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Fatigue may be among the most profound and debilitating consequences of pediatric traumatic brain injury (TBI); however, neurostructural risk factors associated with post-injury fatigue remain elusive. This prospective study aimed to evaluate the independent value of susceptibility-weighted imaging (SWI) biomarkers, over-and-above known risk factors, to predict fatigue symptom severity in children with TBI. Forty-two children were examined with structural magnetic resonance imaging (sMRI), including a SWI sequence, within eight weeks post-injury. The PedsQL Multi-Dimensional Fatigue Scale (MFS) was administered 24 months post-injury. Compared with population expectations, the TBI group displayed significantly higher levels of general fatigue (Cohen

Background Despite a well-established link between childhood traumatic brain injury (TBI) and elevated secondary attention-deficit/hyperactivity disorder (s-ADHD) symptomology, the neurostructural correlates of these symptoms are largely unknown. Based on the influential ‘triple-network model’ of ADHD, this prospective longitudinal investigation aimed to (i) assess the effect of childhood TBI on brain morphometry of higher-order cognitive networks proposed to play a key role in ADHD pathophysiology, including the default-mode network (DMN), salience network (SN) and central executive network (CEN); and (ii) assess the independent prognostic value of DMN, SN and CEN morphometry in predicting s-ADHD symptom severity after childhood TBI. Methods The study sample comprised 155 participants, including 112 children with medically confirmed mild-severe TBI ascertained from consecutive hospital admissions, and 43 typically developing (TD) children matched for age, sex and socio-economic status. High-resolution structural brain magnetic resonance imaging (MRI) sequences were acquired sub-acutely in a subset of 103 children with TBI and 34 TD children. Parents completed well-validated measures of ADHD symptom severity at 12-months post injury. Results Relative to TD children and those with milder levels of TBI severity (mild, complicated mild, moderate), children with severe TBI showed altered brain morphometry within large-scale, higher-order cognitive networks, including significantly diminished grey matter volumes within the DMN, SN and CEN. When compared with the TD group, the TBI group showed significantly higher ADHD symptomatology and higher rates of clinically elevated symptoms. In multivariable models adjusted for other well-established risk factors, altered DMN morphometry independently predicted higher s-ADHD symptomatology at 12-months post-injury, whilst SN and CEN morphometry were not significant independent predictors. Conclusions Our prospective study findings suggest that neurostructural alterations within higher-order cognitive circuitry may represent a prospective risk factor for s-ADHD symptomatology at 12-months post-injury in children with TBI. High-resolution structural brain MRI has potential to provide early prognostic biomarkers that may help early identification of high-risk children with TBI who are likely to benefit from early surveillance and preventive measures to optimise long-term neuropsychiatric outcomes.

Background and Objectives:Bell’s palsy is the third most frequent diagnosis in children with sudden onset neurological dysfunction. The cost-effectiveness of treating Bell’s palsy with prednisolone in children is unknown. We aimed to assess the cost-effectiveness of prednisolone in treating Bell’s Palsy in children compared with placebo.Methods:This economic evaluation was a prospectively planned secondary analysis of a double-blinded, randomized, placebo-controlled superiority trial (BellPIC) conducted from 2015 to 2020. Time horizon was 6 months since randomization. Children aged 6 months to Results:The mean cost per patient was A$760 in the prednisolone group and A$693 in the placebo group over the 6-month period (difference A$66, 95% confidence interval [CI]: -A$47, A$179). QALYs over 6-months was 0.45 in the prednisolone group and 0.44 in the placebo group (difference 0.01, 95%CI: -0.01, 0.03). The incremental cost to achieve one additional recovery was estimated to be A$1577 using prednisolone compared with placebo, and cost per additional QALY gained was A$6625 using prednisolone compared with placebo. Given a conventional willingness-to-pay threshold of A$50,000 per QALY gained (equivalent to US$35,000 or £28,000), prednisolone is very likely cost-effective (probability is 83%), . Sub-group analysis suggests that this was primarily driven by the high probability of prednisolone being cost-effective in children aged 12-18 years (probability is 98%) and much less so for those Discussion:This provides new evidence to stakeholders and policy makers when considering whether to make prednisolone available in treating Bell’s palsy in children aged 12-18 years.Trial Registration:Australian New Zealand Clinical Trials Registry ACTRN12615000563561.

This prospective, longitudinal case-control study examined global and domain-specific aspects of self-esteem 6-months following pediatric traumatic brain injury (TBI) and evaluated the contribution of injury-related factors and parent mental health to child self-esteem. Participants included 103 children with mild-severe TBI representing consecutive admissions to the emergency department of the Royal Children's Hospital, Melbourne, Australia. Forty-three age-and-sex matched typically developing controls were recruited for comparison. Information regarding injury characteristics including age at injury and clinical indicators of TBI severity were collected for participants at recruitment, with research magnetic resonance imaging conducted 2-8 weeks later. At 6 months post-injury, children rated their global and domain-specific self-esteem (Harter Self-Perception Profile for Children), and ratings of parent mental health were collected (General Health Questionnaire). Self-esteem for behavioural and academic domains was significantly poorer for children with TBI relative to TD children. In the TBI group, higher child-rated scores of global and domain-specific aspects of self-esteem were associated with more severe TBI, presence of frontal neuropathology, younger age at injury, and lower parental symptoms of anxiety/insomnia. Given the psychological status of parents represents a potentially modifiable risk factor, it may form the target of clinical interventions designed to bolster child self-esteem following pediatric TBI.

