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Miniaturized magnetic-based pipette tip microextraction is presented as a sample preparation approach for microsamples of serum and urine from newborns.

A graphene oxide/nickel/platinum nanoparticle micromotor (MM)-based fluorescent aptassay is proposed to determine interleukin-6 (IL-6) in serum samples from low-birth-weight infants (gestational age of less than 32 weeks and birthweight below 1000 g) with sepsis suspicion. In this kind of patients, IL-6 has demonstrated good sensitivity and specificity for the diagnosis of sepsis, both for early and late onset sepsis. The approach was based on the adsorption of the aptamer for IL-6 tagged with 6-FAM as a fluorescent label (Apt

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, 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.). 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

The relationship between right ventricular (RV) function and cerebral blood flow (CBF) velocity and cerebral oxygenation was assessed in neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). Echocardiographic, transcranial Doppler, and hemodynamic data from 37 neonates with moderate-severe HIE + TH were reviewed. Twenty healthy newborns served as controls. Cardiac dysfunction in HIE + TH was characterized by a predominant RV dysfunction, with concomitantly reduced CBF velocity. A significant correlation was found between CBF velocity and tricuspid annular plane systolic excursion (TAPSE), RV output (RVO), and stroke volume (SVRV), as well as with left ventricular output and stroke volume. Brain oxygenation (rSO2) correlated significantly with RVO, SVRV, TAPSE, ejection fraction, and fractional shortening, whereas cerebral fractional tissue oxygen extraction (FTOEc) correlated with RVO, SVRV, RV myocardial performance index, and superior vena cava flow. CBF velocity and cerebral NIRS correlations were stronger with parameters of right ventricular performance. Conclusion: CBF velocity and brain oxygenation correlate predominantly with RV function in HIE + TH. This suggests a preferential contribution of RV performance to cerebral hemodynamics in this context.

Resumen: Introducción: Apenas conocemos cómo es la asistencia de los recién nacidos (RN) con encefalopatía hipóxico-isquémica (EHI) en hipotermia terapéutica (HT), especialmente si existen protocolos asistenciales, la neuromonitorización que se realiza o cómo es la aproximación al pronóstico neurológico. Este conocimiento permite detectar e implementar áreas de mejora asistencial. Método: Estudio transversal de los 57 hospitales españoles que realizaban HT en 2015, mediante cuestionario sobre: 1) la disponibilidad de protocolos y de recursos tecnológicos; 2) el uso de herramientas de neuromonitorización; 3) los conocimientos de los profesionales; 4) la información pronóstica que se da los padres, y 5) el informe al alta y del plan de seguimiento. Resultados: El 95% utiliza enfriamiento corporal-total servocontrolado y dispone de protocolos específicos de actuación. El 70% utiliza sedación y el 68% deja al paciente a dieta absoluta. La monitorización con electroencefalografía integrada por amplitud se utiliza en más del 80% de los centros, aunque solo en el 50% la enfermera es capaz de interpretarlo. La saturación de oxígeno cerebral es escasamente monitorizada (16%). Entre los estudios diagnóstico-pronósticos, la neuroimagen es universal, pero los neurobiomarcadores apenas se utilizan (29%). Solo el 21% ofrece información pronóstica antes de las 72 h de vida; sin presencia de la enfermera en el 70%. El seguimiento lo realiza el neuropediatra (84%), con una duración desigual entre centros. Conclusiones: La asistencia del RN con EHI en España es adecuada, con áreas de mejora en: neuromonitorización, sedación, marco temporal de la información pronóstica, trabajo en equipo y estandarización de la duración del seguimiento. Abstract: Introduction: There is not much information about the care of infants with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) in Spain. This includes whether protocols are routinely used, the type of neuro-monitoring performed, and how information on the neurological prognosis is presented to families. The answers to these would allow to detect and implement areas of improvement. Method: A cross-sectional analysis was performed on the responses to structured questionnaires sent to all the Spanish neonatal units that were performing TH in June 2015. Questions were divided into 5 sections: 1) the availability of protocols and technological resources, 2) the use of neuro-monitoring tools, 3) the knowledge and training of the professionals; 4) the prognostic information given to the parents; and 5) the discharge report and the follow-up plan. Results: Most centres (95%) use servo controlled whole-body cooling methods and have specific management protocols. Sedation is used in 70% of centres, and in 68% of them the onset of enteral feeding is delayed until the end of the cooling period. Amplitude-integrated electroencephalography monitoring is used in more than 80% of the centres, although only in 50% are nurses able to interpret it. Cerebral oxygen saturation is not often monitored (16%). As regards diagnostic-prognostic studies, neuroimaging is universal, but brain damage biomarkers are hardly used (29%). Prognostic information is offered within the first 72 posnatal hours in 21% of the centres, and is given without the presence of the nurse in 70% of the centres. Follow-up is performed by a neuro-paediatrician (84%), with an uneven duration between centres. Conclusions: The care of infants with HIE treated with TH in Spain is generally adequate, although there are areas for improvement in neuromonitoring, sedation, prognostic information, teamwork, and duration of follow-up.

