Search

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. 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.

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.

Background: Stability during early postnatal life in preterm infants is related to better outcomes. Although vital signs are monitored continuously in Neonatal Intensive Care Unites, this monitoring does not include all physiological parameters nor data such as movement patterns. Although there are scattered sources of data, there is no centralized data hub for neonates information., Results: We have created the first neonate data hub for easy and interactive access to upload or download postural, physiological, and medical data of neonates: NEOVAULT. NEOVAULT is a platform that provides access to information through two interfaces: 1) via a Web interface (designed for medical personnel, data scientists, researchers); and 2) via a RESTful API (Application Programming Interfaces) -designed for developers-, aiming to integrate access to information into third-party applications. The web access allows searching and filtering according to specific parameters, visualization of data through graphs and images, and generation of datasets in CSV format. Access through the RESTful API is described in OpenAPI, enabling access to information from any device, facilitating it in an interoperable format. Currently, it contains nearly 800,000 postural records and 3.000 physiological data entries. The physiological and postural data stored for each neonate in NEOVAULT are collected through the NRP (Neonates Recording Platform) tool, which allows for the automatic and reliable collection of data., Conclusion: NEOVAULT is an open platform for simple access to postural, physiological, and medical data of neonates that can be utilized by researchers, data scientists, medical personnel, and programmers. It enables integration into third-party applications and the generation of customized datasets., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Puerta del Mar University Hospital (Cadiz, Spain) (reference number 125.22) and after obtaining the informed consent of the parents. All research data are de-identified and securely stored. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In this study, we introduce MGA-Net, a novel mask-guided attention neural network, which extends the U-net model for precision neonatal brain imaging. MGA-Net is designed to extract the brain from other structures and reconstruct high-quality brain images. The network employs a common encoder and two decoders: one for brain mask extraction and the other for brain region reconstruction. A key feature of MGA-Net is its high-level mask-guided attention module, which leverages features from the brain mask decoder to enhance image reconstruction. To enable the same encoder and decoder to process both MRI and ultrasound (US) images, MGA-Net integrates sinusoidal positional encoding. This encoding assigns distinct positional values to MRI and US images, allowing the model to effectively learn from both modalities. Consequently, features learned from a single modality can aid in learning a modality with less available data, such as US. We extensively validated the proposed MGA-Net on diverse and independent datasets from varied clinical settings and neonatal age groups. The metrics used for assessment included the DICE similarity coefficient, recall, and accuracy for image segmentation; structural similarity for image reconstruction; and root mean squared error for total brain volume estimation from 3D ultrasound images. Our results demonstrate that MGA-Net significantly outperforms traditional methods, offering superior performance in brain extraction and segmentation while achieving high precision in image reconstruction and volumetric analysis. Thus, MGA-Net represents a robust and effective preprocessing tool for MRI and 3D ultrasound images, marking a significant advance in neuroimaging that enhances both research and clinical diagnostics in the neonatal period and beyond., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Magnetic Resonance Imaging (MRI) plays an important role in neurology, particularly in the precise segmentation of brain tissues. Accurate segmentation is crucial for diagnosing brain injuries and neurodegenerative conditions. We introduce an Enhanced Spatial Fuzzy C-means (esFCM) algorithm for 3D T1 MRI segmentation to three tissues, i.e. White Matter (WM), Gray Matter (GM), and Cerebrospinal Fluid (CSF). The esFCM employs a weighted least square algorithm utilizing the Structural Similarity Index (SSIM) for polynomial bias field correction. It also takes advantage of the information from the membership function of the last iteration to compute neighborhood impact. This strategic refinement enhances the algorithm's adaptability to complex image structures, effectively addressing challenges such as intensity irregularities and contributing to heightened segmentation accuracy. We compare the segmentation accuracy of esFCM against four variants of FCM, Gaussian Mixture Model (GMM) and FSL and ANTs algorithms using four various dataset, employing three measurement criteria. Comparative assessments underscore esFCM's superior performance, particularly in scenarios involving added noise and bias fields.The obtained results emphasize the significant potential of the proposed method in the segmentation of MRI images., Competing Interests: Declarations. Ethics Approval and Consent to Participate: The HUPM dataset used in this study received approval from the Research and Ethics Committee, and informed consent was obtained from all parents or guardians of the participants to use MRI data for research purposes. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

Rhinoviruses (RVs) are a leading cause of acute respiratory infections (ARI) in children. The relationship between RV viral loads (VL), RV/viral-co-detections and disease severity, is incompletely understood. We studied children and adolescents ≤21 years with RV-ARI that were identified as inpatients or outpatients using a PCR panel from 2011-2013. RV VL were stratified according to cycle threshold (CT) values in high (≤25), intermediate (26-32) and low (>32). Adjusted analyses were performed to assess the role RV VL and RV/viral codetections on hospital admission, oxygen requirement, PICU care, and length of stay. Of 1,899 children with RV-ARI, 78% had chronic comorbidities and 24% RV/viral co-detections. Single RV vs RV/viral co-detections was associated with higher VL (24.74 vs 26.62 CT; p = 0.001) and older age (14.9 vs 9.5 months; p = 0.0001). Frequency of RV/viral co-detections were inversely proportional to RV loads: 32% with low; 28% with intermediate, and 19% with high VL, p = 0.0001. Underlying conditions were independently associated with all clinical outcomes, high VL with PICU care, and single RV-ARI with higher odds of hospitalization. In summary, single RV vs RV/viral co-detections were associated with higher VL and older age. Underlying diseases, rather than RV loads or RV/viral co-detections, consistently predicted worse clinical outcomes., (© 2024 Wiley Periodicals LLC.)

Introduction: Several studies demonstrate the relationship between preterm birth and a reduced thalamus volume at term-equivalent age. In contrast, this study aims to investigate the link between the thalamic growth trajectory during the early postnatal period and neurodevelopment at two years of age., Methods: Thalamic volume was extracted from 84 early MRI scans at postmenstrual age of 32.33 (± 2.63) weeks and 93 term-equivalent age MRI scans at postmenstrual age of 42.05 (± 3.33) weeks of 116 very preterm infants (56% male) with gestational age at birth of 29.32 (± 2.28) weeks and a birth weight of 1158.92 (± 348.59) grams. Cognitive, motor, and language outcomes at two years of age were assessed with Bayley Scales of Infant and Toddler Development Third Edition. Bivariate analysis was used to describe the clinical variables according to neurodevelopmental outcomes and multilevel linear regression models were used to examine the impact of these variables on thalamic volume and its relationship with neurodevelopmental outcomes., Results: The results suggest an association between severe brain injury and thalamic growth trajectory (β coef = -0.611; p < 0.001). Moreover, thalamic growth trajectory during early postnatal life was associated with the three subscale scores of the neurodevelopmental assessment (cognitive: β coef = 6.297; p = 0.004; motor: β coef = 7.283; p = 0.001; language: β coeficient = 9.053; p = 0.002)., Discussion: These findings highlight (i) the impact of severe brain injury on thalamic growth trajectory during early extrauterine life after preterm birth and (ii) the relationship of thalamic growth trajectory with cognitive, motor, and language outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Trimarco, Jafrasteh, Jiménez-Luque, Marín Almagro, Román Ruiz, Lubián Gutiérrez, Ruiz González, Segado Arenas, Lubián-López and Benavente-Fernández.)

