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Objective Children born very preterm (VPT; gestational age [GA] Methods Parents of 4-year-olds born VPT (n = 55) and FT (n = 38) reported on parental distress, behavior, and cognitive stimulation. Children’s cognition, executive function, motor skills, preacademic abilities, and behavior were assessed via neuropsychological tests and parent-report questionnaires. Results For both groups of children, higher psychological distress and harshness were associated with more behavior problems, and more cognitive stimulation was associated with higher scores on tests of cognitive, motor, and preacademic abilities. More parental distress was associated with lower cognitive ability only for children born VPT and more harshness was associated with lower preacademic skills only for children born FT. Conclusions Identifying modifiable family factors associated with school readiness in children born VPT is essential for informing family-based interventions to improve school readiness in this population. Findings suggest that distress, harshness, and cognitive stimulation may be reasonable targets for interventions to improve school readiness in children born VPT.

Changes in infant night waking during the first year of life are associated with individual (e.g., prematurity) and family (e.g., caregiver psychopathology) factors. This study examined the association between infant night waking and caregiver anxious-depressive symptoms during the first year of life in preterm and term infants. We considered between-person differences and within-person changes in caregiver anxious-depressive symptoms in relation to changes in infant night waking from 2- to 9-months. Racially (30.0% Black, 60.4% White, 9.5% multiracial/other) and socioeconomically (40.0% below median household income) diverse caregivers (N = 445) of full term (n = 258) and preterm (n = 187) infants were recruited from hospitals and clinics in two midwestern states. Caregivers completed measures of anxious-depression and their infant's night waking at four sampling periods (2-, 4-, 6-, and 9-months). Infant night wakings declined from 2- to 9-months. Between-person differences were observed, such that caregivers with higher average anxious-depressive symptoms or infants born full term reported more night wakings. Within-person effects of caregiver anxious-depressive symptoms were not significant. Caregiver anxious-depression is closely associated with infant night wakings. By considering a caregiver's average severity of anxious-depression, healthcare providers can more effectively plan infant sleep interventions. If caregiver anxious-depressive symptoms are ameliorated, night wakings may also decrease.

