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OBJECTIVES: Hearing loss is one of the most prevalent congenital disorders among children. Many countries have implemented Universal Newborn Hearing Screening (UNHS) for early diagnosis and treatment of hearing loss. Despite widespread implementation, the value for money of UNHS is unclear due to lack of cost and outcomes data from rigorous study designs. The objective of this research is to conduct a within-study cost-effectiveness analysis of UNHS compared with targeted screening (targeting children with risk factors of hearing loss) from the Australian healthcare system perspective. This evaluation is the first economic evaluation to assess the cost-effectiveness of UNHS compared to targeted screening using real-world data from a natural experiment. DESIGN: The evaluation assumed the Australian healthcare system perspective and considered a time horizon of five years. Utilities were estimated using responses to the Health Utilities Index Mark III. Screening costs were estimated based on the Victorian Infant Hearing Screening Program. Ongoing costs were estimated based on administrative data, while external data sources were used to estimate costs related to hearing services. Missing data were handled using the multiple imputation method. Outcome measures included Quality-adjusted Life Years (QALYs) and four language and communication-related outcomes: Peabody Picture Vocabulary Test, Wechsler Nonverbal scale of ability, Progressive Achievement Test, and comprehensive, expressive, and total language scores based on the Preschool Language Scale. RESULTS: On average, the UNHS cost an extra Australian dollar (A$)22,000 per diagnosed child and was associated with 0.45 more QALYs per diagnosed child compared with targeted screening to 5 years, resulting in an Incremental Cost-Effectiveness Ratio (ICER) of A$48,000 per QALY gained. Higher screening costs in the UNHS arm were the main drivers of the results. The ICERs for language outcomes lay between A$3,900 (for expressive language score) and A$83,500 per one-point improvement in language score (i.e., for Wechsler Nonverbal scale of ability). UNHS had a 69% probability of being more cost-effective compared to targeted screening at a willingness to pay threshold of A$60,000 per QALY gained. ICERs were most sensitive to the screening costs. CONCLUSIONS: The evaluation demonstrated the usefulness of a within-study economic evaluation to understand the value for money of the UNHS program in the Australian context. Findings from this evaluation suggested that screening costs were the key driver of cost-effectiveness results. Most outcomes were not significantly different between UNHS and targeted screening groups. The ICER may be overestimated due to the short follow-up period. Further research is warranted to include long-term resource use and outcome data, late diagnosis, transition and remission between severity levels, and timing of diagnosis and treatment.

Purpose: To examine (1) the association between low language (LL) and caregiver's health-related quality of life (HRQoL), (2) whether persistent LL affects caregiver's HRQoL and (3) whether child social-emotional-behavioural (SEB) difficulties attenuates the association between LL and caregiver's HRQoL.Method: Data were from the Early Language in Victoria Study (ELVS) and the Longitudinal Study of Australian Children (LSAC). Caregiver's HRQoL was measured using the EuroQoL-5 dimensions and the Assessment of Quality of Life-8 dimensions. Language ability was determined using the Clinical Evaluation of Language Fundamentals (CELF)-Preschool-2nd or 4th edition (ELVS) and the Peabody Picture Vocabulary Test-3rd edition or CELF-4 recalling sentences subscale (LSAC). Child SEB difficulties were measured using the Strengths and Difficulties Questionnaire. Multivariable linear regression was used for the analysis.Result: At 11-12 years, an association between LL and reduced caregiver's HRQoL was found in LSAC, but not in ELVS. Persistent LL from 4-11 years seemed to not affect caregivers' HRQoL in either cohort. Child SEB difficulties attenuated the association between caregiver's HRQoL and LL.Conclusion: Both LL and SEB difficulties contributed to reduced caregiver's HRQoL at children age 11-12 years. Interventions supporting children with LL should consider caregiver's well-being in provision of care that meets families' needs.

‘Digital Mega-Studies’ are entirely or extensively digitised, longitudinal, population-scale initiatives, collecting, storing, and making available individual-level research data of different types and from multiple sources, shaped by technological developments and unforeseeable risks over time. The Australian ‘Gen V’ project exemplifies this new research paradigm. In 2019, we undertook a multidisciplinary, multi-stakeholder process to map Digital Mega-Studies’ key characteristics, legal and governance challenges and likely solutions. We conducted large and small group processes within a one-day symposium and directed online synthesis and group prioritisation over subsequent weeks. We present our methods (including elicitation, affinity mapping and prioritisation processes) and findings, proposing six priority governance principles across three areas—data, participation, trust—to support future high-quality, large-scale digital research in health.

