The effects of cerebral oximetry in mechanically ventilated newborns: a protocol for the SafeBoosC-IIIv randomised clinical trial.

BACKGROUND: The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants' lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. METHODS/DESIGN: SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery. A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children's Abilities-Revised (PARCA-R) at 2 years of corrected age. DISCUSSION: There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. TRIAL REGISTRATION: The protocol is registered at www. CLINICALTRIALS: gov (NCT05907317; registered 18 June 2023).

Surveillance of Viral Respiratory Infections in the Neonatal Intensive Care Unit-Evolution in the Last 5 Years.

Viral respiratory infections (VRIs) in very low birthweight infants can be associated with high rates of morbidity. The COVID-19 pandemic has exerted a strong impact on viral circulation. The purpose of this study is to report on VRIs during NICU admission in infants below 32 weeks' gestation and compare data collected between the pre-and post-COVID-19 pandemic periods. A prospective surveillance study was conducted at a tertiary NICU between April 2016 and June 2022. The COVID-19 post-pandemic period was established as being from March 2020 onwards. Respiratory virus detection was performed by real-time multiplex PCR assays in nasopharyngeal aspirates (NPAs). A total of 366 infants were enrolled. There were no statistical differences between periods regarding infants' birth weight, gestational age, gender distribution, or rates of bronchopulmonary dysplasia. Among the 1589 NPA collected during the pre-COVID-19 period, 8.9% were positive, and among the 1147 NPA collected during the post-pandemic period, only 3% were positive (p < 0.005). The type of viruses detected did not differ according to the study period (pre-COVID19 vs. post-COVID-19): rhinovirus (49.5% vs. 37.5%), adenovirus (22.6% vs. 25%), and human coronavirus (12.9% vs. 16.7%). SARS-CoV-2 was only detected in one patient. In conclusion, the viral profile causing VRI during the pre-COVID-19 and post-COVID-19 era was similar. However, the total number of VRI dropped significantly, most probably due to the global increase in infection prevention measures.

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Near-infrared spectroscopy for perioperative assessment and neonatal interventions.

Perioperative applications of near-infrared spectroscopy (NIRS) to monitor regional tissue oxygenation and perfusion in cardiac and noncardiac surgery are of increasing interest in neonatal care. Complex neonatal surgery can impair adequate oxygen delivery and tissue oxygen consumption and increase the risk of neurodevelopmental delay. Coupled with conventional techniques, NIRS monitoring may enable targeted hemodynamic management of the circulation in both cardiac and noncardiac surgical procedures. In this narrative review, we discuss the application of perioperative NIRS in specific neonatal interventions, including surgical intervention for congenital heart defects, definitive closure of the patent ductus arteriosus, neurological and gastrointestinal disorders, and use of extracorporeal membrane oxygenation. We identified areas for future research within disease-specific indications and offer a roadmap to aid in developing evidence-based targeted diagnostic and management strategies in neonates. IMPACT: There is growing recognition that perioperative NIRS monitoring, used in conjunction with conventional monitoring, may provide critical hemodynamic information that either complements clinical impressions or delivers novel physiologic insight into the neonatal circulatory and perfusion pathways.

Scaling Up the Family Integrated Care Model in a Level IIIC Neonatal Intensive Care Unit: A Systematic Approach to the Methods and Effort Taken for Implementation.

Background: Family Integrated Care (FICare) integrates parents in the direct care of their child while the healthcare personnel act as teachers and guides. To this date, most reports on the feasibility of this model refer to stable preterm infants admitted to Neonatal Intensive Care Units (NICUs). Objectives: To scale up and adapt FICare to make it suitable in level IIIC NICUs, which care for extreme prematurity and other complex medical or surgical neonatal conditions. Materials and Methods: Step 1 was the creation of the FICare implementation team (FICare-IT) and baseline analysis of current procedures for critical care to identify needs, wishes, and requirements; we aimed for protocol elaboration tailored to our cultural, architectural, and clinical context (March 2017 to April 2018). Step 2 as a dissemination strategy by FICare-IT acting as primary trainers and mentors to ensure the education of 90% of nursing staff (May 2018 to July 2018). Step 3 involved piloting and evaluation with the aim to refine the procedure (July 2018 to December 2020). Results: A rigorous but flexible protocol was edited. The FICare educational manual included two curricula: for healthcare professionals/staff (Training the trainers) and for families (Education of caregivers), the latter being categorized in two intervention levels (basic and advanced), depending on the infant care needs and parent's decision. In total, 76 families and 91 infants (74.7% preterm; 18.7% complex surgery; 6.6% others) were enrolled in the pilot. No differences in acceptance rate (overall 86.4%) or in the number of infant-family dyads in the program per month were observed when considering the pre- and post-Covid-19 pandemic periods. All families, except for one who dropped out of the program, completed the agreed individualized training. Mothers spent more time in NICU than fathers (p < 0.05); uninterrupted time spent by mothers in NICU was longer during the pre-pandemic period (p < 0.01). Observed time to reach proficiency by task was within the expected time in 70% of the program contents. The parents revealed educational manuals, workshops, and cot-side teaching sessions as essential for their training, and 100% said they would accept entry into the FICare program again. Conclusions: The principles of the FICare model are suitable for all levels of care in NICUs. Leadership and continuous evaluation/refinement of implementation procedures are essential components to achieve the objectives.