Deficits in executive functions are prevalent among children with traumatic brain injury (TBI). Assessing cognitive impairment is critical for evaluating and monitoring recovery. The present article reports a pilot study to evaluate the preliminary usability and validity of a virtual reality cognitive assessment tool (VR-CAT) specifically designed for children with TBI.A total of 54 children, 24 with TBI and 30 with orthopedic injury, participated in a cross-sectional cohort study at a Level-1 trauma center. The VR-CAT was evaluated in terms of user experience as well as preliminary psychometric properties including test-retest reliability, face validity, concurrent validity with two standard executive function assessment tools, and utility in distinguishing the TBI and orthopedic injury groups.Children in both groups reported high levels of usability (i.e., enjoyment and motivation). The VR-CAT composite and scores on tests of inhibitory control and working memory demonstrated modest test-retest reliability across two independent assessment visits, as well as acceptable face validity, modest concurrent validity, and clinical utility.The present study is among the first to evaluate the applicability of an immersive VR-CAT in children with TBI. The findings support high usability, adequate psychometric properties, and satisfactory clinical utility of the VR-CAT, suggesting it is a promising tool for assessing executive functions in this vulnerable population. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Traumatic brain injury (TBI) is a leading cause of acquired disability in children, who are at risk of significant impairment in executive function (EF). Virtual reality technology provides a novel strategy to offer rich and immersive training content that is both appealing to children and of potential value in improving their daily functioning. The present study aimed to evaluate the feasibility and safety of implementing an innovative VR-based interactive cognitive training (VICT) system for EF rehabilitation designed to meet the developmental and clinical needs of children with TBI.A parallel-group random-block randomized controlled trial was conducted among 26 children 7-17 years with TBI, who completed baseline, postintervention, and 2-month follow-up visits. Feasibility was assessed for recruiting children, measuring outcomes, and implementing the intervention. VR satisfaction was assessed via 5-point Likert scales. Safety outcomes included simulator sickness (0-4) and physical exertion (6-20). Preliminary efficacy was assessed by NIH Toolbox Cognitive Battery tasks.Findings supported the feasibility of recruitment, outcome assessment, and delivery of the intervention. The intervention group reported adequate VR satisfaction in terms of pleasure (The present study found high feasibility, safety, and preliminary efficacy of the VICT system. Further research is required to fully examine the intervention's efficacy as a possible rehabilitation tool for children with TBI. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background Preterm birth and multiple gestation are independently associated with adverse neurodevelopmental outcomes. The objective of this study was to describe risks of screening positive for attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and anxiety in preterm-born twin children by zygosity (monozygotic, dizygotic) and birth order (first-born, second-born). Methods Caregivers of 349 preterm-born twin pairs (42% monozygotic) aged 3–18 years reported child behavioral outcomes on Strengths and Weaknesses of ADHD Symptoms and Normal Behavior; Social Responsiveness Scale, Second Edition; and Preschool Anxiety Scale or Screen for Child Anxiety and Related Emotional Disorders. Results Concordance for behavioral outcomes in twin pairs ranged from 80.06 to 89.31% for ADHD, 61.01 to 84.23% for ASD, and 64.76 to 73.35% for anxiety. Monozygotic twins had a greater risk than dizygotic of screening positive for inattention (risk ratio = 2.91, 95% CI = 1.48–5.72) and social anxiety (1.79, 1.23–2.61). Relative to first-born, second-born twins had a greater risk of screening positive for hyperactivity/impulsivity (1.51, 1.06–2.16); overall ASD (2.38, 1.62–3.49); difficulties with social awareness (2.68, 1.94–3.71), social cognition (4.45, 3.06–6.46), and social communication (2.36, 1.56–3.57); restricted/repetitive behavior (1.91, 1.30–2.81); overall anxiety (1.34, 1.10–1.64); generalized anxiety (1.34, 1.11–1.60); and social anxiety (1.32, 1.06–1.64). Conclusion The current findings emphasize considering zygosity and birth order in preterm and multiple birth outcomes research, and highlight clinical implications for discharge planning, neurodevelopmental surveillance, and facilitating parenting and family support. Impact Zygosity and birth order are important determinants of behavioral and socioemotional outcomes in preterm-born twins. Among 349 preterm-born twin pairs aged 3–18 years (42% monozygotic), 61–89% demonstrated concordance for behavioral and socioemotional outcomes. Monozygosity had greater risks than dizygosity for positive screening of inattention and social anxiety. Second-born twins had greater risks than first-born for hyperactivity/impulsivity, social difficulties (awareness, cognition, communication), restricted/repetitive behavior, and anxiety (generalized, social). These findings have implications for discharge planning, neurodevelopmental surveillance, and facilitating parenting and family support.

Objective:The present study examined the differential effect of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on neuropsychological functioning in children with traumatic brain injury (TBI) relative to orthopedic injury (OI).Methods:Participants were drawn from a prospective, longitudinal study of children who sustained a TBI (n = 69) or OI (n = 72) between 3 and 7 years of age. Children completed a battery of neuropsychological measures targeting attention, memory, and executive functions at four timepoints spanning the immediate post-acute period to 18 months post-injury. Children also completed a comparable age-appropriate battery of measures approximately 7 years post-injury. Parents rated children’s dysexecutive behaviors at all timepoints.Results:Longitudinal mixed models revealed a significant allele status × injury group interaction with a medium effect size for verbal fluency. Cross-sectional models at 7 years post-injury revealed non-significant but medium effect sizes for the allele status x injury group interaction for fluid reasoning and immediate and delayed verbal memory. Post hoc stratified analyses revealed a consistent pattern of poorer neuropsychological functioning in Met carriers relative to Val/Val homozygotes in the TBI group, with small effect sizes; the opposite trend or no appreciable effect was observed in the OI group.Conclusions:The results suggest a differential effect of the BDNF Val66Met polymorphism on verbal fluency, and possibly fluid reasoning and immediate and delayed verbal memory, in children with early TBI relative to OI. The Met allele—associated with reduced activity-dependent secretion of BDNF—may confer risk for poorer neuropsychological functioning in children with TBI.

