culture-positive sepsis. Blood samples were collected when clinical signs became apparent. Total RNA was processed for transcriptomic analysis. Results were validated by both reverse-transcription polymerase chain reaction and a mathematical model. RESULTS: We included 25 septic preterm infants, 17 with Gram-positive and 8 with Gram-negative bacteria. The principal component analysis identified these two clusters of patients. We performed a predictive model based on 21 genes that showed an area under the receiver-operating characteristic curve of 1. Eight genes were overexpressed in Gram-positive septic infants: CD37, CSK, MAN2B2, MGAT1, MOB3A, MYO9B, SH2D3C, and TEP1. The most significantly overexpressed pathways were related to metabolic and immunomodulating responses that translated into an equilibrium between pro- and anti-inflammatory responses. CONCLUSIONS: The transcriptomic profile allowed identification of whether the causative agent was Gram-positive or Gram-negative bacteria. The overexpression of genes such as CD37 and CSK, which control cytokine production and cell survival, could explain the better clinical outcome in sepsis caused by Gram-positive bacteria. IMPACT: Transcriptomic profiles not only enable an early diagnosis of sepsis in very low birth weight infants but also discriminate between Gram-positive and Gram-negative bacteria as causative agents. The overexpression of some genes related to cytokine production and cell survival could explain the better clinical outcome in sepsis caused by Gram-positive bacteria, and could lead us to a future, targeted therapy.

Clinical and immunological aspects of microRNAs in neonatal sepsis.

Neonatal sepsis constitutes a highly relevant public health challenge and is the most common cause of infant morbidity and mortality worldwide. Recent studies have demonstrated that during infection epigenetic changes may occur leading to reprogramming of gene expression. Post-transcriptional regulation by short non-coding RNAs (e.g., microRNAs) have recently acquired special relevance because of their role in the regulation of the pathophysiology of sepsis and their potential clinical use as biomarkers. ~22-nucleotide of microRNAs are not only involved in regulating multiple relevant cellular and molecular functions, such as immune cell function and inflammatory response, but have also been proposed as good candidates as biomarkers in sepsis. Nevertheless, establishing clinical practice guidelines based on microRNA patterns as biomarkers for diagnosis and prognosis in neonatal sepsis has yet to be achieved. Given their differential expression across tissues in neonates, the release of specific microRNAs to blood and their expression pattern can differ compared to sepsis in adult patients. Further in-depth research is necessary to fully understand the biological relevance of microRNAs and assess their potential use in clinical settings. This review provides a general overview of microRNAs, their structure, function and biogenesis before exploring their potential clinical interest as diagnostic and prognostic biomarkers of neonatal sepsis. An important part of the review is focused on immune and inflammatory aspects of selected microRNAs that may become biomarkers for clinical use and therapeutic intervention.

Sedoanalgesia in neonatal units.

Pain recognition and management continues to be a challenge for health professionals in Neonatal Intensive Care Units. Many of the patients are routinely exposed to repeated painful experiences with demonstrated short- and long-term consequences. Preterm babies are a vulnerable high-risk population. Despite international recommendations, pain remains poorly assessed and managed in many Neonatal Intensive Care Units. Due to there being no general protocol, there is significant variability as regards the guidelines for the approach and treatment of pain between the different Neonatal Intensive Care Units. The objective of this article is to review and assess the general principles of pain in the initial stages of development, its recognition through the use of standardised scales. It also includes its prevention and management with the combination of pharmacological and non-pharmacological measures, as well as to establish recommendations that help alleviate pain in daily clinical practice by optimising pain and stress control in the Neonatal Intensive Care Units.

miRNomic Signature in Very Low Birth-Weight Neonates Discriminates Late-Onset Gram-Positive Sepsis from Controls.

BACKGROUND AND OBJECTIVES: Neonatal sepsis is a serious condition with a high rate of mortality and morbidity. Currently, the gold standard for sepsis diagnosis is a positive blood culture, which takes 48-72 h to yield results. We hypothesized that identifying differentially expressed miRNA pattern in neonates with late-onset Gram-positive sepsis would help with an earlier diagnosis and therapy. METHODS: This is a prospective observational study in newborn infants with late-onset Gram positive bacterial sepsis and non-septic controls. Complementary to blood culture, an aliquot of 0.5 mL of blood was used to determine small non-coding RNA expression profiling using the GeneChip miRNA 4.0 Array. RESULTS: A total of 11 very low birth-weight neonates with late-onset Gram-positive sepsis and 16 controls were analyzed. Further, 217 differentially expressed miRNAs were obtained between both groups. Subsequently, a combined analysis was performed with these miRNAs and 4297 differentially expressed genes. We identified 33 miRNAs that regulate our mRNAs, and the most relevant biological processes are associated with the immune system and the inflammatory response. CONCLUSIONS: The miRNA profiling in very low birth-weight neonates distinguishes late-onset Gram-positive sepsis versus control neonates.

Sedoanalgesia en las unidades neonatales / Sedoanalgesia in neonatal units

El reconocimiento del dolor y su tratamiento en las unidades de cuidados intensivos neonatales continúa siendo un desafío para los profesionales sanitarios responsables de la atención de estos niños. Las exposiciones dolorosas repetidas a las que se someten muchos de estos pacientes de manera rutinaria han demostrado presentar efectos deletéreos a corto y largo plazo. Los recién nacidos prematuros, especialmente vulnerables, suponen una población de alto riesgo. Pese a las recomendaciones internacionales, el dolor sigue siendo evaluado actualmente en muchas ocasiones de manera inconsistente, sin protocolización, siendo patente, además, entre las diferentes unidades de cuidados intensivos neonatales una variabilidad importante en cuanto a las pautas para el abordaje y tratamiento del mismo.El objetivo de este artículo es revisar y valorar los principios generales del dolor en las etapas iniciales del desarrollo, su reconocimiento mediante el uso de escalas protocolizadas, y su prevención y manejo, con la combinación de medidas farmacológicas y no farmacológicas; con el fin de establecer recomendaciones que ayuden a aliviar el dolor en la práctica clínica diaria optimizando el control del dolor y el estrés en las unidades de cuidados intensivos neonatales. (AU)

Pain recognition and management continues to be a challenge for health professionals in Neonatal Intensive Care Units. They are routinely exposed to repeated painful experiences with demonstrated short- and long-term consequences. Preterm babies are a vulnerable high-risk population. Despite international recommendations, pain remains poorly assessed and managed in many Neonatal Intensive Care Units. Due to there being no general protocol, there is significant variability as regards the guidelines for the approach and treatment of pain between the different Neonatal Intensive Care Units.The objective of this article is to review and assess the general principles of pain in the initial stages of development, its recognition through the use of standardised scales. It also includes its prevention and management with the combination of pharmacological and non-pharmacological measures, as well as to establish recommendations that help alleviate pain in daily clinical practice by optimising pain and stress control in the Neonatal Intensive Care Units. (AU)