Follow-up visits after a concussion in the pediatric population: An integrative review.

BACKGROUND: Concussions are a significant health issue for children and youth. After a concussion diagnosis, follow-up visits with a health care provider are important for reassessment, continued management, and further education. OBJECTIVE: This review aimed to synthesize and analyse the current state of the literature on follow-up visits of children with a concussive injury and examine the factors associated with follow-up visits. METHODS: An integrative review was conducted based on Whittemore and Knafl's framework. Databases searched included PubMed, MEDLINE, CINAHL, PsycINFO, and Google Scholar. RESULTS: Twenty-four articles were reviewed. We identified follow-up visit rates, timing to a first follow-up visit, and factors associated with follow-up visits as common themes. Follow-up visit rates ranged widely, from 13.2 to 99.5%, but time to the first follow-up visit was only reported in eight studies. Three types of factors were associated with attending a follow-up visit: injury-related factors, individual factors, and health service factors. CONCLUSION: Concussed children and youth have varying rates of follow-up care after an initial concussion diagnosis, with little known about the timing of this visit. Diverse factors are associated with the first follow-up visit. Further research on follow-up visits after a concussion in this population is warranted.

Experiences of Mothers of Preterm Infants in the Neonatal Intensive Care Unit During the COVID-19 Pandemic.

BACKGROUND: The neonatal intensive care unit (NICU) stay following the birth of a preterm infant can be stressful and traumatic for families. During the COVID-19 pandemic, the NICU environment changed precipitously as infection control and visitor restriction measures were implemented. PURPOSE: Our study aimed to examine the impact of the pandemic policies on the experiences of mothers of preterm infants during their stay in the NICU. METHODS: Semistructured interviews were conducted with mothers of preterm infants hospitalized in a Canadian tertiary-level NICU. Informed by interpretive description methodology, interview content was transcribed and analyzed using a thematic analysis approach. The identified themes were validated, clarified, or refined using investigator triangulation. RESULTS: Nine English-speaking mothers, aged 28 to 40 years, were interviewed. Four themes emerged from the analysis of their experiences: (1) disrupted family dynamic, support, and bonding; (2) physical and emotional isolation; (3) negative psychological impact compounded by added concerns, maternal role change, and survival mode mentality; and (4) positive aspects of the pandemic management measures. IMPLICATIONS FOR PRACTICE: During the pandemic, the way that care was provided in the NICU changed. This study helps to explore how neonatal clinicians can foster individual and organizational resilience to keep patients and families at the center of care, even when the healthcare system is under intense stress. IMPLICATIONS FOR RESEARCH: : Our results show that these changes heightened mothers' distress, but also had a modest positive impact. Further research about long-term consequences of pandemic policies on the mother and preterm infant after NICU discharge is warranted.

Non-pharmacological pain interventions for sickle cell crisis in pediatrics: A scoping review.

PROBLEM: Sickle cell crises (SCC) are recurrent, severe pain episodes experienced by people living with sickle cell disease (SCD). Non-pharmacological interventions have been recommended for SCC pain management however, little is known about the impact of these interventions on SCC pain. This scoping review aims to systematically identify evidence on the use and effectiveness of non-pharmacological interventions for pain management during SCC in the pediatric population. ELIGIBILITY CRITERIA: Studies were eligible if they are published in English and focusing on the use of any non-pharmacological interventions on pain during SCC in pediatric patients. Nine databases were searched including Medline, CINAHL and PsychInfo. Also, the reference lists of relevant studies were searched. SAMPLE: The database searching yielded 1517 studies. After the title and abstract screening, 1348 studies were excluded, and 169 full texts were retrieved and screened. One study was identified through handsearching. Finally, 27 articles were included in this scoping review. RESULTS: Across all studies, 27 different non-pharmacological interventions were identified. There were inconsistent results regarding the effectiveness of virtual reality, guided imagery, and cognitive-behavioral interventions in experimental studies. The most common interventions used at home were prayer, massage, and distraction. The main interventions used in hospitals were prayer and fluid intake, but this was explored by a few studies. CONCLUSION: Pediatric SCD patients use numerous non-pharmacological interventions to manage pain during SCC. However, the impact of many interventions on SCC pain has not been empirically investigated. IMPLICATIONS: Further research is necessary to establish the effectiveness of non-pharmacological interventions on SCC pain.

Conducting Patient-Oriented Research in Low-Income and Middle-Income Countries: A Scoping Review.

