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OBJECTIVE: The purpose of this study was to investigate (1) typical trajectories of parent-reported ear infections throughout childhood and (2) their associations with child outcomes. METHOD: Design and participants: Two parallel cohorts assessed biennially from 2004 to 2014 spanning ages 0-1 to 10-11 years (B cohort, n = 3721) and ages 4-5 to 14-15 years (K cohort, n = 3489) in the Longitudinal Study of Australian Children. Ear infection: Parent-reported ongoing ear infections (B: waves 1-6; K: waves 1, 2, 4, and 5). Outcomes (wave 6): National academic standardized test, teacher-reported learning, parent- and teacher-reported behavior, and self-reported quality of life. Analysis: Latent class models identified ear infection trajectories. Linear regression quantified associations between trajectories and outcomes. RESULTS: Four probability trajectories of ear infections emerged in both cohorts: "consistently low" (B 86.2%, K 87.0%), "moderate to low" (5.5%, 9.7%), "low to moderate" (7.0%, 1.5%), and "consistently high" (1.4%, 1.8%). In K cohort, the "consistently high" group had the worst outcomes (effect sizes 0.2-0.8 SDs), with effect sizes largest for psychosocial and language outcomes. "Moderate to low" and "low to moderate" groups showed marginal to no academic associations, although behavior and quality-of-life scores were 0.2 to 0.3 SDs poorer than the "consistently low" group. Similar but attenuated associations were seen in B cohort. CONCLUSION: Sizable adverse adolescent outcomes follow parent reports of persistent ongoing ear infections throughout childhood. Despite a possibility of reverse causation, this suggests that cumulative rather than age-specific ear infections are most important to outcomes. Clinicians may generally be reassuring about ongoing ear infections limited to either early or middle childhood but should proactively identify and manage the small subgroup whose early infections persist throughout the elementary school years.

Reservoir pressure parameters (i.e., reservoir pressure [RP] and excess pressure [XSP]) independently predict cardiovascular events in adults, but this has not been investigated in children. This study aimed to determine (1) the association of reservoir pressure parameters with carotid intima-media thickness (carotid IMT), a preclinical vascular phenotype, and (2) whether a multivariable regression model with or without reservoir pressure parameters fits better for estimating carotid IMT in children. Study participants were 11-12-year-old children (n = 1231, 50% male) from the Child Health CheckPoint study, a cross-sectional substudy of the population-based Longitudinal Study of Australian Children. RP and XSP were obtained using brachial-cuff oscillometry (SphygmoCor XCEL, AtCor, Sydney). Carotid IMT was quantified by vascular ultrasonography. XSP was associated with carotid IMT after adjusting for confounders including age, sex, BMI z-score, heart rate, pubertal stage, moderate-to-vigorous physical activity, and mean arterial pressure (β = 0.93 µm, 95% CI 0.30-1.56 for XSP peak and β = 0.04 µm, 95% CI 0.01-0.08 for XSP integral). The results of the likelihood ratio test indicated a trend that the model with XSP and the above confounders fit better than a similar model without XSP for estimating carotid IMT. Our findings indicate that brachial-cuff device-measured XSP is associated with carotid IMT independent of conventional cardiovascular risk factors, including standard BP. This implies that a clinically convenient cuff approach could provide meaningful information for the early assessment of cardiovascular risk among children.

Background/objectives: Microvascular changes may contribute to obesity-associated cardiovascular disease. We examined whether body mass index (BMI) and waist-to-height ratio (WHtR) (1) at multiple earlier time points and (2) decade-long trajectories predicted retinal microvascular parameters in mid-childhood/adulthood. Methods: Participants/design: 1288 11–12 year olds (51% girls) and 1264 parents (87% mothers) in the population-based Child Health CheckPoint (CheckPoint) module within the Longitudinal Study of Australian Children (LSAC). LSAC exposure measures: biennial BMI z-score and WHtR for children at five time points from age 2–3 to 10–11 years and self-reported parent BMI at six time points from child age 0–1 years to 10–11 years. CheckPoint outcome measures: retinal arteriolar and venular caliber. Analyses: BMI/WHtR trajectories were identified by group-based trajectory modeling; linear regression models estimated associations between BMI/WHtR at each time point/trajectories and later retinal vascular caliber, adjusted for age, sex, and family socioeconomic status. Results: In time point analyses, higher child BMI/WHtR from age 4 to 5 years was associated with narrower arteriolar caliber at the age of 11–12 years, but not venular caliber. For example, each standard deviation higher in BMI z-score at 4–5 years was associated with narrower arteriolar caliber at 11–12 years (standardized mean difference (SMD): −0.05, 95% confidence interval (CI): −0.10 to 0.01); by 10–11 years, associations had doubled to −0.10 (95% CI: −0.16 to −0.05). In adults, these finding were similar, except the magnitude of BMI and arteriolar associations were similar across all time points (SMD: −0.11 to −0.13). In child and adult BMI trajectory analyses, less favorable trajectories predicted narrower arteriolar (p-trend 0.1), caliber. Compared with those in the average BMI trajectory, SMDs in arterial caliber for children and adults in the highest trajectory were −0.25 (95% CI: −0.44 to −0.07) and −0.42 (95% CI: −0.73 to −0.10), respectively. Venular caliber showed late associations with child WHtR, but not with BMI in children or adults. Conclusions: Associations of decade-long high BMI trajectories with narrowed retinal arteriolar caliber emerge in children, and are clearly evident by midlife. Adiposity appears to exert its early adverse life course impacts on the microcirculation more via arteriolar than venular mechanisms.

Background Trimethylamine N-oxide (TMAO) is a microbiome- and diet-derived metabolite implicated in adverse cardiovascular outcomes. To date, studies of plasma TMAO concentrations have largely focused on individuals with metabolic disease. As such, data on TMAO concentrations in population settings and parent–child dyads are lacking. Objectives This study aimed to investigate parent–child concordance, age, and sex effects on plasma concentrations of TMAO and its precursors [l-carnitine, choline, betaine, and dimethylglycine (DMG)]. Associations between concentrations of TMAO and its precursors and self-reported dietary intakes of animal protein (i.e., red meat, meat products, chicken, fish, milk products, and cheese) and fast-food meals were also investigated. Methods A total of 1166 children (mean ± SD age: 11 ± 0.5 y, 51% female) and 1324 parents (mean ± SD age: 44 ± 5.1 y, 87% female) had a biomedical assessment as part of Growing Up in Australia's Child Health Checkpoint. Plasma TMAO and precursor concentrations were quantified using ultra-high-pressure LC coupled with tandem MS. Results Familial dyads significantly contributed to plasma TMAO and precursor concentrations (P, Age, sex, and shared family factors characterize the concentrations of plasma TMAO and those of its precursors in Growing Up in Australia's CheckPoint Study of children and adults.

OBJECTIVES: To examine how overweight and obesity at specific ages and overall BMI growth patterns throughout childhood predict cardiometabolic phenotypes at 11 to 12 years. METHODS: In a population-based sample of 5107 infants, BMI was measured every 2 years between ages 2 to 3 and 10 to 11 years. We identified 5 BMI trajectories using growth curve models. At ages 11 to 12 years, 1811 children completed assessments for metabolic syndrome risk scores, carotid-femoral pulse wave velocity, and carotid intima-media thickness. Multivariable regression models were used to estimate associations, adjusted for potential confounders (eg, age, sex, smoking exposure, and small for gestational age). RESULTS: Overweight and obesity from early childhood onward were strongly associated with higher cardiometabolic risk at 11 to 12 years of age. At age 6 to 7 years, compared with those with a healthy weight, children with overweight had higher metabolic syndrome risk scores by 0.23 SD units (95% confidence interval 0.05 to 0.41) and with obesity by 0.76 SD units (0.51–1.01), with associations almost doubling by age 10 to 11 years. Obese (but not overweight) children had higher outcome pulse wave velocity (0.64–0.73 SD units) from ages 6 to 7 years and slightly higher outcome carotid intima-media thickness (0.20–0.30 SD units) at all ages. Cumulative exposure to high BMI from 2 to 3 years of age carried the greatest cardiometabolic risk, with a gradient of risk across trajectories. CONCLUSIONS: High early-childhood BMI is already silently associated with the development of cardiometabolic risk by 11 to 12 years, highlighting the urgent need for effective action to reduce overweight and obesity in early childhood.

Optimization of children's activity behaviors for skeletal health is a key public health priority, yet it is unknown how many hours of moderate to vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior, or sleep constitute the best day-the "Goldilocks Day"-for children's bone structure and function. To describe the best day for children's skeletal health, we used data from the cross-sectional Child Health CheckPoint. Included participants (n = 804, aged 10.7 to 12.9 years, 50% male) underwent tibial peripheral quantitative CT to assesses cross-sectional area, trabecular and cortical density, periosteal and endosteal circumference, polar moment of inertia, and polar stress-strain index. Average daily time-use composition (MVPA, LPA, sedentary time, and sleep) was assessed through 8-day, 24-hour accelerometry. Skeletal outcomes were regressed against time-use compositions expressed as isometric log-ratios (with quadratic terms where indicated), adjusted for sex, age, pubertal status, and socioeconomic position. The models were used to estimate optimal time-use compositions (associated with best 5% of each skeletal outcome), which were plotted in three-dimensional quaternary figures. The center of the overlapping area was considered the Goldilocks Day for skeletal health. Children's time-use composition was associated with all skeletal measures (all p ≤ 0.001) except cross-sectional area (p = 0.72). Days with more sleep and MVPA, less sedentary time, and moderate LPA were beneficially associated with skeletal measures, except cortical density, which was adversely associated. The Goldilocks daily time-use composition for overall skeletal health was center (range): 10.9 (10.5 to 11.5) hours sleep; 8.2 (7.8 to 8.8) hours sedentary time; 3.4 (2.8 to 4.2) hours LPA, and 1.5 (1.3 to 1.5) hours MVPA. Estimated optimal sleep duration is consistent with current international guidelines (9 to 11 hours), while estimated optimal MVPA exceeds recommendations of at least 60 min/d. This first study to describe optimal durations of daily activities for children's skeletal health provides evidence to underpin guidelines. © 2020 American Society for Bone and Mineral Research (ASBMR).

