The association between ibuprofen administration in children and the risk of developing or exacerbating asthma: a systematic review and meta-analysis.

BACKGROUND: Ibuprofen is one of the most commonly used analgesic and antipyretic drugs in children. However, its potential causal role in childhood asthma pathogenesis remains uncertain. In this systematic review, we assessed the association between ibuprofen administration in children and the risk of developing or exacerbating asthma. METHODS: We searched MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and Scopus from inception to May 2022, with no language limits; searched relevant reviews; and performed citation searching. We included studies of any design that were primary empirical peer-reviewed publications, where ibuprofen use in children 0-18 years was reported. Screening was performed in duplicate by blinded review. In total, 24 studies met our criteria. Data were extracted according to PRISMA guidelines, and the risk of bias was assessed using RoB2 and NOS tools. Quantitative data were pooled using fixed effect models, and qualitative data were pooled using narrative synthesis. Primary outcomes were asthma or asthma-like symptoms. The results were grouped according to population (general, asthmatic, and ibuprofen-hypersensitive), comparator type (active and non-active) and follow-up duration (short- and long-term). RESULTS: Comparing ibuprofen with active comparators, there was no evidence of a higher risk associated with ibuprofen over both the short and long term in either the general or asthmatic population. Comparing ibuprofen use with no active alternative over a short-term follow-up, ibuprofen may provide protection against asthma-like symptoms in the general population when used to ease symptoms of fever or bronchiolitis. In contrast, it may cause asthma exacerbation for those with pre-existing asthma. However, in both populations, there were no clear long-term follow-up effects. CONCLUSIONS: Ibuprofen use in children had no elevated risk relative to active comparators. However, use in children with asthma may lead to asthma exacerbation. The results are driven by a very small number of influential studies, and research in several key clinical contexts is limited to single studies. Both clinical trials and observational studies are needed to understand the potential role of ibuprofen in childhood asthma pathogenesis.

Premature infants display discriminable behavioral, physiological, and brain responses to noxious and nonnoxious stimuli.

Pain assessment in preterm infants is challenging as behavioral, autonomic, and neurophysiological measures of pain are reported to be less sensitive and specific than in term infants. Understanding the pattern of preterm infants' noxious-evoked responses is vital to improve pain assessment in this group. This study investigated the discriminability and development of multimodal noxious-evoked responses in infants aged 28-40 weeks postmenstrual age. A classifier was trained to discriminate responses to a noxious heel lance from a nonnoxious control in 47 infants, using measures of facial expression, brain activity, heart rate, and limb withdrawal, and tested in two independent cohorts with a total of 97 infants. The model discriminates responses to the noxious from the nonnoxious procedure with an overall accuracy of 0.76-0.84 and an accuracy of 0.78-0.79 in the 28-31-week group. Noxious-evoked responses have distinct developmental patterns. Heart rate responses increase in magnitude with age, while noxious-evoked brain activity undergoes three distinct developmental stages, including a previously unreported transitory stage consisting of a negative event-related potential between 30 and 33 weeks postmenstrual age. These findings demonstrate that while noxious-evoked responses change across early development, infant responses to noxious and nonnoxious stimuli are discriminable in prematurity.

The developing Human Connectome Project (dHCP) automated resting-state functional processing framework for newborn infants.

The developing Human Connectome Project (dHCP) aims to create a detailed 4-dimensional connectome of early life spanning 20-45 weeks post-menstrual age. This is being achieved through the acquisition of multi-modal MRI data from over 1000 in- and ex-utero subjects combined with the development of optimised pre-processing pipelines. In this paper we present an automated and robust pipeline to minimally pre-process highly confounded neonatal resting-state fMRI data, robustly, with low failure rates and high quality-assurance. The pipeline has been designed to specifically address the challenges that neonatal data presents including low and variable contrast and high levels of head motion. We provide a detailed description and evaluation of the pipeline which includes integrated slice-to-volume motion correction and dynamic susceptibility distortion correction, a robust multimodal registration approach, bespoke ICA-based denoising, and an automated QC framework. We assess these components on a large cohort of dHCP subjects and demonstrate that processing refinements integrated into the pipeline provide substantial reduction in movement related distortions, resulting in significant improvements in SNR, and detection of high quality RSNs from neonates.