BACKGROUND: Patient-oriented research involves extensive collaboration with patients, their families, caregivers, clinicians and other relevant stakeholders to identify and investigate problems and outcomes relevant to patients. Patient-oriented research can help develop effective patient-centred interventions. Patient-oriented research is an increasingly used approach in high-income countries, but it is unclear how patients are engaged in research in low-income and middle-income countries (LMICs). OBJECTIVES: The aim of this scoping review was to explore how patient-oriented research is conducted in LMICs. The objectives were to determine the levels of involvement of patients in the research, how studies have impacted healthcare and patient outcomes in these countries, the reported benefits of patient-oriented research on the research process and the reported challenges of conducting patient-oriented research in LMICs. METHODS: A scoping review was conducted using the methodological framework suggested by Arksey and O'Malley and the Joanna Briggs Institute guidelines for conducting scoping reviews. The eligibility criteria were any healthcare research using any research design that involved patients of any age group in the research process. Six databases were searched from their inception till January 4, 2022: MEDLINE, Embase, Cumulated Index to Nursing and Allied Health Literature, PsychInfo, Cochrane Central Register of Controlled Trials and EBM Reviews. The reference lists of relevant articles and Google Scholar were combed as well. Data extraction was performed with a self-developed data extraction guide. The findings were narratively summarised. RESULTS: Thirteen articles were included in this scoping review, representing eight LMICs in Africa and Asia. The majority of studies (38%, n = 5) focused on patients living with human immunodeficiency virus. More than half of the studies (n = 8, 62%) were conducted in the adult population, 31% (n = 4) of the studies involved children and/or adolescents. For most of the studies (92%, n = 12), the participants served as consultants; for one study, the authors identified the participants as co-researchers. Across the studies, information regarding patient-oriented research activities was not consistently reported in the same manner (i.e. different locations in the article), with very limited information in some cases. None of the studies used a patient-oriented research framework and the majority did not report on how patient-oriented research impacted healthcare and patient outcomes. Patient-oriented research was beneficial in identifying relevant patients' needs and improving collaboration among stakeholders, but it also led to extended research timelines and increased financial costs for the researchers and patients. CONCLUSIONS: Researchers in LMICs are incorporating patient-oriented research in their research; however, there is a need for improved reporting practices in published articles, and the use of frameworks to guide patient-oriented research in LMICs. In LMICs, patient-oriented research enhances collaboration across stakeholders and gives patients a sense of ownership over the interventions and research process. Future work should focus on developing contextually relevant conceptual frameworks and further studies should explore the impact of patient-oriented research on healthcare and patient outcomes in the LMIC context.

Support interventions offered to family members of a child treated with hematopoietic stem cell transplant: A scoping review.

A scoping review was conducted to explore support interventions for family members of a child treated with hematopoietic stem cell transplant (HSCT). Three databases (CINAHL, Embase, and Medline) were searched to answer the review question: What are the support interventions offered to family members of a child treated with HSCT and are they based on a family-centred care approach? Out of 665 screened articles, nine were selected for full review. Findings revealed two main types of family-centred support interventions: psychological face-to-face and technology-based interventions. The majority of interventions assisted in improving family members' psychological well-being and included a portion of the core concepts from the Institute for Patient and Family-Centered Care Model in their approach. Based on the review findings, interventions that incorporate family-centred care concepts can enhance the psychological well-being and quality of life of family members whose child is undergoing HSCT treatment.

ATTENTIV: Instrumented Peripheral Catheter for the Detection of Catheter Dislodgement in IV Infiltration.

Intravenous (IV) infiltration is a common problem associated with IV infusion therapy in clinical practice. A multitude of factors can cause the leakage of IV fluids into the surrounding tissues, resulting in symptoms ranging from temporary swelling to permanent tissue damage. Severe infiltration outcomes can be avoided or minimized if the patient's care provider is alerted of the infiltration at its earliest onset. However, there is a lack of real-time, continuous infiltration monitoring solutions, especially those suited for clinical use for critically ill patients. Our design of the sensor-integrated ATTENTIV catheter allows direct detection of catheter dislodgement, a root cause of IV infiltration. We verify two detection methods: blood-tissue differentiation with a support vector machine and signal peak identification with a thresholding algorithm. We present promising preliminary testing results on biological and phantom models that utilize bioimpedance as the sensing modality. Clinical relevance- The sensor-embedded ATTENTIV catheter demonstrates potential to automate IV infiltration detection in lieu of using traditional infusion catheters and manual detection methods.