Obesity predicts adverse microvasculature from childhood, potentially via inflammatory pathways. We investigated whether inflammation mediates associations between obesity and microvascular parameters. In 1054 children (mean age 11 years) and 1147 adults (44 years) from a cross-sectional study, we measured BMI (z-scores for children) and WHtR, Glycoprotein acetyls (GlycA), an inflammatory marker, and retinal arteriolar and venular calibre. Causal mediation analysis methods decomposed a “total effect” into “direct” and “indirect” components via a mediator, considering continuous and categorical measures and adjusting for potential confounders. Compared to normal-weight BMI children, those with overweight or obesity had narrower arteriolar calibre (total effects −0.21 to −0.12 standard deviation (SD)): direct (not mediated via GlycA) effects were similar. Children with overweight or obesity had 0.25 to 0.35 SD wider venular calibre, of which 19 to 25% was mediated via GlycA. In adults, those with obesity had 0.07 SD greater venular calibre, which was completely mediated by GlycA (indirect effect: 0.07 SD, 95% CI −0.01 to 0.16). Similar findings were obtained with other obesity measures. Inflammation mediated associations between obesity and retinal venules, but not arterioles from mid-childhood, with higher mediation effects observed in adults. Interventions targeting inflammatory pathways may help mitigate adverse impacts of obesity on the microvasculature.

Objective: Reservoir pressure parameters [e.g. reservoir pressure (RP) and excess pressure (XSP)] measured using tonometry predict cardiovascular events beyond conventional risk factors. However, the operator dependency of tonometry impedes widespread use. An operator-independent cuff-based device can reasonably estimate the intra-aortic RP and XSP from brachial volumetric waveforms, but whether these estimates are clinically relevant to preclinical phenotypes of cardiovascular risk has not been investigated. Methods: The RP and XSP were derived from brachial volumetric waveforms measured using cuff oscillometry (SphygmoCor XCEL) in 1691 mid-life adults from the CheckPoint study (a population-based cross-sectional study nested in the Longitudinal Study of Australian Children). Carotid intima--media thickness (carotid IMT, n = 1447) and carotid--femoral pulse wave velocity (PWV, n = 1632) were measured as preclinical phenotypes of cardiovascular risk. Confounders were conventional risk factors that were correlated with both exposures and outcomes or considered as physiologically important. Results: There was a modest association between XSP and carotid IMT (β = 0.76 μm, 95% CI, 0.25-1.26 partial R2 = 0.8%) after adjusting for age, sex, BMI, heart rate, smoking, diabetes, high-density lipoprotein cholesterol and mean arterial pressure. Neither RP nor XSP were associated with PWV in the similarly adjusted models (β = -0.47 cm/s, 95% CI, -1.15 to 0.20, partial R2 = 0.2% for RP, and β = 0.04 cm/s, 95% CI, -0.59 to 0.67, partial R2 = 0.01% for XSP). Conclusion: Cuff-based XSP associates with carotid IMT independent of conventional risk factors, including traditional BP, but the association was weak, indicating that further investigation is warranted to understand the clinical significance of reservoir pressure parameters.

Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality globally, with the burden largely borne by people living in low- and middle-income countries. Adolescents are central to NCD control through the potential to modify risks and alter the trajectory of these diseases across the life-course. However, an absence of epidemiological data has contributed to the relative exclusion of adolescents from policies and responses. This paper documents the design of a study to measure the burden of metabolic syndrome (a key risk for NCDs) and poor mental health (a key outcome) amongst Indonesian adolescents. Using a mixed-method design, we sampled 16–18-year-old adolescents from schools and community-based settings across Jakarta and South Sulawesi. Initial formative qualitative enquiry used focus group discussions to understand how young people conceptualise mental health and body weight (separately); what they perceive as determinants of these NCDs; and what responses to these NCDs should involve. These findings informed the design of a quantitative survey that adolescents self-completed electronically. Mental health was measured using the Centre for Epidemiologic Studies Depression Scale-Revised (CESD-R) and Kessler-10 (both validated against formal psychiatric interview in a subsample), with the metabolic syndrome measured using biomarkers and anthropometry. The survey also included scales relating to victimisation, connectedness, self-efficacy, body image and quality of life. Adolescents were sampled from schools using a multistage cluster design, and from the community using respondent-driven sampling (RDS). This study will substantially advance the field of NCD measurement amongst adolescents, especially in settings like Indonesia. It demonstrates that high quality, objective measurement is acceptable and feasible, including the collection of biomarkers in a school-based setting. It demonstrates how comparable data can be collected across both in-school and out of school adolescents, allowing a more comprehensive measure of NCD burden, risk and correlates.

Background: Good sleep is a growing public health focus. Given the multidimensional nature of sleep, it is of interest to examine population sleep profiles and determine sociodemographic and lifestyle correlates. Methods: This study uses actigraphy-measured sleep data collected between February 2015 and March 2016 in the Child Health CheckPoint study. Participants wore actigraphy monitors (GENEActiv Original, Cambs, UK) on their non-dominant wrist for seven days and sleep characteristics (duration, efficiency, timing, and variability) were derived from raw actigraphy data. Sleep profiles of 1043 Australian children aged 11–12 years and their parents were determined using K-means cluster analysis. The association between cluster membership and potential sociodemographic and lifestyle correlates were assessed using Generalised Estimating Equations, adjusting for geographic clustering. Results: Four sleep profiles were identified: Short sleepers, Late to bed, Long sleepers, and Overall good sleepers. Compared to Overall good sleepers, Late to bed cluster were of lower socioeconomic position and had the least favourable diet and activity patterns. Compared to Overall good sleepers, those in the Late to bed cluster had higher sedentary time, lower levels of moderate-vigorous physical activity and a higher consumption of savoury snacks. In contrast, sugary drink consumption was higher in Late to bed children and Long sleeper adults. Conclusion: Examining sleep profiles may provide a more holistic way of monitoring sleep at the population level. Future health promotion strategies may be best to consider sleep in terms of profiles, with emphasis on sleep timing and duration. Refereed/Peer-reviewed

Background: Cashew is a common cause of tree nut allergy in children. To date there have been few studies of diagnostic tests for cashew allergy, and positive predictive values (PPVs) for cashew as well as other tree nuts are largely extrapolated from studies of peanut allergy. How relevant these cutoffs are for cashew has not been formally explored. Objective: We aimed to establish skin prick test (SPT) wheal sizes that correlated to 95% PPV for a positive food challenge for cashew. Methods: We included all cashew oral food challenges (OFCs) conducted as part of the HealthNuts (n = 108; age, 4-6 years) and SchoolNuts (n = 37; age, 10-14 years) studies, both recruited from the community (population cohort). A second cohort of all cashew OFCs conducted at the Royal Children's Hospital (RCH) allergy center (n = 343) (2011-2016) and a private allergy clinic based at RCH (n = 43) was included via electronic medical record review (clinic cohort). The 95% PPV for cashew SPT was calculated for both cohorts. Results: Among the population cohort (n = 145), 62% of cashew OFCs were positive compared with 20% of the clinic cohort (n = 386). The SPT cutoff for 95% PPV derived from the population cohort was 10 mm (95% confidence interval [CI], 7.5-12.0). For the clinic cohort, the 95% PPV was 14 mm (95% CI, 9.5-unknown). An SPT wheal size of 8 mm had a PPV of 89% (95% CI, 79-95) in the population cohort and 62% (95% CI, 45-78) in the clinic cohort. Conclusion: A higher SPT wheal size may be more appropriate than the commonly used 8 mm cutoff to guide clinical decisions around when to perform OFC for cashew.