Background and Purpose: The aims of this study were to assess the prevalence of multidimensional fatigue symptoms 5 years after pediatric arterial ischemic stroke and identify factors associated with fatigue. Methods: Thirty-one children (19 males) with pediatric arterial ischemic stroke, participating in a larger prospective, longitudinal study, were recruited to this study at 5 years poststroke. Parent- and self-rated PedsQL Multidimensional Fatigue Scale scores were compared with published normative data. Associations between parent-rated PedsQL Multidimensional Fatigue Scale, demographics, stroke characteristics, and concurrent outcomes were examined. Results: Parent-rated total, general and cognitive fatigue were significantly poorer than population norms, with more than half of all parents reporting fatigue symptoms in their children. One-third of children also reported experiencing fatigue symptoms, but their ratings did not differ significantly from normative expectations, as such, all further analyses were on parent ratings of fatigue. Older age at stroke and larger lesion size predicted greater general fatigue; older age, female sex, and higher social risk predicted more sleep/rest fatigue. No significant predictors of cognitive fatigue were identified and only older age at stroke predicted total fatigue. Greater fatigue was associated with poorer adaptive functioning, motor skills, participation, quality of life, and behavior problems but not attention. Conclusions: Fatigue is a common problem following pediatric arterial ischemic stroke and is associated with the functional difficulties often seen in this population. This study highlights the importance of long-term monitoring following pediatric arterial ischemic stroke and the need for effective interventions to treat fatigue in children.

Background and Objective:Corticosteroids are used to treat the early stages of idiopathic facial paralysis (Bell’s palsy) in children, but their effectiveness is uncertain. We set out to determine if prednisolone improves the proportion of children with Bell’s palsy with complete recovery at one month.Methods:We conducted a double-blind, placebo-controlled, randomised trial of prednisolone in children presenting to emergency departments with Bell’s palsy. Patients aged 6 months to less than 18 years, recruited within 72 hours after symptom onset, were randomly assigned to receive 10 days of treatment with oral prednisolone (approximately 1 mg/kg) or placebo. The primary outcome was complete recovery of facial function at 1 month rated on the House–Brackmann scale. Secondary outcomes included facial function, adverse events and pain up to 6 months. Target recruitment was n=540 (270 per group).Results:Between 13 October 2015 to 23 August 2020, 187 children were randomised (94 to prednisolone and 93 to placebo) and included in the intention-to-treat analysis. At 1 month, the proportions of patients who had recovered facial function were 49% (n=43/87) in the prednisolone group compared with 57% (n=50/87) in the placebo group (risk difference -8.1%, 95% CI -22.8 to 6.7; adjusted odds ratio [aOR] 0.7, 95% CI 0.4 to 1.3). At 3 months these proportion were 90% (n=71/79) for the prednisolone group versus 85% (n=72/85) for the placebo group (risk difference 5.2%, 95%, CI -5.0 to 15.3; aOR 1.2, 95% CI 0.4 to 3.0) and at 6 months 99% (n=77/78) and 93% (n=76/82) respectively (risk difference 6.0%, 95% CI -0.1 to 12.2; aOR 3.0 95% CI 0.5 to 17.7) There were no serious adverse events and little evidence for group differences in secondary outcomes.Discussion:In children with Bell’s palsy the vast majority recover without treatment. The study, although underpowered, does not provide evidence that early treatment with prednisolone improves complete recovery.Registration:Registered with the Australian New Zealand Clinical Trials Registry ACTRN12615000563561, registered 1 June 2015, ://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368505&isReview=trueClassification of evidence:This study provides Class I evidence that for children with Bell's palsy, prednisolone does not significantly change recovery of complete facial function at one month. However, the study lacked the precision to exclude an important harm or benefit from prednisolone.

Submuscular transposition (SMT) for treatment of ulnar nerve entrapment is commonly performed, however published comparisons of surgical techniques exclude a high proportion of the at-risk population encountered in real world practice. To examine the influence of risk factors on the clinical outcome following SMT we performed a retrospective review of all patients who underwent SMT, including patient self-reported outcome and Louisiana State University Medical Centre ulnar nerve grading scale. A total of 403 ulnar nerves were operated, with follow-up data available for 385 cases (359 patients). Risk factors (including smoking, diabetes, previous elbow trauma/pathology, subluxation, workers’ compensation) were reported in 266 of 385 surgeries (69.09%). SMT was the primary procedure in 339 nerves (88.05%), revision procedure in 46 nerves (11.95%). At last follow up 91.05% reported symptomatic improvement. Nerve grade improvement in 71.09% of primary and 67.39% revision surgery (p = 0.605). No significant difference in improvement was identified between demographic and risk categories, except for patient reported improvement in those without peripheral neuropathy (90.59% vs 73.33%, p = 0.027), and those not improved were on average older than those improved (62.94 vs. 55.68 years, p = 0.012). Superficial infection occurred in 2.6% and there were no deep infections. Application of published exclusion criteria would have resulted in exclusion of ½–⅔ of our cohort. SMT in patients with a history of elbow trauma, diabetes, workers compensation, smoking history, nerve subluxation or revision surgery have similar outcomes compared to those without these factors, whilst improved results were observed in younger patients and those without peripheral neuropathy.

What is already known? ### What this study adds? Traumatic brain injury (TBI) in children is the leading cause of disability and is associated with a significant burden of disease globally.1 Population-based studies reporting the incidence of TBI in Australia have focused on hospitalised patients.2 Most paediatric head trauma results in mild TBIs that do not require hospitalisation.1 In Australia, a 13% increase in emergency department (ED) presentations for paediatric head injuries were reported between 2014 and 2018.3 The most common mechanisms of head injuries are falls for children less than 11 years and transportation-related injuries for children 11 to 16 years.2 While falls are the most common mechanism of head injury in children and can be associated with the most long-term costs, transportation-related TBIs incur high acute care costs, with pedestrian injuries having the highest mean per-patient cost.2 3 This research estimates the effect of mechanisms of injury and severity on the acute care costs of TBI in children. A planned subanalysis of children

Objectives In adults, the elevation of cardiac troponin (cTn) above the 99th percentile upper reference limit defines myocardial injury. The use and interpretation of cTn in a paediatric population, however, is difficult given the 99th percentile for different assays is not well established. Using paediatric blood samples from healthy neonates, infants and children we derived continuous and partitioned 97.5th and 99th percentiles for the Ortho VITROS hs-TnI assay. Methods A total of 328 samples for infants, children and adolescents aged 0–17.8 years were obtained. Age partitioned reference limits were derived in accordance with CLSI EP28-A3C. Continuous reference limits were established as described previously by the HAPPI Kids Study team. Results hs-TnI as measured by the Ortho VITROS Assay is highly elevated above the adult 99th percentile at birth and declines to lower levels within the first 6 months of life. The 99th centile upper reference limit for ages 0–3 months was 72 ng/L (90% CI: 52–91) and 9 ng/L (90% CI: 5.2–17.4) for ages 3 months to 18 years. Continuous upper 99th centile reference limits were comparable. Conclusions Partitioned and continuous 99th percentiles for hs-TnI were derived for the new Ortho VITROS assay in healthy neonates and older children. This will assist clinicians to appropriately assess for the presence of myocardial injury in this population.

