Paediatrics (RCH) - Research Publications

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    Nature and correlates of self-esteem in young adult survivors of childhood traumatic brain injury
    Khan, N ; Anderson, V ; Crossley, L ; Hearps, S ; Catroppa, C ; Ryan, NP (Taylor and Francis Group, 2024)
    Despite growing research linking childhood traumatic brain injury (TBI) with reduced wellbeing, self-esteem, and psycho-social health, very few studies have examined self-esteem and its correlates in young adult survivors of childhood TBI. This very-long-term follow-up study evaluated self-esteem in 29 young adults with a history of childhood TBI (M time since injury = 13.84 years; SD = 0.74), and 10 typically developing controls (TDCs). All participants were originally recruited into a larger, longitudinal case-control study between 2007 and 2010. In the current follow-up study, both groups completed well-validated measures of self-esteem and mental health in young adulthood. Although group means for self-esteem did not significantly differ between TBI and TDC groups, a higher proportion of TBI participants rated their self-esteem in the clinical range (TBI group = 17%; TDC group = 0%). While self-esteem was not significantly associated with injury or pre-injury child or family characteristics, lower self-esteem was significantly correlated with greater concurrent feelings of loneliness (p = 0.007) and higher concurrent mood symptoms (p < 0.001).Our results suggest that social isolation and low mood may represent meaningful targets for psycho-social interventions to address poor self-worth in young adults with a history of childhood TBI.
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    Status Epilepticus Australasian Registry for Children: A pilot prospective, observational, cohort study of paediatric status epilepticus
    Furyk, JS ; George, S ; Phillips, N ; Emeto, T ; Watt, K ; O'Brien, S ; Riney, K ; Wilson, C ; Hearps, SJC ; Borland, ML ; Dalziel, SR ; Babl, FE (WILEY, 2022-10)
    OBJECTIVE: Paediatric status epilepticus (SE) has potential for long-term sequelae. Existing data demonstrate delays to aspects of care. The objective of the present study was to examine the feasibility of collecting data on children with paediatric SE and describe current management strategies in pre-hospital and in-hospital settings. METHODS: A pilot, prospective, observational cohort study of children 4 weeks to 16 years of age with SE, in four EDs in Australia. Clinical details including medications administered, duration of seizure and short-term outcomes were collected. Follow up occurred by telephone at 1 month. RESULTS: We enrolled 167 children with SE. Mean age was 5.4 years (standard deviation [SD] 4.1), and 81 (49%) male. Median seizure duration was 10 min (interquartile range 7-30). Midazolam was the first medication administered in 87/100 (87%) instances, mean dose of 0.21 mg/kg (SD 0.13). The dose of midazolam was adequate in 30 (35%), high (>0.2 mg/kg) in 44 (51%) and low (<0.1 mg/kg) in 13 (15%). For second-line agents, levetiracetam was administered on 33/55 (60%) occasions, whereas phenytoin and phenobarbitone were administered on 11/55 (20%) occasions each. Mean dose of levetiracetam was 26.4 mg/kg (SD 13.5). One hundred and four (62%) patients were admitted to hospital, with 13 (8%) admitted to ICU and seven (4%) intubated. CONCLUSION: In children presenting with SE in Australia medical management differed from previous reports, with midazolam as the preferred benzodiazepine, and levetiracetam replacing phenytoin as the preferred second-line agent. This pilot study indicates the feasibility of a paediatric SE registry and its utility to understand and optimise practice.
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    Improving subacute management of post concussion symptoms: a pilot study of the Melbourne Paediatric Concussion Scale parent report.
    Davis, GA ; Rausa, VC ; Babl, FE ; Davies, K ; Takagi, M ; Crichton, A ; McKinlay, A ; Anderson, N ; Hearps, SJ ; Clarke, C ; Pugh, R ; Dunne, K ; Barnett, P ; Anderson, V (Future Medicine Ltd, 2022-05)
    AIM: To pilot a modification of the Post Concussion Symptom Inventory, the Melbourne Paediatric Concussion Scale (MPCS) and examine its clinical utility. MATERIALS & METHODS: A total of 40 families of concussed children, aged 8-18 years, were recruited from the emergency department. Parent responses to the MPCS in the emergency department and 2-weeks post injury determined child symptomatic status. Association between MPCS symptom endorsement and symptomatic group status was examined. RESULTS: All additional MPCS items were endorsed by at least 25% of the parents of symptomatic children at 2 weeks. MPCS items were classified into nine symptom domains, with most falling in mood, neurological, autonomic and vestibular domains. CONCLUSION: The additional items and domain classifications in the MPCS have the potential to improve subacute diagnostic precision, monitoring of clinical recovery and identification of appropriate interventions post pediatric concussion.