This study examines the association between nurses' perception of caring and attitudes toward caring for dying patients in end-of-life care units. We used a descriptive cross-sectional design with convenience sampling. Data were collected from May to June 2021 through self-reported questionnaires from 303 Spanish nurses (mean age = 48 years, 78.9% female). Participants completed the Caring Dimension Inventory (CDI-25) and the Frommelt Attitudes Toward Care of the Dying scale. Demographic and training information were collected. Data were analyzed using Stata 16.0. Attitudes toward Care of the Dying Patient were significantly higher in nurses with palliative care training (β = 2.829, p = 0.018) and those who scored higher on the psychosocial (β = 0.789, p = 0.0001) and technical dimensions (β = 0.487, p = 0.011) of the CDI-25. Multivariate analysis identified the psychosocial dimension of the CDI-25 scale (β = 0.783, p = 0.0001) and palliative care training (β = 2.686, p = 0.017) as the only significant variables associated with Attitudes toward Care of the Dying Patient. Overall, nurses exhibited a positive attitude toward caring for dying patients. Our results could potentially help nursing directors identify those with the necessary qualities and training for optimal end-of-life care and to further plan training courses to provide optimal care in end-of-life situations.

Background: The corpus callosum (CC) is suggested as an indirect biomarker of white matter volume, which is often affected in preterm birth. However, diagnosing mild white matter injury is challenging., Methods: We studied 124 children born preterm (mean age: 8.4 ± 1.1 years), using MRI to assess CC measurements and cognitive/motor outcomes based on the Wechsler Intelligence Scale for Children-V (WPPSI-V) and Movement Assessment Battery for Children-2 (MABC-2)., Results: Children with normal outcomes exhibited greater height (10.2 ± 2.1 mm vs. 9.4 ± 2.3 mm; p = 0.01) and fractional anisotropy at splenium (895[680-1000] vs 860.5[342-1000]) and total CC length (69.1 ± 4.8 mm vs. 67.3 ± 5.1 mm; p = 0.02) compared to those with adverse outcomes. All measured CC areas were smaller in the adverse outcome group. Models incorporating posterior CC measurements demonstrated the highest specificity (83.3% Sp, AUC: 0.65) for predicting neurological outcomes. CC length and splenium height were the only linear measurements associated with manual dexterity and total MABC-2 score while both the latter and genu were related with Full-Scale Intelligence Quotient., Conclusions: CC biometry in children born very preterm at school-age is associated with outcomes and exhibits a specific subregion alteration pattern. The posterior CC may serve as an important neurodevelopmental biomarker in very preterm infants., Impact: The corpus callosum has the potential to serve as a reliable and easily measurable biomarker of white matter integrity in very preterm children. Estimating diffuse white matter injury in preterm infants using conventional MRI sequences is not always conclusive. The biometry of the posterior part of the corpus callosum is associated with cognitive and certain motor outcomes at school age in children born very preterm. Length and splenium measurements seem to serve as reliable biomarkers for assessing neurological outcomes in this population., (© 2024. The Author(s).)

Preterm infants are a highly vulnerable population. The total brain volume (TBV) of these infants can be accurately estimated by brain ultrasound (US) imaging which enables a longitudinal study of early brain growth during Neonatal Intensive Care (NICU) admission. Automatic estimation of TBV from 3D images increases the diagnosis speed and evades the necessity for an expert to manually segment 3D images, which is a sophisticated and time consuming task. We develop a deep-learning approach to estimate TBV from 3D ultrasound images. It benefits from deep convolutional neural networks (CNN) with dilated residual connections and an additional layer, inspired by the fuzzy c-Means (FCM), to further separate the features into different regions, i.e. sift layer. Therefore, we call this method deep-sift convolutional neural networks (DSCNN). The proposed method is validated against three state-of-the-art methods including AlexNet-3D, ResNet-3D, and VGG-3D, for TBV estimation using two datasets acquired from two different ultrasound devices. The results highlight a strong correlation between the predictions and the observed TBV values. The regression activation maps are used to interpret DSCNN, allowing TBV estimation by exploring those pixels that are more consistent and plausible from an anatomical standpoint. Therefore, it can be used for direct estimation of TBV from 3D images without needing further image segmentation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The purpose of this study is to define the impact of early brain growth trajectory in very low birth weight infants (VLBWI) on neurological prognosis at 2 years, assessed using sequential ultrasound (US) scans. This is a prospective cohort study with consecutive inclusion of VLBWI ≤ 32 weeks gestational age and ≤ 1500 g at birth. Total brain volume (TBV) was assessed using sequential 3D-US from birth to discharge. Prognosis at 2 years (corrected age) was assessed using the Bayley Scales of Infant and Toddler Development Third Edition. TBV showed slower growth with postmenstrual age (PMA) in those VLBWI who had an adverse cognitive prognosis compared to those with good cognitive prognosis (mean difference in TBV between prognostic groups from 4.56 cm 3 at 28 weeks to 42.58 cm 3 at 43 weeks) as well as in those with adverse language prognosis (mean difference in TBV from 2.21 cm 3 at 28 weeks to 26.98 cm 3 at 43 weeks) although other variables showed more impact than TBV on language prognosis (gestational age at birth, brain injury at term, and socioeconomic status). No association was found between TBV and motor prognosis. Brain growth rate was also significantly higher in those VLBWI who presented good cognitive scores (18.78 + (0.33 × (PMA-33)) cm 3 /week) compared to those with adverse cognitive outcome (13.73 + (0.64 × (PMA-33)) cm 3 /week).  Conclusion: Early altered brain growth is associated with poor cognitive prognosis at 2 years of age. Using sequential US monitoring, we can detect early brain growth deviation in patients who will have adverse cognitive outcomes. What is known: • The prediction of neurodevelopmental outcome of VLBWI is mostly based on the presence of brain injury in US and structural magnetic resonance imaging (MRI) at term. • Some studies have related brain volume measured on MRI at term with neurodevelopment outcome. What is new: • VLBWI with adverse cognitive prognosis at two years of age present smaller brain volumes detectable by sequential US during NICU admission. • Brain volume can be estimated from 2D and 3D US and has prognostic value in VLBWI., (© 2023. The Author(s).)

