Telethon Kids Institute

Background Urine is an attractive biospecimen for nutritional status and population health surveys. It is an excellent non-invasive alternative to blood for appropriate biomarkers in young children and is suitable for home-based collection, enabling representative collections across a population. However, the bulk of literature in this population is restricted to collection in primary care settings. Feasibility of home-based collection at scale has not been tested. Here, we describe a mixed method approach to collect urine samples in a large cohort study with children under 5 years. Methods The ORIGINS Project is an ongoing birth cohort investigating early life influences on child health outcomes in Perth, Australia. Recruitment began in 2017, with 3713 children consented by December 2022. Urine is collected longitudinally from children between 2 months and 5 years of age. Mixed methods for sample collection and return accommodates requirements across various ages and study timepoints. Uniquely, courier collection and postal kit deliveries were established in response to participant feedback regarding difficulty with in-person sample drop-offs with young children. Results Over half of all eligible caregivers (1929/3713, 52%) returned a sample, 91% meeting quality standards. A third of all samples were returned by courier, with the highest uptake at 2–6 months of age, and increased uptake across all ages during COVID lockdowns. Caregivers cited being time-poor as the greatest barrier to sample completion and very few participants indicated difficulty with study methods. Conclusion Our data suggests that home-based urine collection using a mixed method approach is acceptable to caregivers at a large scale, supporting the use of urine for biomarker studies and population surveys with young children.

Background Health system and environmental factors play a significant role in achieving the World Health Organization (WHO) End Tuberculosis (TB) targets. However, quantitative measures are scarce or non-existent at a global level. We aimed to measure the progress made towards meeting the global End TB milestones from 2015 to 2020 and identify health system and environmental factors contributing to the success. Methods We obtained data from ten different online data repositories and used principal component analysis to create domain-specific health system performance measures. We used radar charts and dumbbell plots to show the country's progress in ending TB with their health systems. Lastly, we used a linear regression model to identify key health systems and environmental predictors of the percent reduction in TB incidence and mortality. Results There was a high variation in TB incidence and mortality reduction between countries and WHO regions. Of all countries included, 75 (39.3%) achieved more than a 20% reduction in TB incidence between 2015 and 2020. However, only 31 (16.2%) reached a 35% reduction in TB mortality. The European Region achieved the highest incidence reduction, exceeding the 2020 milestone with a 25% reduction. The African Region also made notable progress, achieving an 18% mortality reduction despite its relatively poor health systems. Health system factors, such as TB financing, TB-specific health service delivery, access to medicine, and governance, were significantly associated with TB mortality reduction between 2015 and 2020. Environmental factors, such as average annual temperature and air particulate matter concentration, were found to have a significant negative effect on TB incidence and mortality reduction. Conclusions Weak health systems were identified as major barriers to achieving the End TB milestones in most high-burden countries. Hence, strengthening health systems with a special focus on TB financing, service delivery, and access to medicine in these countries should be prioritised to achieve global TB mortality reduction targets. Countries should follow WHO’s air quality guidelines and rapidly reduce carbon dioxide and other greenhouse gas emissions to mitigate the impact of environmental factors.

Introduction:Pulmonary atresia with intact ventricular septum is a rare congenital cardiac lesion with significant anatomical heterogeneity. Surgical planning of borderline cases remains challenging and is primarily based on echocardiography. The aim was to identify echocardiographic parameters that correlate with surgical outcome and to develop a discriminatory calculator. Methods:Retrospective review of all pulmonary atresia with intact ventricular septum cases at a statewide tertiary paediatric cardiac centre was performed between 2004 and 2020. Demographic, clinical, and echocardiographic data were collected. Logistic regression was used to develop a discriminatory tool for prediction of biventricular repair. Results:Forty patients were included. Overall mortality was 27.5% (n = 11) and confined to patients managed as univentricular (11 vs 0, p = 0.027). Patients who underwent univentricular palliation were more likely to have an associated coronary artery abnormality (17 vs 3, p = 0.001). Fifteen surviving patients (51.7%) achieved biventricular circulation while 14 (48.3%) required one-and-a-half or univentricular palliation. Nineteen patients (47.5%) underwent percutaneous pulmonary valve perforation. No patients without tricuspid regurgitation achieved biventricular repair. The combination of tricuspid valve/mitral valve annulus dimension ratio and right ventricle/left ventricle length ratio identified biventricular management with a sensitivity of 93% and specificity of 96%. An online calculator has been made available. Conclusion:Pulmonary atresia with intact ventricular septum is a challenging condition with significant early and interstage morbidity and mortality risk. Patient outcomes were comparable to internationally reported data. Right ventricle/left ventricle length and tricuspid valve/mitral valve annulus dimension ratios identified a biventricular pathway with a high level of sensitivity and specificity. Absent tricuspid regurgitation was associated with a univentricular outcome.

