Development, Reliability, and Testing of a New Rating Scale for Neonatal Encephalopathy.

OBJECTIVE: To develop and test the Neonatal Encephalopathy-Rating Scale (NE-RS), a new rating scale to grade the severity of neonatal encephalopathy (NE) within the first 6 hours after birth. STUDY DESIGN: A 3-phase process was conducted: (1) design of a comprehensive scale that would be specific, sensitive, brief, and unsophisticated; (2) evaluation in a cohort of infants with neonatal encephalopathy and healthy controls; and (3) validation with brain magnetic resonance imaging findings and outcome at 2 years of age. RESULTS: We evaluated the NE-RS in 54 infants with NE and 28 healthy infants. The NE-RS had excellent internal consistency (Cronbach alpha coefficient: 0.93 [95% CI 0.86-0.94]) and reliability (intraclass correlation coefficient in the NE cohort 0.996 [95% CI 0.993-0.998; P < .001]). Alertness, posture, motor response, and spontaneous activity were the top discriminators for degrees of NE. The cut-off value for mild vs moderate NE was 8 points (area under the curve [AUC] 0.99, 95% CI 0.85-1.00) and for moderate vs severe NE, 30 points (AUC 0.93, 95% CI 0.81-0.99). The NE-RS was significantly correlated with the magnetic resonance imaging score (Spearman Rho 0.77, P < .001) and discriminated infants who had an adverse outcome (AUC 0.91, 95% CI 0.83-0.99, sensitivity 0.82, specificity 0.81, positive predictive value 0.87, negative predictive value 0.74). CONCLUSIONS: The NE-RS is reliable and performs well in reflecting the severity of NE within the first 6 hours after birth. This tool could be useful when assessing clinical criteria for therapeutic hypothermia in NE.

Massive Neonatal Arterial Ischemic Stroke.

BACKGROUND: Massive infarction in adults is a devastating entity characterized by signs of extreme swelling of the brain's parenchyma. We explored whether a similar entity exists in neonates, which we call massive neonatal arterial ischemic stroke (M-NAIS), and assess its potential clinical implications. METHODS: Prospective multicenter cohort study comprising 48 neonates with gestational age ≥35 weeks with middle cerebral artery (MCA) NAIS was performed. Diagnosis with magnetic resonance imaging (MRI) was performed within the first three days after symptom onset. The presence of signs of a space-occupying mass, such as brain midline shift and/or ventricular and/or extra-axial space collapse, was recorded. The volume of the infarct and brain midline shift were determined with semiautomatic procedures. Neurodevelopment was assessed at age 24 months. RESULTS: Fifteen (31%) neonates presented MRI signs of a space-occupying mass effect and were considered to have an M-NAIS. The relative volume (infarct volume/total brain volume) of the infarct was on average significantly greater in the M-NAIS subgroup (29% vs 4.9%, P < 0.001). Patients with M-NAIS consistently presented lesions involving the M1 arterial territory of the MCA and showed more apneic and tonic seizures, which had an earlier onset and lasted longer. Moderate to severe adverse neurodevelopmental outcomes were present in most M-NAIS cases (79% vs 6%, P < 0.001). CONCLUSIONS: M-NAIS appears to be a distinctive subtype of neonatal infarction, defined by characteristic neuroimaging signs. Neonates with M-NAIS frequently present a moderate to severe adverse outcome. Early M-NAIS identification would allow for prompt, specific rehabilitation interventions and would provide more accurate prognostic information to families.

Prognostic value of ventricular wall fluorescence during 5-aminolevulinic-guided surgery for glioblastoma.