Objective: To study the potential role of ventricular volume (VV) estimation in the management of posthemorrhagic ventricular dilatation related to the need for ventriculoperitoneal (VP)-shunt insertion and 2-year neurodevelopmental outcome in infants born preterm., Study Design: We included 59 patients from the Early vs Late Ventricular Intervention Study from 4 participating centers. VV was manually segmented in 209 3-dimensional ultrasound scans and estimated from 2-dimensional ultrasound linear measurements in a total of 1226 ultrasounds. We studied the association of both linear measurements and VV to the need for VP shunt and 2-year neurodevelopmental outcome in the overall cohort and in the 29 infants who needed insertion of a reservoir. We used general estimating equations to account for repeated measures per individual., Results: Maximum pre-reservoir VV (β coefficient = 0.185, P = .0001) and gestational age at birth (β = -0.338; P = .0001) were related to the need for VP shunt. The estimated optimal single VV measurement cut point of 17 cm 3 correctly classified 79.31% with an area under the curve of 0.76 (CI 95% 0.74-0.79). Maximum VV (β = 0.027; P = .012) together with VP shunt insertion (β = 3.773; P = .007) and gestational age (β = -0.273; P = .0001) were related to cognitive outcome at 2 years. Maximum ventricular index and anterior horn width before reservoir insertion were independently associated with the need of VP shunt and the proposed threshold groups in the Early vs Late Ventricular Intervention Study trial were associated with long-term outcome., Conclusions: Pre-reservoir VV measurements were associated with the need for VP-shunt insertion and 2-year cognitive outcome among infants born preterm with posthemorrhagic ventricular dilatation., Trial Registration: ISRCTN43171322., Competing Interests: Declaration of Competing Interest I.B. received a grant from the Spanish Neonatology Society (SENeo-research projects grants 2021). No other disclosures are reported. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Preterm infants develop smaller brain volumes compared to term newborns. Our aim is to study early brain growth related to perinatal factors in very low birth weight infants (VLBWI)., Methods: Manual segmentation of total brain volume (TBV) was performed in weekly 3D-ultrasonographies in our cohort of VLBWI. We studied the brain growth pattern related to term magnetic resonance image (term-MRI)., Results: We found different brain growth trajectories, with smaller brain volumes and a decrease in brain growth rate in those VLBWI who would later have an abnormal term-MRI (mean TBV 190.68 vs. 213.9 cm3; P = 0.0001 and mean TBV growth rate 14.35 (±1.27) vs. 16.94 (±2.29) cm3/week; P = 0.0001). TBV in those with normal term-MRI was related to gestational age (GA), being small for gestational age (SGA), sex, and duration of parenteral nutrition (TPN) while in those with abnormal term-MRI findings it was related to GA, SGA, TPN, and comorbidities. We found a deceleration in brain growth rate in those with ≥3 comorbidities., Conclusions: An altered brain growth pattern in VLBWI who subsequently present worst scores on term-MRI is related to GA, being SGA and comorbidities. Early ultrasonographic monitoring of TBV could be useful to detect deviated patterns of brain growth., Impact Statement: We describe the brain growth pattern in very low birth weight infants during their first postnatal weeks. Brain growth may be affected in the presence of certain perinatal factors and comorbidities, conditioning a deviation of the normal growth pattern. The serial ultrasound follow-up of these at-risk patients allows identifying these brain growth patterns early, which offers a window of opportunity for implementing earlier interventions., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Children born preterm have increased rates of paediatric mortality and morbidity. Prematurity has been associated with impaired visual perception and visuo-motor integration. The alteration of the perception of verticality translates into alterations of the vestibular system at central and/or peripheral level, which may manifest itself in symptoms such as imbalance, dizziness or even vertigo. The aim of this study was to compare subjective visual vertical (SVV) test scores in children born preterm with those of children born at term at ages between 7 and 10. One hundred ten children with no neurodevelopmental disorder of 7 to 10 years of age were studied using a mobile application on a smartphone attached to a wall by means of a rotating plate. The SVV test was compared between two groups: a group of 55 preterm children (53 very preterm children born under 32 weeks of gestational age and 2 preterm with very low birth weight) and another group of 55 children born at term (after 37 weeks of gestational age). The SVV results were analysed for comparison with respect to prematurity, sex and age. We found no significant differences in the SVV study in the comparison between preterm and term children. In addition, no significant differences were observed regarding sex or age between 7 and 10 years.  Conclusion: We found no alterations in the perception of vertical subjectivity in children between 7 and 10 years of age, with antecedents of very preterm birth and/or very low birth weight. What is Known: • The different studies published so far suggest the existence of balance disorders in premature children, although in most of these studies the children are examined at an age when the vestibular system is not mature and with non-specific tests for the study of the vestibular system. What is New: • We compared the results of the subjective visual vertical (SVV) test in a group of 55 preterm children (53 very preterm children born under 32 weeks of gestational age and 2 preterm with very low weight at birth) and in a group of 55 children born at term (after 37 weeks of gestational age), at the ages of 7 to 10 years and observed no differences. • We conclude that, if there had been any vestibular alterations due to very premature birth, these must have been compensated by the age of 7., (© 2023. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The purpose of this study was to determine how preterm white matter injury (WMI) and long-term thalamic growth interact to predict 8-year neurodevelopmental outcomes., Methods: A prospective cohort of 114 children born at 24 to 32 weeks' gestational age (GA) underwent structural and diffusion tensor magnetic resonance imaging early in life (median 32 weeks), at term-equivalent age and at 8 years. Manual segmentation of neonatal WMI was performed on T1-weighted images and thalamic volumes were obtained using the MAGeT brain segmentation pipeline. Cognitive, motor, and visual-motor outcomes were evaluated at 8 years of age. Multivariable regression was used to examine the relationship among neonatal WMI volume, school-age thalamic volume, and neurodevelopmental outcomes., Results: School-age thalamic volumes were predicted by neonatal thalamic growth rate, GA, sex, and neonatal WMI volume (p < 0.0001). After accounting for total cerebral volume, WMI volume remained associated with school-age thalamic volume (β = -0.31, p = 0.005). In thalamocortical tracts, fractional anisotropy (FA) at term-equivalent age interacted with early WMI volume to predict school-age thalamic volumes (all p < 0.02). School-age thalamic volumes and neonatal WMI interacted to predict full-scale IQ (p = 0.002) and adverse motor scores among those with significant WMI (p = 0.01). Visual-motor scores were predicted by thalamic volumes (p = 0.04)., Interpretation: In very preterm-born children, neonatal thalamic growth and WMI volume predict school-age thalamic volumes. The emergence at term of an interaction between FA and WMI to impact school-age thalamic volume indicates dysmaturation as a mechanism of thalamic growth failure. Cognition is predicted by the interaction of WMI and thalamic growth, highlighting the need to consider multiple dimensions of brain injury in these children. ANN NEUROL 2021;90:584-594., (© 2021 American Neurological Association.)