Siblings of individuals with neurodevelopmental conditions (NDCs) are at increased genetic and environmental risk for poorer psychosocial and neurocognitive outcomes compared to control groups of siblings of individuals without NDCs. This narrative review presents findings to date on NDC sibling wellbeing, focusing on the psychosocial and objective cognitive functioning of siblings of persons with a range of NDCs. The transdiagnostic individual‐level risk and resilience factors impacting siblings, and their associations with mental health, can be modelled and interpreted holistically within a novel neurobiopsychosocial framework of sibling wellbeing. Enriched by community consultation, the Sibling Project was the first exploration of a range of self‐reported factors influencing mental health cross‐sectionally and over time, adopting a dynamic bioecological approach to identify salient targets for intervention and identify pathways for future research.

Purpose: Autistic children have an increased likelihood of anxiety, but more research is needed on the characteristics that predict various types of anxiety in this population. Methods: In this study, we examined a range of child and family predictors of various types of anxiety using a sample of 452 autistic children from the Australian Autism Biobank. We used logistic regression to examine child and family predictors of four common types of anxiety in autistic children: generalised, phobic, separation, and social anxiety. Results: We found that 62.8% of children in this sample had symptoms of at least one type of anxiety. Poor quality sleep habits were the only predictive factor consistently identified across all anxiety symptom types. Specific to children with indicated generalised, separation, and phobic anxiety symptoms were the predictive factors of being older than five years, and specific to generalised and social anxiety were the predictive factors of higher cognitive abilities. Maternal anxiety was also a predictive factor in indicated children’s separation anxiety. Conclusion: These findings can help inform the provision of more targeted support for autistic people, particularly the interaction of poor sleep habits and anxiety symptoms.

Knowing when and where infected mosquitoes bite is required for estimating accurate measures of malaria risk, assessing outdoor exposure, and designing intervention strategies. This study combines secondary analyses of a human behaviour survey and an entomological survey carried out in the same area to estimate human exposure to malaria-infected Anopheles mosquitoes throughout the night in rural villages in south-eastern Tanzania. Mosquitoes were collected hourly from 6PM to 6AM indoors and outdoors by human landing catches in 2019, and tested for Plasmodium falciparum sporozoite infections using ELISA. In nearby villages, a trained member in each selected household recorded the whereabouts and activities of the household members from 6PM to 6AM in 2016 and 2017. Vector control use was high: 99% of individuals were reported to use insecticide-treated nets and a recent trial of indoor residual spraying had achieved 80% coverage. The risk of being bitten by infected mosquitoes outdoors, indoors in bed, and indoors but not in bed, and use of mosquito nets was estimated for each hour of the night. Individuals were mainly outdoors before 9PM, and mainly indoors between 10PM and 5AM. The main malaria vectors caught were Anopheles funestus sensu stricto and An. arabiensis. Biting rates were higher in the night compared to the evening or early morning. Due to the high use of ITNs, an estimated 85% (95% CI 81%, 88%) of all exposure in children below school age and 76% (71%, 81%) in older household members could potentially be averted by ITNs under current use patterns. Outdoor exposure accounted for an estimated 11% (8%, 15%) of infective bites in children below school age and 17% (13%, 22%) in older individuals. Maintaining high levels of ITN access, use and effectiveness remains important for reducing malaria transmission in this area. Interventions against outdoor exposure would provide additional protection.