Parents of children with serious childhood illness or injury (SCII) are at risk of experiencing poor quality of life (QoL). This study investigated the nature of parent QoL at the time of child diagnosis and seven months post-diagnosis, the change in parent QoL over time, and early factors influencing short-term and longer-term parent QoL. The sample was drawn from a prospective longitudinal cohort study conducted within a paediatric hospital setting. Participants comprised 223 parents of 167 children diagnosed with a life-threatening illness and hospitalised in the cardiology, oncology, or intensive care departments. Examined data included QoL ratings completed by parents within four weeks of diagnosis and seven months post-diagnosis, and demographic, illness-related, and psychosocial predictor measures collected within four weeks of diagnosis, or four months post-diagnosis. Generalised Estimating Equations were utilised to analyse data. Results indicated poor parent QoL at diagnosis, and normalised parent QoL at seven months. Improvement occurred most noticeably in the psychosocial domain. Reduced acute stress symptomatology and increased psychological flexibility were associated with higher parent QoL at diagnosis. Increased perceived emotional resources predicted enhanced parent QoL at seven months. Paediatric medical care teams should consider the challenges to QoL experienced by parents of children with SCII. Parents reporting acute stress symptoms during the acute-illness phase should be prioritised for intervention. Further, parent-dyads presenting at post-acute care settings reporting poor emotional resources would benefit from psychosocial and educative support.

Delayed recovery from concussion can dramatically affect a child's social, emotional, and educational development, yet little is known about what causes some children to recover faster than others. The contribution of white matter disruption in children with delayed recovery has been hypothesized, but findings are limited by methodological issues such as: small heterogeneous samples, bias toward children with delayed recovery, and inconsistencies in timing of brain imaging, both within and between studies. The aim of the present study was to assess diffusion neuroimaging correlates of delayed recovery post-concussion in children. A prospective, longitudinal, observational cohort study was conducted at a statewide tertiary pediatric hospital. Forty-three children who presented to the emergency department (ED) with concussion (defined according to the Zurich/Berlin Consensus Statement on Concussion in Sport) underwent magnetic resonance imaging (MRI) at a 2 weeks post-injury and were classified as either normally recovering (n = 26) or delayed recovering (n = 17). Diffusion imaging comparison using voxelwise tract-based spatial statistics (TBSS) analysis found no difference between the groups in fractional anisotropy, axial diffusion, radial diffusion, or mean diffusivity metrics (p > 0.05 threshold-free cluster enhancement [TFCE] corrected). Post-hoc tract-based Bayesian analysis found evidence for the null in 11 unique white matter tracts (Bayes factor >3). These findings indicate that delayed recovery from post-concussive symptoms in children is unlikely to be caused by white matter microstructural damage.

ObjectiveHead injury (HI) is a common presentation to emergency departments (EDs). The risk of clinically important traumatic brain injury (ciTBI) is low. We describe the relationship between Glasgow Coma Scale (GCS) scores at presentation and risk of ciTBI.MethodsPlanned secondary analysis of a prospective observational study of childrenResultsOf 20 137 evaluable patients with HI, 280 (1.3%) sustained a ciTBI. 82 (29.3%) patients underwent neurosurgery and 13 (4.6%) died. The odds of ciTBI increased steadily with falling GCS. Compared with GCS 15, odds of ciTBI was 17.5 (95% CI 12.4 to 24.6) times higher for GCS 14, and 484.5 (95% CI 289.8 to 809.7) times higher for GCS 3. The area under the ROC curve for the association between GCS and ciTBI was 0.79 (95% CI 0.77 to 0.82), for GCS and mortality 0.91 (95% CI 0.82 to 0.99) and for GCS and neurosurgery 0.88 (95% CI 0.83 to 0.92).ConclusionsOutside clinical decision rules, decreasing levels of GCS are an important indicator for increasing risk of ciTBI, neurosurgery and death. The level of GCS should drive clinician decision-making in terms of urgency of neurosurgical consultation and possible transfer to a higher level of care.

Objective: To investigate somatic and cognitive postconcussive symptoms (PCS) using the symptom evaluation subtest (cSCAT3-SE) of the Child Sports Concussion Assessment Tool 3 (Child SCAT) in tracking PCS up to 2 weeks postinjury.Methods: A total of 96 participants aged 5 to 12 years (Mage = 9.55, SD = 2.20) completed three assessment time points: 48 h postinjury (T0), 2 to 4 days postinjury (T1), and 2 weeks postinjury (T2). The Wilcoxon signed-rank test was used to analyze differences between cognitive and somatic symptoms over time, while the Friedman test was used to analyze differences within symptom type over time.Results: Cognitive PCS were found to be significantly higher than somatic PCS at all assessment time points and were also found to significantly decline from 4 days onwards postinjury; in contrast, somatic PCS significantly declined as early as 48 hpostinjury.Discussion: Differences between cognitive and somatic PCS emerge as early as a few days postinjury, with cognitive PCS being more persistent than somatic PCS across 2 weeks. Research in symptom-specific interventions may be of benefit in helping young children manage severe PCS as early as 2 weeks postinjury.