Sex differences after concussion have been studied largely in high school and college athletes, often without reference to comparison groups without concussion. This study sought to evaluate sex differences in outcomes among all children and adolescents presenting to the Emergency Department (ED) for either mild traumatic brain injury (TBI) or orthopedic injury (OI), regardless of mechanism of injury. The study involved a concurrent cohort, prospective study design with longitudinal follow-up. Participants were eight to 16 years old with mild TBI (n = 143) or OI (n = 73). They were recruited and completed an initial assessment at EDs at two children's hospitals. They returned for a post-acute assessment within two weeks of injury and for follow-up assessments at three and six months. Outcomes included child and parent proxy ratings of somatic and cognitive symptoms, and standardized tests of cognitive functioning and balance. Sex did not moderate group differences in balance, fluid or crystallized cognitive ability, or child or parent proxy ratings of somatic or cognitive symptoms. Both parents and children reported more somatic symptoms in girls than boys, but in both groups. Compared with the OI group, the mild TBI group showed significantly lower fluid cognitive ability at the post-acute assessment and significantly higher somatic and cognitive symptoms according to both child and parent proxy ratings across the first two weeks post-injury. The results suggest that sex does not moderate the outcomes of mild TBI in a pediatric ED population. Previous research pointing to sex differences after concussion may reflect the lack of comparison groups, as well as a focus on adolescents and young adults and sport-related concussion. Future research should investigate whether sex moderates the outcomes of pediatric mild TBI in adolescents but not in pre-adolescent children.

Background Traumatic brain injury (TBI) is one of the leading causes of pediatric trauma morbidity and mortality around the world. However, limited research exists regarding disparities in the incidence of TBI and medical care seeking behaviors and medical expenditures for TBI, particularly using population-based and nationally-representative data. Materials and Methods The present study used the Medical Expenditure Panel Survey (MEPS) Panels 9-19 (2004-2015) to provide nationally-representative estimates for the civilian, non-institutionalized U.S. population. We examined differences in TBI incidence and associated medical care seeking behaviors and expenditures in relation to individual and family sociodemographic characteristics. Results From a total of 50,563 children in the MEPS Panels 9-19, we identified 449 children with TBI. For 82% of these children, medical treatment was sought. The estimated annual total expenditure associated with pediatric TBIs nationally was approximately $667 million, with mean expenditures per TBI being $1,532 and family out of pocket expenditures accounting for 8.3% of total expenditures. Race/ethnicity was the only significant factor associated with both medical care seeking behavior and total expenditures. Conclusions The present study is among the first to compare pediatric TBI-related medical expenditures among different sociodemographic groups in the U.S. Our findings can inform future intervention research and policy-making from the perspectives of both epidemiological and behavioral sciences.

Purpose Adolescent psychosocial outcomes of individuals with histories of childhood apraxia of speech (CAS) were compared to outcomes of individuals with histories of speech sound disorders (SSD) only and SSD with language impairment (LI). It was hypothesized that individuals with more severe and persistent disorders such as CAS would report poorer psychosocial outcomes. Method Groups were compared using analyses of variance on a psychosocial assessment battery that included measures of hyperactivity and inattention, anxiety, depression, internalizing and externalizing behaviors, thought problems, and social outcomes. Results Results revealed significant group differences on self-report of social problems and parent report of hyperactivity, thought problems, and social problems at adolescence. Compared to the SSD-only group, the CAS group had significantly higher parental ratings of hyperactivity and social problems in adolescence. The CAS and SSD + LI groups did not differ on psychosocial measures, possibly due to the high rate of comorbid LI in the CAS group. The CAS group also had more individuals who scored in the borderline/clinical range on self-report of social problems than the SSD-only group. The CAS group did not differ from the SSD + LI group in the number of participants scoring in the borderline/clinical range on measures. Conclusions Individuals with histories of CAS demonstrate increased rates of social problems and hyperactivity based on parent ratings compared to adolescents with histories of SSD only; however, most do not score within the clinical range. The persistence of speech sound errors combined with self-reported and parent-reported social difficulties suggests that speech-language pathologists should be sensitive to the social and emotional impact of CAS and make appropriate referrals to mental health professionals when warranted.