Child anthropometric deficits remain a major public health problem in Sub-Saharan Africa (SSA) and are a key target of the UN Sustainable Development Goals (SDGs). The SDGs recommend disaggregation of health indicators by ethnic group. However, few studies have assessed how ethnicity is associated with anthropometric deficits across SSA. Data were extracted from 37 georeferenced Demographic and Health Surveys carried out during 2006–2019 across SSA that recorded anthropometric data for children aged <5 years. In a cross-sectional analysis, the odds of stunting (low height-for-age), wasting (low weight-for-height) and underweight (low weight-for-age) were modelled in relation to ethnic group using a generalised linear hierarchical mixed-effects model, controlling for survey design and environmental, socioeconomic and clinical variables. The study population comprised 138,312 children spanning 45 ethnic groups across 18 countries. In pairwise comparisons (accounting for multiple comparisons) between ethnic groups, height-for-age z-scores differed by at least 0.5 standard deviations in 29% of comparisons, weight-for-height z-scores in 36% of comparisons and weight-for-age z-scores in 20% of comparisons. Compared to a reference group of Fula children (the largest ethnic group), ethnic group membership was associated with both increases and decreases in growth faltering, ranging from a 69% reduction to a 32% increase in odds of stunting (Igbo: adjusted odds ratio (aOR) 0.31, 95% confidence intervals (CI) 0.27–0.35, p<0.0001; Hausa: aOR 1.32, 95% CI 1.21–1.44, p<0.0001); a 13% to 87% reduction in odds of wasting (Mandinka: aOR 0.87, 95% CI 0.76–0.99, p = 0.034; Bamileke: aOR 0.13, 95% CI 0.05–0.32, p<0.0001) and an 85% reduction to 13% increase in odds of underweight (Bamileke: aOR 0.15, 95% CI 0.08–0.29, p<0.0001; Hausa: aOR 1.13, 95% CI 1.03–1.24, p = 0.010). Major ethnic disparities in stunting, wasting and underweight were observed across 18 countries in SSA. Understanding and accounting for these differences is essential to support progress monitoring and targeting of nutrition interventions in children.

Australian Aboriginal people experience stressors from inequalities across crucial social determinants, including deep and entrenched disadvantage and exclusion. The impact of unaddressed historical issues is pervasive and intergenerational. The disproportionate rates of Aboriginal youth suicide, juvenile detention and imprisonment highlight the inadequacy of existing social and emotional wellbeing programs and services for Aboriginal children and young people. There is increasing recognition in Australia that aligning social and emotional wellbeing interventions with Western values and conceptions of mental health is one of the main barriers to service uptake among Aboriginal people. This suggests fundamental questions remain unanswered about what type of services effectively address the complex constellation of social-emotional and wellbeing challenges arising from intergenerational poverty and trauma. Yawardani Jan-ga is an Aboriginal-led, operated, culturally secure, Equine-Assisted Learning (EAL) project designed by and with local Aboriginal young people, community Elders, members, and experts to address the complex constellation of social-emotional, spiritual and wellbeing needs of Aboriginal children and young people, aged 6–26 years, across multiple communities in the Kimberley region of Western Australia. EAL is a strengths-based learning approach where participants work with horses’ inherent characteristics to learn transferable life skills, such as communication skills, self-awareness, and emotional regulation, to promote social and emotional growth and wellbeing. Although EAL has been previously used with Aboriginal children and young people internationally, they are yet to be widely used with Aboriginal people in Australia. Here, we describe the three subcomponents of the Yawardani Jan-ga implementation science project and the planned Participatory Action Research and phenomenological approaches to capture the distinctive experiences of participants and the local communities where the intervention is implemented. We anticipate that findings will build an evidence base that informs policy and practice by understanding key intervention elements of social and emotional wellbeing support for Aboriginal youth, how to incorporate Aboriginal worldviews across different stages of interventions, and how to capture impact best using culturally secure methods.