BACKGROUND: The meaning of the ventricular wall fluorescence during 5-aminolevulinic (5-ALA)-guided surgery in patients with glioblastoma (GBM) is still unknown. The authors studied the association between ventricle fluorescence, clinical outcome and survival, and described the histopathological findings of selective biopsies from the ventricular wall. METHODS: One hundred and forty patients diagnosed of GBM underwent fluorescence-guided surgery (FGS); 65 of them were naive GBM and ventricle fluorescence during surgery was annotated prospectively. Selective biopsies were collected from the ventricular wall when possible. Clinical and radiological data were registered, including age, Karnofsky Performance Scale (KPS) score, presence of hydrocephalus, overall survival (OS), tumour volume and location (periventricular vs non-periventricular) and leptomeningeal dissemination. RESULTS: During FGS the ventricle wall was opened just when the tumour was periventricular in the preoperative MRI (45 out of 65). In 28 of them (60 %) the fluorescence extended far away from the site of opening, while in 17 it ended just in the few millimetres around the tumour. All four patients who developed hydrocephalus had periventricular tumours and the ventricle wall had been opened during surgery. Statistically significant differences were seen in OS according to periventricular location (15 m vs 33 m, P = 0.008 log rank). However, there was not significant relationship between ventricle fluorescence and hydrocephalus (P = 0.75), nor survival (14 m vs 15.5 m, P = 0.64). CONCLUSIONS: Preoperative MRI predicts if the ventricle will be opened using the 5-ALA fluorescence, according to tumour location. It does not predict, however if the ventricle wall is going to be fluorescent or not. The fluorescence of the ventricle wall is not a predictor for complications or survival. Periventricular tumour location is an independent bad prognostic factor in GBM.

Inter-observer reliability for amplitude-integrated electroencephalography in the newborn with perinatal asphyxia.

INTRODUCTION: Amplitude integrated electroencephalography (aEEG) is a tool widely used for neuromonitoring in the critical neonate. In the patient with perinatal asphyxia, its interpretation is key to identifying candidates for therapeutic hypothermia, detecting subclinical seizures and providing pronostic information. Our aim was to analyze the concordance in the interpretation of aEEG among neonatologists with different levels of experience. MATERIAL AND METHODS: Unicenter retrospective study of newborns ≥ 35 weeks with perinatal asphyxia included consecutively over a two-year period and monitored with aEEG for at least 6 h. The bedside neonatologist interpreted aEEG regarding background pattern, sleep-wake cycling, and seizures. The aEEG tracings were blindly reviewed by two neonatologists with different experience. The aEEG tracings were divided into periods of 0-3 h and 3-6 h of life, and the concordance (Cohen Kappa coefficient, k), between the two examiners and that of their consensus with the bedside neonatologist, was analyzed. RESULTS: Seventy-five newborns were included, 5 of them were not aEEG-monitored. 132 tracings were analyzed with a very good concordance between the two examiners in the three characteristics of the aEEG. The k for the bedside neonatologist was very good for background pattern (k = 0.93), moderate (k = 0.52) for sleep-wake cycling, and weak (k = 0.32) for seizures. CONCLUSIONS: This study supports that background pattern is easily interpreted compared to sleep-wake cycling or crisis, improving when targeted training on aEEG is received.

Posthemorrhagic ventricular dilatation late intervention threshold and associated brain injury.

OBJECTIVE: To systematically assess white matter injury (WMI) in preterm infants with posthemorrhagic ventricular dilatation (PHVD) using a high-threshold intervention strategy. STUDY DESIGN: This retrospective analysis included 85 preterm infants (≤34 weeks of gestation) with grade 2-3 germinal matrix-intraventricular hemorrhage. Cranial ultrasound (cUS) scans were assessed for WMI and ventricular width and shape. Forty-eight infants developed PHVD, 21 of whom (intervention group) underwent cerebrospinal fluid drainage according to a predefined threshold (ventricular index ≥p97+4 mm or anterior horn width >10 mm, and the presence of frontal horn ballooning). The other 27 infants underwent a conservative approach (non-intervention group). The two PHVD groups were compared regarding ventricular width at two stages: the worst cUS for the non-intervention group (scans showing the largest ventricular measurements) versus pre-intervention cUS in the intervention group, and at term equivalent age. WMI was classified as normal/mild, moderate and severe. RESULTS: The intervention group showed significantly larger ventricular index, anterior horn width and thalamo-occipital diameter than the non-intervention group at the two timepoints. Moderate and severe WMI were more frequent in the infants with PHVD (p<0.001), regardless of management (intervention or conservative management). There was a linear relationship between the severity of PHVD and WMI (p<0.001). CONCLUSIONS: Preterm infants with PHVD who undergo a high-threshold intervention strategy associate an increased risk of WMI.

Norovirus-associated White Matter Injury in a Term Newborn With Seizures.

Neonatal seizures with white matter injury have been associated with rotavirus, enterovirus and parechovirus. Neurological symptoms caused by norovirus have been occasionally reported in older children. We describe a case of a neonate with seizures and white matter lesions, with detection of human norovirus in stool samples from the patient and her mother.

