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Objective . This study provides an adaptive threshold algorithm for burst detection in electroencephalograms (EEG) of preterm infantes and evaluates its performance using clinical real-world EEG data. Approach . We developed an adaptive threshold algorithm for burst detection in EEG recordings from preterm infants. To assess its applicability in the real-world, we tested the algorithm on a dataset of 30 clinical EEG recordings which were not preselected for good quality, to ensure a real-world scenario. Main results . Interrater agreement was substantial at a kappa of 0.73 (0.68-0.79 inter-quantile range). The performance of the algorithm showed a similar agreement with one clinical expert of 0.73 (0.67-0.76) and a sensitivity and specificity of 0.90 (0.82-0.94) and 0.95 (0.93-0.97), respectively. Significance . The adaptive threshold algorithm demonstrated robust performance in detecting burst patterns in clinical EEG data from preterm infants, highlighting its practical utility. The fine-tuned algorithm achieved similar performance to human raters. The algorithm proves to be a valuable tool for automated burst detection in the EEG of preterm infants., (Creative Commons Attribution license.)

Objective: The aim of this study was the evaluation of the impact of a respiratory function monitor (RFM, Neo100, Monivent AB, Gothenburg, Sweden) on the quality of ventilation in neonates., Methods: This single-center two-phase intervention study was conducted at the Neonatal Intensive Care Unit and the delivery room of the Medical University of Vienna. Patients with clinical need for positive pressure ventilation were included in either of two consecutive study phases: (i) patients were ventilated with a hidden RFM (control) or (ii) visible RFM (intervention) during manual positive pressure ventilations. The duration of each phase was approximately six months. The primary outcome was the percentage of ventilations within a tidal volume range of 4-8 ml/kg (pV Te )., Results: A total of 90 patients (GA 22-66 weeks) were included. The primary outcome was significantly higher in the intervention group with a visible RFM (53.7%, SD 22.6) than in the control group without the monitor (37.3%, SD 20.5); (p < 0.001, mean difference [i.e., change in percentage points]: 16.95% CI: 7.4-35). In terms of secondary outcomes, excessive tidal volumes (>8ml/kg), potentially associated with an increased risk of brain injury, could be significantly reduced when a RFM was visible during ventilation (10.9% [IQR 26.4] vs. 29.5% [IQR 38.1]; p = 0.004). Furthermore, mask leakage could be significantly decreased (37.3% [SD 22.7] vs. 52.7% [SD 23.0]; p = 0.002)., Conclusion: Our results suggest that the clinical application of a RFM for manual ventilation of preterm and term infants leads to a significant improvement in ventilation parameters., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael Wagner reports financial support and equipment, or supplies were provided by Monivent AB. All other 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To define percentile charts for arterial oxygen saturation (SpO 2 ), heart rate (HR), and cerebral oxygen saturation (crSO 2 ) during the first 15 minutes after birth in neonates born very or extremely preterm and with favorable outcome., Study Design: We conducted a secondary-outcome analysis of neonates born preterm included in the Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth III (COSGOD III) trial with visible cerebral oximetry measurements and with favorable outcome, defined as survival without cerebral injuries until term age. We excluded infants with inflammatory morbidities within the first week after birth. SpO 2 was obtained by pulse oximetry, and electrocardiogram or pulse oximetry were used for measurement of HR. crSO 2 was assessed with near-infrared spectroscopy. Measurements were performed during the first 15 minutes after birth. Percentile charts (10th to 90th centile) were defined for each minute., Results: A total of 207 neonates born preterm with a gestational age of 29.7 (23.9-31.9) weeks and a birth weight of 1200 (378-2320) g were eligible for analyses. The 10th percentile of SpO 2 at minute 2, 5, 10, and 15 was 32%, 52%, 83%, and 85%, respectively. The 10th percentile of HR at minute 2, 5, 10, and 15 was 70, 109, 126, and 134 beats/min, respectively. The 10th percentile of crSO 2 at minute 2, 5, 20, and 15 was 15%, 27%, 59%, and 63%, respectively., Conclusions: This study provides new centile charts for SpO 2 , HR, and crSO 2 for neonates born extremely or very preterm with favorable outcome. Implementing these centiles in guiding interventions during the stabilization process after birth might help to more accurately target oxygenation during postnatal transition period., Competing Interests: Declaration of Competing Interest The COSGOD III trial received support from the Austrian Science Fund and the Health Research Board (HRB) Clinical Research Facility at the University of Cork for the submitted work and from the Stollery Children’s Hospital Foundation facilitated by the Women and Children’s Health Research Institute; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. The COSGOD III trial was funded by the Austrian Science Fund (Fonds zur Förderung der wissenschaftlichen Forschung [FWF] Austria) through an unconditional and unrestricted grant (KLI 586-B31). Health Research Board (HRB) Clinical Research Facility at University College Cork supported the study at the Infant Centre, University College Cork, Cork University Maternity Hospital, Cork, Ireland. G.S. was a recipient of the Heart and Stroke Foundation/University of Alberta Professorship of Neonatal Resuscitation, a National New Investigator of the Heart and Stroke Foundation Canada, and an Alberta New Investigator of the Heart and Stroke Foundation Alberta. This research was facilitated by the Women and Children’s Health Research Institute through the support of the Stollery Children’s Hospital Foundation. No funding was received for the analysis of the data presented in the submitted manuscript, and funders had no influence on analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors have no conflicts of interest relevant to this article., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Purpose: Neonates born at < 28 weeks of gestation are at risk for neurodevelopmental delay. The aim of this study was to identify quantitative MR-based metrics for the prediction of neurodevelopmental outcomes in extremely preterm neonates., Methods: T1-/T2-relaxation times (T1R/T2R), ADC, and fractional anisotropy (FA) of the left/right posterior limb of the internal capsule (PLIC) and the brainstem were determined at term-equivalent ages in a sample of extremely preterm infants (n = 33). Scores for cognitive, language, and motor outcomes were collected at one year corrected-age. Pearson's correlation analyses detected relationships between quantitative measures and outcome data. Stepwise regression procedures identified imaging metrics to estimate neurodevelopmental outcomes., Results: Cognitive outcomes correlated significantly with T2R (r = 0.412; p = 0.017) and ADC (r = -0.401; p = 0.021) (medulla oblongata). Furthermore, there were significant correlations between motor outcomes and T1R (pontine tegmentum (r = 0.346; p = 0.049), midbrain (r = 0.415; p = 0.016), right PLIC (r = 0.513; p = 0.002), and left PLIC (r = 0.504; p = 0.003)); T2R (right PLIC (r = 0.405; p = 0.019)); ADC (medulla oblongata (r = -0.408; p = 0.018) and pontine tegmentum (r = -0.414; p = 0.017)); and FA (pontine tegmentum (r = -0.352; p = 0.045)). T2R/ADC (medulla oblongata) (cognitive outcomes (R 2  = 0.296; p = 0.037)) and T1R (right PLIC)/ADC (medulla oblongata) (motor outcomes (R 2  = 0.405; p = 0.009)) revealed predictive potential for neurodevelopmental outcomes., Conclusion: There are relationships between relaxometry‑/DTI-based metrics determined by neuroimaging near term and neurodevelopmental outcomes collected at one year of age. Both modalities bear prognostic potential for the prediction of cognitive and motor outcomes. Thus, quantitative MRI at term-equivalent ages represents a promising approach with which to estimate neurologic development in extremely preterm infants., (© 2024. The Author(s).)