Focus and outcomes for participants “Children are our future” - the wellbeing of our future adults will influence the future of the world. However, this generation of children and mid-life adults face increasing rates of complex health and development problems, and many of them are preventable. Traditional research approaches are not keeping pace with need. Discovery and testing of solutions is blocked by the lack of fast, cheap, large-scale, low burden and effective ways to conduct research for the population and its many subgroups. Innovation in epidemiological methods is required to deliver large scale studies of unprecedented scale and scope. These will support research that enables better prevention, prediction and treatment – all of which are needed to solve today’s pressing child and adult health problems. This 90-minute symposium will draw on the forthcoming Generation Victoria (GenV) to illustrate innovative epidemiological methods established in its foundation phase to enable large-scale studies. GenV is designed to address physical, mental and social issues experienced during childhood and mid-adulthood, as well as the antecedents of a wide range of diseases of ageing. Parents of all newborns (estimated. 170,000) in the state of Victoria (population 6.5 million), Australia, will be approached from 2021 for two full years. Following consent, GenV proposes to bank biosamples collected during routine care, link to administrative and clinical data, and directly collect parent and child data using interactive electronic interfaces with the potential for face-to-face assessment during the school years. Encompassing clinical trials, registries, health services and geospatial as well as discovery research, GenV’s initial focus will be on pregnancy and newborns, reaching into regional and rural communities and traditionally hard-to-reach groups in sizeable numbers. Permission will be sought to link trials, registries, and health services research with existing pre- and post-birth administrative and electronic health record datasets, and also to bank biospecimens collected during routine care. We will discuss why innovation is essential to the next wave of large-scale studies such as GenV, and share practical examples of method innovations being developed within GenV. We will forecast the opportunities and challenges of large-scale studies for improving wellbeing and reducing the disease burden with children and adults. Focus: Outcomes: Rationale for the symposium, including for its inclusion in the Congress The future wellbeing and productivity of our societies depend on wellbeing and good health of our children and adults. However, today’s children and mid-life adults are facing both old and new challenges. Traditional research approaches have largely failed to deliver progress towards solving these challenges. For example, most existing cohorts only allow for observational follow up, and children are greatly under-represented in gold-standard clinical trials, which leads to less evidence to children’s treatment and prevention. Multi-purpose, low burden, high up-take innovative large studies are required to address these gaps. GenV seeks to generate translatable evidence (prediction, prevention, treatments, and services) to improve future wellbeing and reduce the future disease burden of children and adults. It will allow researchers, clinicians and policy makers to better understand the issues affecting Victorian children and their families with greater speed and precision, and therefore outcomes be translated more quickly into practice. Also it will help facilitate an environment where researchers, clinicians, policy makers, and other organisations can come together to enact change for future generations’ wellbeing. With this symposium, we intend to share our reflections on how the scale of cohort studies is changing, and showcase new trends in research design. The GenV team will then show how we practically achieve innovation in large-study methodology and design, with the aim of encouraging others to think ambitiously at large-scale. We will share our intentions and rationale for these innovations as well as the challenges. The symposium is designed to spark a discussion with the audience, seeking their reflections and suggestions on shaping our innovations. Finally, we aim to encourage researchers (especially early career researchers) to exchange their vision and views on innovations and methods for cohort studies. Presentation program (90 minutes) Names of presenters Prof Melissa Wake, Dr Susan Clifford, Dr Yanhong Jessika Hu, A/Prof Jo Said, Dr Joan Leong, Dr Suzanne Mavoa.

Background Inflammation is one of key mechanisms linking childhood experiences to later chronic disease risk. Childhood adversity is associated with inflammation, but little is known about positive experiences. We examine how adverse and positive experiences are associated with inflammatory markers in late childhood, and whether they have an interaction effect. Methods Data sources: Longitudinal Study of Australian Children (LSAC; N = 1237) and Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3488). Exposures: Adverse and positive experiences assessed from 0 to 11 (LSAC) and 0-14 years (ALSPAC). Adversity indicators included parent legal problems, family violence, mental illness, substance abuse, harsh parenting, parental divorce, neighbourhood violence, family member death, and bullying victimization. Positive experiences included positive parenting practice, trusting and supportive relationships, supportive neighbourhood and home learning environments, social engagement and enjoyment. Outcomes: Inflammation quantified by high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA). Analyses: Linear regression was used to estimate relative change in inflammatory markers, adjusted for sociodemographics. Outcomes were log-transformed. Results Exposure to adversity was associated with higher levels of inflammation (e.g., CRP: β = 8.8%, 95% CI= -16.5% to 34.2% in LSAC), whereas exposure to positive experiences was associated with lower levels (e.g., CRP: β=-18.9%, 95% CI= -45.8% to 7.9% in LSAC), after adjusting for sociodemographics. There was no interaction effect of adverse and positive experiences on inflammation. Conclusions Adverse and positive experiences have independent and small effects on children’s inflammation across two cohorts. Key messages Positive experiences are critical to inform interventions to improve inflammatory outcomes for children who face adversity.