Neonatal arterial stroke location is associated with outcome at 2 years: a voxel-based lesion-symptom mapping study.

OBJECTIVE: In contrast to motor impairments, the association between lesion location and cognitive or language deficits in patients with neonatal arterial ischaemic stroke remains largely unknown. We conducted a voxel-based lesion-symptom mapping cross-sectional study aiming to reveal neonatal arterial stroke location correlates of language, motor and cognitive outcomes at 2 years of age. DESIGN: Prospective observational multicentre study. SETTING: Six paediatric university hospitals in Spain. PARTICIPANTS: We included 53 patients who had a neonatal arterial ischaemic stroke with neonatal MRI and who were followed up till 2 years of age. MAIN OUTCOME MEASURES: We analysed five dichotomous clinical variables: speech therapy (defined as the need for speech therapy as established by therapists), gross motor function impairment, and the language, motor and cognitive Bayley scales. All the analyses were controlled for total lesion volume. RESULTS: We found that three of the clinical variables analysed significantly correlated with neonatal stroke location. Speech therapy was associated with lesions located mainly at the left supramarginal gyrus (p=0.007), gross motor function impairment correlated with lesions at the left external capsule (p=0.044) and cognitive impairment was associated with frontal lesions, particularly located at the left inferior and middle frontal gyri (p=0.012). CONCLUSIONS: The identification of these susceptible brain areas will allow for more precise prediction of neurological impairments on the basis of neonatal brain MRI.

Randomized controlled trial of early arachidonic acid and docosahexaenoic acid enteral supplementation in very preterm infants.

Objective: To evaluate changes in blood long-chain polyunsaturated fatty acid (LCPUFA) and oxylipin concentrations in very preterm infants from birth to 36 weeks' postmenstrual age (WPA) after providing an emulsified arachidonic acid (ARA):docosahexaenoic acid (DHA) supplement at two different concentrations. Study design: This prospective, randomized trial assigned infants to receive a supplement (1) 80:40 group (80 mg/kg/day ARA and 40 mg/kg/day DHA, n = 9) or (2) 120:60 group (120 mg/kg/day ARA and 60 mg/kg/day DHA, n = 9). Infants received supplement daily from birth until 36 WPA. At baseline, 21 days of life and 36 WPA, the LCPUFAs were measured in plasma by gas chromatography/mass spectrophotometry. Additionally, LCPUFAs and oxylipins were analyzed in whole blood by ultra-high-performance liquid chromatography-tandem mass spectrometry. Furthermore, a sample of oral mucosa was obtained to analyze single-nucleotide polymorphism located in the FADS1 gene by PCR. Results: Gestational age was similar between groups (80:40 = 28+6 [27+3; 30+3] completed weeks+days ; 120:60 = 29+6 [27+3; 30+5] completed weeks+days , p = 0.83). At 36 WPA, the change in plasma ARA was significantly different between groups (80:40 group = 0.15 [-0.67; 0.69] %nmol, 120:60 = 1.68 [1.38; 3.16] %nmol, p = 0.031). In whole blood, the levels of ARA-derived oxylipins (5-, 8-, 9-, 11-, 15-HETE and 8,9-EET) and EPA-derived oxylipins (18-HEPE) significantly increase from baseline to 36 WPA in the 120:60 group than the 80:40 group. Conclusion: Supplementation at high doses (120:60 mg/kg/day) increased levels of ARA, and EPA- and ARA-derived oxylipins compared to low doses (80:40 mg/kg/day). Differences were detected in EPA metabolites without a significant increase in plasma DHA.

Nursing Students' Perceptions on Healthcare-Associated Infection Control and Prevention Teaching and Learning Experience in Portugal.

Healthcare-associated infections (HAI) are one of the major concerns worldwide, posing significant challenges to healthcare professionals' education and training. This study intended to measure nursing students' perceptions regarding their learning experiences on HAI prevention and control. In the first phase of the study, a cross-sectional and descriptive study with a convenience sample composed of undergraduate nursing students from Portugal, Spain, Poland, and Finland was conducted to develop the InovSafeCare questionnaire. In the second phase, we applied the InovSafeCare scale in a sample of nursing students from two Portuguese higher education institutions to explore which factors impact nursing students' adherence to HAI prevention and control measures in clinical settings. In phase one, the InovSafeCare questionnaire was applied to 1326 students internationally, with the instrument presenting adequate psychometric qualities with reliability results in 14 dimensions. During phase two, the findings supported that Portuguese nursing students' adherence to HAI prevention and control measures is influenced not only by the curricular offerings and resources available in academic settings, but also by the standards conveyed by nursing tutors during clinical placements. Our findings support the need for a dedicated curricular focus on HAI prevention and control learning, not only through specific classroom modules, innovative resources, and pedagogical approaches, but also through a complementary and coordinated liaison between teachers and tutors in academic and clinical settings.