A new fluorescence micromotor-based immunoassay (FMIm) has been developed for procalcitonin (PCT) determination as an early sepsis diagnostic analytical tool. The micromotors combine the high binding capacity of the specific antibodies onto their polymeric polypyrrole outer layer (PPy layer), with their magnetic guidance (Ni layer) and self-propulsion by catalytic generation of oxygen bubbles (PtNP inner layer) to actively recognize the PCT antigen. This FMIm allowed a sensitive (LOD = 0.07 ng mL-1) and direct PCT determination in clinical samples from very low-birth-weight infants (VLBWI) with sepsis suspicion, using small volumes of sample (25 μL) in a clinically relevant range of concentrations (0.5-150 ng mL-1). The good agreement between PCT levels obtained by our micromotor-based method and routine immunofluorescence hospital determination demonstrates the feasibility for the analysis in VLBWI samples and its potential as a point-of-care diagnostic tool for sepsis.

The use of dexmedetomidine (DEX) has been extended in preterm newborns, but the effects on cerebral activity and their relationship with haemodynamic changes has not been studied.We retrospectively studied the effects of DEX administered to 10 preterm newborns, assessing amplitude-integrated EEG (aEEG) parameters, brain regional SO2(brSO2), heart rate, non-invasive mean blood pressure (MBP), transcutaneous oxygen saturation (SpO2), venous pCO2 and haemoglobin (Hb) values, in two 6-hour periods: one starting 6 hours before the beginning of DEX perfusion and the other 6 hours afterwards.DEX infusion led to brSO2decrease not associated to heart rate, MBP, SpO2, Hb or pCO2 variation, which suggests that brSO2decrease could be related to local vasoconstriction. DEX infusion led to prolongation of interburst interval and reduction of cycling. Such effects, not been described so far, should be considered in the assessment of aEEG traces after DEX administration to avoid misinterpretations regarding patient’s prognosis. More studies are needed to assess the safety of DEX use in the newborn.

Background Although electrocardiogram (ECG) can detect heart rate (HR) faster compared to pulse oximetry, it remains unknown if routine use of ECG for delivery room (DR) resuscitation reduces the time to stabilization in preterm infants. Methods Neonates 100 b.p.m., time to stabilization, or use of resuscitation interventions such as PPV for preterm infants

Objective Hypothermia, the gold standard after a hypoxic-ischemic insult, is not beneficial in all treated newborns. Cannabidiol is neuroprotective in animal models of newborn hypoxic-ischemic encephalopathy. This study compared the relative efficacies of cannabidiol and hypothermia in newborn hypoxic-ischemic piglets and assessed whether addition of cannabidiol augments hypothermic neuroprotection. Methods One day-old HI (carotid clamp and FiO2 10% for 20 min) piglets were randomized to vehicle or cannabidiol 1 mg/kg i.v. u.i.d. for three doses after being submitted to normothermia or 48 h-long hypothermia with a subsequent rewarming period of 6 h. Non-manipulated piglets (naive) served as controls. Hemodynamic or respiratory parameters as well as brain activity (aEEG amplitude) were monitored throughout the experiment. Following termination, brains were obtained for histological (TUNEL staining, apoptosis; immunohistochemistry for Iba-1, microglia), biochemical (protein carbonylation, oxidative stress; and TNFα concentration, neuroinflammation) or proton magnetic resonance spectroscopy (Lac/NAA: metabolic derangement; Glu/NAA: excitotoxicity). Results HI led to sustained depressed brain activity and increased microglial activation, which was significantly improved by cannabidiol alone or with hypothermia but not by hypothermia alone. Hypoxic-ischemic-induced increases in Lac/NAA, Glu/NAA, TNFα or apoptosis were not reversed by either hypothermia or cannabidiol alone, but combination of the therapies did. No treatment modified the effects of HI on oxidative stress or astroglial activation. Cannabidiol treatment was well tolerated. Conclusions cannabidiol administration after hypoxia-ischemia in piglets offers some neuroprotective effects but the combination of cannabidiol and hypothermia shows some additive effect leading to more complete neuroprotection than cannabidiol or hypothermia alone.