While bacille-calmette–guerin (BCG) vaccination is one of the recommended strategies for preventing tuberculosis (TB), its coverage is low in several countries, including Ethiopia. This study investigated the spatial co-distribution and drivers of TB prevalence and low BCG coverage in Ethiopia. This ecological study was conducted using data from a national TB prevalence survey and the Ethiopian demographic and health survey (EDHS) to map the spatial co-distribution of BCG vaccination coverage and TB prevalence. A Bayesian geostatistical model was built to identify the drivers for the spatial distribution of TB prevalence and low BCG vaccination coverage. BCG vaccination coverage was defined as the number of children who received the vaccine divided by the total number of children born within five years preceding the EDHS surveys. Parameter estimation was done using binary logistic regression. Prediction maps for the co-distribution of high TB prevalence and low BCG vaccination coverage were created by overlying spatial prediction surfaces of the two outcomes. Posterior means and a 95% Bayesian credible interval (CrI) were used to summarize the parameters of the model. The national prevalence was 0.40% (95% confidence interval (CI) 0.34%, 0.47%) for TB and 47% (95% CI 46%, 48%) for vaccination coverage. Substantial spatial variation in TB prevalence and low BCG coverage was observed at a regional and local level, particularly in border areas of the country, including the Somali, Afar, and Oromia regions. Approximately 58% of the pixels (i.e., geographical area or spatial units) with high TB prevalence exhibited low BCG coverage in the same location. While travel time to cities (Mean = 0.28, 95% BCI: 0.15, 0.41) and distance to health facilities (Mean = 0.43, 95% CI 0.22, 0.63), were positively associated, population density (Mean = −0.04, 95% BCI −0.05, −0.02) was negatively associated, with the proportion of unvaccinated children for BCG indicating areas near health facilities and cities have better BCG coverage. However, there were no significant predictors for TB prevalence. Substantial spatial co-distribution between high TB prevalence and low BCG coverage was observed in some parts of the country, indicating that there are areas where the TB burden is not being adequately managed through the provision of vaccines in Ethiopia. Scaling up BCG vaccination coverage and TB diagnosis and treatment through improving access to health services in border regions such as Somalia and Afar would be important to reduce the prevalence of TB in Ethiopia.

Early infancy is a critical period for immune development. In addition to being the primary food source during early infancy, human milk also provides multiple bioactive components that shape the infant gut microbiome and immune system and provides a constant source of exposure to maternal microbiota. Given the potential interplay between allergic diseases and the human microbiome, this study aimed to characterise the milk microbiome of allergic mothers. Full‐length 16S rRNA gene sequencing was performed on milk samples collected at 3 and 6 months postpartum from 196 women with allergic disease. Multivariate linear mixed models were constructed to identify the maternal, infant, and environmental determinants of the milk microbiome. Human milk microbiome composition and beta diversity varied over time (PERMANOVA R² = 0.011, p = 0.011). The season of infant birth emerged as the strongest determinant of the microbiome community structure (PERMANOVA R² = 0.014, p = 0.011) with impacts on five of the most abundant taxa. The milk microbiome also varied according to the type of maternal allergic disease (allergic rhinitis, asthma, atopic dermatitis, and food allergy). Additionally, infant formula exposure reduced the relative abundance of several typical oral taxa in milk. In conclusion, the milk microbiome of allergic mothers was strongly shaped by the season of infant birth, maternal allergic disease phenotype, and infant feeding mode. Maternal allergic disease history and infant season of birth should therefore be considered in future studies of infant and maternal microbiota. Trial Registration: ClinicalTrials.gov identifier: ACTRN12606000281594

Background Remission is the desired outcome following OIT as it allows individuals to discontinue treatment and eat the allergen freely. Early initiation of OIT in infants and toddlers has been embraced as an approach to increase the likelihood of remission. However, there is no high‐quality evidence supporting younger age as an independent factor driving remission; available studies are limited by small samples of younger subjects and lack of adjustment for confounding covariates, particularly peanut‐specific IgE (sIgE) levels which is closely correlated with age. Methods This study examined relationships between peanut sIgE and age at baseline and remission, in children aged 1–10 who completed 18 months of OIT in the PPOIT‐003 RCT (n = 162). Remission was defined as absence of clinical reactivity to peanut after 8 weeks of allergen avoidance/treatment discontinuation. Age and sIgE were examined as continuous variables in univariate and multivariate regression models. Results Higher peanut sIgE was consistently predictive of lower likelihood of remission, independent of age. In contrast, there was no independent association between age and remission after adjusting for baseline sIgE (OR 0.94 [0.79–1.12], p = 0.5). Conclusions Findings do not support age as an independent predictor of remission following OIT. Additional studies examining safety and efficacy of OIT in infants and younger children are urgently needed, ahead of widespread adoption of early intervention.