IntroductionTo investigate the effects of different strategies and cognitive load we explored brain hemodynamic responses associated with the use of different strategies to solve subtraction of fractions. We focused on those born extremely preterm (EPT; MethodsFunctional MRI was acquired while the participants mentally solved fraction equations using either a strategy based on improper or mixed fractions. Different fraction item types were given, which affected respective required cognitive loads per strategy. Diffusion and T1-weighted structural images were also acquired.ResultsThe EPT and FT groups differed in terms of task-related hemodynamic responses. Functional group differences were greatest when strategies were applied to item types that result in high cognitive load. Other findings showed reduced white and grey matter volume and reduced white matter connectivity in widespread areas in the EPT group compared to the FT group.ConclusionThe understanding of function and structure presented here may help inform pedagogical practices by allowing for tailoring of mathematical education through identifying suitable strategy adoption that depends on item type, to circumvent weaknesses in cognitive skills.

Purpose: The aims of this study were, in a cohort of children with neonatal opioid withdrawal syndrome (NOWS), (a) to report 1-year neurodevelopmental outcomes and specifically characterize speech, language, and hearing outcomes and (b) to report the prevalence of cleft lip and/or cleft palate. Method: This prospective observational cohort study includes newborns with confirmed in utero opioid exposure who received pharmacological treatment for NOWS. During 1-year-old developmental visits, we administered standardized assessments (Bayley Scales of Infant and Toddler Development–Third Edition [Bayley-III] or Developmental Assessment of Young Children–Second Edition [DAYC-2]—due to COVID-19 restrictions). We compared Bayley-III scores to standardized population means using one-sample z tests. We report estimates, 95% confidence intervals, and two-sided p values. Results: We enrolled 202 infants (October 2018 to March 2020). Follow-up at 1-year was 80%. Infants with NOWS had lower Bayley-III scores at 1 year compared to published norms for cognitive, language, and motor domains. One infant with NOWS was diagnosed with isolated cleft palate and Pierre Robin sequence. All infants passed the newborn hearing screen, and 7.5% had a formal hearing evaluation after neonatal intensive care unit discharge, with 40% having abnormal or inconclusive results; middle ear effusion was the leading cause of abnormal hearing (66.7%). Ten percent of children received a speech-language pathology referral prior to 2 years of age. Infants born to mothers with mental health conditions were more likely to have Bayley-III or DAYC-2 scores below 95 in language or motor domains. Conclusions: Infants with pharmacologically treated NOWS have significantly lower cognitive, language, and motor scores on standardized developmental testing compared to population means at 1 year of age. Early speech-language pathology referral is frequently necessary to promote optimal development in this population. Supplemental Material: https://doi.org/10.23641/asha.20044403

This study is the first to examine cognitive outcomes after pediatric mild TBI using the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB), a computerized cognitive test battery. The NIHTB-CB includes two complex measures of attention and executive function that allow differentiation of accuracy and response speed. We compared performance on the NIHTB-CB among children 8–16 years of age with mild TBI (n = 143) versus children with orthopedic injuries (OIs; n = 74) recruited in emergency departments and followed for 6 months post-injury. Mixed-model analyses showed that the mild TBI group showed significantly lower Fluid Cognition composite scores than the OI group at 10 days (group intercept, p = 0.018); the magnitude of group differences declined modestly over time (group × time interaction, p = 0.055). Effect sizes were d = 0.34 at 10 days post-injury, d = 0.27 at 3 months, and d = 0.10 at 6 months. No significant effects of group or time were found for the Crystallized Cognition composite. Analyses of Fluid Cognition subtests indicated that children with mild TBI displayed deficits for as long as 3 months on measures of attention and executive function (e.g., cognitive flexibility, inhibitory control), but not on measures of explicit memory, working memory, or processing speed. The poorer performance of the mild TBI group on measures of attention and executive function was attributable largely to slowed reaction time, not decreased accuracy. The findings suggest that children with mild TBI demonstrate persistent deficits in fluid cognition that are most apparent on tasks that combine demands for both speed and executive function.