Evaluation of the suitability and clinical applicability of different electrodes for aEEG/cEEG monitoring in the extremely premature infant.

INTRODUCTION: Monitoring of brain function using continuous electroencephalography (aEEG/cEEG) is an essential tool in the standard care of the term infant, and its use is growing in the premature infant as a biomarker of lesion and brain maturity. However, the placing of the electrodes is a great challenge, particularly in the extremely premature infant, which often discourages neuromonitoring. The aim of this study is to assess the different electrodes available, to select the one that best suits the peculiarities of the extremely premature infant, and evaluate its applicability in clinical practice. POPULATION AND METHODS: With the aim of designing a neuromonitoring study protocol using aEEG/cEEG in <28 weeks premature infants, an analysis was made of our experience with the type of electrodes available. The electrode that was considered most suitable for this population was chosen by assessing: the need of preparing the scalp, speed in positioning the electrodes, if the application was invasive or not, the possibility of repositioning, risk of skin injuries, sterility of the technique, and durability. The electrode chosen was used for continuous electroencephalographic monitoring started in the first 24 h of life, and maintained until at least 72 h of life. RESULTS: The electrodes evaluated were: subdermal needles, silver cups, and 2 types of self-adhesive electrodes (solid hydrogel and wet gel). The wet gel electrodes were chosen. They were used on 41 neonates with a mean gestational age of 25.8 ±â€¯1.1 weeks. Good stable impedance was rapidly obtained, without the need of excessive manipulations, and no skin injuries were observed. The satisfaction of the staff involved in positioning them was very high. CONCLUSION: The self-adhesive disposable electrodes with wet gel and integrated cable enabled the electrodes to be positioned rapidly and provided continuous non-invasive and good quality aEEG/cEEG monitoring in the extremely premature infant.

[Inter-observer reliability for amplitude-integrated EEG in the newborn with perinatal asphyxia]. / Concordancia interobservador del electroencefalograma integrado por amplitud en el neonato con asfixia perinatal.

INTRODUCTION: Amplitude integrated electroencephalography (aEEG) is a widely tool used for neuromonitoring in the critical neonate. In the patient with perinatal asphyxia, its interpretation is key to identifying candidates for therapeutic hypothermia, detecting subclinical seizures and providing pronostic information. Our aim was to analyze the concordance in the interpretation of aEEG among neonatologists with different level of experience. MATERIAL AND METHODS: Unicenter retrospective study of newborns ≥35 weeks with perinatal asphyxia included consecutively over a two-year period and monitored with aEEG for at least 6h. The bedside neonatologist interpreted aEEG regarding background pattern, sleep-wake cycling, and seizures. The aEEG tracings were blindly reviewed by two neonatologists with different experience. The aEEG tracings were divided into periods of 0-3h and 3-6h of life, and the concordance (Cohen Kappa coefficient, k), between the two examiners and that of their consensus with the bedside neonatologist, was analyzed. RESULTS: Seventy-five newborns were included, 5 of them were not aEEG-monitored. 132 tracings were analyzed with a very good concordance between the two examiners in the three characteristics of the aEEG. The k for the bedside neonatologist was very good for background pattern (k=0.93), moderate (k=0.52) for sleep-wake cycling, and weak (k=0.32) for seizures. CONCLUSIONS: This study supports that background pattern is easily interpreted compared to sleep-wake cycling or crisis, improving when targeted training on aEEG is received.

Nursing Students' Perceptions on Healthcare-Associated Infection Control and Prevention Teaching and Learning Experience: Development and Validation of a Scale in Four European Countries.