Background: Extrauterine growth restriction is common in the preterm infant, and it is associated with poor neurodevelopment. Nutrition plays an important role in postnatal growth, but growth is also influenced by other factors like co-morbidity, and, also, there might be sex differences. Methods: This is a cohort study including preterm infants < 32 weeks at birth (n = 21,825) from the Spanish Neonatal Network database. The effect of sex and morbidity (patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing enterocolitis and late-onset sepsis) on weight gain as well as linear and head growth from birth to discharge/death was assessed with linear regression models adjusted by gestational age and Z-scores at birth. Results: The 4 selected morbidities had an independent effect on all 6 growth parameters studied, which was greater in the case of necrotizing enterocolitis: changes in weight, length and head Z-scores were –0.60 (95% CI: –0.66 to –0.55), –0.62 (95% CI: –0.70 to –0.54) and –0.63 (95% CI: –0.71 to –0.56), respectively. Weight gain and linear growth were overall more affected than head growth. Girls lost slightly more weight Z-scores (–0.03; 95% CI: –0.06 to –0.002) than boys after adjustment by morbidity. There were no significant gender differences regarding linear and head growth velocity (cm/week), although girls lost more head Z-scores (–0.14; 95% CI: –0.18 to –0.10). Conclusions: Main co-morbidities associated with prematurity have an impact on postnatal growth. Head growth is less affected than length and weight. Girls are at slightly higher risk of postnatal weight and head restriction after adjustment by morbidity.

Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in infants and presents as a consequence of preterm birth. Due to the lack of effective preventive and treatment strategies, BPD currently represents a major therapeutic challenge that requires continued research efforts at the basic, translational, and clinical levels. However, not all very low birth weight premature babies develop BPD, which suggests that in addition to known gestational age and intrauterine and extrauterine risk factors, other unknown factors must be involved in this disease's development. One of the main goals in BPD research is the early prediction of very low birth weight infants who are at risk of developing BPD in order to initiate the adequate preventive strategies. Other benefits of determining the risk of BPD include providing prognostic information and stratifying infants for clinical trial enrollment. In this article, we describe new opportunities to address BPD's complex pathophysiology by identifying prognostic biomarkers and develop novel, complex in vitro human lung models in order to develop effective therapies. These therapies for protecting the immature lung from injury can be developed by taking advantage of recent scientific progress in -omics, 3D organoids, and regenerative medicine.

Background Bronchopulmonary dysplasia (BPD) is the most prevalent sequelae of premature birth, for which therapeutic options are currently limited. Mesenchymal stromal cells (MSCs) are a potential therapy for prevention or reversal of BPD. Series of cases We report on two infants with severe BPD in whom off-label treatment with repeated intravenous doses of allogeneic bone marrow–derived MSCs were administered. We analyzed the temporal profile of serum and tracheal cytokines and growth factors as well as safety, tolerability and clinical response. The administration of repeated intravenous doses of MSCs in two human babies with severe and advanced BPD was feasible and safe and was associated with a decrease of pro-inflammatory molecules and lung injury biomarkers. Both patients were at very advanced stages of BPD with very severe lung fibrosis and did not survive the disease. Conclusions MSCs are a promising therapy for BPD, but they should be administered in early stages of the disease.

Congenital cutaneous candidiasis is an infrequent invasive fungal infection that usually appears in the first days of life. Extremely low birth weight infants are the most frequently affected. Classic presentation includes diffuse extensive erythematous rash with papules, plaques, pustules and vesicles, which later undergoes desquamation. Systemic dissemination is common in extremely low birth weight infants. Blood, urine and cerebrospinal fluid evaluation should be included in the initial assessment. Early and prolonged treatment has been associated with decreased mortality. We report the case of congenital cutaneous candidiasis in a preterm infant. Early skin lesion recognition allowed establishing adequate treatment in the first hours of life.