Fat-soluble vitamers (FSV) are a class of diverse organic substances important in a wide range of biological processes, including immune function, vision, bone health, and coagulation. Profiling FSV in parents and children enables insights into gene-environment contributions to their circulating levels, but no studies have reported on the population epidemiology of FSV in these groups as of yet. In this study, we report distributions of FSV, their parent-child concordance and variation by key characteristics for 2490 children (aged 11–12 years) and adults (aged 28–71 years) in the Child Health CheckPoint of the Longitudinal Study of Australian Children. Ten A, D, E and K vitamers were quantified using a novel automated LC-MS/MS method. All three K vitamers (i.e., K1, MK-4, MK-7) and 1-α-25(OH)2D3 were below the instrument detection limit and were removed from the present analysis. We observed a strong vitamer-specific parent-child concordance for the six quantifiable A, D and E FSVs. FSV concentrations all varied by age, BMI, and sex. We provide the first cross-sectional population values for multiple FSV. Future studies could examine relative genetic vs. environmental determinants of FSV, how FSV values change longitudinally, and how they contribute to future health and disease.

Background and aims Adverse changes to the microcirculation play an important role in the pathogenesis of cardiovascular disease (CVD), and inflammation is a key causal mechanism. We investigated the relationship between inflammatory markers and retinal microvascular parameters. Methods Studies up to April 2021 were identified in Medline, Embase and PubMed with the following terms: retinal microvascular parameters, inflammatory markers, and observational studies. Correlation coefficients of inflammatory markers and retinal vascular caliber were pooled using the random-effects model. Results Of 4783 studies identified, 36 met the inclusion criteria (general population 26, patients with diseases 10). C-reactive protein (CRP) and white blood cell count (WBC) were most frequently reported. We conducted meta-analysis with 12 CRP studies (22422 participants) and six WBC studies (15209 participants), and also performed a narrative review of all studies. There was consistent evidence of a modest association between CRP and venular caliber (r = 0.09, 95%CI 0.05 to 0.12), but little evidence of an association between CRP with retinal arteriolar caliber (r = 0.00, 95%CI -0.02 to 0.02). Similarly, WBC had stronger associations with venular (r = 0.18, 95%CI 0.05 to 0.31) than arteriolar caliber (r = 0.05, 95%CI 0.01 to 0.09). Narrative review of other inflammatory markers showed consistent findings. There was little evidence of associations between inflammation markers and other microvascular parameters, fractal dimension and tortuosity. Conclusions There was more evidence for an association of inflammation with retinal venular than with arterial caliber. The findings suggest a potential druggable mechanism contributing to microvascular damage that has been relatively overlooked in CVD pathogenesis and treatment.

Background The home environment is the most important location in young children’s lives, yet few studies have examined the relationship between the outdoor home environment and child physical activity levels, and even fewer have used objectively measured exposures and outcomes. This study examined relationships between objectively assessed home yard size and greenness, and child physical activity and outdoor play. Methods Data were drawn from the HealthNuts study, a longitudinal study of 5276 children in Melbourne, Australia. We used cross-sectional data from a sample at Wave 3 (2013–2016) when participants were aged 6 years (n = 1648). A sub-sample of 391 children had valid accelerometer data collected from Tri-axial GENEActive accelerometers worn on their non-dominant wrist for 8 consecutive days. Yard area and greenness were calculated using geographic information systems. Objective outcome measures were minutes/day in sedentary, light, and moderate-vigorous physical activity (weekday and weekend separately). Parent-reported outcome measures were minutes/day playing outdoors (weekend and weekday combined). Multi-level regression models (adjusted for child’s sex, mother’s age at the birth of child, neighbourhood socioeconomic index, maternal education, and maternal ethnicity) estimated effects of yard size and greenness on physical activity. Results Data were available on outdoor play for 1648 children and usable accelerometer data for 391. Associations between yard size/greenness and components of physical activity were minimal. For example, during weekdays, yard size was not associated with daily minutes in sedentary behaviour (β: 2.4, 95% CI: − 6.2, 11.0), light physical activity (β: 1.4, 95% CI: − 5.7, 8.5) or MVPA (β: -2.4, 95% CI: − 6.5, 1.7), with similar patterns at weekends. There was no relationship between median annual yard greenness and physical activity or play. Conclusion In our study of young children residing in higher socio-economic areas of Melbourne yard characteristics did not appear to have a major impact on children’s physical activity. Larger studies with greater variation in yard characteristics and identification of activity location are needed to better understand the importance of home outdoor spaces and guide sustainable city planning.