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    Association of neurostructural biomarkers with secondary attention-deficit/hyperactivity disorder (ADHD) symptom severity in children with traumatic brain injury: a prospective cohort study
    Ryan, NP ; Catroppa, C ; Ward, SC ; Yeates, KO ; Crossley, L ; Hollenkamp, M ; Hearps, S ; Beauchamp, MH ; Anderson, VA (CAMBRIDGE UNIV PRESS, 2023-08)
    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.
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    Prospective Associations of Susceptibility-Weighted Imaging Biomarkers with Fatigue Symptom Severity in Childhood Traumatic Brain Injury
    Ryan, NP ; Catroppa, C ; Beauchamp, MH ; Beare, R ; Ditchfield, M ; Coleman, L ; Kean, M ; Crossley, L ; Hearps, S ; Anderson, VA (MARY ANN LIEBERT, INC, 2023-03-01)
    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 d = 0.44), cognitive fatigue (Cohen d = 0.59), sleep/rest fatigue (Cohen d = 0.37), and total fatigue (Cohen d = 0.63). In multi-variate models adjusted for TBI severity, child demographic factors, and depression, we found that subacute volume of SWI lesions was independently associated with all fatigue symptom domains. The magnitude of the brain-behavior relationship varied by fatigue symptom domain, such that the strongest relationships were observed for the cognitive fatigue and total fatigue symptom scales. Overall, we found that total subacute volume of SWI lesions explained up to 24% additional variance in multi-dimensional fatigue, over-and-above known risk factors. The subacute SWI has potential to improve prediction of post-injury fatigue in children with TBI. Our preliminary findings suggest that volume of SWI lesions may represent a novel, independent biomarker of post-injury fatigue, which could help to identify high-risk children who are likely to benefit from targeted psychoeducation and/or preventive strategies to minimize risk of long-term post-injury fatigue.
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    Treatment patterns and frequency of key outcomes in acute severe asthma in children: a Paediatric Research in Emergency Departments International Collaborative (PREDICT) multicentre cohort study
    Craig, S ; Powell, CVE ; Nixon, GM ; Oakley, E ; Hort, J ; Armstrong, DS ; Ranganathan, S ; Kochar, A ; Wilson, C ; George, S ; Phillips, N ; Furyk, J ; Lawton, B ; Borland, ML ; O'Brien, S ; Neutze, J ; Lithgow, A ; Mitchell, C ; Watkins, N ; Brannigan, D ; Wood, J ; Gray, C ; Hearps, S ; Ramage, E ; Williams, A ; Lew, J ; Jones, L ; Graudins, A ; Dalziel, S ; Babl, FE (BMJ PUBLISHING GROUP, 2022-03)
    RATIONALE: Severe acute paediatric asthma may require treatment escalation beyond systemic corticosteroids, inhaled bronchodilators and low-flow oxygen. Current large asthma datasets report parenteral therapy only. OBJECTIVES: To identify the use and type of escalation of treatment in children presenting to hospital with acute severe asthma. METHODS: Retrospective cohort study of children with an emergency department diagnosis of asthma or wheeze at 18 Australian and New Zealand hospitals. The main outcomes were use and type of escalation treatment (defined as any of intensive care unit admission, nebulised magnesium, respiratory support or parenteral bronchodilator treatment) and hospital length of stay (LOS). MEASUREMENTS AND MAIN RESULTS: Of 14 029 children (median age 3 (IQR 1-3) years; 62.9% male), 1020 (7.3%, 95% CI 6.9% to 7.7%) had treatment escalation. Children with treatment escalation had a longer LOS (44.2 hours, IQR 27.3-63.2 hours) than children without escalation 6.7 hours, IQR 3.5-16.3 hours; p<0.001). The most common treatment escalations were respiratory support alone (400; 2.9%, 95% CI 2.6% to 3.1%), parenteral bronchodilator treatment alone (380; 2.7%, 95% CI 2.5% to 3.0%) and both respiratory support and parenteral bronchodilator treatment (209; 1.5%, 95% CI 1.3% to 1.7%). Respiratory support was predominantly nasal high-flow therapy (99.0%). The most common intravenous medication regimens were: magnesium alone (50.4%), magnesium and aminophylline (24.6%) and magnesium and salbutamol (10.0%). CONCLUSIONS: Overall, 7.3% children with acute severe asthma received some form of escalated treatment, with 4.2% receiving parenteral bronchodilators and 4.3% respiratory support. There is wide variation treatment escalation.
