Longitudinal Functional Connectome in Pediatric Concussion: An Advancing Concussion Assessment in Pediatrics Study.

Advanced magnetic resonance imaging (MRI) techniques indicate that concussion (i.e., mild traumatic brain injury) disrupts brain structure and function in children. However, the functional connectivity of brain regions within global and local networks (i.e., functional connectome) is poorly understood in pediatric concussion. This prospective, longitudinal study addressed this gap using data from the largest neuroimaging study of pediatric concussion to date to study the functional connectome longitudinally after concussion as compared with mild orthopedic injury (OI). Children and adolescents (n = 967) 8-16.99 years with concussion or mild OI were recruited from pediatric emergency departments within 48 h post-injury. Pre-injury and 1-month post-injury symptom ratings were used to classify concussion with or without persistent symptoms based on reliable change. Subjects completed a post-acute (2-33 days) and chronic (3 or 6 months via random assignment) MRI scan. Graph theory metrics were derived from 918 resting-state functional MRI scans in 585 children (386 concussion/199 OI). Linear mixed-effects modeling was performed to assess group differences over time, correcting for multiple comparisons. Relative to OI, the global clustering coefficient was reduced at 3 months post-injury in older children with concussion and in females with concussion and persistent symptoms. Time post-injury and sex moderated group differences in local (regional) network metrics of several brain regions, including degree centrality, efficiency, and clustering coefficient of the angular gyrus, calcarine fissure, cuneus, and inferior occipital, lingual, middle occipital, post-central, and superior occipital gyrus. Relative to OI, degree centrality and nodal efficiency were reduced post-acutely, and nodal efficiency and clustering coefficient were reduced chronically after concussion (i.e., at 3 and 6 months post-injury in females; at 6 months post-injury in males). Functional network alterations were more robust and widespread chronically as opposed to post-acutely after concussion, and varied by sex, age, and symptom recovery at 1-month post-injury. Local network segregation reductions emerged globally (across the whole brain network) in older children and in females with poor recovery chronically after concussion. Reduced functioning between neighboring regions could negatively disrupt specialized information processing. Local network metric alterations were demonstrated in several posterior regions that are involved in vision and attention after concussion relative to OI. This indicates that functioning of superior parietal and occipital regions could be particularly susceptibile to the effects of concussion. Moreover, those regional alterations were especially apparent at later time periods post-injury, emerging after post-concussive symptoms resolved in most and persisted up to 6 months post-injury, and differed by biological sex. This indicates that neurobiological changes continue to occur up to 6 months after pediatric concussion, although changes emerge earlier in females than in males. Changes could reflect neural compensation mechanisms.

Altered longitudinal structural connectome in paediatric mild traumatic brain injury: an Advancing Concussion Assessment in Paediatrics study.

Advanced diffusion-weighted imaging techniques have increased understanding of the neuropathology of paediatric mild traumatic brain injury (i.e. concussion). Most studies have examined discrete white-matter pathways, which may not capture the characteristically subtle, diffuse and heterogenous effects of paediatric concussion on brain microstructure. This study compared the structural connectome of children with concussion to those with mild orthopaedic injury to determine whether network metrics and their trajectories across time post-injury differentiate paediatric concussion from mild traumatic injury more generally. Data were drawn from of a large study of outcomes in paediatric concussion. Children aged 8-16.99 years were recruited from five paediatric emergency departments within 48 h of sustaining a concussion (n = 360; 56% male) or mild orthopaedic injury (n = 196; 62% male). A reliable change score was used to classify children with concussion into two groups: concussion with or without persistent symptoms. Children completed 3 T MRI at post-acute (2-33 days) and/or chronic (3 or 6 months, via random assignment) post-injury follow-ups. Diffusion-weighted images were used to calculate the diffusion tensor, conduct deterministic whole-brain fibre tractography and compute connectivity matrices in native (diffusion) space for 90 supratentorial regions. Weighted adjacency matrices were constructed using average fractional anisotropy and used to calculate global and local (regional) graph theory metrics. Linear mixed effects modelling was performed to compare groups, correcting for multiple comparisons. Groups did not differ in global network metrics. However, the clustering coefficient, betweenness centrality and efficiency of the insula, cingulate, parietal, occipital and subcortical regions differed among groups, with differences moderated by time (days) post-injury, biological sex and age at time of injury. Post-acute differences were minimal, whereas more robust alterations emerged at 3 and especially 6 months in children with concussion with persistent symptoms, albeit differently by sex and age. In the largest neuroimaging study to date, post-acute regional network metrics distinguished concussion from mild orthopaedic injury and predicted symptom recovery 1-month post-injury. Regional network parameters alterations were more robust and widespread at chronic timepoints than post-acutely after concussion. Results suggest that increased regional and local subnetwork segregation (modularity) and inefficiency occurs across time after concussion, emerging after post-concussive symptom resolve in most children. These differences persist up to 6 months after concussion, especially in children who showed persistent symptoms. While prognostic, the small to modest effect size of group differences and the moderating effects of sex likely would preclude effective clinical application in individual patients.

Dietary changes among pregnant individuals compared to pre-pandemic: A cross-sectional analysis of the Pregnancy during the COVID-19 Pandemic (PdP) study.