Pediatric concussion is a major public health concern. Despite the prevalence of behavior problems following concussion and their potential role in prolonged symptoms, little is known about how child and adolescent behavior may impact post-concussion recovery. We sought to examine change in behavioral and emotional functioning in a sample of children ages 5 to

PurposeThe Asking Questions about Alcohol in Pregnancy (AQUA) study, established in 2011, is a prebirth cohort of 1570 mother and child pairs designed to assess the effects of low to moderate prenatal alcohol exposure and sporadic binge drinking on long-term child development. Women attending general antenatal clinics in public hospitals in Melbourne, Australia, were recruited in their first trimester, followed up three times during pregnancy and at 12 and 24 months postpartum. The current follow-up of the 6–8-year-old children aims to strengthen our understanding of the relationship between these levels of prenatal alcohol exposure and neuropsychological functioning, facial dysmorphology, brain structure and function.ParticipantsBetween June 2018 and April 2021, 802 of the 1342 eligible AQUA study families completed a parent-report questionnaire (60%). Restrictions associated with COVID-19 pandemic disrupted recruitment, but early school-age neuropsychological assessments were undertaken with 696 children (52%), and 482 (36%) craniofacial images were collected. A preplanned, exposure-representative subset of 146 children completed a brain MRI. An existing biobank was extended through collection of 427 (32%) child buccal swabs.Findings to dateOver half (59%) of mothers consumed some alcohol during pregnancy, with one in five reporting at least one binge-drinking episode prior to pregnancy recognition. Children’s craniofacial shape was examined at 12 months of age, and low to moderate prenatal alcohol exposure was associated with subtle midface changes. At 2 years of age, formal developmental assessments showed no evidence that cognitive, language or motor outcome was associated with any of exposure level.Future plansWe will investigate the relationship between prenatal alcohol exposure and specific aspects of neurodevelopment at 6–8 years, including craniofacial shape, brain structure and function. The contribution of genetics and epigenetics to individual variation in outcomes will be examined in conjunction with national and international collaborations.

ObjectiveTo estimate traumatic brain injuries (TBIs) and acute care costs due to sports activities.MethodsA planned secondary analysis of 7799 children from 5 years old to ResultsThere were 2903 children (37%) with sports-related TBIs. Mean age was 12.0 years (95% CI 11.9 to 12.1 years); 78% were male. Bicycle riding was associated with the most TBIs (14%), with mean per-patient costs of £802 (95% CI £644 to £960) and 17% of acute costs. The highest acute costs (21%) were from motorcycle-related TBIs (3.8% of injuries), with mean per-patient costs of £3795 (95% CI £1850 to £5739). For younger boys and girls, bicycle riding was associated with the highest TBIs and total costs; however, the mean per-patient costs were highest for motorcycle and horse riding, respectively. For older boys, rugby was associated with the most TBIs. However, motorcycle riding had the highest total and mean per-patient acute costs. For older girls, horse riding was associated with the most TBIs and highest total acute costs, and motorcycle riding was associated with the highest mean per-patient costs.ConclusionInjury prevention strategies should focus on age-related and sex-related sports activities to reduce the burden of TBIs in children.Trial registration numberACTRN12614000463673.

Objective: We examined the contribution of attention and executive cognitive processes to ADHD symptomatology in NF1, as well as the relationships between cognition and ADHD symptoms with functional outcomes. Methods: The study sample consisted of 141 children and adolescents with NF1. Children were administered neuropsychological tests that assessed attention and executive function, from which latent cognitive variables were derived. ADHD symptomatology, adaptive skills, and quality of life (QoL) were assessed using parent-rated questionnaires. Path analyses were conducted to test relationships among cognitive functioning, ADHD symptomatology, and functional outcomes. Results: Significant deficits were observed on all outcome variables. Cognitive variables did not predict ADHD symptomatology. Neither did they predict functional outcomes. However, elevated ADHD symptomatology significantly predicted functional outcomes. Conclusion: Irrespective of cognitive deficits, elevated ADHD symptoms in children with NF1 negatively impact daily functioning and emphasize the importance of interventions aimed at minimizing ADHD symptoms in NF1.

Aim Abusive head trauma (AHT) is associated with high morbidity and mortality. We aimed to describe characteristics of cases where clinicians suspected AHT and confirmed AHT cases and describe how they differed. Methods This was a planned secondary analysis of a prospective multicentre cohort study of head injured children aged

Objective Rapid developments in understanding the molecular mechanisms underlying cognitive deficits in neurodevelopmental disorders have increased expectations for targeted, mechanism‐based treatments. However, translation from preclinical models to human clinical trials has proven challenging. Poor reproducibility of cognitive endpoints may provide one explanation for this finding. We examined the suitability of cognitive outcomes for clinical trials in children with neurofibromatosis type 1 (NF1) by examining test‐retest reliability of the measures and the application of data reduction techniques to improve reproducibility. Methods Data were analyzed from the STARS clinical trial (n = 146), a multi‐center double‐blind placebo‐controlled phase II trial of lovastatin, conducted by the NF Clinical Trials Consortium. Intra‐class correlation coefficients were generated between pre‐ and post‐performances (16‐week interval) on neuropsychological endpoints in the placebo group to determine test‐retest reliabilities. Confirmatory factor analysis was used to reduce data into cognitive domains and account for measurement error. Results Test‐retest reliabilities were highly variable, with most endpoints demonstrating unacceptably low reproducibility. Data reduction confirmed four distinct neuropsychological domains: executive functioning/attention, visuospatial ability, memory, and behavior. Test‐retest reliabilities of latent factors improved to acceptable levels for clinical trials. Applicability and utility of our model was demonstrated by homogeneous effect sizes in the reanalyzed efficacy data. Interpretation These data demonstrate that single observed endpoints are not appropriate to determine efficacy, partly accounting for the poor test‐retest reliability of cognitive outcomes in clinical trials in neurodevelopmental disorders. Recommendations to improve reproducibility are outlined to guide future trial design.

