Less Invasive Surfactant Administration in Spain: A Survey Regarding Its Practice, the Target Population, and Premedication Use.

OBJECTIVE: Scientific evidence supports the use of less invasive surfactant administration (LISA) techniques, but certain issues may be limiting its generalized incorporation in clinical practice. The objectives were to determine the level of acceptance of LISA techniques in Spanish hospitals, the types of methods used, the target population, and the premedication administered. STUDY DESIGN: An online survey was designed and sent to various secondary/tertiary hospitals in Spain. RESULTS: Among 67 neonatal units contacted, 44 (65.7%) participated. LISA was used in 89%, and those that did not perform the technique were contemplating its use in the future. In total, 77% of hospitals used some type of pharmacologic sedation/analgesia before the procedure: 28% always and 49% sometimes. In all cases, the reason for premedication was concerned about pain and discomfort. The types of drugs and doses varied. CONCLUSION: LISA has been incorporated in clinical practice of the hospitals surveyed, with a utilization rate higher than what has been reported to date. Sedation and analgesia are commonly administered. LISA is viewed as potentially involving some degree of pain and discomfort. Further studies are needed to determine the safest and most effective pharmacologic and nonpharmacologic measures to apply in these procedures.

Underdosing of Surfactant for Preterm Babies with Respiratory Distress Syndrome in Clinical Practice: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the initial doses of surfactant administered to preterm infants with respiratory distress syndrome. STUDY DESIGN: This is a retrospective cohort study of 206 preterm infants admitted in four level III neonatal intensive care units of acute tertiary care hospitals in Spain between 2013 and 2015. RESULTS: The mean initial dose of surfactant was 173.9 (37.3) mg/kg, and 47.5% of infants received a dose of 200 mg/kg ± 10% (180-220 mg/kg), 47% less than 180 mg/kg (-10%), and 5.4% more than 220 mg/kg (+10%). Very preterm infants (<28 weeks) received higher initial doses than more mature infants, but in all cases, the mean doses were below the recommended 200 mg/kg (by 9.2% in gestational age 23-28 weeks, by 15.9% in 29-32 weeks, and by 24.3% in >32 weeks). CONCLUSION: Administration of surfactant below the prescribed dose is a frequent error in clinical practice. Inadvertently rounding down doses seems a plausible explanation.

Brain Natriuretic Propeptide as an Early Marker of Bronchopulmonary Dysplasia or Death in the Preterm Newborn.

Aim To investigate whether increased brain natriuretic propeptide (NT-proBNP) levels at 48 to 72 h of life are associated with the development of bronchopulmonary dysplasia (BPD) or death in premature neonates. Methods A retrospective study was performed in neonates born before 32 weeks' gestation or with birth weight below 1500 grams, in whom NT-proBNP determination and echocardiography were performed at 48 to 72 h of life. Associations between NT-proBNP levels and the combined outcome BPD or death were analyzed using multivariate logistic regression analysis. Results 117 neonates with mean gestational age 27.8±2.1 weeks and birth weight 949.7±267.5 grams were included. Forty (34.2%) had an outcome of BPD or death. The risk of this combined outcome was found to be 3.95-fold higher (OR 3.95; 95% CI 1.1-14.6) in neonates with NT-proBNP levels above 17800 pg/mL. Conclusion Increased NT-proBNP levels may be associated with a significant decrease in BPD-free survival in very immature newborns.

Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants?

BACKGROUND: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. METHODS: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). DISCUSSION: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Brainstem dysgenesis during the neonatal period: diagnosis and management.