Introduction: Dietary changes are common in pregnancy and may affect pregnancy outcomes, yet these changes and the associated contributory factors during the COVID-19 pandemic have been understudied. We aimed to investigate the association between dietary change and socioeconomic variables, pre-pregnancy BMI, and mental health symptoms; the change in intake of seven food categories and their reasons; and the association between intake of these food categories and mental health symptoms. Materials and methods: In this cross-sectional analysis, we used data from the Pregnancy during the COVID-19 Pandemic (PdP) cohort study that collected data from pregnant Canadian individuals (n = 9,870, gestational age ≤ 35 weeks) on socioeconomic factors, pandemic-related hardships, pre-pregnancy body mass index (BMI), dietary changes compared to pre-pandemic and the reasons for these changes. We assessed depressive and anxiety symptoms using the Edinburgh Postpartum Depression Scale (EPDS) and Patient-Reported Outcomes Measurement Information System (PROMIS)-Anxiety, respectively. Results: 54.3% of the participants reported a change in their diet. Non-white ethnicity (OR = 1.33), job loss (OR = 1.29), clinically elevated depressive and anxiety symptoms (OR = 1.26 and 1.14, respectively), self-isolation (OR = 1.20), pre-pregnancy BMI (OR = 1.19), fear of COVID-19 (OR = 1.15), and pandemic phase at enrolment (OR = 0.90) significantly predicted dietary change. Most participants ate about the same amounts of dairy, meats and canned foods/dried goods as pre-pandemic (61.5, 61.7, and 60.2%, respectively), increased their intake of fresh vegetables/fruits and sweets/snacks (43.2 and 54.5%, respectively), and decreased fast-food and take-out/home delivery (53.2 and 43.1%, respectively). Changes in consumption of the food categories had a curvilinear association with mental health symptoms (except resilience) indicating greater symptoms with either decreased or increased intakes. Changes in craving, having more time for cooking/preparing foods, and being unable to go grocery shopping frequently (but not reduced affordability) were the main reasons driving these dietary changes. Conclusion: Some factors increase the odds of dietary change among pregnant individuals during the pandemic, with some changes toward a healthy and others toward an unhealthy diet. Given the importance of a healthy diet during gestation, identifying the risk and protective factors might be the first essential step in reducing the detrimental effects of unfavorable dietary changes during the pandemic on this vulnerable population.

Elevated depression and anxiety symptoms among pregnant individuals during the COVID-19 pandemic.

BACKGROUND: Anxiety and depression symptoms in pregnancy typically affect between 10 and 25% of pregnant individuals. Elevated symptoms of depression and anxiety are associated with increased risk of preterm birth, postpartum depression, and behavioural difficulties in children. The current COVID-19 pandemic is a unique stressor with potentially wide-ranging consequences for pregnancy and beyond. METHODS: We assessed symptoms of anxiety and depression among pregnant individuals during the current COVID-19 pandemic and determined factors that were associated with psychological distress. 1987 pregnant participants in Canada were surveyed in April 2020. The assessment included questions about COVID-19-related stress and standardized measures of depression, anxiety, pregnancy-related anxiety, and social support. RESULTS: We found substantially elevated anxiety and depression symptoms compared to similar pre-pandemic pregnancy cohorts, with 37% reporting clinically relevant symptoms of depression and 57% reporting clinically relevant symptoms of anxiety. Higher symptoms of depression and anxiety were associated with more concern about threats of COVID-19 to the life of the mother and baby, as well as concerns about not getting the necessary prenatal care, relationship strain, and social isolation due to the COVID-19 pandemic. Higher levels of perceived social support and support effectiveness, as well as more physical activity, were associated with lower psychological symptoms. CONCLUSION: This study shows concerningly elevated symptoms of anxiety and depression among pregnant individuals during the COVID-19 pandemic, that may have long-term impacts on their children. Potential protective factors include increased social support and exercise, as these were associated with lower symptoms and thus may help mitigate long-term negative outcomes.

Advancing Concussion Assessment in Pediatrics (A-CAP): a prospective, concurrent cohort, longitudinal study of mild traumatic brain injury in children: protocol study.

INTRODUCTION: Paediatric mild traumatic brain injury (mTBI) is a public health burden. Clinicians urgently need evidence-based guidance to manage mTBI, but gold standards for diagnosing and predicting the outcomes of mTBI are lacking. The objective of the Advancing Concussion Assessment in Pediatrics (A-CAP) study is to assess a broad pool of neurobiological and psychosocial markers to examine associations with postinjury outcomes in a large sample of children with either mTBI or orthopaedic injury (OI), with the goal of improving the diagnosis and prognostication of outcomes of paediatric mTBI. METHODS AND ANALYSIS: A-CAP is a prospective, longitudinal cohort study of children aged 8.00-16.99 years with either mTBI or OI, recruited during acute emergency department (ED) visits at five sites from the Pediatric Emergency Research Canada network. Injury information is collected in the ED; follow-up assessments at 10 days and 3 and 6 months postinjury measure a variety of neurobiological and psychosocial markers, covariates/confounders and outcomes. Weekly postconcussive symptom ratings are obtained electronically. Recruitment began in September 2016 and will occur for approximately 24 months. Analyses will test the major hypotheses that neurobiological and psychosocial markers can: (1) differentiate mTBI from OI and (2) predict outcomes of mTBI. Models initially will focus within domains (eg, genes, imaging biomarkers, psychosocial markers), followed by multivariable modelling across domains. The planned sample size (700 mTBI, 300 OI) provides adequate statistical power and allows for internal cross-validation of some analyses. ETHICS AND DISSEMINATION: The ethics boards at all participating institutions have approved the study and all participants and their parents will provide informed consent or assent. Dissemination will follow an integrated knowledge translation plan, with study findings presented at scientific conferences and in multiple manuscripts in peer-reviewed journals.