Optimising neonatal fMRI data analysis: Design and validation of an extended dHCP preprocessing pipeline to characterise noxious-evoked brain activity in infants.

The infant brain is unlike the adult brain, with considerable differences in morphological, neurodynamic, and haemodynamic features. As the majority of current MRI analysis tools were designed for use in adults, a primary objective of the Developing Human Connectome Project (dHCP) is to develop optimised methodological pipelines for the analysis of neonatal structural, resting state, and diffusion MRI data. Here, in an independent neonatal dataset we have extended and optimised the dHCP fMRI preprocessing pipeline for the analysis of stimulus-response fMRI data. We describe and validate this extended dHCP fMRI preprocessing pipeline to analyse changes in brain activity evoked following an acute noxious stimulus applied to the infant's foot. We compare the results obtained from this extended dHCP pipeline to results obtained from a typical FSL FEAT-based analysis pipeline, evaluating the pipelines' outputs using a wide range of tests. We demonstrate that a substantial increase in spatial specificity and sensitivity to signal can be attained with a bespoke neonatal preprocessing pipeline through optimised motion and distortion correction, ICA-based denoising, and haemodynamic modelling. The improved sensitivity and specificity, made possible with this extended dHCP pipeline, will be paramount in making further progress in our understanding of the development of sensory processing in the infant brain.

Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels.

BACKGROUND: Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis. METHODS: We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L). RESULTS: After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21-34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22-1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47-69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18-1.82). CONCLUSIONS: About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.

Matched pair analysis of the effect of longer hypothermic machine perfusion time on kidney transplant outcomes.

BACKGROUND: Hypothermic machine perfusion (HMP) has demonstrated benefits in terms of early kidney transplant function compared to static cold storage. While longer preservation times have shown detrimental effects, a previous paired study indicated that longer pump times (the second kidney in a pair) might lead to improved outcomes. AIM: To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience. METHODS: A total of 61 pairs of transplant recipients who received kidneys from the same donor (2012-2021) were analyzed. Patients were divided into two groups depending on whether they were transplanted first (K1) or second (K2). Therefore, the patients in each pair had identical donor characteristics, except for time on the pump. Statistical analyses included Kaplan-Meyer analysis and paired tests, including McNemar's test, student's paired t-test, or Wilcoxon's test, as appropriate. RESULTS: The two groups of recipients had similar demographics (age, body mass index, diabetes, time on dialysis, sensitization and retransplants). Cold ischemic times for K1 and K2 were 8.9 (95%CI: 7.9, 9.8) and 14.7 hours (13.7, 15.8) (P < 0.0001), respectively. Overall, K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year (P = 0.015). Delayed graft function was less common in K2, 12/61 (20%) than in K1, 20/61 (33%) (P = 0.046). Finally, K2 showed a higher graft survival than K1 (P = 0.023). CONCLUSION: Our results agree with a previous study that suggested possible advantages to longer pump times. Both studies should encourage further research into HMP's potential anti-inflammatory effect.

Tripping into the unknown: Exploring the experiences of first-time LSD users through global drug survey insights.

BACKGROUND: The recreational use of LSD, a synthetic psychedelic drug, has surged in recent years, coinciding with a renewed research focus on its potential psychotherapeutic properties. AIM: This study aims to describe the experiences and perceptions of individuals engaging in LSD use for the first time, derived from a large international sample. METHODS: This study utilised 2018 Global Drug Survey data collected from 6 November 2017 to 10 January 2018. Participants who initiated LSD use in the preceding 12 months answered questions on their experiences, social settings, harm-reduction behaviours, and demographics. Descriptive statistics were employed, and characteristics of those seeking emergency medical treatment (EMT) and those not planning further LSD use were compared with other respondents. RESULTS: Among 3340 respondents who used LSD in the past year, their first-time experiences generally exceeded expectations, with 97.7% expressing excitement. Adverse and unwanted side effects were rarely reported, and only 17 individuals needed EMT. Feelings of fear were reported by most (64.1%), but only very mildly and not enough to put them off from wanting to use LSD again. DISCUSSION: Although the occurrence of unwanted side effects seems low and the LSD experience is generally pleasurable, vigilance amid the rising illicit use of LSD through harm-reduction education is still important in preventing possible risks.