Traditional retinal microvascular parameters (smaller arteriolar and greater venular caliber) are associated with cardiovascular risk factors, pre-clinical vascular phenotypes and clinical cardiovascular events in adults.Although novel retinal microvascular geometric parameters showed analogous associations in adults, less is known whether these parameters are associated with cardiovascular health from childhood. In a populationbasedcross-sectional study in children (n = 1126, mean age 11.4 years, 50.3% girls), we examined associations of cardiovascular risk factors and pre-clinical arterial phenotypes with retinal geometric parameters.Cardiovascular parameters included body mass index (BMI), an inflammatory marker (GlycA), low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, systolic (SBP) and diastolic blood pressure, large artery functional (pulse wave velocity, PWV and carotid arterial elasticity) and structural (carotid intima-media thickness) phenotypes. Retinal geometric parameters (fractal dimension (Df) and tortuosity) were quantified from retinal images. Multivariable regression models were performed and adjusted for potential confounders.Higher values for BMI, SBP and PWV showed weak associations with lower (i.e. worse) arteriolar but not venularDf (standardized mean difference (SMD) ranging from −0.07 to −0.09, 95% CIs −0.15 to −0.01). Higher HDL was associated with greater arteriolar Df (SMD 0.07, 95% CI 0.01 to 0.13). Only higher SBP was associated with higher (i.e. worse) arteriolar but not venular tortuosity (SMD 0.09, 95% CI 0.02 to 0.16). In generally healthy children, some risk factors and pre-clinical arterial phenotypes show small associations with retinal geometric parameters. In childhood, emerging relationships between microvascular parameters and cardiometabolic risk may be better described by retinal vascular caliber than by geometric parameters. Refereed/Peer-reviewed

This study investigates how dietary patterns and scores are associated with subsequent BMI and waist:height ratio (WHtR), and how BMI and WHtR are associated with subsequent dietary patterns or scores, from 2–3 to 10–11 and 4–5 to 14–15 years of age. In the Longitudinal Study of Australian Children, height, weight and waist circumference were measured biennially in children, yielding BMI z-score and WHtR. Parents, latterly children, reported frequency of child consumption of 12–16 food/drink items during the previous 24 h. At each wave, we empirically derived dietary patterns using factor analyses, and dietary scores based on the 2013 Australian Dietary Guidelines. We used structural-equation modelling to investigate cross-lagged associations (n 1972–2882) between diet and body composition measures in univariable and multivariable analyses. Dietary scores/patterns did not consistently predict WHtR and BMI z-score in the next wave, nor did BMI z-score and WHtR consistently predict diet in the next wave. The few associations seen were weak and often in the opposite direction to that hypothesised. The largest effect, associated with each standard deviation increase in BMI in wave 5 of the K cohort (age 12–13 years), was a 0·06 standard deviation estimated mean increase in dietary score (higher quality diet) in the subsequent wave (95 % CI 0·02, 0·11, P=0·003). Associations between dietary patterns/scores and body composition were not strongly evident in either direction. Better quantitative childhood dietary tools feasible for large-scale administration are needed to quantify how dietary patterns, energy intake and anthropometry co-develop.

BackgroundChronic conditions are the leading cause of mortality, morbidity and disability in children. However, children and caregivers are rarely involved in identifying research priorities, which may limit the value of research in supporting patient-centred practice and policy.ObjectiveTo identify priorities of patients, caregivers and health professionals for research in childhood chronic conditions and describe the reason for their choices.SettingAn Australian paediatric hospital and health consumer organisations.MethodsRecruited participants (n=73) included patients aged 8 to 14 years with a chronic condition (n=3), parents/caregivers of children aged 0 to 18 years with a chronic condition (n=19), representatives from consumer organisations (n=13) and health professionals including clinicians, researches (n=38) identified and discussed research priorities. Transcripts were thematically analysed.ResultsSeventy-eight research questions were identified. Five themes underpinned participants’ priorities: maintaining a sense of normality (enabling participation in school, supporting social functioning, promoting understanding and acceptance), empowering self-management and partnership in care (overcoming communication barriers, gaining knowledge and skills, motivation for treatment adherence, making informed decisions, access and understanding of complementary and alternative therapies),strengthening ability to cope (learning to have a positive outlook, preparing for home care management, transitioning to adult services), broadening focus to family (supporting sibling well-being, parental resilience and financial loss, alleviating caregiver burden), and improving quality and scope of health and social care (readdressing variability and inequities, preventing disease complications and treatment side effects, identifying risk factors, improving long-term outcomes, harnessing technology, integrating multidisciplinary services).ConclusionResearch priorities identified by children, caregivers and health professionals emphasise a focus on life participation, psychosocial well-being, impact on family and quality of care. These priorities may be used by funding and policy organisations in establishing a paediatric research agenda.

Congenital hearing impairment (HI) is the most common sensory impairment and can be isolated or part of a syndrome. Diagnosis through newborn hearing screening and management through early intervention, hearing aids and cochlear implantation is well established in the Australian setting; however understanding the genetic basis of congenital HI has been missing. This population-derived cohort comprised infants with moderate-profound bilateral HI born in the 2016-2017 calendar years, detected through newborn hearing screening. Participants were recruited through an integrated paediatric, otolaryngology and genetics HI clinic and offered whole exome sequencing (WES) on a HiSeq4000 or NextSeq500 (Illumina) platform with a targeted average sequencing depth of 100x and chromosome microarray on the Illumina Infinium core exome-24v1.2 platform. Of those approached, 68% (106/156) consented to participate. The rate of genetic diagnosis was 56% (59/106), significantly higher than standard of care (GJB2/6 sequencing only), 21% (22/106). There were clinical implications for the 106 participants: 36% required no further screening, 9% had tailored screening initiated, 2% were offered treatment and 4% had informed care for a complex neurodevelopmental syndrome. WES in this cohort demonstrates the range of diagnoses associated with congenital HI and confirms the genetic heterogeneity of congenital HI. The high diagnostic yield and clinical implications emphasises the need for genomic sequencing to become standard of care.

In a community sample of slow-to-talk toddlers, we aimed to (a) quantify how well maternal responsive behaviors at age 2 years predict language ability at age 4 and (b) examine whether maternal responsive behaviors more accurately predict low language status at age 4 than does expressive vocabulary measured at age 2 years.Prospective community-based longitudinal study. At child age 18 months, 1,138 parents completed a 100-word expressive vocabulary checklist within a population survey; 251 (22.1%) children scored ≤20th percentile and were eligible for the current study. Potential predictors at 2 years were (a) responsive language behaviors derived from videotaped parent-child free-play samples and (b) late-talker status. Outcomes were (a) Clinical Evaluation of Language Fundamentals-Preschool Second Edition receptive and expressive language standard score at 4 years and (b) low language status (standard score 1.25 standard deviations below the mean on expressive or receptive language).Two hundred eight (82.9% of 251) participants were retained to age 4. In adjusted linear regression analyses, maternal expansions predicted higher receptive (p 0.001, partial RA combination of short measures of different dimensions, such as parent responsive behaviors, in addition to a child's earlier language skills increases the ability to predict language outcomes at age 4 to a precision that is approaching clinical value. Research to further enhance predictive values should be a priority, enabling health professionals to identify which slow-to-talk toddlers most likely will or will not experience later poorer language.

We explored whether supported (SJE) or coordinated joint engagement (CJE) between mothers recruited from the community and their 24-month-old children who were slow-to-talk at 18 months old were associated with child language scores at ages 24, 36, and 48 months (n = 197). We further explored whether SJE or CJE modified the concurrent positive associations between maternal responsive behaviours and language scores. Previous research has shown that SJE, maternal expansions, imitations, and responsive questions were associated with better language scores. Our main finding was that SJE but not CJE was consistently positively associated with 24- and 36-month-old expressive and receptive language scores, but not with 48-month-old language scores. SJE modified how expansions and imitations, but not responsive questions, were associated with language scores; the associations were evident in all but the highest levels of SJE. Further research is necessary to test these findings in other samples before clinical recommendations can be made.

AIM: Cardiovascular disease and mental illness commonly co-occur in later life, but it is unknown how early these associations arise. We aimed to determine the extent to which: (i) childhood mental health is associated with functional and structural cardiovascular risk phenotypes and adiposity in late childhood/adolescence, and (ii) associations between mental health and cardiovascular phenotypes may be explained by differential body mass index. METHODS: This cross-sectional study drew on three longitudinal community-based cohort studies (two enriched for overweight/obesity) in metropolitan Melbourne, Australia, with harmonized follow-up in 2014. Mental health exposures included emotional and behavioural problems (Strength and Difficulties Questionnaire) and psychosocial health and general well-being (Pediatric Quality of Life Inventory (PedsQL)), which were assessed by self- and parent-proxy report. Cardiovascular risk phenotypes and adiposity measures included mean arterial pressure, pulse wave velocity, carotid artery intima-media thickness, retinal arterioleto-venule ratio, waist circumference, % body fat, and BMI z-score. We used multivariable linear regression models, adjusting for age, sex and neighbourhood disadvantage, to examine associations. RESULTS: Of the 364 participants (mean age 14.7, standard deviation 2.0, years), 30% were overweight and 16% obese. All adiposity indicators were positively associated with higher behavioural/emotional problems and poorer psychosocial health and negatively associated with better ratings of positive general well-being, as reported by parents and children (all P ≤ 0.03). However, there was little evidence that cardiovascular functional or structural phenotypes varied by mental health. CONCLUSIONS: By late childhood/adolescence, mental health is strongly associated with adiposity but not with cardiovascular structure or function. This suggests that the known relationship between these constructs may not develop until early or mid-adulthood.