Engaging nursing students in a COVID-19 Point-of-Care rapid screening clinic.

BACKGROUND: The COVID-19 pandemic has globally impacted nursing education, particularly clinical learning opportunities for undergraduate nursing students. PURPOSE: In this paper, we report on an educational activity wherein students participated in a COVID-19 Rapid Antigen Testing (RAT) clinic on a Canadian university campus. METHODS: Between February-April 2021, in the second term of a five-term accelerated program, nursing students (n = 60) participated in a nurse-led COVID-19 RAT clinic for students and staff living or working in congregate housing. Students participated in education activities which exposed nursing students to the full range of community health nursing roles in a pandemic. RESULTS: From clinical, research, policy, and public health, this educational activity acted as a microcosm of the critical roles that nurses employ in the health ecosystem. CONCLUSION: We offer lessons learned about implementing this activity, and how these lessons can be applied to routine and exceptional nursing curriculum.

Participants' experience in using a point of Care Rapid Antigen Test (RAT) for SARS-CoV-2.

Learning objectives: On completion of this presentation, participant should be able to: Understand the feasibility of RAT for SARS-CoV-2 screening in primary care Understand the role of RAT for SARS-CoV-2 screening in prevention of COVID-19 transmission in community Context: The COVID-19 pandemic has paralyzed human interactions worldwide. At least half of COVID-19 transmissions could originate from asymptomatic individuals. Rapid Antigen Testing (RAT) with nasal sampling at the point of care is inexpensive, fast and less invasive than PCR testing. Objective: The overall study objective was to examine the feasibility of point-of-care RAT for detecting SARS-CoV-2 amongst an asymptomatic population living in congregate housing. Design: Cross-sectional survey. Setting: This study was conducted at the University of British Columbia (UBC). Approximately 1500 undergraduate student were at the study site during February-April 2021. Population: Students living in UBC housing and staff working in the UBC housing sites were eligible. People testing positive for COVID-19 in the prior 90 days were excluded from the study. Intervention: The BD Veritor testing kit was used to test bilateral nasal specimens. Results were ready by the small BD Veritor reader. Outcome measures: Experiences of surveyed participants completing RAT. The survey was conducted during the last three weeks the site was open. Results: A total of 223 participants consisting of 134 (60%) females and 89 (40%) males completed the survey for a 37% response rate. Participants were mainly of European descent (45%), though there were East Asians (18%), African/ Caribbean (5%) and Indigenous (3%) people who also completed the survey. Almost all (98%) reported that RAT was acceptable/very acceptable and 97% would take another test. Participants believed they would test negative given their careful observation of public health measures such as hand washing, mask wearing and restricting contacts to their small "bubble". Their expectation of testing negative was based on having no or minimal interactions with any person who had tested positive. More than two thirds of participants reported RAT provide them peace of mind and reduced anxiety levels. Participants found the RAT to be safe, easy, accessible and rapid. Conclusions: Rapid antigen testing for detecting COVID-19 is well accepted and could support the detection of infection at an early stage amongst asymptomatic individuals while easing their worries.

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.

Sex-specific effects of neonatal oral sucrose treatment on growth and liver choline and glucocorticoid metabolism in adulthood.

Hospitalized preterm infants experience painful medical procedures. Oral sucrose is the nonpharmacological standard of care for minor procedural pain relief. Infants are treated with numerous doses of sucrose, raising concerns about potential long-term effects. The objective of this study was to determine the long-term effects of neonatal oral sucrose treatment on growth and liver metabolism in a mouse model. Neonatal female and male mice were randomly assigned to one of two oral treatments (n = 7-10 mice/group/sex): sterile water or sucrose. Pups were treated 10 times/day for the first 6 days of life with 0.2 mg/g body wt of respective treatments (24% solution; 1-4 µL/dose) to mimic what is given to preterm infants. Mice were weaned at age 3 wk onto a control diet and fed until age 16 wk. Sucrose-treated female and male mice gained less weight during the treatment period and were smaller at weaning than water-treated mice (P ≤ 0.05); no effect of sucrose treatment on body weight was observed at adulthood. However, adult sucrose-treated female mice had smaller tibias and lower serum insulin-like growth factor-1 than adult water-treated female mice (P ≤ 0.05); these effects were not observed in males. Lower liver S-adenosylmethionine, phosphocholine, and glycerophosphocholine were observed in adult sucrose-treated compared with water-treated female and male mice (P ≤ 0.05). Sucrose-treated female, but not male, mice had lower liver free choline and higher liver betaine compared with water-treated female mice (P < 0.01). Our findings suggest that repeated neonatal sucrose treatment has long-term sex-specific effects on growth and liver methionine and choline metabolism.