Immune response to vaccination in people with psychotic disorders relative to healthy controls: prospective study of SARS-CoV-2 vaccination.

This prospective study examines the immune response to SARS-CoV-2 vaccination in patients with psychotic disorders compared with healthy volunteers. Participants were recruited naturalistically as part of the UK's COVID-19 vaccination programme. Prior to receiving their first COVID-19 vaccine, blood samples were provided by participants to examine anti-SARS-CoV-2 immunoglobulins (IgG) at baseline, followed by a repeat assay 1 month after receiving their first vaccine to assess vaccine response. The increase of IgG levels from baseline to 1 month post-vaccination was significantly lower in patients compared with controls, supporting evidence of impaired vaccine response in people with psychotic disorders. When excluding patients treated with clozapine from the analysis, this difference was no longer significant, suggesting that effects may be particularly marked in people taking clozapine.

A machine learning artefact detection method for single-channel infant event-related potential studies.

Objective. Automated detection of artefact in stimulus-evoked electroencephalographic (EEG) data recorded in neonates will improve the reproducibility and speed of analysis in clinical research compared with manual identification of artefact. Some studies use very short, single-channel epochs of EEG data with little recorded EEG per infant-for example because the clinical vulnerability of the infants limits access for recording. Current artefact-detection methods that perform well on adult data and resting-state and multi-channel data in infants are not suitable for this application. The aim of this study was to create and test an automated method of detecting artefact in single-channel 1500 ms epochs of infant EEG.Approach. A total of 410 epochs of EEG were used, collected from 160 infants of 28-43 weeks postmenstrual age. This dataset-which was balanced to include epochs of background activity and responses to visual, auditory, tactile and noxious stimuli-was presented to seven independent raters, who independently labelled the epochs according to whether or not they were able to visually identify artefacts. The data was split into a training set (340 epochs) and an independent test set (70 epochs). A random forest model was trained to identify epochs as either artefact or not artefact.Main results. This model performs well, achieving a balanced accuracy of 0.81, which is as good as manual review of data. Accuracy was not significantly related to the infant age or type of stimulus.Significance. This method provides an objective tool for automated artefact rejection for short epoch, single-channel EEG in neonates and could increase the utility of EEG in neonates in both the clinical and research setting.

Identifying factors that can be used to assess a country's readiness to deploy a new vaccine or improve uptake of an underutilised vaccine: a scoping review.

OBJECTIVES: Identifying whether a country is ready to deploy a new vaccine or improve uptake of an existing vaccine requires knowledge of a diverse range of interdependent, context-specific factors. This scoping review aims to identify common themes that emerge across articles, which include tools or guidance that can be used to establish whether a country is ready to deploy a new vaccine or increase uptake of an underutilised vaccine. DESIGN: Scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. DATA SOURCES: Embase, CINAHL, Cochrane Library, Google Scholar, MEDLINE, PsycINFO and Web of Science were searched for articles published until 9 September 2023. Relevant articles were also identified through expert opinion. ELIGIBILITY CRITERIA: Articles published in any year or language that included tools or guidance to identify factors that influence a country's readiness to deploy a new or underutilised vaccine. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened records and performed data extraction. Findings were synthesised by conducting a thematic analysis. RESULTS: 38 articles met our inclusion criteria; these documents were created using methodologies including expert review panels and Delphi surveys and varied in terms of content and context-of-use. 12 common themes were identified relevant to a country's readiness to deploy a new or underutilised vaccine. These themes were as follows: (1) legal, political and professional consensus; (2) sociocultural factors and communication; (3) policy, guidelines and regulations; (4) financing; (5) vaccine characteristics and supply logistics; (6) programme planning; (7) programme monitoring and evaluation; (8) sustainable and integrated healthcare provision; (9) safety surveillance and reporting; (10) disease burden and characteristics; (11) vaccination equity and (12) human resources and training of professionals. CONCLUSIONS: This information has the potential to form the basis of a globally applicable evidence-based vaccine readiness assessment tool that can inform policy and immunisation programme decision-makers.