ObjectiveTo evaluate the cost-effectiveness of planned observation on cranial CT use in children with minor head trauma.DesignPlanned secondary analysis of a multicentre prospective observation study.SettingAustralia and New Zealand.PatientsAn analytic cohort of 18 471 children aged InterventionA plan for observation and immediate CT scan were documented after the initial assessment. The planned observation group included those with planned observation and no immediate plan for CT.Main outcome measuresTaking an Australian public-funded healthcare perspective, we estimated the cost-effectiveness of planned observation on the adjusted mean costs per child and CT use reduction by net benefit regression analysis using ordinary least squares with robust SEs and bootstrapping. All costs presented in 2018 euros.ResultsPlanned observation in 4945 (27%) children was cost-saving of €85 (95% CI −120 to −51) with 10.4% lower CT use (95% CI 9.6 to 11.2). This strategy was cost-saving for the PECARN high-risk (−€757 (95% CI −961 to −554)) and intermediate-risk (−€52 (95% CI −99 to −4.3)) categories, with 43% (95% CI 39 to 47) and 11% (95% CI 9.6 to 12.4) lower CT use, respectively. The very low-risk category incurred more cost of €86 (95% CI 67 to 104) with planned observation and 0.05% lower CT use (95% CI −0.61 to 0.71).ConclusionPlanned ED observation in selected children with minor head trauma is cost-effective for reducing CT use for the PECARN intermediate-risk and high-risk categories.Trial registration numberACTRN12614000463673.

BACKGROUND . Demographic and environmental factors can affect child recovery after traumatic brain injury (TBI); however, little is known about their role in predicting child perceptions of competence (i.e., subjective judgments of ability or a sense of adequacy). OBJECTIVES . This prospective, cohort study examined the contribution of participant sex, age at assessment, socioeconomic status, parent-reported change in academic performance post-injury, and the quality of a child's relationship with their family (i.e., family affective involvement, intimacy, integration, and the nature of family roles) to child perceptions of global and academic competence 12 months after pediatric TBI. METHODS . Participants included 127 children, 84 with a TBI (53 mild, 31 moderate-severe TBI; injury age: 5-15 years) and 43 age-matched typically developing (TD) controls. Children rated their perceptions of global and academic competence and degree of family intimacy and integration. Parents completed questionnaires measuring socioeconomic status, family affective involvement, and the nature of family roles. Parents also indicated whether they perceived a change in their child's post-injury academic performance. RESULTS . Child perceptions of academic competence were significantly lower for children with moderate-severe TBI relative to TD children. In contrast, child perceptions of global competence were comparable between TBI and TD control groups. Socioeconomic status, age at assessment, parent-reported relative change in academic performance post-TBI, and family roles were associated with child perceptions of academic competence. Degree of family integration was the sole predictor of child perceptions of global competence. CONCLUSIONS . Child perceptions of academic competence are vulnerable to the effects of moderate-severe TBI, particularly among older children and those from low socioeconomic backgrounds. Well-defined family roles for handling family functions and greater integration of family units might enhance perceptions of global and academic competence in children with TBI.

Susceptibility weighted imaging (SWI) and resting state functional magnetic resonance imaging have been highlighted as two novel neuroimaging modalities that have been underutilized when attempting to predict whether a child with concussion will recover normally or have a delayed recovery course. This study aimed to investigate whether there was a difference between children who recover normally from a concussion and children with delayed recovery in terms of SWI lesion burden and resting state network makeup. Forty-one children who presented to the emergency department of a tertiary level pediatric hospital with concussion participated in this study as a part of a larger prospective, longitudinal observational cohort study into concussion assessment and recovery. Children underwent neuroimaging 2 weeks post-injury and were classified as either normally recovering (n = 27), or delayed recovering (n = 14) based on their post-concussion symptoms at 2 weeks post-injury. No participants showed lesions detected using SWI; therefore, no group differences could be assessed. No between-group resting state network differences were uncovered using dual regression analysis. These findings, alongside previously published work, suggest that potential causes of delayed recovery from concussion may not be found using current neuroimaging paradigms.

ObjectiveTo investigate the changes in mental health and activities of children with chronic health conditions (CHC) during the pandemic. Additionally, to gather information from parents about their children’s healthcare experience, family stressors and mental health during the COVID-19 pandemic.DesignA prospective longitudinal single site cohort studySettingRoyal Children’s Hospital, Melbourne, AustraliaParticipants151 parents of children aged 1.5-17 years (M = 9.8 years, 58.3% male) with a CHC (colorectal disorder, cleft palate and neurofibromatosis type 1) completed the survey.Main outcome measuresAn adapted version of the COVID-19 Wellbeing and Mental Health Survey for Children and Adolescents (Parent/Caregiver version) (CRISIS) was utilised. The CRISIS tool provides data on child’s activities and mental health and parent mental health prior to, and during, the COVID-19 pandemic. Healthcare experiences families was also examined. Parents completed the Kessler 10.ResultsCompared to pre-COVID lockdown, parents reported their children were experiencing higher rates of loneliness, irritability, worry and anxiety. Parents reported that the restrictions in face-to-face contact with family and friends had been stressful for 80.0% of children. Children’s activities changed considerably during the COVID-19 pandemic with screen time increasing by 40%. Thirty percent of parents reported significant distress of their own. Parents felt telehealth were of poorer quality than face-to-face appointments.ConclusionsChildren with CHC experienced a significant increase in mental health symptoms during lockdown for the COVID-19 pandemic. Our findings highlight the increased need for clinical monitoring for children with CHC during periods of community stress and restrictions.