AIMS: To report our neonatal management experience in patients who received a diagnosis of brainstem dysgenesis (BSD). PATIENTS AND METHODS: This study retrospectively reviewed the medical records of 15 neonates with BSD diagnosed between 1984 and 2011. Data on the perinatal period, physical examination, laboratory findings, and management by systems were systematically analyzed. RESULTS: All cases were sporadic. Cocaine abuse and misoprostol use were recorded in two pregnancies. The reason for admission was prematurity (2 of 15), respiratory distress (8 of 15), gastroschisis (1 of 15), and abnormal neurological examination (4 of 15). Clinically, the most commonly affected cranial nerves were the 7th (13 of 15), 9th (11 of 15), 10th (8 of 15), 5th (7 of 15), 12th (7 of 15), 6th (3 of 15), 4th (1 of 15), and 3rd (1 of 15). Five patients required positive pressure ventilation during delivery room resuscitation, three had difficult airways, and two needed tracheostomy during admission. Most patients required nasogastric tube feeding shortly after birth, and four patients had a gastrostomy on discharge. Two patients died of respiratory and cardiac failure. Electromyography and nerve conduction velocity were used to exclude generalized neuromuscular disorders, and in conjunction with other neurophysiological and gastrointestinal tract studies, helped uncover the extent of brainstem involvement in most cases. Cranial magnetic resonance imaging supported the diagnosis in more than half of the patients. CONCLUSIONS: Early diagnosis of BSD is mainly clinical, difficult to establish unless suspected, and crucial to prevent complications. Neonatal care of patients with BSD requires a comprehensive approach that must take into consideration the etiological, anatomical, and pathogenic aspects contributing to the clinical manifestations of this disorder. Care should be provided by multidisciplinary teams, in which neonatologists, pediatric neurologists, nutritionists, physical therapists, and other professionals participate, depending on the associated morbidity in order to improve its management and prognosis.

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.

Failure of early non-invasive ventilation in preterm infants with respiratory distress syndrome in current care practice in Spanish level-III neonatal intensive care units - a prospective observational study.

Introduction: Despite advances in respiratory distress syndrome (RDS) management over the past decade, non-invasive ventilation (NIV) failure is frequent and associated with adverse outcomes. There are insufficient data on the failure of different NIV strategies currently used in clinical practice in preterm infants. Methods: This was a prospective, multicenter, observational study of very preterm infants [gestational age (GA) <32 weeks] admitted to the neonatal intensive care unit for RDS that required NIV from the first 30 min after birth. The primary outcome was the incidence of NIV failure, defined as the need for mechanical ventilation for <72 h of life. Secondary outcomes were risk factors associated with NIV failure and complication rates. Results: The study included 173 preterm infants with a median GA of 28 (IQR 27-30) weeks and a median birth weight of 1,100 (IQR 800-1,333) g. The incidence of NIV failure was 15.6%. In the multivariate analysis, lower GA (OR, 0.728; 95% CI, 0.576-0.920) independently increased the risk of NIV failure. Compared to NIV success, NIV failure was associated with higher rates of unfavorable outcomes, including pneumothorax, intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, and a combined outcome of moderate-to-severe bronchopulmonary dysplasia or death. Conclusion: NIV failure occurred in 15.6% of the preterm neonates and was associated with adverse outcomes. The use of LISA and newer NIV modalities most likely accounts for the reduced failure rate. Gestational age remains the best predictor of NIV failure and is more reliable than the fraction of inspired oxygen during the first hour of life.

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.

Recommendations on the skills profile and standards of the neonatal transport system in Spain.

The first hours of life of a sick or premature newborn are crucial for its prognosis and therefore delivery should take place in a center prepared for that degree of complexity. When this condition is not met, the newborn must be transferred in an optimal and safe way to the center that can offer the necessary care. The training, staffing, organization and coordination of the neonatal transport team are essential to guarantee a safe transfer. Being aware of the interest and the advances that are currently taking place in this area of ​​pediatrics, the Standards Commission and the Neonatal Transport Commission of the Spanish Society of Neonatology have prepared this document. In it, both the provision of human and material resources necessary as well as the bases of clinical stabilization in transport to carry out the neonatal transfer in a safe way and proportionate to the needs of the critical newborn have been exhaustively reviewed and detailed.