A new fluorescence micromotor-based immunoassay (FMIm) has been developed for procalcitonin (PCT) determination as an early sepsis diagnostic analytical tool. The micromotors combine the high binding capacity of the specific antibodies onto their polymeric polypyrrole outer layer (PPy layer), with their magnetic guidance (Ni layer) and self-propulsion by catalytic generation of oxygen bubbles (PtNP inner layer) to actively recognize the PCT antigen. This FMIm allowed a sensitive (LOD = 0.07 ng mL

Postnatal steroids, often used to prevent and treat bronchopulmonary dysplasia, may influence the growth of preterm infants, although data are scarce in the literature. This is a multicenter cohort study including surviving preterm infants &lt, 32 weeks at birth (n = 17,621) from the Spanish Neonatal Network SEN1500 database, without major congenital malformations. Linear regression models were adjusted for postnatal steroids, respiratory severity course (invasive mechanical ventilation at 28 days), progression to moderate&ndash, severe bronchopulmonary dysplasia (O2 at 36 weeks), length of stay, sex, gestational age and z-scores at birth. A subgroup analysis depending on the timing of administration, ventilation status at 28 days and moderate&ndash, severe BPD diagnosis was also performed. Overall, systemic postnatal steroids were not independently associated with poorer weight gain (0.1, 95% CI: &minus, 0.05 to 0.2 g/kg/day), linear growth (0, 0.03 to 0.01 cm/week) or head circumference growth (&minus, 0.01, 0.02 to 0 cm/week). Patients who received steroids after 28 days or who were not O2 dependent at 36 weeks after having received steroids gained more weight (0.22, 95% CI: 0.04 to 0.4 and 0.2, 95% CI: 0.004 to 0.5 g/kg/day, respectively). Globally, systemic postnatal steroids had no significant adjusted effect on postnatal growth.

ObjectivesCurrent neonatal resuscitation guidelines suggest the use of ECG in the delivery room (DR) to assess heart rate (HR). However, reliability of ECG compared with pulse oximetry (PO) in a situation of bradycardia has not been specifically investigated. The objective of the present study was to compare HR monitoring using ECG or PO in a situation of bradycardia (HR Study designVideo recordings of resuscitations of infants ResultsA total of 29 episodes of bradycardia registered by the ECG in 39 video recordings were included in the analysis (n=29). PO did not detect the start of these events in 20 cases (69%). PO detected the start and the end of bradycardia later than the ECG (median (IQR): 5 s (0–10) and 5 s (0–7.5), respectively). A decline in PO accuracy was observed as bradycardia progressed so that by the end of the episode PO offered significantly lower HR readings than ECG.ConclusionsPO detects the start and recovery of bradycardia events slower and less accurately than ECG during stabilisation at birth of very preterm infants. ECG use in this scenario may contribute to an earlier initiation of resuscitation manoeuvres and to avoid unnecessary prolongation of resuscitation efforts after recovery.

Parainfluenza 3 virus is a frequent cause of respiratory infections in the pediatric population although it is uncommonly diagnosed in neonates, being usually reported as neonatal intensive care unit microepidemics. We report a case of parainfluenza 3 respiratory infection associated with pericardial effusion in a very low birthweight infant.

Early diagnosis of sepsis, combining blood cultures and inflammation biomarkers, continues to be a challenge, especially in very low birth weight (VLBW) infants because of limited availability of blood samples. Traditional diagnostic procedures are cumbersome, not fast enough, and require relatively large volumes of sample. Empiric use of antibiotics, before diagnostic confirmation, is required to decrease mortality, leading to potential antibiotic resistance and side effects in VLBW infants. To solve such a serious problem, a dual magnetoimmunosensor is proposed for simultaneous assessment of two of the most important sepsis biomarkers: procalcitonin (PCT for early phase) and C-reactive protein (CRP for late phase). This "sample-to-result" approach exhibited excellent sensitivity, selectivity, precision, and stability using low sample volumes (

Aim: We describe the postnatal weight gain, linear and head growth trends of surviving preterm infants from 2005 to 2017. Methods: Multicentre cohort study, including surviving preterm infants

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in childhood, related to prematurity, and the most common cause of pulmonary hypertension (PH) secondary to pulmonary disease in children. Moderate and severe BPD have a worse outcome and relate more frequently with PH. The prediction of moderate or severe BPD development in extremely premature newborns is vital to implement preventive strategies. Starting with the hypothesis that molecular biomarkers were better than clinical and echocardiographic factors, this study aims to explore the ability of clinical, echocardiographic and analytical variables to predict moderate or severe BPD in a cohort of extremely preterm infants. PATIENTS AND METHODS: We designed a prospective longitudinal study, in which we followed a cohort of preterm newborns (gestational age

Background: Heart rate (HR) assessment is essential during neonatal resuscitation, and it is usually done by auscultation or pulse oximetry (PO). The aim of the present study was to determine whether HR assessment with ECG is as fast and reliable as PO during preterm resuscitation. Material and methods: Thirty-nine preterm (

