Health Care Professionals' and Parents' Perspectives on the Use of AI for Pain Monitoring in the Neonatal Intensive Care Unit: Multisite Qualitative Study.

BACKGROUND: The use of artificial intelligence (AI) for pain assessment has the potential to address historical challenges in infant pain assessment. There is a dearth of information on the perceived benefits and barriers to the implementation of AI for neonatal pain monitoring in the neonatal intensive care unit (NICU) from the perspective of health care professionals (HCPs) and parents. This qualitative analysis provides novel data obtained from 2 large tertiary care hospitals in Canada and the United Kingdom. OBJECTIVE: The aim of the study is to explore the perspectives of HCPs and parents regarding the use of AI for pain assessment in the NICU. METHODS: In total, 20 HCPs and 20 parents of preterm infants were recruited and consented to participate from February 2020 to October 2022 in interviews asking about AI use for pain assessment in the NICU, potential benefits of the technology, and potential barriers to use. RESULTS: The 40 participants included 20 HCPs (17 women and 3 men) with an average of 19.4 (SD 10.69) years of experience in the NICU and 20 parents (mean age 34.4, SD 5.42 years) of preterm infants who were on average 43 (SD 30.34) days old. Six themes from the perspective of HCPs were identified: regular use of technology in the NICU, concerns with regard to AI integration, the potential to improve patient care, requirements for implementation, AI as a tool for pain assessment, and ethical considerations. Seven parent themes included the potential for improved care, increased parental distress, support for parents regarding AI, the impact on parent engagement, the importance of human care, requirements for integration, and the desire for choice in its use. A consistent theme was the importance of AI as a tool to inform clinical decision-making and not replace it. CONCLUSIONS: HCPs and parents expressed generally positive sentiments about the potential use of AI for pain assessment in the NICU, with HCPs highlighting important ethical considerations. This study identifies critical methodological and ethical perspectives from key stakeholders that should be noted by any team considering the creation and implementation of AI for pain monitoring in the NICU.

A Systematic Review of Neurodevelopmental Assessments in Infancy and Early Childhood: Developing a Conceptual Framework, Repository of Measures, and Clinical Recommendations.

The first 6 years of life are when 90% of brain development occurs, setting the foundation for lifelong neurodevelopment. The field of infant and early childhood neurodevelopment has made marginal advancements since introduced in 1988. There remains a gap in knowledge around early neurodevelopmental domains and trajectories given that there are few established assessment procedures for infants and young children and controversies around reserving assessments until school age. Throughout this systematic review, we (1) identified neurodevelopmental assessment measures employed in the literature by domain and age of assessment, (2) compiled a repository of 608 domain-specific neurodevelopmental assessment measures, and (3) established a preliminary conceptual framework for cross-domain neurodevelopmental assessments across infancy and early childhood. This review adhered to PRISMA guidelines and spanned three databases (PsycINFO, MEDLINE, PubMed). Articles were reviewed for (1) infancy and early childhood (0-6 years), (2) neurodevelopmental measures, and (3) English language. This systematic review spanned 795 articles from 1978 to 2020 with international representation. Advancements in assessment methods (e.g. measures, domains, frameworks) are essential for the evaluation of early neurodevelopmental profiles to inform early interventions, thus harnessing the neuroplasticity and dynamic development notable during early childhood. We hope this work catalyzes future research and clinical guidelines around early assessments methods.

Non-pharmacological management of infant and young child procedural pain.