Accurate information on dose, frequency and timing of maternal alcohol consumption is critically important when investigating fetal risks from prenatal alcohol exposure. Identification of distinct alcohol use behaviours can also assist in developing directed public health interventions to prevent adverse child outcomes, including Fetal Alcohol Spectrum Disorder. We aimed to determine group-based trajectories of time-specific, unit-level, alcohol consumption using data from 1458 pregnant women in the Asking Questions about Alcohol in Pregnancy (AQUA) longitudinal study in Melbourne, Australia. Six alcohol consumption trajectories were identified incorporating four timepoints across gestation. Labels were assigned based on consumption in trimester one and whether alcohol use was continued throughout pregnancy: abstained (33.8%); low discontinued (trimester one) (14.4%); moderate discontinued (11.7%); low sustained (13.0%); moderate sustained (23.5%); and high sustained (3.6%). Median weekly consumption in trimester one ranged from 3 grams (low discontinued) to 184 grams of absolute alcohol (high sustained). Alcohol use after pregnancy recognition decreased dramatically for all sustained drinking trajectories, indicating some awareness of fetal risk. Improved understanding of factors that contribute to alcohol consumption in pregnancy in specific sub-populations is critical when developing prevention strategies. Maternal characteristics associated with different trajectories can inform the strategic development of such initiatives.

BackgroundParamedics are frequently called to attend seizures in children. High-quality evidence on second-line treatment of benzodiazepine (BZD)-refractory convulsions with parenteral long-acting antiepileptic drugs in children has become available from the ED. In order to address the potential need for an alternative agent, we set out to determine the association of BZD use prehospital and the need for respiratory support.MethodsWe conducted a retrospective observational study of state-wide ambulance service data (Ambulance Victoria in Victoria, Australia, population: 6.5 million). Children aged 0–17 years assessed for seizures by paramedics were analysed for demographics, process factors, treatment and airway management. We calculated adjusted ORs (AOR) of the requirement for respiratory support in relation to the number of BZD doses administered.ResultsParamedics attended 5112 children with suspected seizures over 1 year (1 July 2018 to 30 June 2019). Overall, need for respiratory support was low (n=166; 3.2%). Before ambulance arrival, 509 (10.0%) had already received a BZD and 420 (8.2%) were treated with midazolam by paramedics. Of the 846 (16.5%) patients treated with BZD, 597 (70.6%) received 1 BZD dose, 156 (18.4%) 2 doses and 93 (11.0%) >2 doses of BZD. Patients who were administered 1, 2 and >2 doses of BZD received respiratory support in 8.9%, 32.1% (AOR 4.6 vs 1 dose, 95% CI 2.9 to 7.4) and 49.5% (AOR 10.3 vs 1 dose, 95% CI 6.0 to 17.9), respectively.ConclusionsIncreasing administration of BZD doses was associated with higher use of respiratory support. Alternative prehospital antiepileptic drugs to minimise respiratory depression should be investigated in future research.

Objective To determine the health outcomes for adults aged 22–35 years old who were conceived via assisted reproduction technology (ART) compared with adults of the same age conceived without use of ART. Design Cohort study. Setting Not applicable. Patient(s) Adult men and women aged 22–35 years who were conceived with and without use of ART. Intervention(s) Questionnaire and clinical review. Main Outcome Measure(s) Vascular structure (carotid artery intima-media thickness, pulse wave velocity), vascular function (blood pressure), metabolic markers (fasting blood glucose, insulin, and standard lipid profiles), anthropometric measurements, and respiratory function (spirometry). Result(s) The mean age of the 193 ART and 86 non-ART participants was 27.0 and 26.9 years, respectively. There were no substantial intragroup differences in demographics or vascular intermediate phenotypes, metabolic parameters, or anthropometric measures, before or after adjusting for perinatal factors and a quality of life measure with four domains. Diastolic blood pressure was lower in the ART men than the non-ART men (adjusted mean difference −4.4 mm Hg, 95% CI, −8.7 to −0.1). The ART group reported a higher prevalence of ever having asthma, (40.8% vs. 28.6%; odds ratio 1.7; 95% CI, 1.0–3.0), but expiratory flow rates were similar. Conclusion(s) This study of the health of 193 adults conceived via ART, the largest to date globally, found no evidence of increased vascular or cardiometabolic risk, or growth or respiratory problems in the ART group compared with a non-ART group from the same source population. Follow-up observation for reproductive and later-onset adverse health effects remains important.

© 2018 American College of Emergency Physicians Study objective: To determine the cost-effectiveness of 3 clinical decision rules in comparison to Australian and New Zealand usual care: the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE), the Pediatric Emergency Care Applied Research Network (PECARN), and the Canadian Assessment of Tomography for Childhood Head Injury (CATCH). Methods: A decision analytic model was constructed from the Australian health care system perspective to compare costs and outcomes of the 3 clinical decision rules compared with Australian and New Zealand usual care. The study involved multicenter recruitment from 10 Australian and New Zealand hospitals; recruitment was based on the Australian Pediatric Head Injury Rules Study involving 18,913 children younger than 18 years and with a head injury, and with Glasgow Coma Scale score 13 to 15 on presentation to emergency departments (EDs). We determined the cost-effectiveness of the 3 clinical decision rules compared with usual care. Results: Usual care, CHALICE, PECARN, and CATCH strategies cost on average AUD $6,390, $6,423, $6,433, and $6,457 per patient, respectively. Usual care was more effective and less costly than all other strategies and is therefore the dominant strategy. Probabilistic sensitivity analyses showed that when simulated 1,000 times, usual care dominated all clinical decision rules in 61%, 62%, and 60% of simulations (CHALICE, PECARN, and CATCH, respectively). The difference in cost between all rules was less than $36 (95% confidence interval –$7 to $77) and the difference in quality-adjusted life-years was less than 0.00097 (95% confidence interval 0.0015 to 0.00044). Results remained robust under sensitivity analyses. Conclusion: This evaluation demonstrated that the 3 published international pediatric head injury clinical decision rules were not more cost-effective than usual care in Australian and New Zealand tertiary EDs. Understanding the usual care context and the likely cost-effectiveness is useful before investing in implementation of clinical decision rules or incorporation into a guideline.

Purpose: To assess objective sleep outcomes and correlates in young adults with a history of childhood traumatic brain injury.Materials and methods: Participants included 45 young adults who sustai...