Viral respiratory infections in very low birthweight infants at neonatal intensive care unit: prospective observational study.

BACKGROUND AND OBJECTIVE: Very low birthweight (VLBW) infants are highly susceptible to respiratory infections. Information about prevalence of viral respiratory infections (VRIs) in neonatal intensive care unit (NICU) is scarce. Recent evidence suggests short-term and long-term impact of VRI in morbidity of VLBW infants. The goal of this study is to conduct a VRI surveillance in VLBW infants during NICU admission to address the prevalence, type of viruses and associated clinical features. METHODS: Prospective observational cohort study on infants below 32 gestational weeks admitted to a tertiary NICU during a 2-year period. Respiratory virus detection (influenza, parainfluenza, rhinovirus (hRV), enterovirus, respiratory syncytial virus, metapneumovirus, coronavirus, bocavirus and adenovirus) was performed by real time multiplex PCR assays in nasopharyngeal aspirates (NPAs), within the first 72 hours after birth and weekly, until discharge. Additional samples were taken if clinically indicated. RESULTS: 147 out of 224 eligible infants were enrolled. At least one positive NPA was found in 38% of the study cohort. Main viruses identified were hRV (58%) and adenovirus (31%). Among the 56 infants with positive NPA, 26 showed non-specific respiratory features in 58% (increased respiratory workload, tachypnoea, apnoea) or typical cold features in 38% (rhinorrhea, cough, fever), at least in one episode. Antibiotics were prescribed in 29% of cases. Positive infants showed higher rates of bronchopulmonary dysplasia (BPD), need for supplemental oxygen and mechanical ventilation, and had longer hospital stay. Cox regression analysis found BPD as an independent risk factor for viral infection (p<0.001) and symptomatic VRI (p<0.04). CONCLUSIONS: Systematic surveillance in VLBW infants reports VRI is frequent, particularly by hRV. Asymptomatic infection is highly prevalent which is critical in the face of establishing appropriate preventive strategies. Infants with BPD are especially vulnerable to such infections.

Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery.

BACKGROUND: Inodilators are routinely used in cardiovascular surgery with cardiopulmonary bypass (CPB). Information regarding safety and tolerability of the novel molecule, levosimendan (LEVO), in newborns is anecdotal; no pharmacokinetic data in this population are available. METHODS: This was a phase I, randomized, and blinded study. Neonates undergoing surgical repair for congenital heart defects received stepwise dose increases of milrinone (MR; 0.5-1 µg/kg/min, n = 9) or LEVO (0.1-0.2 µg/kg/min, n = 11) as an i.v. continuous infusion, starting before CPB. Infants had continuous, time-locked, physiological, and near-infrared spectroscopy (NIRS) (cerebral and peripheral) recordings during the first 24 h, and at 48 and 96 h postsurgery. Serial biochemistry and pharmacokinetic studies were performed. RESULTS: During the first 24 h postsurgery, patients showed time-related, group-independent increased cerebral tissue oxygenation and decreased diastolic blood pressure; in addition, group-dependent differences in heart rate and peripheral perfusion were found. Early postsurgery, MR-treated infants showed lower pH, higher glycemia, and higher inotrope score. The groups differed in cerebral NIRS-derived variables from 24 to 96 h. Study drug withdrawal at 96 h was more frequent with LEVO. LEVO intermediate metabolites were detected in plasma at day 14 after surgery. CONCLUSION: LEVO is well tolerated in critically ill neonates. LEVO may have advantages over MR in terms of the dosing regimen.

Segundo Consenso Clínico de la Sociedad Iberoamericana de Neonatología: manejo hemodinámico del recién nacido / Second Clinical Consensus of the Ibero-American Society of Neonatology: hemodynamic management of newborns

Este trabajo informa acerca del proceso y los resultados del Segundo Consenso Clínico de la SIBEN (Sociedad Iberoamericana de Neonatología), en el cual 80 neonatólogos de 23 países fueron invitados a participar y colaborar. Se desarrollaron varias preguntas de importancia clínico-fisiológica sobre el manejo hemodinámico del recién nacido. Los participantes fueron distribuidos en grupos, facilitando así la interacción y el trabajo conjunto, con la consigna de responder de tres a cinco preguntas mediante el análisis de bibliografía y factores locales. El Grupo de Consenso se reunió en Mar del Plata, Argentina, donde se llevaron a cabo diversas ponencias, debates y presentaciones. En total participaron 54 neonatólogos de 21 países, con el objetivo de desarrollar un consenso sobre aspectos que incluyeron conceptos y definiciones de inestabilidad hemodinámica, la fisiopatología del cuadro de compromiso hemodinámico, las estrategias terapéuticas recomendadas y el monitoreo hemodinámico. Se espera que esta experiencia internacional sirva como una iniciativa útil tanto para la búsqueda de futuros consensos como para reducir las disparidades existentes entre los tratamientos y resultados de los diferentes países de la Región.