Objective/Background: Determine the effects and costs of a brief behavioral sleep intervention, previously shown to improve child social-emotional functioning, sleep, and parent mental health, in a translational trial. Participants: Three hundred thirty-four school entrant children from 47 primary schools in Melbourne, Australia, with parent-reported moderate to severe behavioral sleep problems. Methods: intervention group received sleep hygiene practices and standardized behavioral strategies delivered by trained school nurses in 2013 and 2014. Control group children could receive usual community care. Results: Outcome measures: child social-emotional functioning (Pediatric Quality of Life Inventory 4.0 psychosocial health summary score-primary outcome), sleep problems (parent-reported severity, Children's Sleep Habits Questionnaire), behavior, academic function, working memory, child and parent quality of life, and parent mental health. At six months post randomization, 145 (of 168) intervention and 155 (of 166) control families completed the primary outcome for which there was no difference. Intervention compared with control children had fewer sleep problems (35.2% vs. 52.7% respectively, OR 0.5; 95% CI 0.3 to 0.8, p = 0.002) and better sleep patterns (e.g., longer sleep duration). Their parents reported fewer symptoms of depression. All differences attenuated by 12 months. There was no difference in other outcomes at either time point. Intervention costs: $AUS 182/child. Conclusions: A brief behavioral sleep intervention, delivered by school nurses to children with behavioral sleep problems, does not improve social emotional functioning. Benefits to child sleep and parent mental health are evident at 6 but not 12 months. Approaches that increase intervention dosage may improve outcomes.

ObjectiveTo evaluate research priority setting approaches in childhood chronic diseases and to describe the priorities of stakeholders including patients, caregivers/families and health professionals.DesignWe conducted a systematic review of MEDLINE, Embase, PsycINFO and CINAHL from inception to 16 October 2016. Studies that elicited stakeholder priorities for paediatric chronic disease research were eligible for inclusion. Data on the prioritisation process were extracted using an appraisal checklist. Generated priorities were collated into common topic areas.ResultsWe identified 83 studies (n=15 722). Twenty (24%) studies involved parents/caregivers and four (5%) children. The top three health areas were cancer (11%), neurology (8%) and endocrine/metabolism (8%). Priority topic areas were treatment (78%), disease trajectory (48%), quality of life/psychosocial impact (48%), disease onset/prevention (43%), knowledge/self-management (33%), prevalence (30%), diagnostic methods (28%), access to healthcare (25%) and transition to adulthood (12%). The methods included workshops, Delphi techniques, surveys and focus groups/interviews. Specific methods for collecting and prioritising research topics were described in only 60% of studies. Most reviewed studies were conducted in high-income nations.ConclusionsResearch priority setting activities in paediatric chronic disease cover many discipline areas and have elicited a broad range of topics. However, child/caregiver involvement is uncommon, and the methods often lack clarity. A systematic and explicit process that involves patients and families in partnership may help to inform a more patient and family-relevant research agenda in paediatric chronic disease.

ObjectiveTo determine which parental health behaviours early in childhood most strongly predict whole-of-childhood dietary trajectories.DesignPopulation-based Longitudinal Study of Australian Children (LSAC, waves 1–6; 2004–2014). Exposures were parents’ fruit/vegetable consumption, alcohol, smoking and physical activity at child age 0–1 years (B Cohort) or 4–5 years (K Cohort). Outcomes, from repeated biennial short diet diaries, were group-based trajectories of (i) dietary scores and empirically derived patterns of (ii) healthful and (iii) unhealthful foods consumed, spanning ages 2–3 to 10–11 years (B Cohort) and 4–5 to 14–15 years (K Cohort). We investigated associations of baseline parental health behaviours with child dietary trajectories using multinomial logistic regression.SettingAustralian homes.SubjectsOf children, 4443 (87·0 %) from the B Cohort and 4620 (92·7 %) from the K Cohort were included in all trajectories. Multivariable analyses included 2719 to 2905 children and both parents.ResultsChildren whose primary caregiver reported the lowest fruit/vegetable consumption had markedly higher odds of belonging to the least healthy score and pattern trajectories (K Cohort: OR=8·7, 95 % CI 5·0, 15·1 and OR=8·4, 95 % CI 4·8, 14·7, respectively); associations were weaker (K Cohort: OR=2·3, 95 % CI 1·0, 5·2) for the unhealthiest pattern trajectory. Secondary caregiver fruit/vegetable associations were smaller and inconsistent. Parental alcohol, smoking and physical activity were not predictive in multivariable analyses. Results were largely replicated for the B Cohort.ConclusionsLow primary caregiver fruit/vegetable consumption increased nearly ninefold the odds of children being in the lowest intake of healthy, but only weakly predicted unhealthy, food trajectories. Healthy and unhealthy food intake may have different determinants.

ObjectiveIn a national study of Australian children aged 11–12 years old, we examined the (1) prevalence and characteristics of hearing loss, (2) its demographic risk factors and (3) evidence for secular increases since 1990.MethodsThis is a cross-sectional CheckPoint wave within the Longitudinal Study of Australian Children. 1485 children (49.8% retention; 49.7% boys) underwent air-conduction audiometry. Aim 1: hearing loss (≥16 decibels hearing level (dB HL)) was defined in four ways to enable prior/future comparisons: high Fletcher Index (mean of 1, 2 and 4 kHz; primary outcome relevant to speech perception), four-frequency (1, 2, 4 and 8 kHz), lower frequency (1 and 2 kHz) and higher frequency (4 and 8 kHz); aim 2: logistic regression of hearing loss by age, gender and disadvantage index; and aim 3: P for trend examining CheckPoint and reported prevalence in studies arranged by date since 1990.ResultsFor high Fletcher Index, the prevalence of bilateral and unilateral hearing loss ≥16 dB HL was 9.3% and 13.3%, respectively. Slight losses (16–25 dB HL) were more prevalent than mild or greater (≥26 dB HL) losses (bilateral 8.5% vs 0.8%; unilateral 12.5% vs 0.9%), and lower frequency more prevalent than higher frequency losses (bilateral 11.0% vs 6.9%; unilateral 15.4% vs 11.5%). Demographic characteristics did not convincingly predict hearing loss. Prevalence of bilateral/unilateral lower and higher frequency losses ≥16 dB HL has risen since 1990 (all P for trend Conclusions and relevanceChildhood hearing loss is prevalent and has risen since 1990. Future research should investigate the causes, course and impact of these changes.

Background Adaptive working memory training is being implemented without an adequate understanding of developmental trajectories of working memory. We aimed to quantify from Grade 1 to Grade 3 of primary school (1) changes in verbal and visuospatial working memory and (2) whether low verbal and visuospatial working memory in Grade 1 predicts low working memory in Grade 3. Method The study design includes a population-based longitudinal study of 1,802 children (66% uptake from all 2,747 Grade 1 students) at 44 randomly selected primary schools in Melbourne, Australia. Backwards Digit Recall (verbal working memory) and Mister X (visuospatial working memory) screening measures from the Automated Working Memory Assessment (M = 100; SD = 15) were used to assess Grades 1 and 3 (ages 6-7 and 8-9 years) students. Low working memory was defined as ≥1 standard deviation below the standard score mean. Descriptive statistics addressed Aim 1, and predictive parameters addressed Aim 2. Results One thousand seventy (59%) of 1802 Grade 1 participants were reassessed in Grade 3. As expected for typically developing children, group mean standard scores were similar in Grades 1 and 3 for verbal, visuospatial, and overall working memory, but group mean raw scores increased markedly. Compared to "not low" children, those classified as having low working memory in Grade 1 showed much larger increases in both standard and raw scores across verbal, visuospatial, and overall working memory. Sensitivity was very low for Grade 1 low working memory predicting Grade 3 low classifications. Conclusion Although mean changes in working memory standard scores between Grades 1 and 3 were minimal, we found that individual development varied widely, with marked natural resolution by Grade 3 in children who initially had low working memory. This may render brain-training interventions ineffective in the early school year ages, particularly if (as population-based programmes usually mandate) selection occurs within a screening paradigm.

Background Identifying risk and protective factors for language development informs interventions for children with developmental language disorder (DLD). Maternal responsive and intrusive communicative behaviours are associated with language development. Mother-child interaction quality may influence how children use these behaviours in language learning. Aims To identify (1) communicative behaviours and interaction quality associated with language outcomes; (2) whether the association between a maternal intrusive behaviour (directive) and child language scores changed alongside a maternal responsive behaviour (expansion); and (3) whether interaction quality modified these associations. Methods & procedures Language skills were assessed at 24, 36 and 48 months in 197 community-recruited children who were slow to talk at 18 months. Mothers and 24-month-olds were video-recorded playing at home. Maternal praise, missed opportunities, and successful and unsuccessful directives (i.e., whether followed by the child) were coded during a 10-min segment. Interaction quality was rated using a seven-point fluency and connectedness (FC) scale, during a 5-min segment. Linear regressions examined associations between these behaviours/rating and language scores. Interaction analysis and simple slopes explored effect modification by FC. Outcomes & results There was no evidence that missed opportunities or praise were associated with language scores. Higher rates of successful directives in the unadjusted model and unsuccessful directives in the adjusted model were associated with lower 24-month-old receptive language scores (e.g., unsuccessful directives effect size (ES) = -0.41). The association between unsuccessful directives and receptive language was weaker when adjusting for co-occurring expansions (ES = -0.34). Both types of directives were associated with poorer receptive and expressive language scores in adjusted models at 36 and 48 months (e.g., unsuccessful directive and 48-month receptive language, ES = -0.66). FC was positively associated with 24-, 36- and 48-month language scores in adjusted models (e.g., receptive language at 24 months, ES = 0.21, at 48 months, ES = 0.18). Interaction analysis showed the negative association between successful directives and 24-month receptive language existed primarily in poorly connected dyads with low FC levels. Conclusions & implications These findings illustrate the effects of the combined interaction between different maternal communicative behaviours and features of the interaction itself on child language development, and the need to consider both in research and practice. Whilst more intrusive directives were associated with poorer language scores, this association attenuated when adjusting for co-occurring responsive expansions, and the association was strongest for children in lower quality interactions. This work may inform clinical practice by helping clinicians target the most appropriate communicative behaviours for specific mother-child dyads.