Summary Background Rapid demographic, epidemiological, and nutritional transitons have brought a pressing need to track progress in adolescent health. Here, we present country-level estimates of 12 headline indicators from the Lancet Commission on adolescent health and wellbeing, from 1990 to 2016. Methods Indicators included those of health outcomes (disability-adjusted life-years [DALYs] due to communicable, maternal, and nutritional diseases; injuries; and non-communicable diseases); health risks (tobacco smoking, binge drinking, overweight, and anaemia); and social determinants of health (adolescent fertility; completion of secondary education; not in education, employment, or training [NEET]; child marriage; and demand for contraception satisfied with modern methods). We drew data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, International Labour Organisation, household surveys, and the Barro-Lee education dataset. Findings From 1990 to 2016, remarkable shifts in adolescent health occurred. A decrease in disease burden in many countries has been offset by population growth in countries with the poorest adolescent health profiles. Compared with 1990, an additional 250 million adolescents were living in multi-burden countries in 2016, where they face a heavy and complex burden of disease. The rapidity of nutritional transition is evident from the 324·1 million (18%) of 1·8 billion adolescents globally who were overweight or obese in 2016, an increase of 176·9 million compared with 1990, and the 430·7 million (24%) who had anaemia in 2016, an increase of 74·2 million compared with 1990. Child marriage remains common, with an estimated 66 million women aged 20–24 years married before age 18 years. Although gender-parity in secondary school completion exists globally, prevalence of NEET remains high for young women in multi-burden countries, suggesting few opportunities to enter the workforce in these settings. Interpretation Although disease burden has fallen in many settings, demographic shifts have heightened global inequalities. Global disease burden has changed little since 1990 and the prevalence of many adolescent health risks have increased. Health, education, and legal systems have not kept pace with shifting adolescent needs and demographic changes. Gender inequity remains a powerful driver of poor adolescent health in many countries. Funding Australian National Health and Medical Research Council, and the Bill & Melinda Gates Foundation.

Childhood and adolescence represent sensitive developmental periods for brain networks implicated in a range of complex skills, including executive functions (EF; inhibitory control, working memory, and cognitive flexibility). As a consequence, these skills may be particularly vulnerable to injuries sustained during these sensitive developmental periods. The present study investigated 1) whether age at injury differentially affects EF 6 months and 2 years after TBI in children aged 5-15 years, and 2) whether the association between brain lesions and EF depend on age at injury. Children with TBI (n = 105) were categorized into four age-at-injury groups based on previous studies and proposed timing of cerebral maturational spurts: early childhood (5-6 years, n = 14), middle childhood (7-9 years, n = 24), late childhood (10-12 years, n = 52), and adolescence (13-15 years, n = 15). EF were assessed with performance-based tasks and a parent-report of everyday EF. TBI patients' EF scores 6 months and 2 years post-injury were compared to those of typically developing (TD) controls (n = 42). Brain lesions were identified using susceptibility weighted imaging (SWI). Results indicated that inhibitory control performance 2 years post-injury was differentially affected by the impact of TBI depending on age at injury. Follow-up analyses did not reveal significant differences within the age groups, preventing drawing strong conclusions regarding the contribution of age at injury to EF outcome after TBI. Tentatively, large effect sizes suggest that vulnerability is most apparent in early childhood and adolescence. Everyday inhibitory control behaviour was worse for children with TBI than TD children across childhood and adolescence at the 2-year assessment. There was no evidence for impairment in working memory or cognitive flexibility after TBI at the group level. Given small group sizes, findings from analyses into correlations between EF and SWI lesions should be interpreted with caution. Extent, number and volume of brain lesions correlated with adolescent everyday EF behaviour 6 months post-injury. Taken together, the results emphasize the need for long-term follow-up after paediatric TBI during sensitive developmental periods given negative outcomes 2-year post injury. Inhibitory control seems to be particular vulnerable to the impact of TBI. Findings of associations between EF and SWI lesions need to be replicated with larger samples.

AIM: Paediatric head injuries (PHI) are the most common cause of trauma-related emergency department (ED) presentations. This study sought to report the incidence of PHI in Australia, examine the temporal trends from 2014 to 2018 and estimate the patient and population-level acute care costs. METHODS: Taking a public-sector health-care perspective, we applied direct and indirect hospital costs for PHI-related ED visits and acute admissions. All costs were inflated to 2018 Australian dollars ($). The patient-level analysis was performed with data from 17 841 children

The Sports Concussion Assessment Tool-5th Edition (SCAT5) and the child version (Child SCAT5) are the current editions of the SCAT and have updated the memory testing component from previous editions. This study aimed to validate this new memory component against the Rey Auditory Verbal Learning Test (RAVLT) as the validated standard. This prospective, observational study, carried out within The Royal Children's Hospital Emergency Department, Melbourne, Australia, recruited 198 participants: 91 with concussion and 107 upper limb injury or healthy sibling controls. Partial Pearson correlations showed that memory acquisition and recall on delay aspects of the SCAT5 were significantly correlated with the RAVLT equivalents when controlling for age (

BACKGROUND AND AIMS: Alcohol consumption is common in adolescence and young adulthood and may continue into pregnancy, posing serious risk to early fetal development. We examine the frequency of periconception alcohol use (prior to pregnancy awareness) and the extent to which adolescent and young adult alcohol use prospectively predict periconception use. DESIGN: A longitudinal, population-based study. SETTING: Victoria, Australia. PARTICIPANTS: A total of 289 women in trimester three of pregnancy (age 29-35 years; 388 pregnancies). MEASURES: The main exposures were binge [≥ 4.0 standard drinks (SDs)/day] and frequent (≥ 3 days/week) drinking in adolescence (mean age = 14.9-17.4 years) and young adulthood (mean age 20.7-29.1 years). Outcomes were frequency (≥ 3 days/week, ≥ monthly, never) and quantity (≥ 4.0 SDs, ≥ 0.5 and

Objectives Children with very short telomeres commonly develop bone marrow failure and other severe diseases. Identifying the individuals with short telomeres can improve outcome of bone marrow transplantation, with accurate diagnosis requiring the use of age-matched reference intervals (RIs). This study aimed to establish RIs for telomere length (TL) in children using three commonly used methods for TL measurement. Methods Healthy children aged 30 days to 18 years were recruited for assessment using age as a continuous variable. Venous blood samples were collected and leukocyte TL was measured using terminal restriction fragment (TRF) analysis, quantitative PCR (QPCR) and flow cytometry with fluorescence in situ hybridization (Flow-FISH). Fractional polynomial model and quantile regression were performed to generate continuous RIs. Factors that might contribute to variation in TL, such as gender, were also examined. Results A total of 212 samples were analyzed. Continuous RIs are presented as functions of age. TRF analysis and QPCR showed significant negative correlation between TL and age (r=−0.28 and r=−0.38, p Conclusions This study provides three options to assess TL in children by establishing method-specific continuous RIs. Choosing which method to use will depend on several factors such as amount and type of sample available and required sensitivity to age-related change.