Objective:To examine the impact of early traumatic brain injury (TBI) on effortful control (EC) over time and the relationship of EC and executive functioning (EF) to long-term functional and social outcomes.Method:Parents of children (N = 206, ages 3–7) with moderate-to-severe TBI or orthopedic injuries (OIs) rated EC using the Child Behavior Questionnaire at 1 (pre-injury), 6, 12, and 18 months post-injury. Child functioning and social competence were assessed at 7 years post-injury. Mixed models examined the effects of injury, time since injury, and their interaction on EC. General linear models examined the associations of pre-injury EC and EC at 18 months with long-term functional and social outcomes. Models controlled for EF to assess the unique contribution of EC to outcomes.Results:Children with severe TBI had significantly lower EC than both the OI and moderate TBI groups at each post-injury time point. Both pre-injury and 18-month EC were associated with long-term outcomes. Among those with low EC at baseline, children with moderate and severe TBI had more functional impairment than those with OI; however, no group differences were noted at high levels of EC. EC had main effects on parent-reported social competence that did not vary by injury type.Conclusions:Findings suggest that EC is sensitive to TBI effects and is a unique predictor of functional outcomes, independent of EF. High EC could serve as a protective factor, and as such measures of EC could be used to identify children for more intensive intervention.

Objective This prospective, longitudinal cohort study examined the trajectory, classification, and features of posttraumatic headache after pediatric mild traumatic brain injury. Methods Children ( N = 213; ages 8.00 to 16.99 years) were recruited from two pediatric emergency departments Results PTH risk was greater after mild traumatic brain injury than mild orthopedic injury at 10 days (odds ratio = 197.41, p Conclusions Posttraumatic headache risk increases after mild traumatic brain injury relative to mild orthopedic injury for approximately three months postinjury, but is not clearly associated with a distinct phenotype.

Objective The study sought to present normative and psychometric data and reliable change formulas for the Health and Behavior Inventory (HBI), a postconcussive symptom rating scale embedded in the Child Sport Concussion Assessment Tool 5th edition (Child SCAT5). Design Prospective cohort study with longitudinal follow-up. Setting Pediatric emergency departments (EDs). Participants As part of 3 studies conducted in the United States and Canada between 2001 and 2019, 450 children aged 8 to 16 years with mild orthopedic injuries were recruited during ED visits and assessed postacutely (M = 9.38 days, SD = 3.31) and 1 month and 3 months postinjury. Independent variables were rater (child vs parent), sex, and age at injury. Main outcome measure HBI ratings. Methods Children and parents rated children's symptoms at each time point; parents also rated children's preinjury symptoms retrospectively. Normative data (mean, SD, skewness, kurtosis, and percentiles) were computed for child and parent ratings. Internal consistency was assessed using Cronbach alpha (α), and test-retest reliability and interrater agreement were assessed with intraclass correlations (ICCs). Reliable change formulas were computed using linear regression and mixed models. Results HBI ratings were positively skewed. Mean ratings and percentiles were stable over time. Child and parent ratings demonstrated good-to-excellent internal consistency (α 0.76-0.94) and moderate-to-good test-retest reliability (ICC 0.51-0.76 between adjacent assessments). However, parent-child agreement was poor to moderate (ICC 0.31-0.69). Conclusions The HBI demonstrates acceptable normative and psychometric characteristics. Modest parent-child agreement highlights the importance of multiple informants when assessing postconcussive symptoms. The results will facilitate the use of the HBI in research and clinical practice.

