Caregiver Ratings of Toddler Pain: The Role of Caregiver Psychological Predictors.

INTRODUCTION/AIM: Young children's limited ability to self-report pain necessitates an understanding of the factors that influence pain ratings. The current paper examines the relative prediction of caregiver psychological factors and toddler pain behaviors on caregiver pain ratings post-vaccination. METHODS: One hundred fifty-six parent-toddler dyads were video recorded during pediatric vaccinations. Child pain behaviors were coded before, during, and after the needle using the Face, Legs, Activity, Cry, Consolability Scale and the Neonatal Facial Coding System). Caregivers rated their child's pain after the needle, reported pre- and post-needle worry during the visit, and completed rating scales assessing other areas of psychological functioning within 2 weeks after the appointment. Regression models were estimated to examine the relative contribution of child and caregiver factors to the prediction of caregiver pain ratings. RESULTS: The regression model predicting caregiver pain ratings from the toddlers' pain-related distress (facial activity immediately after the needle, overall pain-related behavior immediately after, 1-min and 2-min post-needle) and caregiver worry were significant (adjusted R-square = 0.21), with caregiver pre- and post-needle worry being the only significant predictors of caregiver pain ratings. CONCLUSIONS: This study outlines that although child distress behavior remains a significant influence on pain ratings during toddlerhood, when caregiver worry (pre- and post-needle) was entered into the model, they were the only significant predictors of caregiver pain ratings.

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.

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.

Trajectories of distress regulation during preschool vaccinations: child and caregiver predictors.

ABSTRACT: Recent research has highlighted the need for a deeper understanding of the heterogeneity in trajectories of children's distress after acute pain exposure, moving beyond the group means of behavioural pain scores at a single timepoint. During preschool vaccinations, 3 distinct trajectories of postvaccination pain regulation have been elucidated, with approximately 75% of children displaying trajectories characterized by downregulation to no distress by 2 minutes postneedle and 25% concerningly failing to downregulate by 2 minutes. The objective of this study was to examine child and caregiver predictors of preschool children's postvaccination regulatory patterns. Our results indicated that higher child baseline distress, more caregiver coping-promoting verbalizations in the first minute after the needle, less coping-promoting verbalizations in the second minute, and more caregiver distress-promoting verbalizations in the second minute after the needle were associated with membership in the trajectories characterized by high distress. Furthermore, although all children's pain-related distress at various timepoints throughout the appointment was most strongly predicted by previous pain scores, different patterns of associations emerged depending on the trajectory exhibited. This research highlights both the need to minimize distress before the needle to avoid the highly distressed trajectory and the importance of considering the heterogeneity of trajectories of preschool pain responding when examining the factors that are associated with children's pain-related distress.

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.

Maternal experiences of childhood maltreatment moderate patterns of mother-infant cortisol regulation under stress.

The relation between maternal and infant cortisol responses has been a subject of intense research over the past decade. Relatedly, it has been hypothesized that maternal history of childhood maltreatment (MCM) impacts stress regulation across generations. The current study employed four statistical approaches to determine how MCM influences the cortisol responses of 150 mothers and their 4-month-old infants during the Still-Face Paradigm. Results indicated that MCM moderated cortisol patterns in several ways. First, lower MCM mothers and infants had strong positive associations between cortisol levels measured at the same time point, whereas higher MCM mothers and infants did not show an association. Second, infants of higher MCM mothers had cortisol levels that were moderately high and remained elevated over the procedure, whereas infants of lower MCM mothers had decreasing cortisol levels over time. Third, higher MCM mothers and infants showed increasingly divergent cortisol levels over time, compared to lower MCM dyads. Finally, patterns of cross-lagged influence of infant cortisol on subsequent maternal cortisol were moderated by MCM, such that lower MCM mothers were influenced by their infants' cortisol levels at earlier time points than higher MCM mothers. These findings highlight MCM as one contributor to processes of stress regulation in the mother-infant dyad.

Case Report of Dual-Site Neurostimulation and Chronic Recording of Cortico-Striatal Circuitry in a Patient With Treatment Refractory Obsessive Compulsive Disorder.

Psychiatric disorders are increasingly understood as dysfunctions of hyper- or hypoconnectivity in distributed brain circuits. A prototypical example is obsessive compulsive disorder (OCD), which has been repeatedly linked to hyper-connectivity of cortico-striatal-thalamo-cortical (CSTC) loops. Deep brain stimulation (DBS) and lesions of CSTC structures have shown promise for treating both OCD and related disorders involving over-expression of automatic/habitual behaviors. Physiologically, we propose that this CSTC hyper-connectivity may be reflected in high synchrony of neural firing between loop structures, which could be measured as coherent oscillations in the local field potential (LFP). Here we report the results from the pilot patient in an Early Feasibility study (https://clinicaltrials.gov/ct2/show/NCT03184454) in which we use the Medtronic Activa PC+ S device to simultaneously record and stimulate in the supplementary motor area (SMA) and ventral capsule/ventral striatum (VC/VS). We hypothesized that frequency-mismatched stimulation should disrupt coherence and reduce compulsive symptoms. The patient reported subjective improvement in OCD symptoms and showed evidence of improved cognitive control with the addition of cortical stimulation, but these changes were not reflected in primary rating scales specific to OCD and depression, or during blinded cortical stimulation. This subjective improvement was correlated with increased SMA and VC/VS coherence in the alpha, beta, and gamma bands, signals which persisted after correcting for stimulation artifacts. We discuss the implications of this research, and propose future directions for research in network modulation in OCD and more broadly across psychiatric disorders.

Perceptual boundaries cause mnemonic trade-offs between local boundary processing and across-trial associative binding.

Episodic memories are not veridical records of our lives, but rather are better described as organized summaries of experience. Theories and empirical research suggest that shifts in perceptual, temporal, and semantic information lead to a chunking of our continuous experiences into segments, or "events." However, the consequences of these contextual shifts on memory formation and organization remains unclear. In a series of 3 behavioral studies, we introduced context shifts (or "event boundaries") between trains of stimuli and then examined the influence of the boundaries on several measures of associative memory. In Experiment 1, we found that perceptual event boundaries strengthened associative binding of item-context pairings present at event boundaries. In Experiment 2, we observed reduced temporal order memory for items encoded in distinct events relative to items encoded within the same event, and a trade-off between the speed of processing at boundaries, and temporal order memory for items that flanked those boundaries. Finally, in Experiment 3 we found that event organization imprinted structure on the order in which items were freely recalled. These results provide insight into how boundary- and event-related organizational processes during encoding shape subsequent representations of events in episodic memory. (PsycINFO Database Record