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.

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.

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.

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.

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.

Innovating in pain assessment of the critically ill: exploring cerebral near-infrared spectroscopy as a bedside approach.

Nurses play a crucial role in the evaluation and treatment of pain in the critically ill patient. This responsibility is all the more critical with this particular population because many may not be able to self-report their pain level and the typical behavioral signs of pain may be subtle or absent. According to recent recommendations, vital signs should not be used as primary indicators of pain but rather considered as a cue to begin further assessment. Other than vital signs, human brain reactivity to pain has been extensively studied with the use mainly of magnetic resonance imaging and positron-emission tomography. However, the use of these sophisticated methods may be unrealistic in the critically ill. Of interest to assessing these patients in a clinical setting is the noninvasive measurement of regional cerebral tissue oxygenation with the near-infrared spectroscopy (NIRS) technique. There are indications that NIRS is capable of detecting the cerebral hemodynamic changes associated with sensory stimuli, including pain. The objective of this review paper is to provide nurses with a better understanding of NIRS technology, including a review of the literature on functional studies that have used NIRS in critically ill populations, and how it could be used in both research and practice. Current NIRS techniques have well recognized limitations which must be considered carefully during the measurement and interpretation of signals. Thus, its clinical use is yet to be fully established. Nonetheless, cerebral NIRS technique as an approach to assess brain activity in response to pain should not be abandoned.

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.

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.

Maternal touch and talk for invasive procedures in infants and toddlers in the pediatric intensive care unit.

The aim of this single-blind, randomized, crossover trial was to test the effect of Touch & Talk (T&T) for infants and toddlers less than 36 months of age (N = 65) in the pediatric intensive care unit on their physiological stability and recovery to an invasive procedure. In the T&T condition, mothers touched, sang, or told stories or rhymes to their child during an invasive procedure. In the control condition, the mothers did not have contact with their child. Physiological measures included heart rate, heart rate variability, and oxygen saturation range during the procedure and change from baseline. Time from the end of the procedure until the heart rate returned to baseline levels gave the recovery time. Analysis was conducted using repeated-measures analysis of covariance. There were no significant differences on any of the physiological parameters by condition during the procedure. However, when controlling for severity of illness, recovery was faster with mothers.

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.

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.

Cerebral near-infrared spectroscopy as a measure of nociceptive evoked activity in critically ill infants.

Signs of pain may be subtle or absent in a critically ill infant. The complex nature of pain may further obscure its identification and measurement. Because the use of monitoring and neuroimaging techniques has become more common in pain research, an understanding of these specialized technologies is important. Near-infrared spectroscopy (NIRS) is a noninvasive technique for monitoring tissue hemodynamics and oxygenation. There are indications that NIRS is capable of detecting the cerebral hemodynamic changes associated with sensory stimuli, including pain, in infants. These developments suggest that NIRS may play an important role in research focusing on pain perception in critically ill infants. The present review briefly describes the cortical responses to noxious stimuli, which parallel cerebral hemodynamic responses to various stimuli. This is followed by an overview of NIRS technology including a summary of the literature on functional studies that have used NIRS in infants. Current NIRS techniques have well-recognized limitations that must be considered carefully during the measurement and interpretation of the signals. Nonetheless, until more advanced NIRS techniques emerge, the current devices have strengths that should be exploited.

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.

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.

Incidence of self-limiting back pain in children following caudal blockade: an exploratory study.

BACKGROUND: Currently, in pediatric anesthesia, there is no evidence-based information available to pediatric patients and their parents regarding the incidence of back pain after neuraxial injections performed for postoperative analgesia. Back pain postepidural blockade has been reported in numerous studies with adult patients; however, it has not been investigated in children. The main objective of this study is to examine the incidence of back pain symptoms after caudal blockade (early and late onset) in children. METHODS: Patients under the age of 18 years, who received caudal blockade at the Montreal Children's Hospital between July 2006 and December 2008 were recruited in this prospective observational study. Back pain was measured prospectively by patient self-report and parental observation during the 15-day postoperative period. Patients, or their parents, were contacted by phone on postoperative day 2 (POD2) and postoperative day 15 (POD15) to answer a seven-item symptom questionnaire. RESULTS: In a sample of 135 children, the incidence of back pain symptoms was 4.7% and 1.1% on POD2 and POD15, respectively. CONCLUSIONS: The results of this study provide support that transient self-limiting back pain after caudal blockade does occur in pediatric patients. Clinically, this is useful information for physicians to provide to their patients. An exploration of factors that may be associated with back pain following caudal blockade in children is an interesting area of future research.

An acute pain service improves postoperative pain management for children undergoing selective dorsal rhizotomy.

BACKGROUND: A continuous epidural infusion of morphine is the pain treatment modality for children undergoing selective dorsal rhizotomy (SDR) in our institution. The aim of the study was to evaluate the impact of having an organized acute pain service (APS) on postoperative pain management of these children. METHODS: We conducted a retrospective cohort study using anesthetic records and the APS database to compare the postoperative pain management of children undergoing SDR before and after the introduction of the APS at the Montreal Children's Hospital in April 2001. Ninety-two consecutive children who had their surgery between January 1997 and July 2006 were included. We collected data regarding postoperative pain, opioid-induced side effects, complications (sedation, desaturations < 92%), and hospital length of stay. RESULTS: Pain scores were documented more frequently after the implementation of the APS (61% vs 48.5%). Sedation scores were documented only after the implementation of the APS. Postoperative desaturation was significantly more frequent in the pre-APS group compared to the APS group (45.5% vs 6.8%, P < 0.001). Despite the fact that the epidural catheter was in place for the same duration for both groups [median of 3 days (3-3 25-75%ile)], the duration of hospitalization was 1 day shorter in the APS group compared to the pre-APS group [median of 5 (5-5 25-75%ile) vs 6 (5-6 25-75%ile) days, P < 0.001]. CONCLUSIONS: Although we recognize that it is possible that there were changes in care not related specifically to the introduction of a dedicated APS that occurred in our institution that resulted in improvements in general postoperative care and in length of stay, our study did show that having an organized APS allowed to significantly decrease the incidence of postoperative oxygen desaturation and to decrease the hospital length of stay by 1 day.

Controlling bias in complex nursing intervention studies: a checklist.

Bias is defined as any systematic error resulting in an inaccurate estimate of the outcome of a study. In studies of complex nursing interventions, bias is particularly difficult to control because of issues related to blinding and choice of controls. The authors identify strategies to control bias in intervention studies. They conduct a literature review and consult expert opinion to identify 6 areas of study protocol development that have potential for reducing bias: study concept, definition of intervention, selection of comparisons, randomization/allocation, integrity of intervention, and ascertainment of outcomes. They provide a checklist to help researchers reduce the potential for bias in preparing protocols for complex nursing intervention trials. Use of the checklist can enhance scientific rigour and thus help to ensure that clinicians are ultimately provided with reliable information.

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.