Identifying characteristics that enable resilient immunisation programmes: a scoping review.

OBJECTIVES: The COVID-19 pandemic highlighted the fragility of immunisation programmes and resulted in a significant reduction in vaccination rates, with increasing vaccine-preventable disease outbreaks consequently reported. These vulnerabilities underscore the importance of resilient immunisation programmes to ensure optimal performance during crises. To date, a framework for assessing immunisation programme resilience does not exist. We conducted a scoping review of immunisation programmes during times of crisis to identify factors that characterise resilient immunisation programmes, which may inform an Immunisation Programme Resilience Tool. DESIGN: Scoping review design followed the Arksey and O'Malley framework, and manuscript reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. DATA SOURCES: CINAHL, CENTRAL, Embase, Google Scholar, MEDLINE, PsycINFO and Web of Science and databases were searched between 1 January 2011 and 2 September 2023. Citation searching of identified studies was also performed. ELIGIBILITY CRITERIA: We included primary empirical peer-reviewed studies that discussed the resilience of immunisation programme to crises, shocks or disruptions. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened records and performed data extraction. We extracted data on study location and design, crisis description, and resilience characteristics discussed, and identified evidence gaps in the literature. Findings were synthesised using tabulation and an evidence gap map. RESULTS: Thirty-seven studies met the eligibility criteria. These studies captured research conducted across six continents, with most concentrated in Africa, Asia and Europe. One study had a randomised controlled trial design, while 36 studies had observational designs (15 analytical and 21 descriptive). We identified five characteristics of resilient immunisation programmes drawing on the Health System Resilience Index (Integration, Awareness, Resource Availability and Access, Adaptiveness and Self-regulation) and several evidence gaps in the literature. CONCLUSIONS: To our knowledge, no immunisation programme resilience tool exists. We identified factors from the Health System Resilience Index coupled with factors identified through primary empirical evidence, which may inform development of an immunisation programme resilience tool.

Sensory event-related potential morphology predicts age in premature infants.

OBJECTIVE: We investigated whether sensory-evoked cortical potentials could be used to estimate the age of an infant. Such a model could be used to identify infants who deviate from normal neurodevelopment. METHODS: Infants aged between 28- and 40-weeks post-menstrual age (PMA) (166 recording sessions in 96 infants) received trains of visual and tactile stimuli. Neurodynamic response functions for each stimulus were derived using principal component analysis and a machine learning model trained and validated to predict infant age. RESULTS: PMA could be predicted accurately from the magnitude of the evoked responses (training set mean absolute error and 95% confidence intervals: 1.41 [1.14; 1.74] weeks,p = 0.0001; test set mean absolute error: 1.55 [1.21; 1.95] weeks,p = 0.0002). Moreover, we show that their predicted age (their brain age) is correlated with a measure known to relate to maturity of the nervous system and is linked to long-term neurodevelopment. CONCLUSIONS: Sensory-evoked potentials are predictive of age in premature infants and brain age deviations are related to biologically and clinically meaningful individual differences in nervous system maturation. SIGNIFICANCE: This model could be used to detect abnormal development of infants' response to sensory stimuli in their environment and may be predictive of neurodevelopmental outcome.

Establishing a standardised approach for the measurement of neonatal noxious-evoked brain activity in response to an acute somatic nociceptive heel lance stimulus.

