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Background: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45-50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol - a xanthine oxidase inhibitor - reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE., Methods/design: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years., Results: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and ."will be stratified for the two treatment groups., Discussion: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines., Trial Registration: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017., (© 2024. The Author(s).)

Background: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks' postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability, or any harm in trial participants at 2 years of corrected age. One important challenge is the lack of funding for local costs for a trial-specific assessment., Methods: Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks' postmenstrual age and will potentially be available for the 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 30 months of corrected age. If no routine follow-up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children's Abilities-Revised. There will be two co-primary outcomes: the composite of death or moderate or severe neurodevelopmental disability and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss to follow-up assuming that little data is better than no data at all., Discussion: Follow-up at the age of 2 years is important for intervention trials in the newborn period as only time can show real benefits and harms later in childhood. To decrease the risk of generalisation and data-driven biased conclusions, we present a detailed description of the methodology for the SafeBoosC-III follow-up study. As funding is limited, a pragmatic approach is necessary., Trial Registration: ClinicalTrials.gov NCT05134116 . Registered on 24 November 2021., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In neonates with hypoxic ischemic encephalopathy, the computation of wavelet coherence between electroencephalogram (EEG) power and regional cerebral oxygen saturation (rSO2) is a promising method for the assessment of neurovascular coupling (NVC), which in turn is a promising marker for brain injury. However, instabilities in arterial oxygen saturation (SpO2) limit the robustness of previously proposed methods. Therefore, we propose the use of partial wavelet coherence, which can eliminate the influence of SpO2. Furthermore, we study the added value of the novel NVC biomarkers for identification of brain injury compared to traditional EEG and NIRS biomarkers. 18 neonates with HIE were monitored for 72 h and classified into three groups based on short-term MRI outcome. Partial wavelet coherence was used to quantify the coupling between C3-C4 EEG bandpower (2-16 Hz) and rSO2, eliminating confounding effects of SpO2. NVC was defined as the amount of significant coherence in a frequency range of 0.25-1 mHz. Partial wavelet coherence successfully removed confounding influences of SpO2 when studying the coupling between EEG and rSO2. Decreased NVC was related to worse MRI outcome. Furthermore, the combination of NVC and EEG spectral edge frequency (SEF) improved the identification of neonates with mild vs moderate and severe MRI outcome compared to using EEG SEF alone. Partial wavelet coherence is an effective method for removing confounding effects of SpO2, improving the robustness of automated assessment of NVC in long-term EEG-NIRS recordings. The obtained NVC biomarkers are more sensitive to MRI outcome than traditional rSO2 biomarkers and provide complementary information to EEG biomarkers., (© 2022. The Author(s).)

Background: Recent studies explored the relationship between early brain function and brain morphology, based on the hypothesis that increased brain activity can positively affect structural brain development and that excitatory neuronal activity stimulates myelination., Objective: To investigate the relationship between maturational features from early and serial aEEGs after premature birth and MRI metrics characterizing structural brain development and injury, measured around 30weeks postmenstrual age (PMA) and at term. Moreover, we aimed to verify whether previously developed maturational EEG features are related with PMA., Design/methods: One hundred six extremely preterm infants received bedside aEEGs during the first 72h and weekly until week 5. 3T-MRIs were performed at 30weeks PMA and at term. Specific features were extracted to assess EEG maturation: (1) the spectral content, (2) the continuity [percentage of spontaneous activity transients (SAT%) and the interburst interval (IBI)], and (3) the complexity. Automatic MRI segmentation to assess volumes and MRI score was performed. The relationship between the maturational EEG features and MRI measures was investigated., Results: Both SAT% and EEG complexity were correlated with PMA. IBI was inversely associated with PMA. Complexity features had a positive correlation with the cerebellar size at 30weeks, while event-based measures were related to the cerebellar size at term. Cerebellar width, cortical grey matter, and total brain volume at term were inversely correlated with the relative power in the higher frequency bands., Conclusions: The continuity and complexity of the EEG steadily increase with increasing postnatal age. Increasing complexity and event-based features are associated with cerebellar size, a structure with enormous development during preterm life. Brain activity is important for later structural brain development., (© 2021. The Author(s).)

Unlabelled: Brain injuries remain a significant problem for preterm infants, despite extensive physiological monitoring. Near infrared spectroscopy (NIRS) monitoring in the neonatal intensive care unit has to date remained limited to research activities., Conclusion: This review highlights the increasing clinical application of NIRS in delivery suites and neonatal units. Four randomised controlled trials incorporating NIRS monitoring suggest that the future may indeed be brighter for this technology in the care of very preterm infants., (©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Since some important forms of brain injury in premature infants are caused in considerable part by disturbances in cerebral blood flow (CBF), it is important to be able to detect whether the cerebrovascular autoregulation, the mechanism by which CBF is maintained constant despite alterations in mean arterial blood pressure (MAP), is working properly. A recent study suggested that concordant changes in MAP and cerebral intravascular oxygenation (HbD), measured non-invasively by near-infrared spectroscopy (NIRS) as the difference between the concentration changes of oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (Hb), reflect impaired cerebrovascular autoregulation. Consequently, premature infants with impaired cerebrovascular autoregulation could be identified by simultaneous, continuous measurements of HbD and MAP. From several premature babies, MAP, HbD and arterial oxygen saturation (SaO2) were measured simultaneously at the University Hospital Leuven, Belgium. The concordance between MAP and HbD was quantitated using three different measures, among which a newly developed measure that looks for similarity of the dynamics between signals. Some preliminary results obtained from the measured data are given.

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