Objective: To determine the usefulness of video recordings for validating neonatal encephalopathy (NE) exams., Design: Population-based prospective cohort study. NE was assessed and recorded at 1, 3 and 5 hours after birth by the attending physician. Recordings were reviewed blindly after the recruitment period by two specialists. Outcome was assessed at 36 months of age., Setting: Twelve intensive care units in Spain., Patients: Infants of ≥35 weeks' gestational age with perinatal asphyxia., Main Outcomes Measures: Weighted kappa to measure disagreement between the two specialists and between the attending physician and the specialists' classification agreed on by consensus. Regression models to test the association of disagreement on NE assessment and outcome., Results: Of the 32 325 liveborn infants, 217 met the inclusion criteria. Video-recordings were not available for 43 infants (20%). Weighted kappa statistic was 0.74 (95% CI 0.67 to 0.81) between the specialists and the attending physicians. Disagreement occurred in 93 of the 417 (22%) videos, specifically in 39 (14%), 43 (47%), 11 (34%) and 0 exams categorised as no, mild, moderate and severe NE, respectively. According to the specialist consensus assessment, there was disagreement on the therapeutic hypothermia decision in 10 infants.When there was consensus among the specialists assessing a more severe NE degree compared with the attending physicians in 170 infants, those infants had lower cognitive scores with a median of -5.33 points (95% CI -9.85 to -8.16; p=0.02)., Conclusions: This study supports the feasibility and benefit of using video recordings to identify NE in infants with perinatal asphyxia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to explore if manually segmented total brain volume (TBV) from 3D ultrasonography (US) is comparable to TBV estimated by magnetic resonance imaging (MRI). We then wanted to test 2D based TBV estimation obtained through three linear axes which would enable monitoring brain growth in the preterm infant during admission. Methods: We included very low birth weight preterm infants admitted to our neonatal intensive care unit (NICU) with normal neuroimaging findings. We measured biparietal diameter, anteroposterior axis, vertical axis from US and MRI and TBV from both MRI and 3D US. We calculated intra- and interobserver agreement within and between techniques using the intraclass correlation coefficient and Bland-Altman methodology. We then developed a multilevel prediction model of TBV based on linear measurements from both US and MRI, compared them and explored how they changed with increasing age. The multilevel prediction model for TBV from linear measures was tested for internal and external validity and we developed a reference table for ease of prediction of TBV. Results: We used measurements obtained from 426 US and 93 MRI scans from 118 patients. We found good intra- and interobserver agreement for all the measurements. US measurements were reliable when compared to MRI, including TBV which achieved excellent agreement with that of MRI [ICC of 0.98 (95% CI 0.96-0.99)]. TBV estimated through 2D measurements of biparietal diameter, anteroposterior axis, and vertical axis was comparable among both techniques. We estimated the population 95% confidence interval for the mean values of biparietal diameter, anteroposterior axis, vertical axis, and total brain volume by post-menstrual age. A TBV prediction table based on the three axes is proposed to enable easy implementation of TBV estimation in routine 2D US during admission in the NICU. Conclusions: US measurements of biparietal diameter, vertical axis, and anteroposterior axis are reliable. TBV segmented through 3D US is comparable to MRI estimated TBV. 2D US accurate estimation of TBV is possible through biparietal diameter, vertical, and anteroposterior axes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Benavente-Fernández, Ruiz-González, Lubian-Gutiérrez, Lubián-Fernández, Cabrales Fontela, Roca-Cornejo, Olmo-Duran and Lubián-López.)

Introduction: Acute appendicitis (AA) is the most frequent surgical pathology in pediatrics. However, publications discussing the most adequate antibiotic therapy for AA prophylaxis and treatment in children are limited., Material and Methods: A retrospective analysis of patients under 14 years of age hospitalized as a result of AA was carried out. The periods pre- and post- implementation of an antimicrobial optimization program (AOPR) were compared. The pre-AOPR period went from September 2017 to March 2019, while the post-AOPR period went from April 2019 to September 2019., Results: 206 patients were included, 139 in the pre-AOPR group, and 67 in the post-AOPR group. Dual therapy (ceftriaxone + metronidazole) and single therapy (cefoxitin) were more commonly used in the post-AOPR group (p= 0.0001), with reduced use of amoxicillin + clavulanic acid and piperacillin + tazobactam as an empirical therapy (p= 0.0001). To determine whether conversion to oral therapy was feasible or not, a number of clinical (no fever, sustained transit, adequate tolerance with satisfactory oral pain control) and blood test (a 20-50% CRP decrease from its highest level and a ≤ 12,000/mm3 leukocyte count) criteria were established. This allowed conversion to oral treatment to increase in the post-AOPR period (p=0.03). No differences in terms of hospital stay or complications were found between periods, but narrower spectrum oral antimicrobials were used earlier in the post-AOPR period., Conclusions: Implementing an AOPR for surgical pathologies and establishing protocols adapted to the resistance and microbiological profile found at each unit is strongly recommended.

The role of rhinoviruses (RVs) in children with clinical syndromes not classically associated with RV infections is not well understood. We analyzed a cohort of children ≤21 years old who were PCR+ for RV at a large Pediatric Hospital from 2011 to 2013. Using univariate and multivariable logistic regression, we analyzed the associations between demographic, clinical characteristics, microbiology data, and clinical outcomes in children with compatible symptoms and incidental RV detection. Of the 2473 children (inpatients and outpatients) with an RV+ PCR, 2382 (96%) had compatible symptoms, and 91 (4%) did not. The overall median age was 14 months and 78% had underlying comorbidities. No differences in RV viral loads were found according to the presence of compatible symptoms, while in children with classic RV symptoms, RV viral loads were higher in single RV infections versus RV viral co-infections. Bacterial co-infections were more common in RV incidental detection (7.6%) than in children with compatible symptoms (1.9%, p < 0.001). The presence of compatible symptoms independently increased the odds ratio (OR, 95% CI) of hospitalization 4.8 (3.1-7.4), prolonged hospital stays 1.9 (1.1-3.1), need for oxygen 12 (5.8-25.0) and pediatric intensive care unit (PICU) admission 4.13 (2.0-8.2). Thus, despite comparable RV loads, disease severity was significantly worse in children with compatible symptoms.