Resumen: Introducción: La medición de frecuencia cardíaca (FC) es esencial durante la reanimación neonatal y se realiza habitualmente mediante auscultación o pulsioximetría (PO). El objetivo de este estudio es analizar si durante la reanimación del recién nacido prematuro la medición de la FC mediante ECG es tan precoz y fiable como la PO. Material y métodos: Se realizó video-grabación de la reanimación de 39 recién nacidos prematuros (

AimTo investigate the frequency and characteristics of adverse drug reactions (ADRs) in hospitalised neonates to obtain a better understanding of and improvement in neonatal healthcare.MethodologyA prospective cohort study. Data were collected on 313 neonates and 2166 drug prescriptions. Clinical characteristics of patients, drugs administered and ADRs were prospectively recorded and analysed. Informed consent was obtained in all cases.Results116 different ADRs were detected. 17% of the neonates experienced at least one of these ADRs. Systemic antimicrobials and caffeine citrate were the drugs that most commonly caused ADRs. According to the ADR Severity Assessment Scale, 41% were mild, 42% were moderate and 17% were severe. Of the ADRs identified, 11% were classified as ‘certain’ by the Naranjo method and 20% were classified as ‘defined’ by the Karch and Lasagna modified algorithm. Most of the ADRs detected were related to feed intolerance, phlebitis and tachycardia. Most were acute (73%) and lasted between 1 and 7 days (39%). After the occurrence of an ADR, it was necessary to initiate specific treatment in 44 cases, discontinue the drugs involved in 30 cases, and reduce the drug dose in another 30 cases. An association was shown between the number of drugs prescribed and ADR onset.ConclusionsThere is a high incidence of ADRs in hospitalised newborns, which increases with the number of prescriptions.

Based on the exceptional and new opened biosensing possibilities of self-propelled micromotors, a micromotor-based immunoassay (MIm) has smartly been designed for C-reactive protein (CRP) determination in plasma of preterm infants with sepsis suspicion. The design of the micromotors involved the electrosynthesis of a carbon-based outer layer (for antibody functionalization), an intermediate Ni layer (for magnetic guidance and stopped flow operations) and PtNPs inner catalytic layer (for catalytic bubble propulsion). Micromotors biofunctionalization on the outer layer (using carbon black (CB), reduced graphene oxide (rGO) and multi-walled carbon nanotubes (MWCNTs), and biocompatible propulsion capabilities, were carefully studied. Magnetic rGO/Ni/PtNPs micromotors exhibited the most efficient and reproducible (CV = 9%) anti-CRP functionalization, controlled stopped-flow operations as well as efficient bubble propulsion (1% H2O2, 1,5% NaCh, speed 140 μm s-1). Analytical performance of MIm was excellent, allowing the direct (without dilution), sensitive (LOD = 0.80 μg/mL), and accurate CRP determination (Er = 1%) in hardly available preterm babies’ plasma samples with suspected sepsis using very low volumes ( Overall, the results obtained allowed the fast and reliable sepsis diagnostics in preterm babies’ individuals with suspected sepsis, not only proving the usefulness of the approach as its potential utilization as point-of-care device for clinical analysis but drawing new horizons in extremely low sample volumes-based diagnostics.

Background Complications of intravenous lipid administration are relatively uncommon. However, inadvertent rapid infusion of intravenous fat emulsion (IVFE) is an inherent risk when fats are infused separately from the dextrose-amino acid solution. Case report Extremely preterm infant, born at 25 weeks and 6 days of gestational age weighing 920 g, who inadvertently received a massive overdose of IVFE due to a device failure. He developed lethargy, apnea, metabolic acidosis and hemodynamic instability requiring mechanical ventilation and inotropic support. Despite discontinuation of IVFE and supportive care, clinical course and metabolic acidosis worsened, so a double-volume exchange transfusion was performed. The procedure was well tolerated, without complications. Serum triglyceride concentration as well as other laboratory data normalized immediately after the exchange transfusion. The patient was extubated to continuous positive airway pressure and inotropic support was discontinued 24 hours after the procedure. He was discharged home at 40 weeks of corrected age with normal magnetic resonance imaging and neurological examination. Conclusion In cases of profound, symptomatic hypertriglyceridemia due to lipid overdose, double-volume exchange transfusion should be considered, even in extremely preterm infants.