Background A MenABCWY vaccine containing 4CMenB and MenACWY-CRM vaccine components has been developed to protect against the five meningococcal serogroups that cause most invasive disease cases. Methods In this phase 3 study (NCT04707391), healthy participants aged 15–25 years, who had received MenACWY vaccination ≥4 years previously, were randomized (1:1) to receive two MenABCWY doses six months apart or one MenACWY-CRM dose. Primary objectives were to demonstrate the non-inferiority of MenABCWY 1 month post-vaccination versus MenACWY-CRM, with a lower limit of 2-sided 95% confidence interval above -10% for group differences in 4-fold rise in human serum bactericidal antibody (hSBA) titers against serogroups ACWY, and to evaluate reactogenicity and safety. Secondary endpoints included percentages of participants with hSBA titers ≥lower limit of quantitation (LLOQ) against serogroups ACWY and vaccine antigen-specific serogroup B (MenB) indicator strains. Results Non-inferiority of MenABCWY versus MenACWY-CRM was demonstrated following each MenABCWY dose. Percentages of participants with hSBA titers ≥LLOQ for serogroups ACWY were 97.9–98.9% and 99.5–100% following one and two MenABCWY doses, respectively, and 96.8–99.0% following one MenACWY-CRM dose. After two MenABCWY doses, 75.6–96.3% of participants had hSBA titers ≥LLOQ against MenB indicator strains. The MenABCWY vaccine was well tolerated in MenACWY-primed individuals with a favorable safety profile. Conclusions Immune responses against serogroups ACWY following one and two doses of investigational MenABCWY vaccine are non-inferior to those following MenACWY-CRM in MenACWY-primed adolescents and young adults. Robust immune responses were observed against MenB indicator strains after two MenABCWY doses administered 6 months apart.

Background In Australia, there are concerns that unrestricted junk food advertising during sports broadcasts increases short‐term junk food consumption among viewers. Therefore, the present study aimed to estimate the impact of junk food and anti‐junk food advertising on consumption inclinations. Methods We conducted a content analysis across a sample ( N = 16) of Australian Football League (AFL) and National Rugby League (NRL) matches to determine the prevalence of junk food and anti‐junk food advertising video clips. We also exposed participants ( N = 428) to a single randomly selected junk food advertisement or a single anti‐junk food advertisement and measured the immediate impact on craving and consumption intentions for both healthy weight and high body mass index (BMI) participants. Results Junk food and anti‐junk food advertising video clips comprised 10.85% and .003% of all advertisements across the broadcasts, respectively. For both healthy and overweight participants, junk food advertisement exposure did not increase immediate craving or consumption intentions. However, decreases were observed in craving and consumption intentions following an anti‐junk food advertisement. Conclusions Junk food advertising prevalence across national sports was high. Junk food advertisements did not increase immediate inclinations to consume junk food, but an anti‐junk food advertisement was effective in reducing immediate craving and consumption intentions, particularly for healthy BMI participants. So What? Given the potential efficacy of health promotion adverts, governments should consider investing in a higher frequency of health messages during broadcasts that are known to readily promote junk food, such as national sports.