The authors were recently notified of an error in the way the child accelerometry data were processed in the Child Health CheckPoint study, and regret that some of the data reported need to be revised. Incorrect cutpoints were used when determining time spent in sedentary behaviour and light physical activity and moderate-to-vigorous physical activity. Details of the error and the steps taken to correct it have been reported elsewhere.1 We received the new, updated variables from CheckPoint and have repeated the analyses for the above paper. The new variables are very highly correlated with the old variables, so the overall message of the paper remains the same. However, (minimal) changes have been made to the manuscript's text and Table 1. Results presented in Table 2 and 4 have been updated. Figure 2 has been redrawn with the corrected data (and appears visually similar). Supplement files have also been updated. The authors would like to apologise for any inconvenience caused. 1. Davies, Sarah; Clifford, Susan; Gillespie, Alanna; Lange, Katherine; Muller, Josh; Wang, Yichao; et al. (2018): Longitudinal Study of Australian Children's Child Health CheckPoint Data Issues Paper – July 2021. Murdoch Childrens Research Institute. Journal contribution. https://doi.org/10.25374/MCRI.5821230.v2.

Background ‘Nudges' subtly alter the social and physical environment to enhance capacity for subconscious, self-interested behaviors, without actively restricting options. Nudges could offer a much-needed strategy to foster sustainable improvements in dietary behaviors and weight status. Aim To systematically review the effectiveness of nudge interventions designed to improve children's dietary behaviors within the family home (or another environment if judged transferable to the home). Methods English-language studies published January 1996–January 2015 were identified in MEDLINE, Embase, CINAHL, PsycINFO and PubMed, followed by dual screening and quality evaluation. Inclusion : controlled studies; nudge with in-home potential. Exclusion : medical health conditions. Results Of the 40 included studies, 33 (83%) showed improvement in dietary behaviors (e.g. more vegetables, smaller unhealthy portions) and were more effective in older children/adolescents. The quality of most studies was rated as weak (43%) or moderate (40%), with only six studies rated strong (15%), reflecting major issues with quality, effectiveness and generalizability. Nudges were typically assessed in isolation and examined immediate effects on behavior. Conclusion Despite substantial methodological limitations and inconsistencies, the literature indicates that nudges may improve children's immediate dietary behaviors. It is unclear whether these improvements could be sustained or affect body weight (PROSPERO, CRD42016036373).

Background Universal newborn hearing screening (UNHS) targets moderate or greater hearing loss. However, UNHS also frequently detects children with mild loss that results in many receiving early treatment. The benefits of this approach are not yet established. We aimed to (i) compare language and psychosocial outcomes between four hearing loss detection systems for children aged 5–8 years with congenital mild–moderate hearing loss; (ii) determine whether age of detection predicts outcomes; and (iii) compare outcomes between children identified via well-established UNHS and the general population. Methods Linear regression adjusted for potential confounding factors was used throughout. Via a quasi-experimental design, language and psychosocial outcomes were compared across four population-based Australian systems of hearing loss detection: opportunistic detection, born 1991–1993, n = 50; universal risk factor referral, born 2003–2005, n = 34; newly established UNHS, born 2003–2005, n = 41; and well-established UNHS, born 2007–2010, n = 21. In pooled analyses, we examined whether age of detection predicted outcomes. Outcomes were similarly compared between the current well-established UNHS system and typically developing children in the Early Language in Victoria Study, born 2003, n = 1217. Results Age at diagnosis and hearing aid fitting fell steadily across the four systems. For moderate losses, mean expressive language (P for trend .05) and receptive vocabulary (P for trend .06) improved across the four systems, but benefit was not obvious for mild losses. In pooled analyses, diagnosis before age six months predicted better language outcomes for moderate losses. Children with mild–moderate losses exposed to well-established UNHS continue to experience expressive language scores well below children in the general population (adjusted mean difference −8.9 points, 95% CI −14.7 to −3.1). Conclusions Treatment arising from UNHS appears to be clearly benefitting children with moderate hearing losses. However, rigorous trials are needed to quantify benefits, versus costs and potential harms, of early aiding of children with mild losses.

Objectives To determine which of multiple early-life exposures predict onset or resolution of overweight/obesity during a 9-year period. Methods Design: longitudinal cohort from three harmonised community-based cohorts enriched for overweight and obesity. Early-life exposures: child—gestational age; delivery; birth weight; breast feeding; solids introduction; baseline body mass index (BMI); waist circumference; diet; activity; global, physical and psychosocial health. Mother—baseline BMI; education; age; neighbourhood disadvantage; concern for child9s weight. Outcome: change in BMI category. Analyses: adjusted logistic regression. Results On average, the 363 children (57% retention) were 6 and 15 years old at baseline and follow-up. Children were classified as ‘never’ overweight/obese (38%), ‘resolving’ overweight/obese (15%), ‘becoming’ overweight/obese (8%) or ‘always’ overweight/obese (39%). Compared with ‘never overweight/obese’ children, odds of ‘becoming overweight/obese’ were greater with higher child (OR 2.33, 95% CI 1.02 to 5.29) and maternal BMI (OR 1.18, CI 1.07 to 1.31), and lower with higher maternal education (OR 0.09, CI 0.02 to 0.34). Compared with ‘always overweight/obese’ children, odds of ‘resolving overweight/obese’ were lower with higher maternal BMI (OR 0.87, CI 0.78 to 0.97), and higher with better child physical health (OR 1.06, CI 1.02 to 1.10) and higher maternal age (OR 1.11, CI 1.01 to 1.22) and education (OR 4.07, CI 1.02 to 16.19). Conclusions Readily available baseline information (child/maternal BMI, maternal age, education and child health) were the strongest predictors of both onset and resolution of overweight/obesity between the primary school and adolescent years. Perinatal, breastfeeding and lifestyle exposures were not strongly predictive. Results could stimulate development of algorithms identifying children most in need of targeted prevention or treatment.

Study ObjectivesPoor sleep patterns in older adults are associated with chromosomal telomere shortening, a marker of cellular senescence. However, studies have relied on self-reported sleep characteristics, with few data for younger individuals. We investigated whether sleep measured via actigraphy was cross-sectionally associated with telomere length in children and midlife adults.MethodsA population-based sample of 1874 11–12 year olds and midlife adults (mean age 44 years, SD 5.1) had biological and physical assessments at centers across Australia in 2015–2016. Sleep characteristics, including duration, onset, offset, day-to-day variability, and efficiency, were derived from actigraphy. Relative telomere length (T/S ratio) was measured by quantitative polymerase chain reaction on genomic DNA from peripheral blood. Multivariable regression models estimated associations, adjusting for prespecified confounders.ResultsBoth sleep and telomere data were available for 728 children and 1070 adults. Mean (SD) T/S ratio was 1.09 (0.55) in children and 0.81 (0.38) in adults. T/S ratio was not predicted by sleep duration (β 0.04, 95% confidence interval [CI] −0.02 to 0.09, p = .16, children; β −0.004, 95% CI −0.03 to 0.02, p = .70, adults) or most other sleep metrics. The only exception was a weak association between later sleep timing (the midpoint of sleep onset and offset) and longer telomeres in adults (β 0.03, 95% CI 0.01 to 0.06, p = .01).ConclusionsObjective sleep characteristics show no convincing associations with telomere length in two largely healthy populations up to at least midlife. Sleep–telomere associations may be a late-life occurrence or may present only with a trigger such as presence of other morbidities.

OBJECTIVE: Telomere length is associated with poorer lung health in older adults, possibly from cumulative risk factor exposure, but data are lacking in pediatric and population-based cohorts. We examined associations of telomere length with lung function in children and mid-life adults. METHODS: Data were drawn from a population-based cross-sectional study of 11 to 12 year-olds and mid-life adults. Lung function was assessed by spirometric FEV1 , FVC, FEV 1 /FVC ratio, and MMEF 25-75 . Telomere length was measured by quantitative polymerase chain reaction from blood and expressed as the amount of telomeric genomic DNA to the beta-globin gene (T/S ratio). Associations of telomere length with spirometric parameters were tested by linear and logistic regression models, adjusting for potential confounders of sex, age, body mass index, socioeconomic position, physical activity, inflammation, asthma, pubertal status, and smoking. RESULTS: Mean T/S ratio was 1.09 (n = 1206; SD 0.55) in children and 0.81 (n = 1343; SD 0.38) in adults. In adults, for every additional unit in T/S ratio, FEV 1 /FVC and MMEF 25-75 z-scores were higher (β 0.21 [95% confidence interval, CI; 0.06-0.36] and 0.23 [95% CI; 0.08-0.38], respectively), and the likelihood of being in the lowest quartile for FEV 1 /FVC and MMEF 25-75 z-scores was lower (odds ratios 0.59 [95% CI, 0.39-0.89] and 0.64 [95% CI, 0.41-0.99], respectively). No evidence of association was seen for adult FEV 1 or FVC, or any childhood spirometric index after adjustments. CONCLUSION: Shorter telomere length showed moderate associations with poorer airflow parameters, but not vital capacity (lung volume) in mid-life adults. However, there was no convincing evidence of associations in children.