Cerebral hemodynamic response to a therapeutic bed for procedural pain management in preterm infants in the NICU: a randomized controlled trial.

INTRODUCTION: We developed a novel device, Calmer, that mimics key components of skin-to-skin holding to reduce stress in preterm infants. Our feasibility trial showed that Calmer worked 50% better than no treatment and no differently from our standard of care, facilitated tucking (FT), for reducing pain scores during a heel lance in preterm infants in the neonatal intensive care unit. OBJECTIVE: We compared the effects of Calmer on regional cerebral hemodynamic activity during a noxious stimulation to FT. METHODS: During a clinically required heel lance, we measured frontal cortex tissue oxygenation in a subsample of 29 preterm infants (27-33 weeks gestational age) from our larger randomized controlled trial. Infants were randomized to either FT (n = 16) or Calmer treatment (n = 12). The outcome measure, obtained using near-infrared spectroscopy, was a change in the tissue oxygenation index (TSI) across study phases (Baseline, Heel Lance, Recovery; median duration 517 seconds [421-906 seconds]). RESULTS: No statistically significant differences were found between groups in the median TSI during any of the study phases. In response to the heel lance, 7 infants (27.6%) had a TSI that dipped below the 60% threshold (3 in the Calmer group 25% and 4 in the FT group 25%); none below 50%. CONCLUSIONS: Infants on Calmer maintained normal regional cerebral oxygen levels (55%-85%) no differently from infants receiving a human touch intervention during blood collection. Parental skin-to-skin holding is one of the most effective strategies to relieve procedural pain in preterm infants. When parents or FT are not available, Calmer shows potential for filling this gap in care.

Early Life Maternal Separation and Maternal Behaviour Modulate Acoustic Characteristics of Rat Pup Ultrasonic Vocalizations.

Early separation of preterm infants from their mothers has adverse, long-term neurodevelopmental consequences. We investigated the effects of daily maternal separation (MS) of rat pups from postnatal days 2-10 (PND2-10) on neurobehavioural responses to brief isolation at PND12 compared with pups receiving controlled handling without MS. Ultrasonic vocalizations (USV) were measured at PND12 during two, 3-minute isolations occurring immediately before and after a 3-minute maternal reunion. There were no significant differences in acoustic characteristics between MS and control animals in the first isolation. However, in the second isolation, MS pups produced a greater proportion of high (~60 kHz) vs low (~40 kHz) frequency calls. During this isolation, control pups made longer and louder low frequency calls compared to the first isolation, whereas MS pups did the opposite. Maternal behaviour of control and MS mothers modulated pup acoustic characteristics in opposite directions; higher maternal care was associated with more low frequency calls in control pups but more high frequency calls in MS pups. We hypothesize that MS results in USV emission patterns reflective of a greater stress response to isolation. This translational model can be used to identify mechanisms and interventions that may be exploited to overcome the negative, long-term effects of MS.

Hippocampus, Amygdala, and Thalamus Volumes in Very Preterm Children at 8 Years: Neonatal Pain and Genetic Variation.

Altered hippocampal morphology and reduced volumes have been found in children born preterm compared to full-term. Stress inhibits neurogenesis in the hippocampus, and neonatal stress/noxious stimulation in rodent pups are associated with long-term alterations in hippocampal volumes. We have previously shown reduced cortical thickness and cerebellar volumes in relation to more exposure to pain-related stress of neonatal invasive procedures in children born very preterm. We have reported targeted gene-by-pain environment interactions that contribute to long-term brain development and outcomes in this population. We now aim to determine whether exposure to pain-related stress (adjusted for clinical factors and genotype) differentially impacts regional structures within the limbic system and thalamus, and investigate relationships with outcomes in very preterm children. Our study included 57 children born very preterm (<32 weeks GA) followed longitudinally from birth who underwent 3-D T1 MRI neuroimaging at ∼8 years. Hippocampal subfields and white matter tracts, thalamus and amygdala were automatically segmented using the MAGeT Brain algorithm. The relationship between those subcortical brain volumes (adjusted for total brain volume) and neonatal invasive procedures, gestational age (GA), illness severity, postnatal infection, days of mechanical ventilation, number of surgeries, morphine exposure, and genotype (COMT, SLC6A4, and BDNF) was examined using constrained principal component analysis. We found that neonatal clinical factors and genotypes accounted for 46% of the overall variance in volumes of hippocampal subregions, tracts, basal ganglia, thalamus and amygdala. After controlling for clinical risk factors and total brain volume, greater neonatal invasive procedures was associated with lower volumes in the amygdala and thalamus (p = 0.0001) and an interaction with COMT genotype predicted smaller hippocampal subregional volume (p = 0.0001). More surgeries, days of ventilation, and lower GA were also related to smaller volumes in various subcortical regions (p < 0.002). These reduced volumes were in turn differentially related to poorer cognitive, visual-motor and behavioral outcomes. Our findings highlight the complexity that interplays when examining how exposure to early-life stress may impact brain development both at the structural and functional level, and provide new insight on possible novel avenues of research to discover brain-protective treatments to improve the care of children born preterm.