Purpose Virtual reality is used as a distraction tool during medical procedures that can cause anxiety and pain. We assessed the usefulness, engagement, value and feasibility of virtual reality to help children cope with routine clinical procedures. Design and Methods Quality improvement study. Children, 4–16 years old, were given the option to use virtual reality during their procedure in oncology, immunology or diabetes clinics, or during an induction of general anesthesia. The emotional state of the child was documented using the children's emotional manifestation scale. We assessed feedback from patients, parents, and clinicians. Results Across all clinics, children responded positively to the virtual reality and 80% would choose to use virtual reality again for health‐related procedures. Parents and clinicians, respectively, reported that virtual reality helped children tolerate the procedure (82% and 87%), engaged children well (82% and 89%) and was a valuable tool (85% and 98%). Clinicians (90%) endorsed the feasibility of using virtual reality during procedures. Practice Implications This project demonstrated that virtual reality can be implemented as a useful, engaging and feasible tool to help children tolerate a variety of routine medical procedures. However, ensuring comfortable fit of virtual reality devices and diversifying the visual content is necessary.

Interventions to support autistic children are often described as developmental, behavioral, or naturalistic developmental behavioral interventions; however, developmental approaches have not been well defined as a class of therapeutic intervention. We present the position of an interdisciplinary group of researchers and clinicians regarding the common features of developmental interventions. The term Developmental Relationship-Based Interventions (DRBI) is proposed as a useful way to represent this classification of interventions. The defining features of DRBI are: (a) a developmental framework based on a child’s innate motivation for social engagement and learning, and (b) a primary focus on supporting parent-child and other social interactions and relationships. Four strategies consistently used in DRBI are: Social Play, Sensitive Responding, Following the Child’s Lead, and Presenting Challenges. We also describe the features that differentiate DRBI from Naturalistic Developmental Behavioral Interventions (NDBI). The proposed description of DRBI may aid clinical decision-making, policy formation and research design.

Introduction This analysis aimed to investigate diabetes-specific psychological outcomes among adults with type 1 diabetes (T1D) using hybrid closed-loop (HCL) versus standard therapy. Research design and methods In this multicenter, open-label, randomized, controlled, parallel-group clinical trial, adults with T1D were allocated to 26 weeks of HCL (MiniMed™ 670G) or standard therapy (insulin pump or multiple daily injections without real-time continuous glucose monitoring). Psychological outcomes (awareness and fear of hypoglycemia; and diabetes-specific positive well-being, diabetes distress, diabetes treatment satisfaction, and diabetes-specific quality of life (QoL)) were measured at enrollment, mid-trial and end-trial. Linear mixed models were conducted, using restricted maximum likelihood estimation, unadjusted and adjusted (for covariates: age, sex, diabetes duration, glycated hemoglobin, recent severe hypoglycemia, pre-trial insulin delivery modality, enrollment and mid-study scores). Results 120 participants (mean age 44±12 years) were randomized to intervention (n=61) or standard therapy (n=59). At 13 weeks, the HCL group had better diabetes-specific positive well-being than the standard therapy group (unadjusted: Δ=1.0, p=0.025; adjusted: Δ=1.1, p=0.01), which was maintained at 26 weeks (unadjusted: Δ=0.9, p=0.042; adjusted: Δ=1.0, p=0.023). At 26 weeks, the HCL group also had less diabetes distress (adjusted: Δ=−6.4, p=0.039), fear of hypoglycemia (“maintain high”: adjusted: Δ=−0.8, p=0.034; and “worry”: adjusted: Δ=−1.8, p=0.048), and perceived “unacceptably high glucose levels” (unadjusted: Δ=−1.1, p<0.001; adjusted: Δ=−1.1, p<0.001). HCL did not improve diabetes treatment satisfaction, diabetes-specific QoL, hypoglycemia awareness, or perceived frequency of unacceptably low glucose levels. Conclusions These findings imply that HCL offers important psychological benefits. In particular, improvement in diabetes-specific positive well-being was observed 13 weeks after HCL initiation and maintained at 26 weeks. Reduction in the perceived frequency of hyperglycemia was also apparent by 26 weeks. Adjusted analyses showed significant reductions in diabetes distress and fear of hypoglycemia at 26 weeks, suggesting these benefits were apparent for people with particular characteristics. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12617000520336.

We present lung virome data recovered through shotgun metagenomics in bronchoalveolar lavage fluid from an infant with cystic fibrosis, who tested positive for Stenotrophomonas maltophilia infection. Using a bioinformatic pipeline for virus characterization in shotgun metagenomic data, we identified five viral contigs representing Pseudomonas phages classified as Caudoviricetes.