This study reports on the process and results of the Second Clinical Consensus of the Ibero-American Society of Neonatology. Eighty neonatologists from 23 countries were invited to collaborate and participate in the event. Several questions of clinical-physiological importance in the hemodynamic management of newborns were addressed. Participants were divided into groups to facilitate interaction and teamwork, with instructions to respond to three to five questions by analyzing the literature and local factors. Meeting in Mar del Plata, Argentina, the Consensus Group served as a form for various presentations and discussions. In all, 54 neonatologists from 21 countries attended, with the objective of reaching a consensus on such matters as concepts and definitions of hemodynamic instability, the physiopathology of hemodynamic compromise, recommended therapy strategies, and hemodynamic monitoring. It is hoped that this international experience will serve as a useful initiative for future consensus building and reduction of the existing disparities among the countries of the Region in terms of treatment and outcomes.

Dopamine versus epinephrine for cardiovascular support in low birth weight infants: analysis of systemic effects and neonatal clinical outcomes.

BACKGROUND: Early postnatal adaptation to transitional circulation in low birth weight infants frequently is associated with low blood pressure and decreased blood flow to organs. Catecholamines have been used widely as treatment, despite remarkably little empirical evidence on the effects of vasopressor/inotropic support on circulation and on clinically important outcomes in sick newborn infants. AIMS: To explore the effectiveness of low/moderate-dose dopamine and epinephrine in the treatment of early systemic hypotension in low birth weight infants, evaluate the frequency of adverse drug effects, and examine neonatal clinical outcomes of patients in relation to treatment. DESIGN/METHODS: Newborns of <1501-g birth weight or <32 weeks of gestational age, with a mean blood pressure lower than gestational age in the first 24 hours of life, were assigned randomly to receive dopamine (2.5, 5, 7.5, and 10 microg/kg per minute; n = 28) or epinephrine (0.125, 0.250, 0.375, and 0.5 microg/kg per minute; n = 32) at doses that were increased stepwise every 20 minutes until optimal mean blood pressure was attained and maintained (responders). If this treatment was unsuccessful (nonresponders), sequential rescue therapy was started, consisting first of the addition of the second study drug and then hydrocortisone. OUTCOME MEASURES: These included: (1) short-term changes (first 96 hours, only responders) in heart rate, mean blood pressure, acid-base status, lactate, glycemia, urine output, and fluid-carbohydrate debit; and (2) medium-term morbidity, enteral nutrition tolerance, gastrointestinal complications, severity of lung disease, patent ductus arteriosus, cerebral ultrasound diagnoses, retinopathy of prematurity, and mortality. RESULTS: Patients enrolled in this trial did not differ in birth weight or gestational age (1008 +/- 286 g and 28.3 +/- 2.3 weeks in the dopamine group; 944 +/- 281 g and 27.7 +/- 2.4 weeks in the epinephrine group). Other main antenatal variables were also comparable. However, responders and nonresponders differed significantly with respect to the need for cardiorespiratory resuscitation at birth (3% vs 23%), Critical Risk Index for Babies score (3.8 +/- 3 vs 7 +/- 5), and premature rupture of membranes >24 hours (39.5% vs 13.6%), respectively. No differences were found in the rate of treatment failure (dopamine: 36%; epinephrine: 37%) or need for rescue therapy according to treatment allocation. Groups did not differ in age at initiation of therapy (dopamine: 5.3 +/- 3.9 hours; epinephrine: 5.2 +/- 3.3 hours), but withdrawal was significantly later in the dopamine group. For short-term changes, mean blood pressure showed a significant increase from baseline throughout the first 96 hours with no differences between groups. However, epinephrine produced a greater increase in heart rate than dopamine. After treatment began, epinephrine patients showed higher plasma lactate (first 36 hours) and lower bicarbonate and base excess (first 6 hours) and received more bicarbonate. Patients in the epinephrine group also had higher glycemia (first 24 hours) and needed insulin therapy more often. Groups did not differ in urine output or fluid-carbohydrate supply during the first 96 hours. For medium-term morbidity, there were no differences in neonatal clinical outcomes in responders. However, significant differences were found in the incidence of patent ductus arteriosus, bronchopulmonary dysplasia, need for high-frequency ventilation, occurrence of necrotizing enterocolitis, and death between responders and nonresponders. CONCLUSIONS: Low/moderate-dose epinephrine is as effective as low/moderate-dose dopamine for the treatment of hypotension in low birth weight infants, although it is associated with more transitory adverse effects.