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    A data driven approach to identify trajectories of prenatal alcohol consumption in an Australian population-based cohort of pregnant women
    Muggli, E ; Hearps, S ; Halliday, J ; Elliott, EJ ; Penington, A ; Thompson, DK ; Spittle, A ; Forster, DA ; Lewis, S ; Anderson, PJ (NATURE PORTFOLIO, 2022-03-14)
    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 messages about possible 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 g (low discontinued) to 184 g of absolute alcohol (high sustained). Alcohol use after pregnancy recognition decreased dramatically for all sustained drinking trajectories, indicating some awareness of risk to the unborn child. Further, specific maternal characteristics were associated with different trajectories, which may inform targeted health promotion aimed at reducing alcohol use in pregnancy.
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    Protocol for a prospective, school-based standardisation study of a digital social skills assessment tool for children: The Paediatric Evaluation of Emotions, Relationships, and Socialisation (PEERS) study
    Thompson, EJ ; Beauchamp, MH ; Darling, SJ ; Hearps, SJC ; Brown, A ; Charalambous, G ; Crossley, L ; Darby, D ; Dooley, JJ ; Greenham, M ; Jaimangal, M ; McDonald, S ; Muscara, F ; Turkstra, L ; Anderson, VA (BMJ PUBLISHING GROUP, 2018-05)
    BACKGROUND: Humans are by nature a social species, with much of human experience spent in social interaction. Unsurprisingly, social functioning is crucial to well-being and quality of life across the lifespan. While early intervention for social problems appears promising, our ability to identify the specific impairments underlying their social problems (eg, social communication) is restricted by a dearth of accurate, ecologically valid and comprehensive child-direct assessment tools. Current tools are largely limited to parent and teacher ratings scales, which may identify social dysfunction, but not its underlying cause, or adult-based experimental tools, which lack age-appropriate norms. The present study describes the development and standardisation of Paediatric Evaluation of Emotions, Relationships, and Socialisation (PEERS®), an iPad-based social skills assessment tool. METHODS: The PEERS project is a cross-sectional study involving two groups: (1) a normative group, recruited from early childhood, primary and secondary schools across metropolitan and regional Victoria, Australia; and (2) a clinical group, ascertained from outpatient services at The Royal Children's Hospital Melbourne (RCH). The project aims to establish normative data for PEERS®, a novel and comprehensive app-delivered child-direct measure of social skills for children and youth. The project involves recruiting and assessing 1000 children aged 4.0-17.11 years. Assessments consist of an intellectual screen, PEERS® subtests, and PEERS-Q, a self-report questionnaire of social skills. Parents and teachers also complete questionnaires relating to participants' social skills. Main analyses will comprise regression-based continuous norming, factor analysis and psychometric analysis of PEERS® and PEERS-Q. ETHICS AND DISSEMINATION: Ethics approval has been obtained through the RCH Human Research Ethics Committee (34046), the Victorian Government Department of Education and Early Childhood Development (002318), and Catholic Education Melbourne (2166). Findings will be disseminated through international conferences and peer-reviewed journals. Following standardisation of PEERS®, the tool will be made commercially available.
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    Cohort profile: early school years follow-up of the Asking Questions about Alcohol in Pregnancy Longitudinal Study in Melbourne, Australia (AQUA at 6)
    Muggli, E ; Halliday, J ; Elliott, EJ ; Penington, A ; Thompson, D ; Spittle, AJ ; Forster, D ; Lewis, S ; Hearps, S ; Anderson, PJ (BMJ PUBLISHING GROUP, 2022-01)
    PURPOSE: The 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. PARTICIPANTS: Between 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 DATE: Over 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 PLANS: We 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.
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    Global and domain-specific self-esteem after pediatric traumatic brain injury: Contribution of injury characteristics and parent mental health
    Khan, N ; Ryan, NP ; Crossley, L ; Hearps, S ; Catroppa, C ; Anderson, V (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2022-09-14)
    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.