BACKGROUND: Despite evidence of the long-term implications of unrelieved pain during infancy, it is evident that infant pain is still under-managed and unmanaged. Inadequately managed pain in infancy, a period of exponential development, can have implications across the lifespan. Therefore, a comprehensive and systematic review of pain management strategies is integral to appropriate infant pain management. This is an update of a previously published review update in the Cochrane Database of Systematic Reviews (2015, Issue 12) of the same title. OBJECTIVES: To assess the efficacy and adverse events of non-pharmacological interventions for infant and child (aged up to three years) acute pain, excluding kangaroo care, sucrose, breastfeeding/breast milk, and music. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE-Ovid platform, EMBASE-OVID platform, PsycINFO-OVID platform, CINAHL-EBSCO platform and trial registration websites (ClinicalTrials.gov; International Clinical Trials Registry Platform) (March 2015 to October 2020). An update search was completed in July 2022, but studies identified at this point were added to 'Awaiting classification' for a future update.  We also searched reference lists and contacted researchers via electronic list-serves.  We incorporated 76 new studies into the review.  SELECTION CRITERIA: Participants included infants from birth to three years in randomised controlled trials (RCTs) or cross-over RCTs that had a no-treatment control comparison. Studies were eligible for inclusion in the analysis if they compared a non-pharmacological pain management strategy to a no-treatment control group (15 different strategies). In addition, we also analysed studies when the unique effect of adding a non-pharmacological pain management strategy onto another pain management strategy could be assessed (i.e. additive effects on a sweet solution, non-nutritive sucking, or swaddling) (three strategies). The eligible control groups for these additive studies were sweet solution only, non-nutritive sucking only, or swaddling only, respectively. Finally, we qualitatively described six interventions that met the eligibility criteria for inclusion in the review, but not in the analysis.  DATA COLLECTION AND ANALYSIS: The outcomes assessed in the review were pain response (reactivity and regulation) and adverse events. The level of certainty in the evidence and risk of bias were based on the Cochrane risk of bias tool and the GRADE approach. We analysed the standardised mean difference (SMD) using the generic inverse variance method to determine effect sizes.  MAIN RESULTS: We included total of 138 studies (11,058 participants), which includes an additional 76 new studies for this update. Of these 138 studies, we analysed 115 (9048 participants) and described 23 (2010 participants) qualitatively. We described qualitatively studies that could not be meta-analysed due to being the only studies in their category or statistical reporting issues. We report the results of the 138 included studies here. An SMD effect size of 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect. The thresholds for the I2 interpretation were established as follows: not important (0% to 40%); moderate heterogeneity (30% to 60%); substantial heterogeneity (50% to 90%); considerable heterogeneity (75% to 100%). The most commonly studied acute procedures were heel sticks (63 studies) and needlestick procedures for the purposes of vaccines/vitamins (35 studies). We judged most studies to have high risk of bias (103 out of 138), with the most common methodological concerns relating to blinding of personnel and outcome assessors. Pain responses were examined during two separate pain phases: pain reactivity (within the first 30 seconds after the acutely painful stimulus) and immediate pain regulation (after the first 30 seconds following the acutely painful stimulus). We report below the strategies with the strongest evidence base for each age group. In preterm born neonates, non-nutritive sucking may reduce pain reactivity (SMD -0.57, 95% confidence interval (CI) -1.03 to -0.11, moderate effect; I2 = 93%, considerable heterogeneity) and improve immediate pain regulation (SMD -0.61, 95% CI -0.95 to -0.27, moderate effect; I2 = 81%, considerable heterogeneity), based on very low-certainty evidence. Facilitated tucking may also reduce pain reactivity (SMD -1.01, 95% CI -1.44 to -0.58, large effect; I2 = 93%, considerable heterogeneity) and improve immediate pain regulation (SMD -0.59, 95% CI -0.92 to -0.26, moderate effect; I2 = 87%, considerable heterogeneity); however, this is also based on very low-certainty evidence. While swaddling likely does not reduce pain reactivity in preterm neonates (SMD -0.60, 95% CI -1.23 to 0.04, no effect; I2 = 91%, considerable heterogeneity), it has been shown to possibly improve immediate pain regulation (SMD -1.21, 95% CI -2.05 to -0.38, large effect; I2 = 89%, considerable heterogeneity), based on very low-certainty evidence. In full-term born neonates, non-nutritive sucking may reduce pain reactivity (SMD -1.13, 95% CI -1.57 to -0.68, large effect; I2 = 82%, considerable heterogeneity) and improve immediate pain regulation (SMD -1.49, 95% CI -2.20 to -0.78, large effect; I2 = 92%, considerable heterogeneity), based on very low-certainty evidence.  In full-term born older infants, structured parent involvement was the intervention most studied. Results showed that this intervention has little to no effect in reducing pain reactivity (SMD -0.18, 95% CI -0.40 to 0.03, no effect; I2 = 46%, moderate heterogeneity) or improving immediate pain regulation (SMD -0.09, 95% CI -0.40 to 0.21, no effect; I2 = 74%, substantial heterogeneity), based on low- to moderate-certainty evidence. Of these five interventions most studied, only two studies observed adverse events, specifically vomiting (one preterm neonate) and desaturation (one full-term neonate hospitalised in the NICU) following the non-nutritive sucking intervention. The presence of considerable heterogeneity limited our confidence in the findings for certain analyses, as did the preponderance of evidence of very low to low certainty based on GRADE judgements. AUTHORS' CONCLUSIONS: Overall, non-nutritive sucking, facilitated tucking, and swaddling may reduce pain behaviours in preterm born neonates. Non-nutritive sucking may also reduce pain behaviours in full-term neonates. No interventions based on a substantial body of evidence showed promise in reducing pain behaviours in older infants. Most analyses were based on very low- or low-certainty grades of evidence and none were based on high-certainty evidence. Therefore, the lack of confidence in the evidence would require further research before we could draw a definitive conclusion.