BACKGROUND: Electroencephalography (EEG) can be used in neonates to measure brain activity changes that are evoked by noxious events, such as clinically required immunisations, cannulation and heel lancing for blood tests. EEG provides an alternative approach to infer pain experience in infants compared with more commonly used behavioural and physiological pain assessments. Establishing the generalisability and construct validity of these measures will help corroborate the use of brain-derived outcomes to evaluate the efficacy of new or existing pharmacological and non-pharmacological methods to treat neonatal pain. This study aimed to test whether a measure of noxious-evoked EEG activity called the noxious neurodynamic response function (n-NRF), that was originally derived in a sample of term-aged infants at the Oxford John Radcliffe Hospital, UK, in 2017, can reliably distinguish noxious from non-noxious events in two independent datasets collected at University College London Hospital and at Royal Devon & Exeter Hospital. We aimed to reproduce three published results that use this measure to quantify noxious-evoked changes in brain activity. We used the n-NRF to quantify noxious-evoked brain activity to test (i) whether significantly larger noxious-evoked activity is recorded in response to a clinical heel lance compared to a non-noxious control heel lance procedure; (ii) whether the magnitude of the activity evoked by a noxious heel lance is equivalent in independent cohorts of infants; and (iii) whether the magnitude of the noxious-evoked brain activity increases with postmenstrual age (PMA) in premature infants up to 37 weeks PMA. Positive replication of these studies will build confidence in the use of the n-NRF as a valid and reliable pain-related outcome which could be used to evaluate analgesic efficacy in neonates. The protocol for this study was published following peer review (https://doi.org/10.17605/OSF.IO/ZY9MS). RESULTS: The n-NRF magnitude to a noxious heel lance stimulus was significantly greater than to a non-noxious control heel lance stimulus in both the UCL dataset (n = 60; mean difference .88; 95% confidence interval (CI) .64-1.13; p < .0001) and the Exeter dataset (n = 31; mean difference .31; 95% CI .02-.61; p = .02). The mean magnitude and 90% bootstrap confidence interval of the n-NRF evoked by the heel lance did not meet our pre-defined equivalence bounds of 1.0 ± .2 in either the UCL dataset (n = 72; mean magnitude 1.33; 90% bootstrapped CI 1.18-1.52) or the Exeter dataset (n = 35; mean magnitude .92, 90% bootstrapped CI .74-1.22). The magnitude of the n-NRF to the noxious stimulus was significantly positively correlated with PMA in infants up to 37 weeks PMA (n = 65; one-sided Pearson's R, adjusted for site: .24; 95% CI .06-1.00; p = .03). CONCLUSIONS: We have reproduced in independent datasets the findings that the n-NRF response to a noxious stimulus is significantly greater than to a non-noxious stimulus, and that the noxious-evoked EEG response increases with PMA. The pre-defined equivalence bounds for the mean magnitude of the EEG response were not met, though this might be due to either inter-site differences such as the lack of calibration of devices between sites (a true negative) or underpowering (a false negative). This reproducibility study provides robust evidence that supports the use of the n-NRF as an objective outcome for clinical trials assessing acute nociception in neonates. Use of the n-NRF in this way has the potential to transform the way analgesic efficacy studies are performed.

Resting state electroencephalographic brain activity in neonates can predict age and is indicative of neurodevelopmental outcome.

OBJECTIVE: Electroencephalography (EEG) can be used to estimate neonates' biological brain age. Discrepancies between postmenstrual age and brain age, termed the brain age gap, can potentially quantify maturational deviation. Existing brain age EEG models are not well suited to clinical cot-side use for estimating neonates' brain age gap due to their dependency on relatively large data and pre-processing requirements. METHODS: We trained a deep learning model on resting state EEG data from preterm neonates with normal neurodevelopmental Bayley Scale of Infant and Toddler Development (BSID) outcomes, using substantially reduced data requirements. We subsequently tested this model in two independent datasets from two clinical sites. RESULTS: In both test datasets, using only 20 min of resting-state EEG activity from a single channel, the model generated accurate age predictions: mean absolute error = 1.03 weeks (p-value = 0.0001) and 0.98 weeks (p-value = 0.0001). In one test dataset, where 9-month follow-up BSID outcomes were available, the average neonatal brain age gap in the severe abnormal outcome group was significantly larger than that of the normal outcome group: difference in mean brain age gap = 0.50 weeks (p-value = 0.04). CONCLUSIONS: These findings demonstrate that the deep learning model generalises to independent datasets from two clinical sites, and that the model's brain age gap magnitudes differ between neonates with normal and severe abnormal follow-up neurodevelopmental outcomes. SIGNIFICANCE: The magnitude of neonates' brain age gap, estimated using only 20 min of resting state EEG data from a single channel, can encode information of clinical neurodevelopmental value.