We aimed to investigate whether neonatal hypoxic–ischemic (HI) brain injury induces inflammatory lung damage. Thus, hypoxic (HYP, FiO2 10% for 30 min), ischemic (ISC, bilateral carotid flow interruption for 30 min), or HI event was performed in 1–2-d-old piglets. Dynamic compliance (Cdyn), oxygenation index (OI), and extravascular lung water (EVLW) were monitored for 6 h. Then, histologic damage was assessed in brain and lung (lung injury severity score). Total protein content (TPC) was determined in broncoalveolar lavage fluid (BALF), and IL-1β concentration was measured in lung and brain tissues and blood. Piglets without hypoxia or ischemia served as controls (SHM). HI-induced brain damage was associated with decreased Cdyn, increased OI and EVLW, and histologic lung damage (interstitial leukocyte infiltration, congestive hyperemia, and interstitial edema). BALF TPC was increased, suggesting inflammatory damage. In agreement, tissue IL-1β concentration increased in the brain and lung, in correspondence with increased IL-1β serum concentration. Neither HYP nor ISC alone led to brain or lung damage. HI brain damage in newborn piglets led to inflammatory lung damage, suggesting an additional mechanism accounting for the development of lung dysfunction after neonatal HI encephalopathy.

Bronchopulmonary dysplasia (BPD) is one of the most serious chronic lung diseases in infancy and one of the most important sequels of premature birth (prevalence of 15-50%). Our objective was to estimate the cost of BPD of one preterm baby, with no other major prematurity-related complications, during the first 2 years of life in Spain. Data from the Spanish Ministry of Health regarding costs of diagnosis-related group of preterm birth, hospital admissions and visits, palivizumab administration, and oxygen therapy in the year 2013 were analyzed. In 2013, 2628 preterm babies were born with a weight under 1500 g; 50.9% were males. The need for respiratory support was 2.5% needed only oxygen therapy, 39.5% required conventional mechanical ventilation, and 14.9% required high-frequency ventilation. The incidence of BPD was of 34.9%. The cost of the first 2 years of life of a preterm baby with BPD and no other major prematurity-related complications ranged between 45,049.81 € and 118,760.43 €, in Spain, depending on birth weight and gestational age. If the baby required home oxygen therapy or developed pulmonary hypertension, this cost could add up to 181,742.43 €.Prematurity and BPD have an elevated cost, even for public health care systems. This cost will probably increase in the coming years if the incidence and survival of preterm babies keeps rising. The development of new therapies and preventive strategies to decrease the incidence of BPD and other morbidities associated with prematurity should be a priority. What is known: • Bronchopulmonary dysplasia (BPD) is a serious chronic lung disease related with premature birth. • BPD is an increasing disease due to the up-rise in the number of premature births. What is new: • The economic cost of preterm birth and BPD has never before been estimated in Spain nor published with European data. • Preterm babies with BPD and a good clinical outcome carry also an important economic and social burden.

Brain hypoxic–ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario. Newborn piglets received intravenous vehicle, CBD, or CBD+WAY100635 (5-HT1A receptor antagonist) after HI brain damage (carotid flow interruption and FiO2 0.10 for 30 min). Total lung compliance (TLC), oxygenation index (OI), and extravascular lung water content (EVLW) were monitored for 6 h. Histological damage, interleukin (IL)-1β concentration, and oxidative stress were assessed in brain and lung tissue. Total protein content was determined in bronchoalveolar lavage fluid (BALF). CBD prevented HI-induced deleterious effects on TLC and OI and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted the beneficial effects of CBD on histological damage, IL-1 concentration, and EVLW. CBD reduced brain HI-induced distant lung damage, with 5-HT1A receptor involvement in these effects. Whether the effects of CBD on the lungs were due to the anti-inflammatory effects on the brain or due to the direct effects on the lungs remains to be elucidated.