The Paediatric Quality of Life InventoryTo develop a mapping algorithm for converting the 23-item PedsQL instrument onto the CHU9D instrument and provide an external validation of two recently published algorithms that might be considered alternatives.Data from children in the Longitudinal Study of Australian Children (LSAC) were used (N = 1801). Six econometric methods were compared to identify the best algorithms, assessed against a series of goodness-of-fit criteria. The same data and goodness-of-fit criteria were used in the external validation exercise for previously published mapping algorithms.The optimal mapping algorithm was identified, which used PedsQL dimension scores to predict the CHU9D utilities. It performed well against standard goodness-of-fit tests. The external validation exercise revealed the recently published alternative algorithms also performed relatively well.The identified mapping algorithms can be used to facilitate cost-utility analysis in comparable populations when only the PedsQL instrument is available. Results from this population indicate the algorithms identified in this paper are well suited for estimating CHU9D self-report utilities when the full 23-item self-report PedsQL instrument has been used.

Objective A translational trial evaluated the effectiveness of screening for inhibited childhood temperament, followed by a preventive parenting program -Cool Little Kids. This study determined the cost-effectiveness from societal and health sector perspectives using trial data. Method Resources to deliver the screening and parenting sessions were determined from study records. Parents completed a questionnaire reporting resources used at one-year follow-up. Standard Australian unit costs were applied. Clinical outcomes for children and parental quality adjusted life-years (QALYs) were used to calculate incremental cost-effectiveness ratios (ICERs). Results Total societal costs were lower, but non-significant for the intervention compared to the control group (mean difference -$500 p = 0.937). Total health sector costs were significantly greater (mean difference $1,956; p = 0.015). The intervention led to significantly fewer internalising symptoms (Strengths and Difficulties Questionnaire (SDQ)-emotional difficulties adjusted mean difference −0.5; p = 0.006), fewer children with SDQ-emotional symptoms in the abnormal range (24.2 % vs. 33.0 % p = .014) and fewer with diagnosed anxiety (44.2 % vs. 50.2 % p = 0.427). From the societal perspective, the intervention would likely be cost-effective. Health sector ICERs were $1,171/SDQ-emotional symptom decrease, $51/abnormal SDQ avoided and $77/anxiety case avoided. Conclusions This economic analysis alongside an implementation study provides an early indication that Cool Little Kids may be cost-effective.

BackgroundMuscle weakness and muscle wasting can be a consequence of aging (sarcopenia) and neuromuscular disorders (NMD). Genome-wide association (GWA) studies have identified genetic variants associated with grip strength (GS, an inverse measure of muscle weakness) and NMD (multiple sclerosis (MS), myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS)). However, how these variants contribute to the muscle weakness caused by aging or NMD remains obscure.MethodsWe have integrated GS and NMD associated SNPs in a multimorbid analysis that leverages high-throughput chromatin interaction (Hi-C) data and expression quantitative trait loci (eQTL) data to identify allele-specific gene regulation (i.e. eGenes). Pathways and shared drug targets that are enriched by colocalised eGenes were then identified using pathway and drug enrichment analysis.ResultsWe identified gene regulatory mechanisms (eQTL-eGene effects) associated with GS, MG, MS and ALS. The eQTLs associated with GS regulate a subset of eGenes that are also regulated by the eQTLs of MS, MG and ALS. Yet, we did not find any eGenes commonly regulated by all four phenotypes associated eQTLs. By contrast, we identified three pathways (mTOR signaling, axon guidance, and alcoholism) that are commonly affected by the gene regulatory mechanisms associated with all four phenotypes. 13% of the eGenes we identified were known drug targets, and GS shares at least one druggable eGene and pathway with each of the NMD phenotypes.ConclusionsCollectively, these findings identify significant biological overlaps between GS and NMD, demonstrating the potential for spatial genetic analysis to identify mechanisms underlying muscle weakness due to aging and NMD.

Background High‐throughput nuclear magnetic resonance profiling of circulating metabolites is suggested as an adjunct for cardiovascular risk evaluation. The relationship between metabolites and subclinical atherosclerosis remains unclear, particularly among children. Therefore, we examined the associations of metabolites with carotid intima‐media thickness ( cIMT ) and arterial pulse wave velocity ( PWV ). Methods and Results Data from two independent population‐based studies was examined; (1) cross‐sectional associations with cIMT and PWV in 1178 children (age 11–12 years, 51% female) and 1316 parents (mean age 45 years, 87% female) from the CheckPoint study (Australia); and (2) longitudinal associations in 4249 children (metabolites at 7–8 years, PWV at 10–11 years, 52% female), and cross‐sectional associations in 4171 of their mothers (mean age 48 years, cIMT data) from ALSPAC (The Avon Longitudinal Study of Parents and Children; UK ). Metabolites were measured by the same nuclear magnetic resonance platform in both studies, comprising of 69 biomarkers. Biophysical assessments included body mass index, blood pressure, cIMT and PWV . In linear regression analyses adjusted for age, sex, body mass index, and blood pressure, there was no evidence of metabolite associations in either children or adults for cIMT at a 10% false discovery threshold. In CheckPoint adults, glucose was positively, and some high‐density lipoprotein‐cholesterol derived measures and amino acids (glutamine, histidine, tyrosine) inversely associated with PWV. Conclusions These data suggest that in children circulating metabolites have no consistent association with cIMT and PWV once adjusted for body mass index and blood pressure. In their middle‐aged parents, some evidence of metabolite associations with PWV were identified that warrant further investigation.

Objective Intermediate phenotypes of microcirculation (retinal microvascular caliber) are associated with cardiovascular (CV) risk factors and independently predict CV events. However, the effect of microcirculation variation on the vascular system is unclear. We conducted a systematic review and meta-analysis of observational studies to quantify associations of retinal microvascular caliber (arteriolar, venular caliber, arteriole-to-venule ratio) and preclinical CV measures (large arterial function and structure). Methods We identified studies in MEDLINE, EMBASE, and PubMed (1946 to March 2018) studying (a) general population samples and (b) patients with cardiometabolic disease. Study-specific correlation estimates were combined into meta-analysis where possible. Results Of 1294 studies identified, 26 met inclusion criteria (general population 16, patients 10), of which five studies were included in meta-analysis. Most studied middle-aged adults cross-sectionally, with one childhood study. Large arterial function and structure were predominantly assessed by pulse wave velocity and carotid intima-media thickness, respectively. Only arteriolar caliber was consistently associated with arterial function and structure, with stronger associations observed in cardiometabolic patients. Narrower (worse) arteriolar caliber was associated with faster (poorer) pulse wave velocity (correlation coefficient (r) -0.17, 95% CI -0.25 to -0.10) and greater (poorer) intima-media thickness (r -0.05, 95%CI -0.09 to -0.02) across all adult participants. Conclusions Retinal arteriolar, but not venular caliber, was modestly associated with large arterial function and weakly associated with large arterial structure, with stronger evidence in patients with cardiometabolic disease. This suggests that preclinical changes in large arteries and the microcirculation have some shared but mainly unique pathways to associate with cardiovascular disease.

ObjectivesTo describe the epidemiology and parent–child concordance of vascular function in a population-based sample of Australian parent–child dyads at child age 11–12 years.DesignCross-sectional study (Child Health CheckPoint), nested within a prospective cohort study, the Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven major Australian cities and eight regional towns or home visits, February 2015–March 2016.ParticipantsOf all participating CheckPoint families (n=1874), 1840 children (49% girls) and 1802 parents (88% mothers) provided vascular function data. Survey weights and methods were applied to account for LSAC’s complex sample design and clustering within postcodes and strata.Outcome measuresThe SphygmoCor XCEL assessed vascular function, generating estimates of brachial and central systolic blood pressure and diastolic blood pressure, central pulse pressure, augmentation index and carotid–femoral pulse wave velocity. Pearson’s correlation coefficients and multivariable linear regression models estimated parent–child concordance.ResultsHypertension was present in 3.9% of children and 9.0% of parents. Mean child and parent values for augmentation index were 4.5% (SD 11.6) and 21.3% (SD 12.3), respectively, and those for carotid–femoral pulse wave velocity were 4.48 m/s (SD 0.59) and 6.85 m/s (SD 1.14), respectively. Parent–child correlation for brachial systolic blood pressure was 0.20 (95% CI 0.15 to 0.24), brachial diastolic blood pressure 0.21 (95% CI 0.16 to 0.26), central systolic blood pressure 0.21 (95% CI 0.16 to 0.25), central diastolic blood pressure 0.21 (95% CI0.17 to 0.26), central pulse pressure 0.19 (95% CI 0.14 to 0.24), augmentation index 0.28 (95% CI 0.23 to 0.32) and pulse wave velocity 0.22 (95% CI 0.18 to 0.27).ConclusionsWe report Australian values for traditional and more novel vascular function markers, providing a reference for future population studies. Cross-generational concordance in multiple vascular function markers is already established by age 11–12 years, with mechanisms of heritability remaining to be explored.