Adverse Behavioral Changes in Adult Mice Following Neonatal Repeated Exposure to Pain and Sucrose.

Sucrose is recommended for the treatment of pain during minor procedures in preterm infants in the neonatal intensive care unit (NICU) and is currently used worldwide as the standard of care. We recently reported that adult mice repetitively exposed to sucrose compared to water during the first week of life, irrespective of exposure to an intervention, had significantly smaller brain volumes in large white matter, cortical and subcortical structures (e.g., hippocampus, striatum, fimbria). These structures are important for stress regulation and memory formation. Here, we report the effects of repeated neonatal exposure to pain and sucrose on adult behavior in mice. Neonatal C57BL/6J mice (N = 160, 47% male) were randomly assigned to one of two treatments (sucrose, water) and one of three interventions (needle-prick, tactile, handling). Pups received 10 interventions daily from postnatal day 1 (P1) to P6. A single dose of 24% sucrose or water was given orally 2 min before each intervention. At adulthood (P60-85) mice underwent behavioral testing to assess spatial memory, anxiety, motor function, pain sensitivity, and sugar preference. We found that mice that had received sucrose and handling only, had poorer short-term memory in adulthood compared to water/handling controls (p < 0.05). When exposed to pain, mice treated with repetitive sucrose or water did not differ on memory performance (p = 0.1). A sugar preference test showed that adult mice that received sucrose before an intervention as pups consumed less sugar solution compared to controls or those that received water before pain (p < 0.05). There were no significant group differences in anxiety, motor, or pain sensitivity. In a mouse model that closely mimics NICU care, we show for the first time that memory in adulthood was poorer for mice exposed to pain during the first week of life, irrespective of sucrose treatment, suggesting that sucrose does not protect memory performance when administered for pain. In the absence of pain, early repetitive sucrose exposure induced poorer short-term memory, highlighting the importance of accurate pain assessment.

Repeated exposure to sucrose for procedural pain in mouse pups leads to long-term widespread brain alterations.

Oral sucrose is administered routinely to reduce pain of minor procedures in premature infants and is recommended as standard care in international guidelines. No human or animal studies on effects of early repeated sucrose exposure on long-term brain development have been done in the context of pain. We evaluated the effects of repeated neonatal sucrose treatment before an intervention on long-term brain structure in mouse pups. Neonatal C57Bl/6J mice (n = 109) were randomly assigned to one of 2 treatments (vehicle vs sucrose) and one of 3 interventions (handling, touch, or needle-prick). Mice received 10 interventions daily from postnatal day 1 to 6 (P1-6). A dose of vehicle or 24% sucrose was given orally 2 minutes before each intervention. At P85-95, brains were scanned using a multichannel 7.0 T MRI. Volumes of 159 independent brain regions were obtained. Early repetitive sucrose exposure in mice (after correcting for whole brain volume and multiple comparisons) lead to smaller white matter volumes in the corpus callosum, stria terminalis, and fimbria (P < 0.0001). Cortical and subcortical gray matter was also affected by sucrose with smaller volumes of hippocampus and cerebellum (P < 0.0001). These significant changes in adult brain were found irrespective of the type of intervention in the neonatal period. This study provides the first evidence of long-term adverse effects of repetitive sucrose exposure and raises concerns for the use of this standard pain management practice during a period of rapid brain development in very preterm infants.

Neonatal Invasive Procedures Predict Pain Intensity at School Age in Children Born Very Preterm.