Objective To examine the association of objectively measured, self-paced physical and cognitive activities across the first week postconcussion with symptom resolution in youth. Setting Emergency department or concussion clinics. Participants Youth aged 11 to 17 years with physician-confirmed concussion. Design Prospective cohort with repeated measures. Main measures Days from injury to symptom resolution, based on daily ratings by youth on the Post-Concussive Symptom Scale. Physical and cognitive activities were assessed using an ActiGraph and a Narrative Clip, respectively. Results A total of 83 youth participants were included (n = 54 [65%] males; mean age = 14.2 years, SD = 1.9). While self-paced daily physical and cognitive activities increased across the first week postinjury, daily postconcussion symptoms decreased. Increased daily step count was associated with an increased likelihood of early symptom resolution (hazard ratio [HR] = 1.17; 95% confidence interval [CI], 1.02-1.34). However, this association was not statistically significant after adjusting for acute postconcussion symptoms and other covariates. Greater school attendance time was associated with earlier symptom resolution (adjusted HR = 1.14; 95% CI, 1.02-1.27). Conclusion Self-paced physical and cognitive activities across the first week postinjury alone neither hastened nor prolonged concussion recovery. Youth with concussion may have some latitude to determine their activity levels.

To determine whether functional self-care skills and presence of behavior problems in youth with developmental disabilities are associated with parents planning for the youth’s transition to adulthood. This multi-site study consisted of 167 parents of youth aged 10–22 years with autism spectrum disorder, ADHD and/or other developmental disabilities who completed a questionnaire on transition to adulthood. Parent-rated child self-care status was measured using a six-item scale that had excellent reliability (Cronbach’s alpha=0.90). Multivariable logistic regression models revealed that parents were less likely to plan for the youth’s transition to adulthood if their child needed more assistance with functional self-care skills (OR 0.78, 95% CI 0.63–0.96, p=.021). Despite this unexpected finding, greater child need for assistance with self-care was associated with lower parental expectations that their children would live independently by age 22 (OR 0.40, 95%CI 0.24–0.66, p

This study examined the remote learning activities children born very preterm (VPT; gestational age ≤ 30 weeks) received, compared with children born full term (FT; gestational age ≥ 37 weeks), during the COVID-19 pandemic. Parents of 5- to 6-year-olds born VPT ( n = 33) and FT ( n = 33) reported on the provision, frequency, and duration of teacher-provided live instruction, educational materials, and homework; and parent-provided educational materials. More kindergarten children born VPT received small group instruction and fewer received large group instruction than FT children. Preschoolers born VPT engaged in parent-provided learning apps, educational videos, and reading activities less frequently or for shorter durations than FT children. Findings suggest that while teachers generally implemented remote learning similarly for children born VPT and FT, parents did not. Children born VPT are at higher risk for educational problems and may benefit from more intensive school- and home-based educational interventions to help offset the impact of school closures.

Caregivers frequently report poor quality of life (QOL) in children with sleep-disordered breathing (SDB). Our objective is to assess the correlation between caregiver- and child-reported QOL in children with mild SDB and identify factors associated with differences between caregiver and child report.Analysis of baseline data from a multi-institutional randomized trial.Pediatric Adenotonsillectomy Trial for Snoring, where children with mild SDB (obstructive apnea-hypopnea index3) were randomized to observation or adenotonsillectomy.The Pediatric Quality of Life Inventory (PedsQL) assessed baseline global QOL in participating children 5 to 12 years old and their caregivers. Caregiver and child scores were compared. Multivariable regression assessed whether clinical factors were associated with differences between caregiver and child report.PedsQL scores were available for 309 families (mean child age, 7.0 years). The mean caregiver-reported PedsQL score was higher at 75.2 (indicating better QOL) than the mean child-reported score of 67.9 (Caregiver- and child-reported global QOL in children with SDB was weakly correlated, more so for young children. In pediatric SDB, child-perceived QOL may be poorer than that reported by caregivers. Further research is needed to assess whether similar trends exist for disease-specific QOL metrics.