Background: Early sensory experiences have a significant impact on the later life of preterm infants. The NICU soundscape is profoundly influenced by various modalities of respiratory support or ventilation, which are often mandatory early in the care. The incubator, believed to shield from external noise, is less effective against noise originating inside. The objective of this study was to evaluate the sound levels and characteristics of frequently used respiratory support and ventilation modalities, taking into consideration the developing auditory system of premature infants., Methods: To evaluate sound dynamics inside and outside an incubator during respiratory support/ventilation, experimental recordings were conducted at the Center for Pediatric Simulation Training of the Medical University Vienna. The ventilator used was a FABIAN HFOI®., Results: Jet CPAP (Continuous positive airway pressure), whether administered via mask or prongs, generates significantly higher sound levels compared to High-flow nasal cannula (HFNC) and to High-frequency oscillatory ventilation (HFOV) delivered through an endotracheal tube. Upon evaluating the sound spectrum of jet CPAP support, a spectral peak is observed within the frequency range of 4 to 8 kHz. Notably, this frequency band aligns with the range where the hearing threshold of preterm infants is at its most sensitive., Conclusion: Non-invasive HFNC and invasive HFOV generate lower sound levels compared to those produced by jet CPAP systems delivered via masks or prongs. Moreover, HFNC and HFOV show a reduced acoustic presence within the frequency range where the preterm infant's hearing is highly sensitive. Therefore, it is reasonable to speculate that the potential for auditory impairment might be more pronounced in preterm infants who require prolonged use of jet CPAP therapy during their time in the incubator., 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., (© 2024 Stummer, Reuter, Czedik-Eysenberg, Bertsch, Klebermass-Schrehof, Mader, Buchmayer, Bartha-Doering, Berger and Giordano.)

The gut microbiome is associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. The exact underlying mechanism and its associated metabolic signatures in infants are not fully understood. To decipher metabolite profiles linked to neonatal brain injury, we investigate the fecal and plasma metabolome of samples obtained from a cohort of 51 extremely premature infants at several time points, using liquid chromatography (LC)-high-resolution mass spectrometry (MS)-based untargeted metabolomics and LC-MS/MS-based targeted analysis for investigating bile acids and amidated bile acid conjugates. The data are integrated with 16S rRNA gene amplicon gut microbiome profiles as well as patient cytokine, growth factor, and T cell profiles. We find an early onset of differentiation in neuroactive metabolites between infants with and without brain injury. We detect several bacterially derived bile acid amino acid conjugates in plasma and feces. These results provide insights into the early-life metabolome of extremely premature infants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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).)