BACKGROUND: The Pediatric Emergency Care Applied Research Network (PECARN) head trauma clinical decision rules informed the development of algorithms that risk stratify the management of children based on their risk of clinically important traumatic brain injury (ciTBI). We aimed to determine the rate of ciTBI for each PECARN algorithm risk group in an external cohort of patients and that of ciTBI associated with different combinations of high- or intermediate-risk predictors. METHODS: This study was a secondary analysis of a large multicenter prospective data set, including patients with Glasgow Coma Scale scores of 14 or 15 conducted in Australia and New Zealand. We calculated ciTBI rates with 95% confidence intervals (CIs) for each PECARN risk category and combinations of related predictor variables. RESULTS: Of the 15,163 included children, 4,011 (25.5%) were aged

PurposeThe Asking Questions about Alcohol in Pregnancy (AQUA) study, established in 2011, is a pre-birth cohort of 1570 mother and child pairs designed to assess the effects of low to moderate prenatal alcohol exposure and sporadic binge drinking on long-term child development. The current follow-up of the children, now aged 6 to 8 years, aims to strengthen our understanding of the relationship between these levels of prenatal alcohol exposure and neuropsychological functioning, facial dysmorphology, and brain structure & function.Findings to dateOver half (59%) of mothers consumed some alcohol during pregnancy, with one in five reporting at least one binge drinking episode prior to pregnancy recognition. Children’s craniofacial shape was examined at 12 months of age, and low to moderate prenatal alcohol exposure was associated with subtle midface changes. At two years of age, formal developmental assessments showed no evidence that cognitive, language or motor outcome was associated with any of the prenatal alcohol exposures investigated.ParticipantsBetween June 2018 and April 2021, 802 of the 1342 eligible AQUA study families completed a parent-report questionnaire (60%). Restrictions associated with COVID-19 pandemic disrupted recruitment, but early school-age neuropsychological assessments were undertaken with 696 children (52%), and 482 (36%) craniofacial images were collected. A pre-planned, exposure-representative subset of 146 random children completed a brain MRI. The existing AQUA study biobank was extended through collection of 427 (32%) child buccal swabs.Future plansWe will investigate the relationship between prenatal alcohol exposure and specific aspects of neurodevelopment at 6-8 years, including brain structure & function. We will also determine whether craniofacial changes identified at 12 months of age are predictive of later developmental impairments. The contribution of genetics and epigenetics to individual variations in outcomes will be examined in conjunction with established and future national and international collaborations.STRENGTHS AND LIMITATIONSThe Asking Questions about Alcohol in Pregnancy (AQUA) cohort study was specifically designed to prospectively collect high-quality data on low to moderate prenatal alcohol exposure and relevant confounders to investigate the risk to offspring neurodevelopment.The children are being followed up for the third time at 6-8 years, using sensitive measures of neuropsychological function, 3D craniofacial photography, and brain MRI.A biobank of birth samples and maternal and child buccal DNA enables investigation of the contribution of genetic and epigenetic factors to neurodevelopmental outcomes.Despite carefully designed questions, reporting bias will need to be considered in the interpretation of findings, especially around alcohol use.The generalisability of some findings will be limited to a general antenatal population of Caucasian women, from middle-income backgrounds and with a low-risk pregnancy.

OBJECTIVE Children with concussion frequently present to emergency departments (EDs). There is limited understanding of the differences in signs, symptoms, and epidemiology of concussion based on patient age. Here, the authors set out to assess the association between age and acute concussion presentations. METHODS The authors conducted a multicenter prospective observational study of head injuries at 10 EDs in Australia and New Zealand. They identified children aged 5 to < 18 years, presenting with a Glasgow Coma Scale score of 13–15, presenting < 24 hours postinjury, with no abnormalities on CT if performed, and one or more signs or symptoms of concussion. They extracted demographic, injury-related, and signs and symptoms information and stratified it by age group (5–8, 9–12, 13 to < 18 years). RESULTS Of 8857 children aged 5 to < 18 years, 4709 patients met the defined concussion criteria (5–8 years, n = 1546; 9–12 years, n = 1617; 13 to < 18 years, n = 1546). The mean age of the cohort was 10.9 years, and approximately 70% of the patients were male. Sport-related concussion accounted for 43.7% of concussions overall, increasing from 19.1% to 48.9% to 63.0% in the 5–8, 9–12, and 13 to < 18 years age groups. The most common acute symptoms postinjury were headache (64.6%), disorientation (36.2%), amnesia (30.0%), and vomiting (27.2%). Vomiting decreased with increasing age and was observed in 41.7% of the 5–8 years group, 24.7% of the 9–12 years group, and 15.4% of the 13 to < 18 years group, whereas reported loss of consciousness (LOC) increased with increasing age, occurring in 9.6% in the 5–8 years group, 21.0% in the 9–12 years group, 36.7% in the 13 to < 18 years group, and 22.4% in the entire study cohort. Headache, amnesia, and disorientation followed the latter trajectory. Symptom profiles were broadly similar between males and females. CONCLUSIONS Concussions presenting to EDs were more sports-related as age increased. Signs and symptoms differed markedly across age groups, with vomiting decreasing and headache, LOC, amnesia, and disorientation increasing with increasing age.