Acquired brain injury (ABI) is a leading cause of disability among children. An increasing number of programs have emerged to involve family members as an integral component of post-ABI rehabilitation. This study aimed to conduct a systematic review and meta-analysis of such programs among children with ABI.Following PRISMA guidelines, search among six databases (PsycINFO, PsycARTICLES, Scopus, Web of Science, PubMed, Cochrane CENTRAL) was conducted, followed by abstract/full-text screening and data extraction. Hedge's g was computed for effect sizes. The risk of bias was assessed using Cochrane guidelines. Meta-regression analyses were conducted on six moderators.A total of 32 studies (reported in 37 articles) were included in the qualitative analysis. Meta-analysis of 20 studies showed a positive small-to-medium effect of family-oriented interventions on child and parental outcomes but not on family functioning. Study design moderated the effect sizes of parent outcomes.This study synthesized the latest empirical evidence of family-oriented rehabilitation programs for pediatric ABI across interventional strategies, study designs, and outcomes. The findings suggested an overall beneficial impact of such programs on both the pediatric patients and their caregivers.

The present study examined the differential effect of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on behavioral adjustment in children with traumatic brain injury (TBI) relative to children with orthopedic injury (OI). Participants were drawn from a prospective, longitudinal study of children who sustained a TBI (n = 69) or OI (n = 72) between 3 and 7 years of age. Parents completed the Child Behavior Checklist (CBCL) at the immediate post-acute period, 6, 12, and 18 months after injury, and an average of 3.5 and 7 years after injury. Longitudinal mixed models examined the BDNF Val66Met allele status (Met carriers vs. Val/Val homozygotes) × injury group (TBI vs. OI) interaction in association with behavioral adjustment. After adjusting for continental ancestry, socioeconomic status, time post-injury, and pre-injury functioning, the allele status × injury group interaction was statistically significant for Internalizing, Externalizing, and Total Behavior problems. Post hoc within-group analysis suggested a consistent trend of poorer behavioral adjustment in Met carriers relative to Val/Val homozygotes in the TBI group; in contrast, the opposite trend was observed in the OI group. These within-group differences, however, did not reach statistical significance. The results support a differential effect of the BDNF Val66Met polymorphism on behavioral adjustment in children with early TBI relative to OI, and suggest that the Met allele associated with reduced activity-dependent secretion of BDNF may impart risk for poorer long-term behavioral adjustment in children with TBI.

The primary goal was to determine the prevalence and correlates of adaptive competence in 51 very preterm (VPT, gestational age ≤30 weeks) 4-year-old children compared to a group of 35 term-born (Term) children of the same age.

Studies of brain morphometry may illuminate the effects of pediatric mild traumatic brain injury (TBI; e.g., concussion). However, no published studies have examined cortical thickness in the early injury phases of pediatric mild TBI using an appropriate comparison group. The current study used an automated approach (i.e., FreeSurfer) to determine whether cortical thickness differed in children following a mild TBI or a mild orthopedic injury (OI), and to examine whether post-acute cortical thickness predicted post-acute and chronic post-concussive symptoms (PCS). Children ages 8.00-16.99 years with mild TBI (n = 136) or OI (n = 70) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (3–24 days post-injury) assessment, which included a 3 Tesla MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Cortical thickness was estimated using FreeSurfer. Linear mixed effects and multi-variable negative binomial regression models were used to test study aims, with false discovery rate (FDR) correction for multiple comparisons. Groups differed significantly on left parietal cortical thickness (TBI > OI) after FDR correction. Cortical thickness also varied by brain subregion and age, but not sex. Groups differed significantly on PCS post-acutely (TBI > OI), but not at 3 or 6 months. Right frontal thickness was positively related to post-acute PCS in both groups. Right cingulum thickness predicted chronic PCS in the OI group only. Results highlight the complexity of predicting outcomes of pediatric mild TBI from post-acute neuroimaging biomarkers.