Introduction: Cerebral magnetic resonance imaging (cMRI) is an important diagnostic tool in neonatology. In addition to qualitative analysis, quantitative measurements may help identify infants with impaired brain growth. This study aimed to create reference values for brain metrics of various brain areas in neonates without major brain injuries born before 28 weeks of gestation., Methods: This retrospective study analyzes cMRI imaging data of high-risk patients without severe brain pathologies at term-equivalent age, collected over 4 years since November 2017. Nineteen brain areas were measured, reference values created, and compared to published values from fetal and postnatal MRI. Furthermore, correlations between brain metrics and gestational age at birth were evaluated., Results: A total of 174 cMRI examinations were available for analysis. Reference values including cut-offs for impaired brain growth were established for different gestational age groups. There was a significant correlation between gestational age at birth and larger "tissue" parameters, as well as smaller "fluid" parameters, including intracerebral and extracerebral spaces., Discussion: With quantitative brain metrics infants with impaired brain growth might be detected earlier. Compared to preexisting reference values, these are the first of a contemporary collective of extremely preterm neonates without severe brain injuries. Measurements can be easily performed by radiologists as well as neonatologists without specialized equipment or computational expertise., Conclusion: Two-dimensional cMRI brain measurements at term-equivalent age represent an easy and reliable approach for the evaluation of brain size and growth in infants at high risk for neurodevelopmental impairment., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Preterm birth is a significant cause of perinatal morbidity and mortality, especially in multiple pregnancies. Delayed interval delivery can prolong pregnancy for the remaining fetus(es) in an imminent stillbirth or extremely preterm birth of the first fetus, improving the lastborn's outcomes. We present a case of delayed interval delivery of a triplet pregnancy following preterm prelabour rupture of membranes and progressive cervical insufficiency. Following vaginal delivery of the first fetus at 24+1 gestational weeks, the patient received antibiotics and tocolysis. Cerclage was not conducted as the mother had a vaginal infection. A 15-day delivery interval for the second and third fetuses was achieved. The firstborn required mechanical ventilation and inotropic support, while the others only required continuous positive airway pressure. There is no consensus on the best way to perform delayed interval delivery. We achieved a complications-free interval of 15 days with conservative management in a triplet pregnancy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Parents of very low birth weight (VLBW) infants in a neonatal intensive care unit experienced additional stress during the SARS-CoV-2 pandemic due to the related restrictions in hospital visiting policies. Our study aimed to compare parents' burdens before and during the pandemic. This survey included 121 parents of 76 VLBW infants in two European Level IV perinatal centers before and during the pandemic. We performed standardized parent questionnaires with mothers and fathers separately to evaluate their emotional stress and well-being. The pandemic worsened the emotional well-being of parents of VLBW infants, particularly of mothers. During the pandemic, mothers reported significantly higher state anxiety levels (48.9 vs. 42.9, p = 0.026) and hampered bonding with the child (6.3 vs. 5.2, 0 = 0.003) than before. In addition, mothers felt more personally restricted than fathers (6.1 vs. 5.2, p = 0.003). Fathers experienced lower levels of stress than mothers; they were equally burdened before and during the pandemic. Restrictions in visiting policies for families of VLBW infants during the SARS-CoV-2 pandemic have a significant negative impact on parental stress and should therefore be applied cautiously., (© 2023. Springer Nature Limited.)

Background: Given the countrywide lockdown in the first pandemic period and the respective Hospital restrictive policies, we aimed to investigate if the SARS-COV-2 pandemic was associated to a reduced parental presence in the NICU and in which form this had an impact on infant wellbeing., Methods: Retrospective cohort study about altered NICUs parental presence (measured by number of visits and kangaroo care time) due to pandemic restrictive policies and its impact on infant wellbeing (measured through The Neonatal Pain Agitation and Sedation scale and nurses' descriptive documentation)., Results: Presence of both parents at the same time was significantly lower during pandemic. Contrary, maternal presence only and total kangaroo-care time were higher within the pandemic (163.36 ± 94.07 vs 122.71 ± 64.03; p = 0.000). Lower NPASS values were documented during the lookdown (1.28 ± 1.7 vs 1.78 ± 2.2; p = 0.000)., Conclusion: Data collected through the pandemic confirm the importance of parental presence for infants' wellbeing in a NICU setting., Impact: Parental support is an extremely important aspect for infants hospitalized in an intensive care unit. Their presence was limited in many NICUs worldwide during the SARS-COV-2 pandemic. This study confirm the importance of parental presence for infants' wellbeing also in a pandemic situation. Our results support a family-centered newborn individualized developmental care approach in the NICU., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)