To train, evaluate, and validate the application of a deep learning framework in three-dimensional ultrasound (3D US) for the automatic segmentation of ventricular volume in preterm infants with post haemorrhagic ventricular dilatation (PHVD). We trained a 2D convolutional neural network (CNN) for automatic segmentation ventricular volume from 3D US of preterm infants with PHVD. The method was validated with the Dice similarity coefficient (DSC) and the intra-class coefficient (ICC) compared to manual segmentation. The mean birth weight of the included patients was 1233.1 g (SD 309.4) and mean gestational age was 28.1 weeks (SD 1.6). A total of 152 serial 3D US from 10 preterm infants with PHVD were analysed. 230 ventricles were manually segmented. Of these, 108 were used for training a 2D CNN and 122 for validating the methodology for automatic segmentation. The global agreement for manual versus automated measures in the validation data (n = 122) was excellent with an ICC of 0.944 (0.874-0.971). The Dice similarity coefficient was 0.8 (± 0.01). 3D US based ventricular volume estimation through an automatic segmentation software developed through deep learning improves the accuracy and reduces the processing time needed for manual segmentation using VOCAL. 3D US should be considered a promising tool to help deepen our current understanding of the complex evolution of PHVD.

Objective: To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental disability., Study Design: This multicenter randomized controlled trial reviewed lumbar punctures initiated after either a low threshold (ventricular index of >p97 and anterior horn width of >6 mm) or high threshold (ventricular index of >p97 + 4 mm and anterior horn width of >10 mm). The composite adverse outcome was defined as death or cerebral palsy or Bayley composite cognitive/motor scores <-2 SDs at 24 months corrected age., Results: Outcomes were assessed in 113 of 126 infants. The composite adverse outcome was seen in 20 of 58 infants (35%) in the low threshold group and 28 of 55 (51%) in the high threshold (P = .07). The low threshold intervention was associated with a decreased risk of an adverse outcome after correcting for gestational age, severity of intraventricular hemorrhage, and cerebellar hemorrhage (aOR, 0.24; 95% CI, 0.07-0.87; P = .03). Infants with a favorable outcome had a smaller fronto-occipital horn ratio (crude mean difference, -0.06; 95% CI, -0.09 to -0.03; P < .001) at term-equivalent age. Infants in the low threshold group with a ventriculoperitoneal shunt, had cognitive and motor scores similar to those without (P = .3 for both), whereas in the high threshold group those with a ventriculoperitoneal shunt had significantly lower scores than those without a ventriculoperitoneal shunt (P = .01 and P = .004, respectively)., Conclusions: In a post hoc analysis, earlier intervention was associated with a lower odds of death or severe neurodevelopmental disability in preterm infants with progressive posthemorrhagic ventricular dilatation., Trial Registration: ISRCTN43171322., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: This study aimed to describe normal C-reactive protein (CRP) levels of newborns diagnosed with hypoxic-ischemic encephalopathy (HIE) and assess the influence of therapeutic hypothermia (TH) and the severity of HIE., Study Design: We prospectively recruited infants ≥35 weeks of gestational age diagnosed with HIE from 2000 to 2013 and compared CRP levels in the first 120 hours of life according to the severity of HIE and the use of TH, which was introduced in 2009., Results: Moderate HIE was diagnosed in 115 newborns, severe HIE in 90 (hypothermia was performed in 151 cases), and mild HIE in 20. Cooled newborns showed lower levels of CRP in the first 34 hours, but reached higher median maximum CRP levels (15.4 vs. 8.5 mg/L), and at a significantly older age (53 vs. 17 hours). Levels of CRP in mild HIE were lower than those of moderate-severe forms. Moderate and severe HIE had similar CRP levels, but time to maximum CRP was significantly less in moderate cases., Conclusion: CRP levels of mild HIE are similar to healthy newborns, while CRP elevations can be expected in newborns with moderate-severe HIE. TH produced a slower rise, with a higher and late maximum CRP peak level., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Myocardial function in very-low-birth-weight infants (VLBWIs) develops during early postnatal life, but different patterns of temporal evolution that might be related to the development of bronchopulmonary dysplasia (BPD) are not completely understood. Methods: A prospective cohort study including VLBWIs admitted to our NICU from January 2015 to 2017 was conducted. Plasma N-terminal pro B type natriuretic peptide (NTproBNP) levels were measured, and echocardiograms were performed at 24 and 72 h of life and weekly thereafter until 36 weeks of postmenstrual age (PMA). We measured the tricuspid annular plane systolic excursion (TAPSE) by M-mode; the lateral tricuspid E', A', and S' waves; and the myocardial performance index (MPI) by tissue doppler imaging (TDI). The subjects were divided into non-BPD and BPD groups. Results: We included 101 VLBWIs. The TAPSE and E', A', and S' waves increased while MPI-TDI decreased over time. Birth gestational age (GA) and postnatal PMA impacted these parameters, which evolved differently in those who developed BPD compared to those in the non-BPD group. The NTproBNP levels at 14 days of life and different echocardiographic parameters were associated with the development of BPD in different multivariate models. Conclusion: TAPSE and TDI values depend on GA and PMA and follow a different temporal evolution that is related to the later development of BPD. Combined biochemical and echocardiographic biomarkers can help identify which VLBWIs are at higher risk of developing BDP., (Copyright © 2020 Méndez-Abad, Zafra-Rodríguez, Lubián-López and Benavente-Fernández.)