The Paediatric Quality of Life InventoryTM 4.0 Generic Core Scales (PedsQL) is a non-preference based instrument for assessing health related quality of life (HRQoL) in children. Recent papers presented algorithms of parental proxy and short-form versions of the PedsQL onto the validated preference-based Child Health Utility 9D (CHU9D) instrument, to enable conversion of PedsQL scores to quality adjusted life years for use in economic evaluation. However, further research was needed to both validate these algorithms, and assess if use of the full 23-item PedsQL self-report instrument is preferable to other PedsQL versions for mapping onto child self-report CHU9D utilities. To 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.

We examined how combinations of clinical indicators at various ages predict overweight/obesity development, as well as resolution, by 10–11 and 14–15 years of age. Data were derived from Birth (N = 3469) and Kinder (N = 3276) cohorts of the Longitudinal Study of Australian Children, followed from ages 2–3 and 4–5 years, respectively. Every two years, 25 potential obesity-relevant clinical indicators were quantified. Overweight/obesity was defined using International Obesity Taskforce cutpoints at 10–11 years and 14–15 years. In both cohorts, three factors predicted both development and resolution of overweight/obesity in multivariable models. Among normal weight children, increased odds of developing overweight/obesity were associated with higher child (odd ratio (OR) 1.67–3.35 across different study waves) and maternal (OR 1.05–1.09) BMI, and inversely with higher maternal education (OR 0.60–0.62, when assessed at age 2–7 years). Lower odds of resolving existing overweight/obesity were related with higher child (OR 0.51–0.79) and maternal (OR 0.89–0.95) BMI, and inversely with higher maternal education (OR 1.62–1.92, when assessed at age 2–5 years). The prevalence of overweight/obesity at the age of 14–15 years was 13% among children with none of these risk factors at age 6–7 years, compared with 71% among those with all 3 risk factors (P

findings from systematic reviews into infant feeding and later adiposity are largely negative. World Health Organization (WHO) is auspicing Healthy Life Trajectories Initiative (HeLTI), a suite of trials aiming to prevent overweight/obesity in childhood. To inform planning, this narrative review sought to detail potentially effective components of nutrition-related interventions involving children aged 0 to 2 years. Systematic searches of PubMed and the Cochrane Library (2006-2016) identified 108 systematic reviews. These included 31 randomized trials in the age group of interest. Of these, 11 reported greater than or equal to 1 statistically significant (P

ObjectivesNuclear magnetic resonance (NMR) metabolomics is high throughput and cost-effective, with the potential to improve the understanding of disease and risk. We examine the circulating metabolic profile by quantitative NMR metabolomics of a sample of Australian 11–12 year olds children and their parents, describe differences by age and sex, and explore the correlation of metabolites in parent–child dyads.DesignThe population-based cross-sectional Child Health CheckPoint study nested within the Longitudinal Study of Australian Children.SettingBlood samples collected from CheckPoint participants at assessment centres in seven Australian cities and eight regional towns; February 2015–March 2016.Participants1180 children and 1325 parents provided a blood sample and had metabolomics data available. This included 1133 parent–child dyads (518 mother–daughter, 469 mother–son, 68 father–daughter and 78 father–son).Outcome measures228 metabolic measures were obtained for each participant. We focused on 74 biomarkers including amino acid species, lipoprotein subclass measures, lipids, fatty acids, measures related to fatty acid saturation, and composite markers of inflammation and energy homeostasis.ResultsWe identified differences in the concentration of specific metabolites between childhood and adulthood and in metabolic profiles in children and adults by sex. In general, metabolite concentrations were higher in adults than children and sex differences were larger in adults than in children. Positive correlations were observed for the majority of metabolites including isoleucine (CC 0.33, 95% CI 0.27 to 0.38), total cholesterol (CC 0.30, 95% CI 0.24 to 0.35) and omega 6 fatty acids (CC 0.28, 95% CI 0.23 to 0.34) in parent–child comparisons.ConclusionsWe describe the serum metabolite profiles from mid-childhood and adulthood in a population-based sample, together with a parent–child concordance. Differences in profiles by age and sex were observed. These data will be informative for investigation of the childhood origins of adult non-communicable diseases and for comparative studies in other populations.