The addition of genetic factors to prognostic models of neurobehavioral recovery following pediatric traumatic brain injury (TBI) may account for unexplained heterogeneity in outcomes. The present study examined the cumulative influence of candidate genes involved in the inflammatory response on long-term neurobehavioral recovery in children with early childhood TBI relative to children with orthopedic injuries (OI). Participants were drawn from a prospective, longitudinal study evaluating outcomes of children who sustained TBI (n = 67) or OI (n = 68) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at an average of 6.8 years after injury. Exploratory unweighted and weighted polygenic risk scores (PRS) were constructed from single nucleotide polymorphisms (SNPs) across candidate inflammatory response genes (i.e., angiotensin converting enzyme [ACE], brain-derived neurotrophic factor [BDNF], interleukin-1 receptor antagonist [IL1RN], and 5’-ectonucleotidase [NT5E]) that showed nominal (p ≤ 0.20) associations with outcomes in the TBI group. Linear regression models tested the PRS × injury group (TBI vs. OI) interaction term and post-hoc analyses examined the effect of PRS within each injury group. Higher inflammatory response PRS were associated with more executive dysfunction and behavior problems in children with TBI but not in children with OI. The cumulative influence of inflammatory response genes as measured by PRS explained additional variance in long-term neurobehavioral outcomes, over and above well-established predictors and single candidate SNPs tested individually. The results suggest that some of the unexplained heterogeneity in long-term neurobehavioral outcomes following pediatric TBI may be attributable to a child's genetic predisposition to a greater or lesser inflammatory response to TBI.

OBJECTIVE. This study examined whether carrying dopamine-related “risk” genes—either the dopamine transporter (DAT1) 10-repeat allele or dopamine receptor-4 (DRD4) 7-repeat allele—moderated the association of family environment and executive function (EF) following traumatic brain injury in early childhood. METHOD. Caregivers of children with traumatic brain injury (TBI) or orthopedic injury (OI) completed the Behavior Rating Inventory of Executive Function (BRIEF) at post-injury visits. General linear models examined gene-environment interactions as moderators of the effects of TBI on EF at 12 months and 7 years post-injury. RESULTS. At 12 months, we did not find any significant gene by environment interactions. At 7 years, we found a significant 3-way interaction among combined carrier status, level of permissive parenting, and injury type. For children exposed to more optimal parenting, carriers of DAT1 and/or DRD4 risk alleles with TBI showed significantly worse parent-reported EF compared to carriers with OI. In those with less optimal parenting, carriers and non-carriers with TBI, as well as carriers with OI, showed significantly worse parent-reported EF compared to non-carriers with OI, with medium to large effect sizes. CONCLUSIONS. The findings highlight the importance of considering polygenetic and environmental factors in future studies of recovery following TBI and other injuries in childhood.

Childhood traumatic brain injury (TBI) affects over 600 000 children per year in the United States. Following TBI, children are vulnerable to deficits in psychosocial adjustment and neurocognition, including social cognition, which persist long-term. They are also susceptible to direct and secondary damage to related brain networks. In this study, we examine whether brain morphometry of the mentalizing network (MN) and theory of mind (ToM; one component of social cognition) mediates the effects of TBI on adjustment. Children with severe TBI (n = 15, Mage = 10.32), complicated mild/moderate TBI (n = 30, Mage = 10.81) and orthopedic injury (OI; n = 42, Mage = 10.65) completed measures of ToM and executive function and underwent MRI; parents rated children’s psychosocial adjustment. Children with severe TBI demonstrated reduced right-hemisphere MN volume, and poorer ToM, vs children with OI. Ordinary least-squares path analysis indicated that right-hemisphere MN volume and ToM mediated the association between severe TBI and adjustment. Parallel analyses substituting the central executive network and executive function were not significant, suggesting some model specificity. Children at greatest risk of poor adjustment after TBI could be identified based in part on neuroimaging of social brain networks and assessment of social cognition and thereby more effectively allocate limited intervention resources.