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.

Home births: A growing phenomenon with potential risks.

Home birth is a controversial issue that raises safety concerns for paediatricians and obstetricians. Hospital birth was the cornerstone to reduce maternal and neonatal mortality. This reduction in mortality has resulted in considering pregnancy and childbirth as a safe procedure, which, together with a greater social awareness of the need for the humanisation of these processes, have led to an increase in the demand for home birth. Studies from countries such as Australia, the Netherlands, and United Kingdom show that home birth can provide advantages to the mother and the newborn. It needs to be provided with sufficient material means, and should be attended by trained and accredited professionals, and needs to be perfectly coordinated with the hospital obstetrics and neonatology units, in order to guarantee its safety. Therefore, in our environment, there are no safety data or sufficient scientific evidence to support home births at present.

[Home births: A growing phenomenon with potential risks]. / Parto domiciliario: un fenómeno creciente con potenciales riesgos.

Home birth is a controversial issue that raises safety concerns for paediatricians and obstetricians. Hospital birth was the cornerstone to reduce maternal and neonatal mortality. This reduction in mortality has resulted in considering pregnancy and childbirth as a safe procedure, which, together with a greater social awareness of the need for the humanisation of these processes, have led to an increase in the demand for home birth. Studies from countries such as Australia, the Netherlands, and United Kingdom show that home birth can provide advantages to the mother and the newborn. It needs to be provided with sufficient material means, and should be attended by trained and accredited professionals, and needs to be perfectly coordinated with the hospital obstetrics and neonatology units, in order to guarantee its safety. Therefore, in our environment, there are no safety data or sufficient scientific evidence to support home births at present.

Topiramate plus Cooling for Hypoxic-Ischemic Encephalopathy: A Randomized, Controlled, Multicenter, Double-Blinded Trial.

BACKGROUND AND OBJECTIVES: Therapeutic interventions to improve the efficacy of whole-body cooling for hypoxic-ischemic encephalopathy (HIE) are desirable. Topiramate has been effective in reducing brain damage in experimental studies. However, in the clinical setting information is limited to a small number of feasibility trials. We launched a randomized controlled double-blinded topiramate/placebo multicenter trial with the primary objective being to reduce the antiepileptic activity in cooled neonates with HIE and assess if brain damage would be reduced as a consequence. STUDY DESIGN: Neonates were randomly assigned to topiramate or placebo at the initiation of hypothermia. Topiramate was administered via a nasogastric tube. Brain electric activity was continuously monitored. Topiramate pharmacokinetics, energy-related and Krebs' cycle intermediates, and lipid peroxidation biomarkers were determined using liquid chromatography-mass spectrometry and MRI for assessing brain damage. RESULTS: Out of 180 eligible patients 110 were randomized, 57 (51.8%) to topiramate and 53 (48.2%) to placebo. No differences in the perinatal or postnatal variables were found. The topiramate group exhibited less seizure burden in the first 24 h of hypothermia (topiramate, n = 14 [25.9%] vs. placebo, n = 22 [42%]); needed less additional medication, and had lower mortality (topiramate, n = 5 [9.2%] vs. placebo, n = 10 [19.2%]); however, these results did not achieve statistical significance. Topiramate achieved a therapeutic range in 37.5 and 75.5% of the patients at 24 and 48 h, respectively. A significant association between serum topiramate levels and seizure activity (p < 0.016) was established. No differences for oxidative stress, energy-related metabolites, or MRI were found. CONCLUSIONS: Topiramate reduced seizures in patients achieving therapeutic levels in the first hours after treatment initiation; however, they represented only a part of the study population. Our results warrant further studies with higher loading and maintenance dosing of topiramate.

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)

[Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy]. / Estrés oxidativo en la asfixia perinatal y la encefalopatía hipóxico-isquémica.

Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis.

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)

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)