A developmental shift in habituation to pain in human neonates.

Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain. Neonates, especially if preterm, are exposed to repeated noxious procedures during their clinical care. They can mount strong behavioral, autonomic, spinal, and cortical responses to a single noxious stimulus; however, it is not known whether the developing nervous system can adapt to the recurrence of these inputs. Here, we used electroencephalography to investigate changes in cortical microstates (representing the complex sequential processing of noxious inputs) following two consecutive clinically required heel lances in term and preterm infants. We show that stimulus repetition dampens the engagement of initial microstates and associated behavioral and autonomic responses in term infants, while preterm infants do not show signs of habituation. Nevertheless, both groups engage different longer-latency cortical microstates to each lance, which is likely to reflect changes in higher-level stimulus processing with repeated stimulation. These data suggest that while both age groups are capable of encoding contextual differences in pain, the preterm brain does not regulate the initial cortical, behavioral, and autonomic responses to repeated noxious stimuli. Habituation mechanisms to pain are already in place at term age but mature over the equivalent of the last trimester of gestation and are not fully functional in preterm neonates.

Clinical thresholds in pain-related facial activity linked to differences in cortical network activation in neonates.

ABSTRACT: In neonates, a noxious stimulus elicits pain-related facial expression changes and distinct brain activity as measured by electroencephalography, but past research has revealed an inconsistent relationship between these responses. Facial activity is the most commonly used index of neonatal pain in clinical settings, with clinical thresholds determining if analgesia should be provided; however, we do not know if these thresholds are associated with differences in how the neonatal brain processes a noxious stimulus. The objective of this study was to examine whether subclinical vs clinically significant levels of pain-related facial activity are related to differences in the pattern of nociceptive brain activity in preterm and term neonates. We recorded whole-head electroencephalography and video in 78 neonates (0-14 days postnatal age) after a clinically required heel lance. Using an optimal constellation of Neonatal Facial Coding System actions (brow bulge, eye squeeze, and nasolabial furrow), we compared the serial network engagement (microstates) between neonates with and without clinically significant pain behaviour. Results revealed a sequence of nociceptive cortical network activation that was independent of pain-related behavior; however, a separate but interleaved sequence of early activity was related to the magnitude of the immediate behavioural response. Importantly, the degree of pain-related behavior is related to how the brain processes a stimulus and not simply the degree of cortical activation. This suggests that neonates who exhibit clinically significant pain behaviours process the stimulus differently and that neonatal pain-related behaviours reflect just a portion of the overall cortical pain response.

Child Distress Expression and Regulation Behaviors: A Systematic Review and Meta-Analysis.

