Background Despite the availability of continuous conventional electroencephalography (cEEG), accurate diagnosis of neonatal seizures is challenging in clinical practice. Algorithms for decision support in the recognition of neonatal seizures could improve detection. We aimed to assess the diagnostic accuracy of an automated seizure detection algorithm called Algorithm for Neonatal Seizure Recognition (ANSeR). Methods This multicentre, randomised, two-arm, parallel, controlled trial was done in eight neonatal centres across Ireland, the Netherlands, Sweden, and the UK. Neonates with a corrected gestational age between 36 and 44 weeks with, or at significant risk of, seizures requiring EEG monitoring, received cEEG plus ANSeR linked to the EEG monitor displaying a seizure probability trend in real time (algorithm group) or cEEG monitoring alone (nonalgorithm group). The primary outcome was diagnostic accuracy (sensitivity, specificity, and false detection rate) of health-care professionals to identify neonates with electrographic seizures and seizure hours with and without the support of the ANSeR algorithm. Neonates with data on the outcome of interest were included in the analysis. This study is registered with ClinicalTrials.gov, NCT02431780. Findings Between Feb 13, 2015, and Feb 7, 2017, 132 neonates were randomly assigned to the algorithm group and 132 to the non-algorithm group. Six neonates were excluded (four from the algorithm group and two from the non-algorithm group). Electrographic seizures were present in 32 (25•0%) of 128 neonates in the algorithm group and 38 (29•2%) of 130 neonates in the non-algorithm group. For recognition of neonates with electrographic seizures, sensitivity was 81•3% (95% CI 66•7-93•3) in the algorithm group and 89•5% (78•4-97•5) in the non-algorithm group; specificity was 84•4% (95% CI 76•9-91•0) in the algorithm group and 89•1% (82•5-94•7) in the non-algorithm group; and the false detection rate was 36•6% (95% CI 22•7-52•1) in the algorithm group and 22•7% (11•6-35•9) in the non-algorithm group. We identified 659 h in which seizures occurred (seizure hours): 268 h in the algorithm versus 391 h in the nonalgorithm group. The percentage of seizure hours correctly identified was higher in the algorithm group than in the non-algorithm group (177 [66•0%; 95% CI 53•8-77•3] of 268 h vs 177 [45•3%; 34•5-58•3] of 391 h; difference 20•8% [3•6-37•1]). No significant differences were seen in the percentage of neonates with seizures given at least one inappropriate antiseizure medication (37•5% [95% CI 25•0 to 56•3] vs 31•6% [21•1 to 47•4]; difference 5•9% [-14•0 to 26•3]). Interpretation ANSeR, a machine-learning algorithm, is safe and able to accurately detect neonatal seizures. Although the algorithm did not enhance identification of individual neonates with seizures beyond conventional EEG, recognition of seizure hours was improved with use of ANSeR. The benefit might be greater in less experienced centres, but further study is required.

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Background Infants with mild HIE are at risk of significant disability at follow-up. In the pre-therapeutic hypothermia (TH) era, electroencephalography (EEG) within 6 hours of birth was most predictive of outcome. This study aims to identify and describe features of early EEG and heart rate variability (HRV) (<6 hours of age) in infants with mild HIE compared to healthy term infants. Methods Infants >36 weeks with mild HIE, not undergoing TH, with EEG before 6 hours of age were identified from 4 prospective cohort studies conducted in the Cork University Maternity Services, Ireland (2003–2019). Control infants were taken from a contemporaneous study examining brain activity in healthy term infants. EEGs were qualitatively analysed by two neonatal neurophysiologists and quantitatively assessed using multiple features of amplitude, spectral shape and inter-hemispheric connectivity. Quantitative features of HRV were assessed in both the groups. Results Fifty-eight infants with mild HIE and sixteen healthy term infants were included. Seventy-two percent of infants with mild HIE had at least one abnormal EEG feature on qualitative analysis and quantitative EEG analysis revealed significant differences in spectral features between the two groups. HRV analysis did not differentiate between the groups. Conclusions Qualitative and quantitative analysis of the EEG before 6 hours of age identified abnormal EEG features in mild HIE, which could aid in the objective identification of cases for future TH trials in mild HIE. Impact Infants with mild HIE currently do not meet selection criteria for TH yet may be at risk of significant disability at follow-up. In the pre-TH era, EEG within 6 hours of birth was most predictive of outcome; however, TH has delayed this predictive value. 72% of infants with mild HIE had at least one abnormal EEG feature in the first 6 hours on qualitative assessment. Quantitative EEG analysis revealed significant differences in spectral features between infants with mild HIE and healthy term infants. Quantitative EEG features may aid in the objective identification of cases for future TH trials in mild HIE.