ObjectivesOverweight and obesity remain at historically high levels, cluster within families and are established risk factors for multiple diseases. We describe the epidemiology and cross-generational concordance of body composition among Australian children aged 11–12 years and their parents.DesignThe population-based cross-sectional Child Health CheckPoint study, nested within the Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven major Australian cities and eight regional cities, or home visits; February 2015–March 2016.ParticipantsOf all participating CheckPoint families (n=1874), body composition data were available for 1872 children (49% girls) and 1852 parents (mean age 43.7 years; 88% mothers), including 1830 biological parent-child pairs.MeasuresHeight, weight, body mass index (BMI), waist circumference and waist-to-height ratio for all participants; body fat and fat-free mass by four-limb bioimpedence analysis (BIA) at assessment centres, or body fat percentage by two-limb BIA at home visits. Analysis: parent-child concordance was assessed using (i) Pearson’s correlation coefficients, and (ii) partial correlation coefficients adjusted for age, sex and socioeconomic disadvantage. Survey weights and methods accounted for LSAC’s complex sample design.Results20.7% of children were overweight and 6.2% obese, as were 33.5% and 31.6% of parents. Boys and girls showed similar distributions for all body composition measures but, despite similar BMI and waist-to-height ratio, mothers had higher proportions of total and truncal fat than fathers. Parent-child partial correlations were greatest for height (0.37, 95% CI 0.33 to 0.42). Other anthropometric and fat/lean measures showed strikingly similar partial correlations, ranging from 0.25 (95% CI 0.20 to 0.29) for waist circumference to 0.30 (95% CI 0.25 to 0.34) for fat-free percentage. Whole-sample and sex-specific percentile values are provided for all measures.ConclusionsExcess adiposity remains prevalent in Australian children and parents. Moderate cross-generational concordance across all measures of leanness and adiposity is already evident by late childhood.

Objectives‘Growing Up in Australia: The Longitudinal Study of Australian Children’ (LSAC) is Australia's only nationally representative children’s longitudinal study, focusing on social, economic, physical and cultural impacts on health, learning, social and cognitive development. LSAC's first decade collected wide-ranging repeated psychosocial and administrative data; here, we describe the Child Health CheckPoint, LSAC’s dedicated biophysical module.Design, setting and participantsLSAC recruited a cross-sequential sample of 5107 infants aged 0–1 year and a sample of 4983 children aged 4–5 years in 2004, since completing seven biennial visits. CheckPoint was a cross-sectional wave that travelled Australia in 2015–2016 to reach LSAC’s younger cohort at ages 11–12 years between LSAC waves 6 and 7. Parent–child pairs participated in comprehensive assessments at 15 Assessment Centres nationwide or, if unable to attend, a shorter home visit.MeasuresCheckPoint’s intergenerational, multidimensional measures were prioritised to show meaningful variation within normal ranges and capture non-communicable disease (NCD) phenotype precursors. These included anthropometry, physical activity, fitness, time use, vision, hearing, and cardiovascular, respiratory and bone health. Biospecimens included blood, saliva, buccal swabs (also from second parent), urine, hair and toenails. The epidemiology and parent–child concordance of many measures are described in separate papers.Results1874 (54% of eligible) parent–child pairs and 1051 second parents participated. Participants' geographical distribution mirrored the broader Australian population; however, mean socioeconomic position and parental education were higher and fewer reported non-English-speaking or Indigenous backgrounds. Application of survey weights partially mitigates that the achieved sample is less population representative than previous waves of LSAC due to non-random attrition. Completeness was uniformly high for phenotypic data (>92% of eligible), biospecimens (74%–97%) and consent (genetic analyses 98%, accessing neonatal blood spots 97%, sharing 96%).ConclusionsCheckPoint enriches LSAC to study how NCDs develop at the molecular and phenotypic levels before overt disease emerges, and clarify the underlying dimensionality of health in childhood and mid-adulthood.

Background Telomere length has been inversely associated with cardiovascular disease in adulthood, but its relationship to preclinical cardiovascular phenotypes across the life course remains unclear. We investigated associations of telomere length with vascular structure and function in children and midlife adults. Methods and Results Population‐based cross‐sectional CheckPoint (Child Health CheckPoint) study of 11‐ to 12‐year‐old children and their parents, nested within the LSAC (Longitudinal Study of Australian Children). Telomere length (telomeric genomic DNA [T]/β‐globin single‐copy gene [S] [T/S ratio]) was measured by quantitative polymerase chain reaction from blood‐derived genomic DNA. Vascular structure was assessed by carotid intima‐media thickness, and vascular function was assessed by carotid‐femoral pulse‐wave velocity and carotid elasticity. Mean (SD) T/S ratio was 1.09 (0.55) in children (n=1206; 51% girls) and 0.81 (0.38) in adults (n=1343; 87% women). Linear regression models, adjusted for potential confounders, revealed no evidence of an association between T/S ratio and carotid intima‐media thickness, carotid‐femoral pulse‐wave velocity, or carotid elasticity in children. In adults, longer telomeres were associated with greater carotid elasticity (0.14% per 10–mm Hg higher per unit of T/S ratio; 95% CI, 0.04%–0.2%; P =0.007), but not carotid intima‐media thickness (−0.9 μm; 95% CI, −14 to 13 μm; P =0.9) or carotid‐femoral pulse‐wave velocity (−0.10 m/s; 95% CI, −0.3 to 0.07 m/s; P =0.2). In logistic regression analysis, telomere length did not predict poorer vascular measures at either age. Conclusions In midlife adults, but not children, there was some evidence that telomere length was associated with vascular elasticity but not thickness. Associations between telomere length and cardiovascular phenotypes may become more evident in later life, with advancing pathological changes.

Diet and lifestyle are vital to population health, but their true contribution is difficult to quantify using traditional methods. Nutrient-health relations are typically based on epidemiological associations that are assessed at the population level, traditionally using self-reported dietary and lifestyle data. Unfortunately, such measures are inherently inaccurate. New technologies such as metabolomics can measure nutritional and micronutrient profiles in body fluids, providing objective evaluation of nutritional status. A critical step toward accurate health prediction models would be the building of integrated repositories of nutritional measures combining subjective methods of reporting with objective metabolomics profiles and precise phenotypic data. Here we outline a roadmap to achieve this goal and discuss both the advantages and risks of this approach. We also highlight the uncertain associations between the complexity of high-dimensional data generated in 'omics research (along with the public confusion this may engender) and the rapid adoption of 'omics approaches by nutrition and health companies to develop nutritional products and services.

OBJECTIVES: The purpose of this study is to determine if telomere length (a biomarker of aging) is associated with hearing acuity in mid-childhood and midlife. DESIGN: The study was based on the population-based cross-sectional study within the Longitudinal Study of Australian Children with telomere length and audiometry data. We calculated high Fletcher Index (hFI, mean threshold of 1, 2, and 4 kHz), defining hearing loss as threshold >15 dB HL (better ear). Linear and logistic regression analyses quantified associations of telomere length with continuous hearing threshold and binary hearing loss outcomes, respectively. RESULTS: One thousand one hundred ninety-five children (mean age 11.4 years, SD 0.5) and 1334 parents (mean age 43.9 years, SD 5.1) were included in analyses. Mean (SD) telomere length (T/S ratio) was 1.09 (0.55) for children and 0.81 (0.38) for adults; hFI (dB HL) was 8.0 (5.6) for children and 13.1 (7.0) for adults, with 8.4% and 25.9%, respectively, showing hearing loss.Telomere length was not associated with hearing threshold or hearing loss in children (hFI: OR, 0.99; 95% confidence interval, 0.55 to 1.78) or adults (hFI: OR, 1.35; 95% confidence interval, 0.81 to 2.25). CONCLUSIONS: Telomere length was not associated with hearing acuity in children or their midlife parents.

Background Lifelong inflammation – known to be associated with many non-communicable diseases – has not been thoroughly investigated in hearing. We aimed to determine if glycoprotein A (GlycA), a novel biomarker of chronic inflammation, is associated with hearing acuity in mid-childhood and mid-life. Methods Population-based cross-sectional study within the Longitudinal Study of Australian Children with plasma GlycA and audiometry data (1169 children and 1316 parents). We calculated high Fletcher Index (mean threshold across 1, 2 and 4 kHz), defining hearing loss as threshold >15 decibel hearing level (dB HL) (better ear). Linear/logistic regression quantified associations of GlycA with hearing threshold/loss. Results Mean [standard deviation (SD)] high Fletcher Indices (dB HL) were 8.0 (5.7) for children and 13.1 (6.9) for adults, with 8.7% and 26.1% respectively showing hearing loss. 1-SD rise in GlycA (children 0.13 mmol/L, adults 0.17 mmol/L) predicted higher hearing thresholds for the lower individual frequencies [1 kHz: children β 0.8, 95% confidence interval (CI) 0.3–1.3; adults β 0.8, 95% CI 0.2–1.4]. This same pattern was evident for the high Fletcher Index (children β 0.7, 95% CI 0.3–1.1; adults β 0.8, 95% CI 0.3–1.4). This translated into 1-SD rise in GlycA predicting adult hearing loss [odds ratio (OR) 1.2, 95% CI 1.0–1.5] with similar but attenuated patterns in children. Conclusions GlycA is associated with poorer hearing by mid-childhood. This potentially reframes hearing loss as a life-course condition with inflammatory antecedents common to other non-communicable diseases. Replication and mechanistic studies could inform causal inference and early prevention efforts.