Resumen: Introducción: Numerosas publicaciones destacan la utilidad de la ecocardiografía funcional (EcoFn) en neonatología. No existen datos sobre su uso en unidades españolas. Objetivo: Evaluar la frecuencia de uso, pacientes, indicaciones, mediciones y repercusión sobre el tratamiento de la EcoFn en un año en una unidad de cuidados intensivos neonatales (UCIN) española. Métodos: Estudio descriptivo retrospectivo en pacientes ingresados en UCIN en un año. Variables: edad gestacional, peso, diagnóstico principal, días de vida en el momento del estudio, indicación, parámetros medidos y modificaciones del tratamiento. Resultados: Se realizaron 168 ecografías en 50 pacientes, con una media ± desviación estándar de 3,4 ± 2,83 por paciente. Las indicaciones más frecuentes fueron la valoración del ductus (58,3%) seguida de la inestabilidad hemodinámica (22,2%). El resultado de la ecografía modificó el tratamiento en 62 casos (36,9%). En un 17,4% se inició tratamiento con ibuprofeno y en un 1,2% de los casos se adelantó el fin de este. En un 10,8% de los casos, la ecografía modificó el soporte hemodinámico. Los parámetros principales valorados fueron: valoración de presencia/repercusión del ductus 100%; función miocárdica: fracción de eyección/acortamiento 23,8%, gasto ventrículo del izquierdo 24,4%, gasto del ventrículo derecho 21,4%; flujo sistémico 42,3%; signos de hipertensión pulmonar 7,7%. Conclusiones: La EcoFn es utilizada frecuentemente en UCIN y en muchos casos guía el tratamiento de los pacientes. La valoración del ductus y de la inestabilidad hemodinámica son las indicaciones más frecuentes. Queda por determinar si el uso de la EcoFn modifica la evolución de los pacientes de UCIN. Abstract: Introduction: Several publications highlight the usefulness of functional echocardiography (FnECHO) in neonatal intensive care. Data is lacking on its use in units neonatal in Spain. Objectives: To evaluate frequency of use, patient characteristics, indications, measurements, and impact on patient management of FnECHO in a neonatal intensive care unit (NICU) in Spain over a 1 year period. Methods: A retrospective study conducted in NICU patients during 1 year. Variables: gestational age, birthweight, admission criteria, days of life at examination, indication for FnECHO, parameters assessed, and treatment modifications. Results: 168 echocardiographic studies were performed in 50 patients (mean 3,4. SD 2,83). The most frequent indication was patent ductus (PDA) assessment (58.3%), followed by hemodynamic instability (22.2%). The results of FnECHO modified treatment in 62 cases (36.9%). In 17.4% of them treatment with ibuprofen was initiated, and in 1.2% it was discontinued. In 10.8% of the cases, the results of FnECHO modified hemodynamic support. Echocardiographic evaluation included: assessment of presence/hemodynamic significance of PDA (100%); myocardiac function: ejection fraction/shortening fraction (EF/SF) 23.8%, left ventricular output 24.4%, right ventricular output 21.4%, systemic blood flow 42.3%; and signs of pulmonary hypertension 7.7%. Conclusions: FnECHO is frequently used in the NICU, and in many cases it guides treatment. PDA assessment and hemodynamic instability are the most frequent indications. It still needs to be elucidated if the use of FnECHO modifies patient outcomes.

Introduction: Several publications highlight the usefulness of functional echocardiography (FnECHO) in neonatal intensive care. Data are lacking on its use in neonatal units in Spain. Objectives: To evaluate frequency of use, patient characteristics, indications, measurements, and impact on patient management of FnECHO in a neonatal intensive care unit (NICU) in Spain over a 1-year period. Methods: A retrospective study conducted in NICU patients during 1 year. Variables: gestational age, birthweight, admission criteria, days of life at examination, indication for FnECHO, parameters assessed, and treatment modifications. Results: 168 echocardiographic studies were performed in 50 patients (mean 3.4; SD 2.83). The most frequent indication was patent ductus (PDA) assessment (58.3%), followed by haemodynamic instability (22.2%). The results of FnECHO modified treatment in 62 cases (36.9%). In 17.4% of them treatment with ibuprofen was initiated, and in 1.2% it was discontinued. In 10.8% of the cases, the results of FnECHO modified haemodynamic support. Echocardiographic evaluation included: assessment of presence/haemodynamic significance of PDA (100%); myocardiac function: ejection fraction/shortening fraction (EF/SF) 23.8%, left ventricular output 24.4%, right ventricular output 21.4%, systemic blood flow 42.3%; and signs of pulmonary hypertension 7.7%. Conclusions: FnECHO is frequently used in the NICU, and in many cases it guides treatment. PDA assessment and haemodynamic instability are the most frequent indications. It still needs to be elucidated if the use of FnECHO modifies patient outcomes. Resumen: Introducción: Numerosas publicaciones destacan la utilidad de la ecocardiografía funcional (EcoFn) en neonatología. No existen datos sobre su uso en unidades españolas. Objetivo: Evaluar la frecuencia de uso, pacientes, indicaciones, mediciones y repercusión sobre el tratamiento de la EcoFn en un año en una unidad de cuidados intensivos neonatales (UCIN) española. Métodos: Estudio descriptivo retrospectivo en pacientes ingresados en UCIN en un año. Variables: edad gestacional, peso, diagnóstico principal, días de vida en el momento del estudio, indicación, parámetros medidos y modificaciones del tratamiento. Resultados: Se realizaron 168 ecografías en 50 pacientes, con una media ± desviación estándar de 3,4 ± 2,83 por paciente. Las indicaciones más frecuentes fueron la valoración del ductus (58,3%) seguida de la inestabilidad hemodinámica (22,2%). El resultado de la ecografía modificó el tratamiento en 62 casos (36,9%). En un 17,4% se inició tratamiento con ibuprofeno y en un 1,2% de los casos se adelantó el fin de este. En un 10,8% de los casos, la ecografía modificó el soporte hemodinámico. Los parámetros principales valorados fueron: valoración de presencia/repercusión del ductus 100%; función miocárdica: fracción de eyección/acortamiento 23,8%, gasto ventrículo del izquierdo 24,4%, gasto del ventrículo derecho 21,4%; flujo sistémico 42,3%; signos de hipertensión pulmonar 7,7%. Conclusiones: La EcoFn es utilizada frecuentemente en UCIN y en muchos casos guía el tratamiento de los pacientes. La valoración del ductus y de la inestabilidad hemodinámica son las indicaciones más frecuentes. Queda por determinar si el uso de la EcoFn modifica la evolución de los pacientes de UCIN.