ObjectivesTo describe the epidemiology and concordance of bone health in a population-based sample of Australian parent-child dyads at child age 11–12 years.DesignPopulation-based cross-sectional study (the Child Health CheckPoint) nested between waves 6 and 7 of the Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven cities around Australia, February 2015–March 2016.Participants: of all participating CheckPoint families (n=1874), bone data were available for 1222 dyads (1271 children, 50% girls; 1250 parents, 86% mothers).Outcome measuresPeripheral quantitative CT (pQCT) of the non-dominant leg scanned at the 4% (distal) and 66% (mid-calf) tibial sites. Stratec XCT 2000 software generated estimates of bone density, geometry and polar stress-strain index.Parent-child concordance were assessed using Pearson’s correlation coefficients and multivariable linear regression models. Percentiles were determined using survey weights. Survey weights and methods accounted for LSAC’s complex sampling, stratification and clustering within postcodes.ResultsConcordances were greater for the geometric pQCT parameters (periosteal circumference 0.38, 95% CI 0.33 to 0.43; endosteal circumference 0.42, 95% CI 0.37 to 0.47; total cross-sectional area 0.37, 95% CI 0.32 to 0.42) than density (cortical density 0.25, 95% CI 0.19 to 0.30). Mother-child and father-child values were similar. Relationships attenuated only slightly on adjustment for age, sex and body mass index. Percentiles and concordance are presented for the whole sample and by sex.ConclusionsThere is strong parent-child concordance in bone geometry and, to a lesser extent, density even before the period of peak adolescent bone deposition. This geometrical concordance suggests that future intergenerational bone studies could consider using pQCT rather than the more commonly used dual X-ray absorptiometry (DXA).

ObjectivesTo describe objectively measured sleep characteristics in children aged 11–12 years and in parents and to examine intergenerational concordance of sleep characteristics.DesignPopulation-based cross-sectional study (the Child Health CheckPoint), nested within the Longitudinal Study of Australian Children.SettingData were collected between February 2015 and March 2016 across assessment centres in Australian major cities and selected regional towns.ParticipantsOf the participating CheckPoint families (n=1874), sleep data were available for 1261 children (mean age 12 years, 50% girls), 1358 parents (mean age 43.8 years; 88% mothers) and 1077 biological parent–child pairs. Survey weights were applied and statistical methods accounted for the complex sample design, stratification and clustering within postcodes.Outcome measuresParents and children were asked to wear a GENEActive wrist-worn accelerometer for 8 days to collect objective sleep data. Primary outcomes were average sleep duration, onset, offset, day-to-day variability and efficiency. All sleep characteristics were weighted 5:2 to account for weekdays versus weekends. Biological parent–child concordance was quantified using Pearson’s correlation coefficients in unadjusted models and regression coefficients in adjusted models.ResultsThe mean sleep duration of parents and children was 501 min (SD 56) and 565 min (SD 44), respectively; the mean sleep onset was 22:42 and 22:02, the mean sleep offset was 07:07 and 07:27, efficiency was 85.4% and 84.1%, and day-to-day variability was 9.9% and 7.4%, respectively. Parent–child correlation for sleep duration was 0.22 (95% CI 0.10 to 0.28), sleep onset was 0.42 (0.19 to 0.46), sleep offset was 0.58 (0.49 to 0.64), day-to-day variability was 0.25 (0.09 to 0.34) and sleep efficiency was 0.23 (0.10 to 0.27).ConclusionsThese normative values for objective sleep characteristics suggest that, while most parents and children show adequate sleep duration, poor-quality (low efficiency) sleep is common. Parent–child concordance was strongest for sleep onset/offset, most likely reflecting shared environments, and modest for duration, variability and efficiency.

ObjectivesTo (1) describe the epidemiology of child and adult telomere length, and (2) investigate parent–child telomere length concordance.DesignPopulation-based cross-sectional study within the Longitudinal Study of Australian Children.SettingAssessment centres in seven major Australian cities and eight selected regional towns; February 2015 to March 2016.ParticipantsOf 1874 participating families, telomere data were available for analysis for 1206 children and 1343 parents, of whom 1143 were parent–child pairs. There were 589 boys and 617 girls; 175 fathers and 1168 mothers.Outcome measuresRelative telomere length (T/S ratio), calculated by comparing telomeric DNA (T) level with the single copy (S) beta-globin gene in venous blood-derived genomic DNA by quantitative real-time PCR.ResultsMean T/S ratio for all children, boys and girls was 1.09 (SD 0.56), 1.05 (SD 0.53) and 1.13 (SD 0.59), respectively. Mean T/S ratio for all parents, fathers and mothers was 0.81 (SD 0.37), 0.82 (SD 0.36) and 0.81 (SD 0.38), respectively. Parent–child T/S ratio concordance was moderate (correlation 0.24). In adjusted regression models, one unit higher parent T/S ratio was associated with 0.36 (estimated linear regression coefficient (β); 95% CI 0.28 to 0.45) higher child T/S ratio. Concordance was higher in the youngest parent-age tertile (β 0.49; 95% CI 0.34 to 0.64) compared with the middle (β 0.35; 95% CI 0.21 to 0.48) and oldest tertile (β 0.26; 95% CI 0.11 to 0.41; p-trend 0.04). Father–child concordance was 0.34 (95% CI 0.18 to 0.48), while mother–child was 0.22 (95% CI 0.17 to 0.28).ConclusionsWe provide telomere length population values for children aged 11–12 years and their mid-life parents. Relative telomere length was shorter in adults than children, as expected. There was modest evidence of parent–child concordance, which diminished with increasing parent age.