Healthcare-associated infections are one of the major concerns worldwide. This study presents the development and the validation process of the InovSafeCare scale and aimed at identifying and measuring the ecosystem variables related to healthcare-associated infection (HCAI) prevention and control practices in European nurse students. Qualitative and quantitative approaches were used to (1) elaborate an item pool related to the educational environment, the healthcare setting environment, and the attitudes, beliefs, and performance of the nursing students regarding HCAI prevention and control and (2) analyze psychometric properties of the scale using factor analysis. The validated InovSafeCare scale was applied to undergraduate nursing students of five European Higher Education Institutions. The partial least square structural equation modeling (PLS-SEM) method with SMART-PLS3 software was used. The study sample consists of 657 nursing students, who responded a self-report inventory. From the analyzed data were identified 14 factors. The InovSafeCare scale reveals good validity and reliability of the dimensions in different European countries.

[Evaluation of the suitability and clinical applicability of different electrodes for aEEG/cEEG monitoring in the extremely premature infant]. / Evaluación de la idoneidad y aplicabilidad clínica de diferentes electrodos para la monitorización aEEG/cEEG en el niño prematuro extremo.

INTRODUCTION: Monitoring of brain function using continuous electroencephalography (aEEG/cEEG) is an essential tool in the standard care of the term infant, and its use is growing in the premature infant as a biomarker of lesion and brain maturity. However, the placing of the electrodes is a great challenge, particularly in the extremely premature infant, which often discourages neuromonitoring. The aim of this study is to assess the different electrodes available, to select the one that best suits the peculiarities of the extremely premature infant, and evaluate its applicability in clinical practice. POPULATION AND METHODS: With the aim of designing a neuromonitoring study protocol using aEEG/cEEG in<28 weeks premature infants, an analysis was made of our experience with the type of electrodes available. The electrode that was considered most suitable for this population was chosen by assessing: the need of preparing the scalp, speed in positioning the electrodes, if the application was invasive or not, the possibility of repositioning, risk of skin injuries, sterility of the technique, and durability. The electrode chosen was used for continuous electroencephalographic monitoring started in the first 24h of life, and maintained until at least 72h of life. RESULTS: The electrodes evaluated were: subdermal needles, silver cups, and 2 types of self-adhesive electrodes (solid hydrogel and wet gel). The wet gel electrodes were chosen. They were used on 41 neonates with a mean gestational age of 25.8±1.1 weeks. Good stable impedance was rapidly obtained, without the need of excessive manipulations, and no skin injuries were observed. The satisfaction of the staff involved in positioning them was very high. CONCLUSION: The self-adhesive disposable electrodes with wet gel and integrated cable enabled the electrodes to be positioned rapidly and provided continuous non-invasive and good quality aEEG/cEEG monitoring in the extremely premature infant.

A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review.

BACKGROUND: Individuals affected with DiGeorge and Velocardiofacial syndromes present with both phenotypic diversity and variable expressivity. The most frequent clinical features include conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial dysmorphism. The etiology in most patients is a 3 Mb recurrent deletion in region 22q11.2. However, cases of infrequent deletions and duplications with different sizes and locations have also been reported, generally with a milder, slightly different phenotype for duplications but with no clear genotype-phenotype correlation to date. METHODS: We present a 7 month-old male patient with surgically corrected ASD and multiple VSDs, and dysmorphic facial features not clearly suggestive of 22q11.2 deletion syndrome, and a newborn male infant with cleft lip and palate and upslanting palpebral fissures. Karyotype, FISH, MLPA, microsatellite markers segregation studies and SNP genotyping by array-CGH were performed in both patients and parents. RESULTS: Karyotype and FISH with probe N25 were normal for both patients. MLPA analysis detected a partial de novo 1.1 Mb deletion in one patient and a novel partial familial 0.4 Mb duplication in the other. Both of these alterations were located at a distal position within the commonly deleted region in 22q11.2. These rearrangements were confirmed and accurately characterized by microsatellite marker segregation studies and SNP array genotyping. CONCLUSION: The phenotypic diversity found for deletions and duplications supports a lack of genotype-phenotype correlation in the vicinity of the LCRC-LCRD interval of the 22q11.2 chromosomal region, whereas the high presence of duplications in normal individuals supports their role as polymorphisms. We suggest that any hypothetical correlation between the clinical phenotype and the size and location of these alterations may be masked by other genetic and/or epigenetic modifying factors.

Development and Characterization of Medical Phantoms for Ultrasound Imaging Based on Customizable and Mouldable Polyvinyl Alcohol Cryogel-Based Materials and 3-D Printing: Application to High-Frequency Cranial Ultrasonography in Infants.