ObjectiveTo investigate the associations of hearing thresholds and slight to mild hearing loss with academic, behavioural and quality of life outcomes in children at a population level.MethodsDesign and participants:children aged 11–12 years in the population-based cross-sectional Child Health CheckPoint study within the Longitudinal Study of Australian Children. Audiometry:mean hearing threshold across 1, 2 and 4 kHz (better and worse ear); slight/mild hearing loss (threshold of 16–40 decibels hearing loss (dB HL)). Outcomes: National Assessment Program – Literacy and Numeracy, language, teacher-reported learning, parent and teacher reported behaviour and self-reported quality of life. Analysis:linear regression quantified associations of hearing threshold/loss with outcomes.ResultsOf 1483 children (mean age 11.5 years), 9.2% and 13.1% had slight/mild bilateral and unilateral hearing loss, respectively. Per SD increment in better ear threshold (5.7 dB HL), scores were worse on several academic outcomes (eg, reading 0.11 SD, 95% CI 0.05 to 0.16), parent-reported behaviour (0.06 SD, 95% CI 0.01 to 0.11) and physical (0.09 SD, 95% CI 0.04 to 0.14) and psychosocial (0.06 SD, 95% CI 0.01 to 0.11) Pediatric Quality of Life Inventory (PedsQL). Compared with normally hearing children, children with bilateral slight/mild losses scored 0.2–0.3 SDs lower in sentence repetition, teacher-reported learning and physical PedsQL but not other outcomes. Similar but attenuated patterns were seen in unilateral slight/mild losses.ConclusionsHearing thresholds and slight/mild hearing loss showed small but important associations with some child outcomes at 11–12 years. Justifying hearing screening or intervention at this age would require better understanding of its longitudinal and indirect effects, alongside effective management and appropriate early identification programmes.

Objectives: To evaluate how the reallocation of time between sleep, sedentary time, light, and moderate-vigorous activities is associated with children's body composition. Study design: Population-based cross-sectional Child Health CheckPoint within the Longitudinal Study of Australian Children (n = 938 11-12 year-olds, 50% boys). Twenty-four hour activity composition via accelerometry (minutes/day of sleep, sedentary time, light, and moderate-to-vigorous physical activity [MVPA]) and 3-part body composition (percentage truncal fat, percentage nontruncal fat, and percentage fat-free mass) via bioelectrical impedance analysis were measured. We estimated differences in 3-part body composition associated with the incremental reallocation of time between activities, using dual-compositional regression models adjusted for sex, age, puberty, and socioeconomic position. Results: Reallocation of time between MVPA and any other activity was strongly associated with differences in body composition. Adverse body composition differences were larger for a given MVPA decrease than were the beneficial differences for an equivalent MVPA increase. For example, 15 minutes less MVPA (relative to remaining activities) was associated with absolute percentage differences of +1.7% (95% CI 1.2; 2.4) for truncal fat, +0.8% (0.6; 1.2) for nontruncal fat, and −2.6% (−3.5; −1.9) for fat-free mass, and a 15-minute increase was associated with −0.7% (−0.9; −0.5) truncal fat, −0.4% (−0.5; −0.3) nontruncal fat, and +1.1% (0.9; 1.5) fat-free mass. Reallocations between sleep, sedentary time, and light physical activity were not associated with differences in body composition. Conclusions: Preventing declines in MVPA during inactive periods (eg, holidays) may be an important intervention goal. More MVPA, instead of other activities, may benefit body composition Refereed/Peer-reviewed

Objectives: Snacks contribute to overconsumption of energy-dense foods and thence obesity. Previous studies in this area are limited by self-reported data and small samples. In a large population-based cohort of parent–child dyads, we investigated how modification of pre-packaged snack food, i.e. (a) item quantity and variety, and (b) dishware (boxed container) size affected intake. Methods: Design: Randomized trial nested within the cross-sectional Child Health CheckPoint of the Longitudinal Study of Australian Children, clustered by day of visit. Sample: 1299 11–12 year olds, 1274 parents. Exposure: 2 × 2 manipulation of snack box container size and item quantity/variety: (1) small box, few items, (2) large box, few items, (3) small box, more items, (4) large box, more items. Procedure: Participants received a snack box during a 15 min break within their 3.5 h visit; any snacks remaining were weighed. Outcomes: Consumed quantity (grams) and energy intake (kilojoules). Analyses: Unadjusted linear regression. Results: Children who were offered a greater quantity and variety of snack items consumed considerably more energy and a slightly higher food mass (main effect for energy intake: 349 kJ, 95% CI 282–416, standardized mean difference (effect size) 0.66; main effect for mass: 10 g, 95% CI 3–17, effect size 0.17). In contrast, manipulating box size had little effect on child consumption, and neither box size nor quantity/variety of items consistently affected adults’ consumption. Conclusion: In children, reducing the number and variety of snack food items available may be a more fruitful intervention than focusing on container or dishware size. Effects observed among adults were small, although we could not exclude social desirability bias in adults aware of observation. Refereed/Peer-reviewed

Background: Short sleep duration in childhood has often been linked with obesity in later childhood or adolescence. However, whether infant sleep duration affects body composition trajectories and cardiovascular health through to mid-adolescence remains unknown. Methods: Participants were 336 adolescents from a community-based prospective birth cohort in Melbourne, Australia. Mothers completed 24-hour time diaries, including infant sleep in 5-minute intervals at ages 2, 4, and 12 months. BMI and body composition outcomes were measured 6-monthly between 4 and 6.5 years and at 10 and 14 years. Cardiovascular outcomes at 14 years comprised blood pressure, pulse wave velocity, retinal arteriole-to-venule ratio, and carotid intima-media thickness. We used multivariable linear regression and multinomial logistic regression analyses adjusted for sex, age, BMI at birth, gestational age, ethnicity, maternal education, maternal BMI, and neighborhood socioeconomic position. Results: At 2 months, infants slept on average 14.1 hours [standard deviation (SD) 1.9], decreasing to 13.4 hours (SD 2.0) by 12 months. We observed no associations between the different sleep duration time points in infancy and later BMI or body composition. Moreover, a shorter sleep duration did not increase the odds of being on a high body composition trajectory compared with longer sleep (e.g., odds ratio per hour of sleep at 4 months is 0.85, 95% confidence interval 0.65-1.11). Infant sleep duration was also not associated with cardiovascular function or large or small artery structure at 14 years of age. Conclusions: We found no evidence that sleep duration very early in life affects adolescent body composition or cardiovascular health.

We would like to acknowledge Professor Daniel Shaw, Bibi Gerner, Amelia Hicks, Daisy Grinter, Amy Loughman and Kate Lycett for their help to commence this study in 2010, and their contribution to data collection and intervention delivery. We would also like to thank all the maternal child health nurses from the nine participating LGAs (City of Casey, Bayside City Council, Darebin City Council, Hobsons Bay City Council, City of Port Phillip, Mornington Peninsula Shire, Manningham City Council, Knox City Council and Yarra Ranges Shire Council) and the families taking part. We would like to thank the parenting experts at the Parenting Research Centre who co-facilitate the Toddlers Without Tears parenting groups. Murdoch Childrens Research Institute research is supported by the Victorian Government's Operational Infrastructure Support Programme and funded by Australian National Health and Medical Research Council (NHMRC) Partnership 46525 and community partners: Victorian Department of Education and Early Childhood, Victorian Department of Health and the Municipal Associations of Victoria. The researchers acknowledge support of the Australian NHMRC for salary support through Early Career Fellowship 1035100 (LG), Career Development Awards 607351 (HH) and 546405 (MW) and Capacity Building Grants 425855 (LG) and 436914 (HH, JB and OU). OU is supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health in England.

Aim In adult medicine, rates of investigation and prescribing appear to be increasing. Such information is lacking for paediatrics. We audited Australian paediatricians’ practices in 2013 to determine changes since 2008 in: (i) conditions seen; (ii) consultation duration; (iii) imaging and pathology ordered; and (iv) prescribing. Methods This is a patient-level prospective audit of paediatricians’ secondary care practice. Between November and December 2013, members of the Australian Paediatric Research Network were invited to complete standardised forms for 100 consecutive patients or all patients seen over 2 weeks, whichever was completed first. Main measures: diagnoses, consultation duration, pathology and/or imaging investigations ordered, rate of medication prescription. Analyses: hierarchical linear modelling clustered at the paediatrician level. Results One hundred and eighty paediatricians (48% of those eligible) contributed 7102 consultations. The proportion of developmental/behavioural conditions rose from 48% (SD 31%) to 60% (SD 30%) in new and 54% (SD 28%) to 66% (SD 28%) in review consultations in 2013 compared with 2008. More paediatricians reported diagnoses of autism spectrum disorder (39–56%, P = 0.002), attention-deficit/hyperactivity disorder (47–55%, P = 0.05) and intellectual disability (18–36%, P = 0.001) in first consultations. Mean consultation duration and pathology/imaging ordering rates were stable. Prescribing rates increased from 39 to 45% of consultations for the top 10 new diagnoses and from 57 to 68% of consultations for the top 10 review diagnoses. Conclusions Paediatricians are seeing more children with developmental–behavioural conditions, prescribing more and demonstrating wide variation in their practice. The latter suggests both over- and under-treatment.