Aim: To describe early cerebral oxygenation (cSO 2 ) and fractional tissue oxygen extraction (FTOE) values and their evolution over the first days of life in infants with all grades of hypoxic-ischaemic encephalopathy (HIE) and to determine whether cSO 2 and FTOE measured early (6 and 12 h) can predict short-term outcome.Methods: Prospective, observational study of cerebral near-infrared spectroscopy (NIRS) in infants >36 weeks' gestation with HIE. Ten one-hour epochs of cSO 2 and FTOE were extracted for each infant over the first 84 h. Infants with moderate and severe HIE received therapeutic hypothermia (TH). Abnormal outcome was defined as abnormal magnetic resonance imaging (MRI) and/or death.Results: Fifty-eight infants were included (28 mild, 24 moderate, 6 severe). Median gestational age was 39.9 weeks (IQR 38.1-40.7) and birthweight was 3.35 kgs . cSO 2 increased and FTOE decreased over the first 24 h in all grades of HIE. Compared to the moderate group, infants with mild HIE had significantly higher cSO 2 at 6 h (p = 0.003), 9 h (p = 0.009) and 12 h (p = 0.032) and lower FTOE at 6 h (p = 0.016) and 9 h (0.029). cSO 2 and FTOE at 6 and 12 h did not predict abnormal outcome. Conclusion:Infants with mild HIE have higher cSO 2 and lower FTOE than those with moderate or severe HIE in the first 12 h of life. cSO 2 increased in all grades of HIE over the first 24 h regardless of TH status.

Aim To investigate the effect of a musical intervention on neonatal stress response to venepuncture as measured by salivary cortisol levels and pain profile scores. Methods In a randomised control crossover trial, participants were randomised to both a control arm (sucrose) and intervention arm (sucrose and music) for routine venepuncture procedures. Salivary swabs were collected at baseline, 20 minutes post‐venepuncture and 4 hours post‐venepuncture. Pain levels were assessed using the Premature Infant Pain Profile (PIPP). A total of 16 preterm neonates participated in both arms to complete the study. Results Cortisol values were elevated at all timepoints in the intervention arm (baseline, 20 minutes, and 4 hours post‐procedure) but not significantly so (P = .056, P = .3, and P = .575, respectively). Median change in cortisol values from baseline was +128.48 pg/mL (−47.66 to 517.02) at 20 minutes and +393.52 pg/mL (47.88‐1221.34) at 4 hours post‐procedure in the control arm compared to −69.564 pg/mL (−860.96 to 397.289) and +100.48 pg/mL (−560.46 to 842.99) at 20 minutes and 4 hours post‐procedure in the intervention arm. There was no statistically significant difference observed between groups (P = .311 at 20 minutes, and P = .203 at 4 hours post‐procedure). PIPP scores were not significantly different between study arms. Conclusion Our findings did not support the additional benefit of music intervention on neonatal stress response to venepuncture in preterm infants.

Objective: To assess if early clinical and electroencephalography (EEG) features predict later seizure development in infants with hypoxic-ischemic encephalopathy (HIE).Methods: Clinical and EEG parameters <12 h of birth from infants with HIE across eight European Neonatal Units were used to develop seizure-prediction models. Clinical parameters included intrapartum complications, fetal distress,

<b><i>Introduction:</i></b> Hypoxic ischaemic encephalopathy (HIE) remains one of the top 10 contributors to the global burden of disease. Early objective biomarkers are required. Near-infrared spectroscopy (NIRS) may provide a valuable insight into cerebral perfusion and metabolism. We aimed to determine whether early NIRS monitoring (&#x3c;6 h of age) can predict outcome as defined by grade of encephalopathy, brain MRI findings, and/or neurodevelopmental outcome at 1–2 years in infants with HIE. <b><i>Methods:</i></b> We searched PubMed, Scopus, Web of Science, Embase, and The Cochrane Library databases (July 2019). Studies of infants born ≥36⁺⁰ weeks gestation with HIE who had NIRS recording commenced before 6 h of life were included. We planned to provide a narrative of all the studies included, and if similar clinically and methodologically, the results would be pooled in a meta-analysis to determine test accuracy. <b><i>Results:</i></b> Seven studies were included with a combined total of 161 infants. Only 1 study included infants with mild HIE. A range of different oximeters and probes were utilized with varying outcome measures making comparison difficult. Although some studies showed a trend towards higher cSO₂ values before 6 h in infants with adverse neurodevelopmental outcomes, in the majority, this was not significant until beyond 24 h of life. <b><i>Conclusion:</i></b> Very little data currently exists to assess the use of early NIRS to predict outcome in infants with HIE. Further studies using a standardized approach are required before NIRS can be evaluated as a potential objective assessment tool for early identification of at-risk infants.