ObjectivesTo describe the epidemiology of lung function in Australian children aged 11–12 years and their parents, and explore the degree of intergenerational concordance.DesignCross-sectional study (the Child Health CheckPoint) nested in the Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven Australian cities and eight regional towns, February 2015 to March 2016. Families unable to attend a clinic appointment were offered a home visit during the same period.Participants1874 families (53% of all eligible) participated in the study. Lung function data were available for 1759 children aged 11–12 years and 1774 parents (1668 biological pairs).Outcome measuresParticipants completed spirometry with measures including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and mid expiratory flow (MEF), converted to z-scores using Global Lung Initiative equations. Parent–child concordance was assessed using Pearson’s correlation coefficients and multivariable linear regression models. Survey weights and methods accounted for LSAC’s complex sampling, stratification and clustering within postcodes.ResultsAll lung function measures followed approximately normal distributions. Mean (SD) for FEV1, FVC and MEF z-scores in children were 0.33 (1.07), 0.83 (1.14) and −0.48 (1.09), respectively. Mean (SD) in parents were 0.28 (1.10), 0.85 (1.15) and −0.45 (1.10), respectively. Parent FEV1, FVC and MEF were associated with child lung function with significant positive correlation coefficients (0.22, 95% CI 0.17 to 0.26; 0.24, 95% CI 0.20 to 0.29; and 0.24, 95% CI 0.20 to 0.29, respectively).ConclusionsMean lung volumes were larger but with smaller airway size than international standards for both parents and children in this population sample. Modest associations between parent and child lung function highlight the potential for better identification of ‘at risk’ populations. Therefore, these findings may aid the development of health policy that aims to prevent the onset or limit the progression of lung disease.

ObjectivesTo describe the epidemiology and parent-child concordance of hearing, speech reception, vocabulary and language in Australian parent-child dyads at child age 11 to 12 years.DesignPopulation-based cross-sectional study (Child Health CheckPoint) nested within the Longitudinal Study of Australian Children.SettingAssessment centres in seven Australian cities and eight regional towns or home visits around Australia, February 2015 to March 2016.ParticipantsOf all participating CheckPoint families (n=1874), 1516 children (50% female) and 1520 parents (87% mothers, mean age 43.8 years) undertook at least one of four measurements of hearing and language.Outcome measuresHearing threshold (better ear mean of 1, 2 and 4 kHz) from pure-tone audiometry, speech reception threshold, receptive vocabulary, expressive and receptive languages using a sentence repetition task. Parent-child concordance was examined using Pearson’s correlation coefficients and adjusted linear regression models. Survey weights and methods accounted for Longitudinal Study of Australian Children’s complex sampling and stratification.ResultsChildren had a similar speech reception threshold to parents (children mean −14.3, SD 2.4; parents −14.9, SD 3.2 dB) but better hearing acuity (children 8.3, SD 6.3; parents 13.4, SD 7.0 decibels hearing level). Standardised sentence repetition scores were similar (children 9.8, SD 2.9; parents 9.1, SD 3.3) but, as expected, parents had superior receptive vocabularies. Parent-child correlations were higher for the cognitively-based language measures (vocabulary 0.31, 95% CI 0.26 to 0.36; sentence repetition 0.29, 95% CI 0.24 to 0.34) than the auditory measures (hearing 0.18, 95% CI 0.13 to 0.23; speech reception threshold 0.18, 95% CI 0.13 to 0.22). Mother-child and father-child concordances were similar for all measures.ConclusionsWe provide population reference values for multiple measures spanning auditory and verbal communication systems in children and mid-life adults. Concordance values aligned with previous twin studies and offspring studies in adults, in keeping with polygenic heritability that is modest for audition but around 60% for language by late childhood.