Effect of parental touch on relieving acute procedural pain in neonates and parental anxiety (Petal): a multicentre, randomised controlled trial in the UK.

BACKGROUND: Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their baby before a clinically required heel lance, at a speed of approximately 3 cm/s to optimally activate C-tactile nerve fibres, provides effective pain relief. METHODS: Petal is a multicentre, randomised, parallel-group interventional superiority trial conducted in the John Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) and the Royal Devon and Exeter Hospital (Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK). Neonates without neurological abnormalities who were born at 35 weeks gestational age or more and required a blood test via a heel lance in the first week of life were randomly assigned (1:1) to receive parental touch for 10 s either before (intervention group) or after (control group) the clinically required heel lance. Randomisation was managed at the Oxford site using a web-based minimisation algorithm with allocation concealment. The primary outcome measure was the magnitude of noxious-evoked brain activity in response to the heel lance measured with electroencephalography (EEG). Secondary outcome measures were Premature Infant Pain Profile-Revised (PIPP-R) score, development of tachycardia, and parental anxiety score. For all outcomes, the per-protocol effect was estimated via complier average causal effect analysis on the full analysis set. The trial is registered on ISRCTN (ISRCTN14135962) and ClinicalTrials.gov (NCT04901611). FINDINGS: Between Sept 1, 2021, and Feb 7, 2023, 159 parents were approached to participate in the study, and 112 neonates were included. 56 neonates were randomly assigned to the intervention group of parental stroking before the heel lance and 56 to the control group of parental stroking after the heel lance. The mean of the magnitude of the heel lance-evoked brain activity was 0·85 arbitrary units (a.u.; SD 0·70; n=39; a scaled magnitude of 1 a.u. represents the expected mean response to a heel lance in term-aged neonates) in the intervention group and 0·91 a.u. (SD 0·76; n=43) in the control group. Therefore, the primary outcome did not differ significantly between groups, with a mean difference of -0·11 a.u. (lower in intervention group; SD 0·77; 95% CI -0·42 to 0·20; p=0·38; n=82). No significant difference was observed across secondary outcomes. The PIPP-R difference in means was 1·10 (higher in intervention group, 95% CI -0·42 to 2·61; p=0·15; n=100); the odds ratio of becoming tachycardic was 2·08 (95% CI 0·46 to 9·46; p=0·34, n=105) in the intervention group with reference to the control group; and the difference in parental State-Trait Anxiety Inventory-State score was -0·44 (higher in control group; SD 6·85; 95% CI -2·91 to 2·02; p=0·72; n=106). One serious adverse event (desaturation) occurred in a neonate randomly assigned to the control group, which was not considered to be related to the study. INTERPRETATION: Parental stroking delivered at an optimal speed to activate C-tactile fibres for a duration of 10 s before the painful procedure did not significantly change neonates' magnitude of pain-related brain activity, PIPP-R score, or development of tachycardia. The trial highlighted the challenge of translating an experimental researcher-led tactile intervention into a parent-led approach, and the value of involving parents in their baby's pain management. FUNDING: Wellcome Trust and Bliss.

Parental experience of neonatal pain research while participating in the Parental touch trial (Petal).

ABSTRACT: Parental involvement in neonatal comfort care is a core component of family-centred care. Yet, parents experience a range of positive and negative feelings when providing pain-relieving interventions for their infants. Parents of infants who participated in the Parental touch trial ( Petal ), a multicentre randomised controlled trial investigating the impact of gentle parental touch on neonatal pain, were asked to complete an anonymous survey. This survey aimed to (1) explore parent-reported motivations in deciding to participate in the Petal trial; (2) understand parent-reported experiences related to trial participation; (3) understand parents' willingness to participate in future studies; and (4) evaluate parent-reported feelings while they were delivering a gentle touch intervention either before or after a clinically necessary blood test. One hundred six parents (1 parent per infant) took part in the survey. Primary motivators for participation were altruistic. Parents most frequently reported that they wanted their child to take part in the research because it has a potential benefit to babies in the future and because they wanted to improve scientific understanding. Parents reported that providing gentle touch to their children during painful procedures was associated with positive emotions, such as feeling "useful" (64%) and "reassured" (53%). Furthermore, nearly all parents (98%) were pleased to have participated in the Petal trial and would consider, or maybe consider, participating in further research studies. These results underscore the importance of structuring trials around parental involvement and providing opportunities for parents to be involved in providing comfort to their infants during necessary painful clinical procedures.