The goal of the current study was to review and meta-analyze the literature on relationships between child distress expression behaviors (e.g., cry) and three clusters of child distress regulation behaviors (disengagement of attention, parent-focused behaviors, and self-soothing) in the first three years of life. This review was registered with PROSPERO (CRD42020157505). Unique abstracts were identified through Medline, Embase, and PsycINFO (n = 13,239), and 295 studies were selected for full-text review. Studies were included if they provided data from infants or toddlers in a distress task, had distinct behavioral measures of distress expression and one of the three distress regulation clusters, and assessed the concurrent association between them. Thirty-one studies were included in the meta-analysis and rated on quality. Nine separate meta-analyses were conducted, stratified by child age (first, second, and third year) and regulation behavior clusters (disengagement of attention, parent-focused, and self-soothing). The weighted mean correlations for disengagement of attention behaviors were -0.28 (year 1), -0.44 (year 2), and -0.30 (year 3). For parent-focused behaviors, the weighted mean effects were 0.00 (year 1), 0.20 (year 2), and 0.11 (year 3). Finally, the weighted mean effects for self-soothing behaviors were -0.23 (year 1), 0.25 (year 2), and -0.10 (year 3). The second year of life showed the strongest relationships, although heterogeneity of effects was substantial across the analyses. Limitations include only analyzing concurrent relationships and lack of naturalistic distress paradigms in the literature.

Caregiver and Young Child Biological Attunement In Distress Contexts: A Systematic Review and Narrative Synthesis.

The objective of the current study was to systematically review the literature on caregiver-child biological attunement within distress contexts during the first three years of life. A total of 9932 unique abstracts were identified through Medline, Embase, PsycINFO, CINAHL, and Scopus databases. Thirty-six studies provided data from caregivers and their infants or toddlers within a distress paradigm, used biological indicators of distress, and assessed the relations between caregiver and child biological indicators. Findings were synthesized based on biological indicators, type of analysis, and measurement epochs pre- and post-distress. Most articles examined cortisol. Associations between caregiver and child cortisol indicators were moderate to large, though findings varied depending on the analysis used and measurement epochs examined. Many of the findings examining relations between mother and child cardiac, sAA, and EEG indicators were weak or inconsistent, likely due to the limitations of methodological approaches used to capture the complexity of the caregiver-child attunement process. Gaps in the literature and suggestions for future research are discussed.

Psychosocial and Neurobiological Vulnerabilities of the Hospitalized Preterm Infant and Relevant Non-pharmacological Pain Mitigation Strategies.

Background: Preterm pain is common in the Neonatal Intensive Care Unit (NICU), with multiple invasive procedures occurring daily. Objective: To review the psychosocial and neurobiological vulnerabilities of preterm infants and to provide an updated overview of non-pharmacological strategies for acute procedural pain in hospitalized preterm infants. Methods: We utilized a narrative review methodology, which also included a synthesis of key pieces of published systematic reviews that are relevant to the current work. Results and Conclusions: Preterm infants are uniquely susceptible to the impact of painful procedures and prolonged separation from caregivers that are often inherent in a NICU stay. Non-pharmacological interventions can be efficacious for mitigating procedural pain for preterm infants. Interventions should continue to be evaluated with high quality randomized controlled trials, and should endeavor to take into account the neurobiological and psychosocial aspects of preterm vulnerability for pain prevention and management strategies.

Non-pharmacological pain management in the neonatal intensive care unit: Managing neonatal pain without drugs.

Premature infants hospitalized after birth are exposed to repeated painful procedures as part of their routine medical care. Early neonatal exposure to unmanaged pain has been linked to numerous negative long-term outcomes, such as the development of pain hypersensitivity, detrimental psychological symptomology, and altered neurodevelopment. These findings emphasize the crucial role of pain management in neonatal care. The aim of this article is to give an overview of evidence-based non-pharmacological pain management techniques for hospitalized neonates. Research supporting the effectiveness of various proximal, distal, and procedural pain management methods in neonates will be presented. Additionally, understanding the larger biopsychosocial context of the infant that underpins the mechanisms of these pain management methods is essential. Therefore, two important models that inform non-pharmacological approaches to infant pain management (DIAPR-R [The Development of Infant Acute Pain Responding-Revised], Attachment Theory) will be discussed.