Improved intensive care therapies have increased the survival of children born preterm. Yet, many preterm children experience long-term neurodevelopmental sequelae. Indeed, preterm birth remains a leading cause of lifelong neurodevelopmental disability globally, posing significant challenges to the child, family, and society. Neurodevelopmental disability in children born preterm is traditionally linked to acquired brain injuries such as white matter injury and to impaired brain maturation resulting from neonatal illness such as chronic lung disease. Socioeconomic status (SES) has long been recognized to contribute to variation in outcome in children born preterm. Recent brain imaging data in normative term-born cohorts suggest that lower SES itself predicts alterations in brain development, including the growth of the cerebral cortex and subcortical structures. Recent evidence in children born preterm suggests that the response to early-life brain injuries is modified by the socioeconomic circumstances of children and families. Exciting new data points to the potential of more favorable SES circumstances to mitigate the impact of neonatal brain injury. This review addresses emerging evidence suggesting that SES modifies the relationship between early-life exposures, brain injury, and neurodevelopmental outcomes in children born preterm. Better understanding these relationships opens new avenues for research with the ultimate goal of promoting optimal outcomes for those children born preterm at highest risk of neurodevelopmental consequence.

Cerebral oximetry using near-infrared spectroscopy (NIRS) provides continuous, noninvasive assessment of the degree of hemoglobin saturation of the brain tissue. Previous studies suggest that high values of regional cerebral tissue oxygen saturation (rScO 2 ) during the first days in neonates with significant hypoxic-ischemic encephalopathy (HIE) are correlated with an adverse neurological outcome. However, the results are not consistent among the studies. To examine the correlation of rScO 2 values and their variability over time with HIE severity, amplitude integrated electroencephalography (aEEG) background and seizure activity, neuron-specific enolase levels in cerebrospinal fluid, magnetic resonance imaging (MRI) findings, and neurological outcome. Retrospective study that included all consecutive infants with moderate-to-severe HIE born at ≥35 weeks gestational age admitted between January 2011 and December 2014. NIRS monitoring was initiated at admission and maintained during therapeutic hypothermia up to 12 hours after rewarming. To analyze rScO 2 , different periods (0-6, 6-24, 24-48, 48-72, and 72-100 hours of life) and three ranges (<55%, 55-90%, >90%) were considered. Variability in each patient was considered ≤5% when changes in rScO 2 values in all periods were ≤5%. Twenty-three newborns were included. Infants who suffered from severe HIE, seizures, abnormal aEEG background, altered MRI or death, and abnormal outcome had rScO 2 values >90% and with less variability (≤5%). rScO 2 values >90% and a lack of variability over time in infants with HIE during cooling provide useful information about the severity of neurological status.

Objective: To develop a simple imaging rule to predict neurodevelopmental outcomes at 4.5 years in a cohort of preterm neonates with white matter injury (WMI) based on lesion location and examine whether clinical variables enhance prediction., Methods: Sixty-eight preterm neonates born 24-32 weeks' gestation (median 27.7 weeks) were diagnosed with WMI on early brain MRI scans (median 32.3 weeks). 3D T1-weighted images of 60 neonates with 4.5-year outcomes were reformatted and aligned to the posterior commissure-eye plane and WMI was classified by location: anterior or posterior-only to the midventricle line on the reformatted axial plane. Adverse outcomes at 4.5 years were defined as Wechsler Preschool and Primary Scale of Intelligence full-scale IQ <85, cerebral palsy, or Movement Assessment Battery for Children, second edition percentile <5. The prediction of adverse outcome by WMI location, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP) was assessed using multivariable logistic regression., Results: Six children had adverse cognitive outcomes and 17 had adverse motor outcomes. WMI location predicted cognitive outcomes in 90% (area under receiver operating characteristic curve [AUC] 0.80) and motor outcomes in 85% (AUC 0.75). Adding IVH, BPD, and ROP to the model enhances the predictive strength for cognitive and motor outcomes (AUC 0.83 and 0.88, respectively). Rule performance was confirmed in an independent cohort of children with WMI., Conclusions: WMI on early MRI can be classified by location to predict preschool age outcomes in children born preterm. The predictive value of this WMI classification is enhanced by considering clinical factors apparent by term-equivalent age., (© 2019 American Academy of Neurology.)

Internal carotid arterial dissection is a rare and probably underestimated cause of neonatal stroke. We report a case of neonatal stroke underscoring the role of Doppler sonography of the intracranial arteries for the diagnosis and follow-up tool., (© 2019 Wiley Periodicals, Inc.)

The objective is to examine the correlation between plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tissue Doppler imaging (TDI) echocardiographic parameters in the first 28 days of life in very-low-birth-weight infants (VLBWI). VLBWI admitted to the Neonatal Intensive Care Unit (NICU) at Hospital Puerta del Mar, Spain, from January 2015 to January 2017 were prospectively enrolled. Weekly determination of plasma NT-proBNP (pg/mL), and echocardiograms were done during the first 28 days of life. 101 preterm infants with a mean GA of 28.85 weeks (± 1.85 SD) and mean birth weight of 1152 g (± 247.4 SD) were included. A total of 483 echocardiograms and 139 NT-proBNP determinations were performed. We found a negative correlation between plasma NT-proBNP levels and diastolic velocities: mitral A' (ρ = - 0.15, p = 0.04), mitral E' (ρ = - 0.17, p = 0.02), tricuspid A' (ρ = - 0.20, p = 0.006), tricuspid E' (ρ = - 0.24, p = 0.0009). In the first 24 h of life, NT-proBNP levels were strongly correlated with mitral A' and E' velocities in patients with no patent ductus arteriosus (PDA) (ρ = - 0.75, p = 0.04). In preterm patients, elevated NT-proBNP levels are related to worse diastolic myocardial function. In the first 24 h, this correlation is much stronger in the absence of PDA.

The care of the umbilical cord until its detachment still remains controversial. The latest updated recommendations by the World Health Organisation advocate dry cord care in those countries with adequate obstetric care and low neonatal mortality rate. In recent years, new studies and reviews attribute some benefit to applying chlorhexidine on the umbilical stump. An analysis is presented here of the available evidence and results in the advisability of still recommending the dry cord care in the newborns in our setting., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

Objectives: This study aims to analyze the variability between two trained neonatologists when performing consecutive echocardiograms using tissue Doppler imaging (TDI) and conventional methods in very low birth weight infant (VLBWI)., Methods: Two serial echocardiograms were performed in 30 VLBWI infants. The echocardiographic parameters analyzed were tricuspid annular plane systolic excursion (TAPSE), A', E', and S' waves, and myocardial performance index acquired by TDI (MPI-TDI) of both ventricles and shortening fraction (SF). The intra-observer and inter-observer agreements and the intra-operator agreement were analyzed using quantitative and qualitative statistical methods., Results: The intra-observer agreement was very good, TAPSE, and TDI-derived parameters had an intra-class correlation (ICC) > 0.8. TDI-derived velocities had a coefficient of variation (COV) < 11%, while MPI-TDI had a COV between 20%-28%. The inter-observer agreement was excellent. There was greater variability when analyzing intra-operator agreement, with the least variable parameter being TAPSE. According to PABAK, the variability presented moderately substantial agreement., Conclusions: Tricuspid annular plane systolic excursion is very reproducible between observers and operators. Measurements of TDI wave velocities are more reproducible than MPI-TDI. TDI is sufficiently reproducible in the VLBWI if adequate training is performed, and guidelines are followed to obtain standardized echocardiographic images., (© 2019 Wiley Periodicals, Inc.)