ObjectivesTo describe a well-established marker of cardiovascular risk, carotid intima–media thickness (IMT) and related measures (artery distensibility and elasticity) in children aged 11–12 years old and mid-life adults, and examine associations within parent–child dyads.DesignCross-sectional study (Child Health CheckPoint), nested within a prospective cohort study, the Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven Australian major cities and eight selected regional towns, February 2015 to March 2016.ParticipantsOf all participating CheckPoint families (n=1874), 1489 children (50.0% girls) and 1476 parents (86.8% mothers) with carotid IMT data were included. Survey weights and methods were applied to account for LSAC’s complex sample design and clustering within postcodes and strata.Outcome measuresUltrasound of the right carotid artery was performed using standardised protocols. Primary outcomes were mean and maximum far-wall carotid IMT, quantified using semiautomated edge detection software. Secondary outcomes were carotid artery distensibility and elasticity. Pearson’s correlation coefficients and multivariable linear regression models were used to assess parent–child concordance. Random effects modelling on a subset of ultrasounds (with repeated measurements) was used to assess reliability of the child carotid IMT measure.ResultsThe average mean and maximum child carotid IMT were 0.50 mm (SD 0.06) and 0.58 mm (SD 0.05), respectively. In adults, average mean and maximum carotid IMT were 0.57 mm (SD 0.07) and 0.66 mm (SD 0.10), respectively. Mother–child correlations for mean and maximum carotid IMT were 0.12 (95% CI 0.05 to 0.23) and 0.10 (95% CI 0.03 to 0.21), respectively. For carotid artery distensibility and elasticity, mother–child correlations were 0.19 (95% CI 0.10 to 0.25) and 0.11 (95% CI 0.02 to 0.18), respectively. There was no strong evidence of father–child correlation in any measure.ConclusionsWe provide Australian values for carotid vascular measures and report a modest mother–child concordance. Both genetic and environmental exposures are likely to contribute to carotid IMT.

ObjectivesTo describe the distribution of albuminuria among Australian children aged 11–12 years and their parents, and assess its intergenerational concordance within parent–child dyads.DesignPopulation-based cross-sectional study (the Child Health CheckPoint), nested within the Longitudinal Study of Australian Children.SettingAssessment centres (seven Australian cities and eight regional towns) and home visits across Australia, February 2015 to March 2016.ParticipantsOf all participating CheckPoint families (n=1874), 1557 children (46.2% girls) and 1454 parents (85.5% mothers) provided random urine samples at the visit; samples from menstruating females were excluded.Outcome measuresUrine albumin-to-creatinine ratio (ACR) and its components (urine albumin and creatinine concentration); albuminuria was defined as an ACR ≥3.4 mg/mmol. Pearson’s correlation coefficients and multivariable linear regression models assessed parent–child concordance, using log-transformed data due to skewing. Survey weights and methods were applied to account for the complex sample design.ResultsThe median ACR for children was 1.03 mg/mmol (IQR 0.65–1.97) and 1.01 mg/mmol (IQR 0.60–2.09) for adults. The median ACR was higher in girls (1.20, IQR 0.71–2.65) than boys (0.90, IQR 0.61–1.65) and in mothers (1.13, IQR 0.63–2.33) than fathers (0.66, IQR 0.41–1.05). Albuminuria was detected in 15.1% of children (girls 20.8%, boys 10.1%) and 13.5% of adults (15.1% mothers, 4.0% fathers) had albuminuria. There was a small correlation between parent and child ACR (Pearson correlation coefficient 0.06, 95% CI 0.01 to 0.12).ConclusionsAlbuminuria is common among Australian children and adults, which is of concern because it predicts risk for kidney and cardiovascular disease, and mortality. The weak concordance among intergenerational pairs for urine ACR suggests either that genetic heritability is low or that it becomes evident only at later offspring life stages.