INTRODUCTION: Children born very preterm display altered pain thresholds. Little is known about the neonatal clinical and psychosocial factors associated with their later pain perception. OBJECTIVE: We aimed to examine whether the number of neonatal invasive procedures, adjusted for other clinical and psychosocial factors, was associated with self-ratings of pain during a blood collection procedure at school age in children born very preterm. MATERIALS AND METHODS: 56 children born very preterm (24 to 32 weeks gestational age), followed longitudinally from birth, and free of major neurodevelopmental impairments underwent a blood collection by venipuncture at age 7.5 years. The children's pain was self-reported using the Coloured Analog Scale and the Facial Affective Scale. Parents completed the Child Behavior Checklist and the State-Trait Anxiety Inventory. Pain exposure (the number of invasive procedures) and clinical factors from birth to term-equivalent age were obtained prospectively. Multiple linear regression was used to predict children's pain self-ratings from neonatal pain exposure after adjusting for neonatal clinical and concurrent psychosocial factors. RESULTS: A greater number of neonatal invasive procedures and higher parent trait-anxiety were associated with higher pain intensity ratings during venipuncture at age 7.5 years. Fewer surgeries and lower concurrent child externalizing behaviors were associated with a higher pain intensity. CONCLUSIONS: In very preterm children, exposure to neonatal pain was related to altered pain self-ratings at school age, independent of other neonatal factors. Neonatal surgeries and concurrent psychosocial factors were also associated with pain ratings.

Neonatal Pain and Infection Relate to Smaller Cerebellum in Very Preterm Children at School Age.

OBJECTIVE: To examine whether specific neonatal factors differentially influence cerebellar subregional volumes and to investigate relationships between subregional volumes and outcomes in very preterm children at 7 years of age. STUDY DESIGN: Fifty-six children born very preterm (24-32 weeks gestational age) followed longitudinally from birth underwent 3-dimensional T(1)-weighted neuroimaging at median age 7.6 years. Children with severe brain injury were excluded. Cerebellar subregions were automatically segmented using the multiple automatically generated templates algorithm. The relation between cerebellum subregional volumes (adjusted for total brain volume and sex) and neonatal clinical factors were examined using constrained principal component analysis. Cognitive and visual-motor integration functions in relation to cerebellar volumes were also investigated. RESULTS: Higher neonatal procedural pain and infection, as well as other clinical factors, were differentially associated with reduced cerebellar volumes in specific subregions. After adjusting for clinical risk factors, neonatal procedural pain was distinctively associated with smaller volumes bilaterally in the posterior VIIIA and VIIIB lobules. Specific smaller cerebellar subregional volumes were related to poorer cognition and motor/visual integration. CONCLUSIONS: In very preterm children, exposure to painful procedures, as well as additional neonatal risk factors such as infection, were associated with reduced cerebellar volumes in specific subregions and poorer outcomes at school age.

How do babies feel pain?

Functional MRI studies suggest that healthy full-term newborn babies experience some aspects of pain in a similar way to adults.

Neonatal pain and COMT Val158Met genotype in relation to serotonin transporter (SLC6A4) promoter methylation in very preterm children at school age.

Children born very preterm are exposed to repeated neonatal procedures that induce pain and stress during hospitalization in the neonatal intensive care unit (NICU). The COMT Val158Met genotype is involved with pain sensitivity, and early life stress is implicated in altered expression of methylation of the serotonin transporter. We examined: (1) whether methylation of the serotonin transporter gene (SLC6A4) promoter differs between very preterm children and full-term controls at school age, (2) relationships with child behavior problems, and (3) whether the extent of neonatal pain exposure interacts with the COMT Val158Met genotype to predict SLC6A4 methylation at 7 years in the very preterm children. We examined the associations between the COMT genotypes, neonatal pain exposure (adjusted for neonatal clinical confounders), SLC6A4 methylation and behavior problems. Very preterm children had significantly higher methylation at 7/10 CpG sites in the SLC6A4 promoter compared to full-term controls at 7 years. Neonatal pain (adjusted for clinical confounders) was significantly associated with total child behavior problems on the Child Behavior Checklist (CBCL) questionnaire (adjusted for concurrent stressors and 5HTTLPR genotype) (p = 0.035). CBCL Total Problems was significantly associated with greater SLC6A4 methylation in very preterm children (p = 0.01). Neonatal pain (adjusted for clinical confounders) and COMT Met/Met genotype were associated with SLC6A4 promoter methylation in very preterm children at 7 years (p = 0.001). These findings provide evidence that both genetic predisposition and early environment need to be considered in understanding susceptibility for developing behavioral problems in this vulnerable population.