Importance: Studies of socioeconomic status and neurodevelopmental outcome in very preterm neonates have not sensitively accounted for brain injury., Objective: To determine the association of brain injury and maternal education with motor and cognitive outcomes at age 4.5 years in very preterm neonates., Design, Setting, and Participants: Prospective cohort study of preterm neonates (24-32 weeks' gestation) recruited August 16, 2006, to September 9, 2013, at British Columbia Women's Hospital in Vancouver, Canada. Analysis of 4.5-year outcome was performed in 2018., Main Outcomes and Measures: At age 4.5 years, full-scale IQ assessed using the Wechsler Primary and Preschool Scale of Intelligence, Fourth Edition, and motor outcome by the percentile score on the Movement Assessment Battery for Children, Second Edition., Results: Of 226 survivors, neurodevelopmental outcome was assessed in 170 (80 [47.1%] female). Based on the best model to assess full-scale IQ accounting for gestational age, standardized β coefficients demonstrated the effect size of maternal education (standardized β = 0.21) was similar to that of white matter injury volume (standardized β = 0.23) and intraventricular hemorrhage (standardized β = 0.23). The observed and predicted cognitive scores in preterm children born to mothers with postgraduate education did not differ in those with and without brain injury. The best-performing model to assess for motor outcome accounting for gestational age included being small for gestational age, severe intraventricular hemorrhage, white matter injury volume, and chronic lung disease., Conclusions and Relevance: At preschool age, cognitive outcome was comparably associated with maternal education and neonatal brain injury. The association of brain injury with poorer cognition was attenuated in children born to mothers of higher education level, suggesting opportunities to promote optimal outcomes.

Bronchopulmonary dysplasia (BPD) is a severe complication of prematurity that impacts survival and neurodevelopment. Currently, no early marker exists which could help clinicians identify which preterm infants will develop BPD. Given the evidence that NTproBNP is elevated in children with BPD, we hypothesized that it could be used as an early marker of BPD development. We conducted a prospective cohort study including very low birth weight infants (VLBWI) admitted to our NICU between January 2015 and January 2017 in which we determined serial NTproBNP levels on days 1 and 3 and then weekly, until 49 days of life. A total of 101 patients were recruited (mean birth weight 1152 g (SD 247.5), mean gestational age 28.9 weeks (SD 1.9)). NTproBNP levels differed among infants who did and did not develop BPD from 14 to 35 days of life with the greatest difference on day 14 of life (non-BPD group (n = 86): 1155 (IQR 852-1908) pg/mL, BPD (n = 15): 9707 (IQR 3212-29,560) pg/mL; p = 0.0003). The presence of HsPDA did not account for higher levels of NTproBNP at day 14 (p = 0.165). We calculated an optimal cutoff point of 2264 pg/mL at 14 days of life (sensitivity 100%, specificity 86% and AUC 0.93).Conclusions: NTproBNP at 14 days of life could be used as an early marker of later BPD development in VLBWI. What is Known: • Children with BPD have elevated NTproBNP levels, which are related to the severity of BPD and the development of pulmonary hypertension. What is New: • NTproBNP at 14 days of life is higher in those who later develop BPD, regardless of the presence of hemodynamically significant patent ductus arteriosus. • A calculated cutoff point of 2264 pg/mL of NTproBNP at 14 days has a sensitivity of 100% and specificity of 86% in the prediction of BPD.

Objective: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI., Study Design: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis., Results: The total Kidokoro score of the infants in the low-threshold group (n = 44) was lower than in the high-threshold group (n = 44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P < .001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P = .002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P = .001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P = .03)., Conclusions: More brain injury and larger ventricular volumes were demonstrated in the high vs the low-threshold group. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation., Trial Registration: ISRCTN43171322., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (© 2019 S. Karger AG, Basel.)

Objective: To compare a low versus a higher threshold for intervention in preterm infants with posthaemorrhagic ventricular dilatation., Design: Multicentre randomised controlled trial (ISRCTN43171322)., Setting: 14 neonatal intensive care units in six countries., Patients: 126 preterm infants ≤34 weeks gestation with ventricular dilatation after grade III-IV haemorrhage were randomised to low threshold (LT) (ventricular index (VI) >p97 and anterior horn width (AHW) >6 mm) or higher threshold (HT) (VI>p97+4 mm and AHW >10 mm)., Intervention: Cerebrospinal fluid tapping by lumbar punctures (LPs) (max 3), followed by taps from a ventricular reservoir, to reduce VI, and eventually a ventriculoperitoneal (VP) shunt if stabilisation of the VI below the p97+4 mm did not occur., Composite Main Outcome Measure: VP shunt or death., Results: 19 of 64 (30%) LT infants and 23 of 62 (37%) HT infants were shunted or died (P=0.45). A VP shunt was inserted in 12/64 (19%) in the LT and 14/62 (23%) infants in the HT group. 7/12 (58%) LT infants and 1/14 (7%) HT infants required shunt revision (P<0.01). 62 of 64 (97%) LT infants and 36 of 62 (58%) HT infants had LPs (P<0.001). Reservoirs were inserted in 40 of 64 (62%) LT infants and 27 of 62 (43%) HT infants (P<0.05)., Conclusions: There was no significant difference in the primary composite outcome of VP shunt placement or death in infants with posthaemorrhagic ventricular dilatation who were treated at a lower versus a higher threshold for intervention. Infants treated at the lower threshold received more invasive procedures. Assessment of neurodevelopmental outcomes will provide further important information in assessing the risks and benefits of the two treatment approaches., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Current guidelines in Spain recommend performing transthoracic echocardiography (TTE) in all children under 2 years of age with a heart murmur. In 2014, the American Paediatric Association published the first appropriate use criteria (AUC) for outpatient paediatric transthoracic echocardiography (TTE) to promote its cost-efficient use. The aim of this article is to analyse the AUC and other clinical factors as predictors of congenital heart disease (CHD) in children less than 2 years of age with a heart murmur, and to develop a safe and efficient referral strategy., Patients and Method: Case-control study conducted with children less than 2 years of age, referred from Paediatric Primary Care to Paediatric Cardiology during a 4-year study. A predictive model for CHD was determined using multivariate analysis., Results: A total of 688 patients were included, with 129 (19%) cases of CHD. An age less than 3 months (adjusted odds ratio [ORa] 3.8 [1.5-8.4], p=.030) and fulfilling AUC (ORa 16.3 [9.4-28.3], p<.001) were predictors of CHD. Concurrent infection (ORa 0.6 [0.2-0.8], p<.001) and a negative neonatal screening with pulse oximetry (ORa 0.1 [0.05-0.4], p=.001) decreased the risk of CHD. The referral strategy that included these criteria had a 98% sensitivity, 39% specificity, and positive and negative predictive values of 27% and 99%, respectively. It could not diagnose 2% of CHD (all mild), and showed a 32% TTE reduction rate compared to our current strategy., Conclusion: To refer children less than 3 months old, fulfilling AUC, without a concurrent infection, or without negative neonatal pulse oximetry screening, is a safe and efficient strategy for the management of heart murmur in children under 2 years of age., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background  Neonatal encephalopathy with seizures after general anesthesia not occurring in infants undergoing cardiac or major neurosurgery is very uncommon. An ischemic origin due to cerebral hypoperfusion from perioperative hypotension has been suggested, but there is a lack of a consensus definition for intraoperatory hypotension in neonates. Case Report  We report the first case of neonatal encephalopathy with seizures in a neonate with anorectal malformation. He underwent a colostomy with caudal anesthesia combined with light general anesthesia. Intraoperative systolic blood pressure and mean blood pressure values were considered normal. Thirty-two hours after the intervention, the patient presented electroclinical seizures. Diffusion-weighted imaging showed bilateral involvement with reduced diffusivity in the watershed areas of the middle cerebral artery and posterior cerebral artery. Conclusion  Perioperative monitoring of blood pressure is not enough in neonatal surgery. Cerebral magnetic resonance imaging should be considered in infants with noncardiac congenital anomalies after neonatal surgery and long-term follow-up is required.