The effect of acute respiratory events and respiratory stimulants on EEG-recorded brain activity in neonates: A systematic review.

Objective: We conducted a systematic review to investigate electroencephalography (EEG) changes during periods of acute respiratory events such as apnoea and the effect of respiratory stimulants on EEG features in infants. Methods: Studies examining respiration and EEG-recorded brain activity in human neonates between 28 and 42 weeks postmenstrual age were included. Two reviewers independently screened all records and included studies were assessed using the Joanna Briggs Institute Critical Appraisal Tool. The protocol was registered in PROSPERO (CRD42022339873). Results: We identified 14 studies with a total of 534 infants. Nine articles assessed EEG changes in relation to apnoea, one assessed hiccups, and four investigated the effect of respiratory stimulants. The relationship between neonatal apnoea and EEG changes was inconsistent; EEG suppression and decreased amplitude and frequency were observed during some, but not all, apnoeas. Respiratory stimulants increased EEG continuity compared with before use. Conclusions: Current studies in this area are constrained by small sample sizes. Diverse exposure definitions and outcome measures impact inference. Significance: This review highlights the need for further work; understanding the relationship between respiration and the developing brain is key to mitigating the long-term effects of apnoea.

Concurrent mapping of brain ontogeny and phylogeny within a common space: Standardized tractography and applications.

Developmental and evolutionary effects on brain organization are complex, yet linked, as evidenced by the correspondence in cortical area expansion across these vastly different time scales. However, it is still not possible to study concurrently the ontogeny and phylogeny of cortical areal connections, which is arguably more relevant to brain function than allometric measurements. Here, we propose a novel framework that allows the integration of structural connectivity maps from humans (adults and neonates) and nonhuman primates (macaques) onto a common space. We use white matter bundles to anchor the common space and use the uniqueness of cortical connection patterns to these bundles to probe area specialization. This enabled us to quantitatively study divergences and similarities in connectivity over evolutionary and developmental scales, to reveal brain maturation trajectories, including the effect of premature birth, and to translate cortical atlases between diverse brains. Our findings open new avenues for an integrative approach to imaging neuroanatomy.

The impact of premature extrauterine exposure on infants' stimulus-evoked brain activity across multiple sensory systems.

Prematurity can result in widespread neurodevelopmental impairment, with the impact of premature extrauterine exposure on brain function detectable in infancy. A range of neurodynamic and haemodynamic functional brain measures have previously been employed to study the neurodevelopmental impact of prematurity, with methodological and analytical heterogeneity across studies obscuring how multiple sensory systems are affected. Here, we outline a standardised template analysis approach to measure evoked response magnitudes for visual, tactile, and noxious stimulation in individual infants (n = 15) using EEG. By applying these templates longitudinally to an independent cohort of very preterm infants (n = 10), we observe that the evoked response template magnitudes are significantly associated with age-related maturation. Finally, in a cross-sectional study we show that the visual and tactile response template magnitudes differ between a cohort of infants who are age-matched at the time of study but who differ according to whether they are born during the very preterm or late preterm period (n = 10 and 8 respectively). These findings demonstrate the significant impact of premature extrauterine exposure on brain function and suggest that prematurity can accelerate maturation of the visual and tactile sensory system in infants born very prematurely. This study highlights the value of using a standardised multi-modal evoked-activity analysis approach to assess premature neurodevelopment, and will likely complement resting-state EEG and behavioural assessments in the study of the functional impact of developmental care interventions.