Aims The purpose of this study is to investigate circulating endothelial progenitor cells (EPCs) and the signaling pathways involved in their recruitment in the ischemic retina of the 50/10 rat model of oxygen-induced retinopathy (OIR). Main methods Within 12 h after birth, litters of Sprague–Dawley rats and their mothers were exposed to alternating oxygen concentrations, followed by a room air exposition, to induce OIR. Retinopathy was quantified by ADPase stain in flat-mounted retinas and pre-ILM nuclei count in retinal sections. Semiquantitative real-time PCR and immunofluorescence were assessed in retinas to study stromal cell-derived factor 1 (SDF-1), its receptor CXCR4 and vascular endothelial growth factor (VEGF) expression. Circulating EPCs were evaluated by flow cytometry in peripheral blood. Key findings Our results showed increased immunolabelling of SDF-1 in endothelial cells and strong expression of CXCR4 in Muller cells in OIR retinas as compared to control retinas. We found increased levels of CXCR4 and VEGF mRNA in OIR retinas, especially during the vascular attenuation stage. The number of circulating EPCs was decreased in OIR rats as compared to control rats. Significance The decrease in circulating EPCs could be implied in vessel growth arrest during normal retinal development in OIR rats, while pro-angionenic signals released by Muller cells in the hypoxic retina could drive pathological neovascularization in the ischemic retina. These data warrant further studies to investigate new therapeutic approaches for ROP.

OBJECTIVE: The goal was to reduce adverse pulmonary adverse outcomes, oxidative stress, and inflammation in neonates of 24 to 28 weeks of gestation initially resuscitated with fractions of inspired oxygen of 30% or 90%. METHODS: Randomized assignment to receive 30% (N = 37) or 90% (N = 41) oxygen was performed. Targeted oxygen saturation values were 75% at 5 minutes and 85% at 10 minutes. Blood oxidized glutathione (GSSG)/reduced glutathione ratio and urinary o-tyrosine, 8-oxo-dihydroxyguanosine, and isoprostane levels, isofuran elimination, and plasma interleukin 8 and tumor necrosis factor α levels were determined. RESULTS: The low-oxygen group needed fewer days of oxygen supplementation (6 vs 22 days; P < .01) and fewer days of mechanical ventilation (13 vs 27 days; P < .01) and had a lower incidence of bronchopulmonary dysplasia at discharge (15.4% vs 31.7%; P < .05). GSSG/reduced glutathione × 100 ratios at day 1 and 3 were significantly higher in the high-oxygen group (day 1: high-oxygen group: 13.36 ± 5.25; low-oxygen group: 8.46 ± 3.87; P < .01; day 3: high-oxygen group: 8.87 ± 4.40; low-oxygen group: 6.97 ± 3.11; P < .05). Urinary markers of oxidative stress were increased significantly in the high-oxygen group, compared with the low-oxygen group, in the first week after birth. GSSG levels on day 3 and urinary isofuran, o-tyrosine, and 8-hydroxy-2′-deoxyguanosine levels on day 7 were correlated significantly with development of chronic lung disease. CONCLUSIONS: Resuscitation of preterm neonates with 30% oxygen causes less oxidative stress, inflammation, need for oxygen, and risk of bronchopulmonary dysplasia.