This work presents an affordable and easily customizable methodology for phantom manufacturing, which can be used to mimic different anatomic organs and structures. This methodology is based on the use of polyvinyl alcohol-based cryogels as a physical substitute for biologic soft tissues and of 3-D printed polymers for hard tissues, moulding and supporting elements. Thin and durable soft-tissue mimicking layers and multilayer arrangements can be obtained using these materials. Special attention was paid to the acoustic properties (sound speed, attenuation coefficient and mechanical impedance) of the materials developed to simulate soft tissues. These properties were characterized as a function of the additives concentration (propylene-glycol and alumina particles). The polyvinyl alcohol formulation proposed in this work is stable over several freeze-thaw cycles, allowing the manufacturing of multilayer materials with controlled properties. The manufacturing methodology presented was applied to the development of a phantom for high-frequency cranial ultrasonography in infants. This phantom was able to reproduce the main characteristics of the ultrasound images obtained in neonates through the anterior fontanel, down to 8-mm depth.

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.

[Incidence of hypoxic-ischaemic encephalopathy and use of therapeutic hypothermia in Spain]. / Incidencia de la encefalopatía hipóxico-isquémica e implementación de la hipotermia terapéutica por regiones en España.

INTRODUCTION: There are no data on the incidence of hypoxic-ischaemic encephalopathy (HIE) and the implementation of therapeutic hypothermia (TH) in Spain. METHODS: This is a cross-sectional, national study, performed using an on-line questionnaire targeting level III neonatal care units in Spain. Participants were requested to provide data of all newborns ≥ 35 weeks of gestational age diagnosed with moderate-severe HIE over a two year-period (2012-2013), and of the implementation of TH up to June 2015. RESULTS: All (90) contacted hospitals participated. HIE incidence rate was 0.77/1000 live newborns (95% CI 0.72 - 0.83). During 2012-2013, 86% of the newborns diagnosed with moderate-severe HIE received TH (active or passive). Active TH was increasingly used, from 78% in 2012 to 85% in 2013 (P=.01). Of the 14% that did not receive TH, it was mainly due to a delay in the diagnosis or inter-hospital transfer, and to the fact that the treatment was not offered. More than half (57%) were born in hospitals where TH was not provided, and passive hypothermia was used for inter-hospital patient transfer, and in 39% of the cases by inappropriately trained personnel. By June 2015, 57 out of 90 centres had implemented TH, of which 54 performed whole-body TH (using servo-controlled devices). The geographical distribution of centres with active TH, and the number of newborn that received TH, was heterogeneous. CONCLUSIONS: The incidence of moderate-severe HIE is homogeneous across Spanish territory. Significant progress is being made in the implementation of TH, however it is necessary to increase the availability of active TH between Autonomous Communities, to improve early diagnosis, and to guarantee high quality patient transfer to referral centres.

Population-Based Study of the National Implementation of Therapeutic Hypothermia in Infants with Hypoxic-Ischemic Encephalopathy.

Data on the incidence of hypoxic-ischemic encephalopathy (HIE) in the first 6 hours of life together with the implementation of therapeutic hypothermia (TH) are relevant to delineate actions to achieve the lowest rates of neonatal mortality, morbidity, and long-term impact on health associated with HIE. This is population-based national survey study, including newborns ≥35 weeks of gestation with moderate-to-severe HIE from all level III neonatal care units, to provide the incidence of HIE for the period 2012-2013, and the implementation of TH up to June 2015 in Spain. Incidence rate was 0.77 per 1000 live births (95% confidence interval 0.72-0.83). By June 2015, 63% (57/90) of the units had implemented TH; 95% of them performed servo-controlled whole-body TH. For the 2-year period, 86% of the newborns diagnosed with moderate-to-severe HIE received TH. Active TH increased in use from 78% in 2012 to 85% in 2013 (p = 0.01). The main reasons for not cooling were a delay in the diagnosis (31/682) and the fact that the treatment was not offered (20/682). Interhospital patient transfer was performed using passive hypothermia, by appropriately trained personnel in 61% of centers. Eighteen percent of newborns with moderate or severe HIE died, without significant differences between the 2 years. Up-to-date knowledge of the national coverage of neonatal care of infants with HIE in developed countries is a prerequisite to reducing the load of HIE in this area and to facilitating coordinated, eliminate investigation.