Purpose To establish cross-sectional and longitudinal reference values for cerebellar size in preterm infants with normal neuroimaging findings and normal 2-year neurodevelopmental outcome by using cranial ultrasonography (US). Materials and Methods This prospective study consecutively enrolled preterm infants admitted to a neonatal intensive care unit from June 2011 to June 2014 with a birth weight of less than or equal to 1500 g and/or gestational age (GA) of less than or equal to 32 weeks. They underwent weekly cranial US from birth to term-equivalent age and magnetic resonance (MR) imaging at term-equivalent age. The infants underwent neurodevelopmental assessments at age 2 years with Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). Patients with adverse outcomes (death or abnormal neuroimaging findings and/or BSID-III score of <85) were excluded. The following measurements were performed: vermis height, craniocaudal diameter, superior width, inferior width, vermis area, and transcerebellar diameter. Statistical analyses were conducted by using multilevel analyses. Results A total of 137 infants with a mean GA at birth of 29.4 weeks (range, 25-32 weeks) were included. Transcerebellar diameter increased by 1.04 mm per week on average; vermis height and craniocaudal diameter increased by 0.55 mm and 0.59 mm, respectively. Superior vermian width increased by an average of 0.45 mm, whereas inferior vermian width increased by an average of 0.51 mm per week. Vermis area was found to increase by 0.22 cm 2 per week on average. The sex effect was significant (female lower than male) for vermis height (P < .05), craniocaudal diameter (P < .05), inferior vermian width (P <. 05), and vermis area (P <. 05). Conclusion Cross-sectional and longitudinal reference values were established for cerebellar growth in preterm infants, which may be included in routine cranial US., (© RSNA, 2018 Online supplemental material is available for this article.)

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., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Neonatal facial palsy is very uncommon and is generally diagnosed at birth. We present the first published case of neonatal facial palsy with identification of herpes simplex virus 1 in cerebrospinal fluid. A 35-day-old male was presented at the Emergency Department with mouth deviation to the left and impossibility of full closure of the right eye. There were no symptoms of infection or relevant medical history. Physical examination was compatible with peripheral facial palsy. Studies performed at admission were normal (blood count, biochemical analysis and coagulation blood tests and cerebrospinal fluid analysis). The patient was admitted on oral prednisolone and intravenous aciclovir. Cranial magnetic resonance was normal. Polymerase chain reaction test for herpes simplex virus 1 in cerebrospinal fluid was reported positive after 48 hours of admission. Patient followed good evolution and received prednisolone for 7 days and acyclovir for 21 days. At discharge, neurological examination was normal., (Sociedad Argentina de Pediatría.)

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.

Due to its severity, as well as the consequences of a late diagnosis, critical congenital heart defects (CCHD) represent a challenging situation, making an early diagnosis necessary and ideally before symptoms appear when circulatory collapse or death of the newborn can occur. Due to this, a prenatal and very early postnatal diagnosis is very important. Prenatal ultrasound screening and physical examination of the newborn can miss a considerable number of CCHD cases. Pulse oximetry screening has been demonstrated to be an effective, non-invasive, inexpensive, and well accepted tool in the early diagnosis of CCHD. The Spanish National Society of Neonatology, through its Standards Committee, and based on the current evidence, recommend the implementation of pulse oximetry screening of CCHD in Spain, and then to offer the best therapy possible to these newborn infants., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Therapeutic hypothermia (TH) initiated within 6 h from birth is the most effective therapeutic approach for moderate to severe hypoxic-ischemic encephalopathy (HIE). However, underlying mechanisms and effects on the human metabolism are not yet fully understood. This work aims at studying the evolution of several energy related key metabolites in newborns with HIE undergoing TH employing gas chromatography - mass spectrometry. The method was validated following stringent FDA requirements and applied to 194 samples from a subgroup of newborns with HIE (N = 61) enrolled in a multicenter clinical trial (HYPOTOP) for the determination of lactate, pyruvate, ketone bodies and several Krebs cycle metabolites at different sampling time points. The analysis of plasma samples from newborns with HIE revealed a decrease of lactate, pyruvate and β-hydroxybutyrate concentrations, whereas rising malate concentrations were observed. In healthy control newborns (N = 19) significantly lower levels of pyruvate and lactate were found in comparison to age-matched newborns with HIE undergoing TH, whereas acetoacetate and β-hydroxybutyrate levels were clearly increased. Access to a validated analytical method and a controlled cohort of newborns with HIE undergoing hypothermia treatment for the first time allowed the in-depth study of the evolution of key metabolites of metabolic junctions in this special population.