ObjectivesTo describe the epidemiology and parent–child concordance of objectively measured physical activity in a population-based sample of Australian parent–child dyads.DesignCross-sectional study (Child Health CheckPoint) nested within the Longitudinal Study of Australian Children.SettingAssessment centres in seven Australian cities and eight regional towns or home visits; February 2015–March 2016.ParticipantsOf all CheckPoint families (n=1874), 1261 children (50% girls) and 1358 parent (88% mothers) provided objectively measured activity data, comprising 1077 parent–child dyads.Outcome measuresActivity behaviour was assessed by GENEActiv accelerometer. Duration of moderate-to-vigorous physical activity (MVPA) and vigorous physical activity and sedentary behaviour (SB) were derived usingCobracustom software, along with MVPA/SB fragmentation and mean daily activity. Pearson’s correlation coefficients and linear regression estimated parent–child concordance. Survey weights and methods accounted for the complex sample design and clustering.ResultsAlthough parents had average lower accelerometry counts than children (mean [SD] 209 [46] vs 284 [71] g.min), 93% of parents met MVPA daily duration guidelines on published cutpoints (mean [SD] 125 [63] min/day MVPA), compared with only 15% of children (mean 32 [27] min). Parents showed less daily SB duration (parents: 540 [101], children: 681 [69] minutes) and less fragmented accumulation of MVPA (parents: α=1.85, children: α=2.00). Parent–child correlation coefficients were 0.16 (95% CI 0.11 to 0.22) for MVPA duration, 0.10 (95% CI 0.04 to 0.16) for MVPA fragmentation, 0.16 (95% CI 0.11 to 0.22) for SB duration and 0.18 (95% CI 0.12 to 0.23) for SB fragmentation.ConclusionsStandardised cutpoints are needed for objective activity measures to inform activity guidelines across the lifecourse. This may reflect large amounts of time in non-shared environments (school and work).

ObjectivesTo describe distributions and concordance of retinal microvasculature measurements in a population-based sample of Australian parent–child dyads at child age 11–12 years.DesignCross-sectional Child Health CheckPoint study, between waves 6 and 7 of the national population-based Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven Australian cities, February 2015–March 2016.ParticipantsOf the 1874 participating families, 1288 children (51% girls) and 1264 parents (87% mothers, mean age 43.7) were analysed. Diabetic participants and non-biological pairs were excluded from concordance analyses.Outcome measuresRetinal photographs were taken by non-mydriatic fundus camera. Trained graders scored vascular calibre using semi-automated software, yielding estimates of central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) and arteriolar–venular ratio (AVR). Pearson’s correlation coefficients and multivariable linear regression models assessed parent–child concordance. Survey weights and methods accounted for LSAC’s complex sampling, stratification and clustering within postcodes.ResultsMean (SD) of CRAE and CRVE were larger in children (159.5 (11.8) and 231.1 (16.5) μm, respectively) than parents (151.5 (14.0) and 220.6 (19.0) μm), yielding similar AVR (children 0.69 (0.05), parents 0.69 (0.06)). Correlation coefficients for parent–child pairs were 0.22 (95% CI 0.16 to 0.27) for CRAE, 0.23 (95% CI 0.17 to 0.28) for CRVE and 0.18 (95% CI 0.13 to 0.24) for AVR. Mother–child and father–child values were similar (0.20 and 0.32 for CRAE, 0.22 and 0.29 for CRVE, respectively). Relationships attenuated slightly on adjustment for age, sex, blood pressure, diabetes and body mass index. Percentiles and concordance are presented for the whole sample and by sex.ConclusionsArteriolar and venular calibre were similar to previously documented measures in midlife adult and late childhood populations. Population parent–child concordance values align with moderate polygenic heritability reported in smaller studies.

Despite known associations between eating disorders and obesity, little is known about the current prevalence of symptoms of eating disorders across the weight spectrum. This study therefore aimed to estimate the population prevalence of eating disorder symptoms in relation to weight status in adolescents.The sample comprised 3,270 participants (14-15 years; 52% boys) drawn from Wave 6 of the Longitudinal Study of Australian Children. Symptoms of anorexia nervosa (AN) and bulimia nervosa (BN) were assessed using self-report on the Branched Eating Disorder Test. This measure identifies clinically significant symptoms in the past 3 months according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Using study-derived cross-sectional population weights, the prevalence of each symptom was estimated for the total population and by sex and weight status.The estimated population prevalence was high (14.3-25.7%) for body image symptoms such as fear of weight gain and overvaluation of body weight but lower (0.5-3.7%) for behavioral symptoms such as binge eating and compensatory behaviors. Symptoms were more prevalent among adolescents with overweight or obesity. Although most symptoms tended to have higher prevalence among girls than boys, boys with obesity had higher prevalence of binge eating and excessive exercise than girls with obesity. The overall estimated population prevalence for AN and BN was 0.20% and 0.10%, respectively.The study highlights a need for clinicians to be cognizant of disordered eating behaviors regardless of weight status and has implications for both eating disorder and obesity prevention and intervention.

Objectives Although presbycusis typically becomes symptomatic only in older age, slight and mild hearing loss may be detectable well before this. We studied current prevalence and characteristics of hearing loss in Australian mid-life adults. Study design This was a population-derived national cross-sectional study nested within the Longitudinal Study of Australian Children. Methods A total of 1485 parents/guardians (87.3% female) aged 30–59 years underwent air-conduction audiometry. Hearing loss was defined in three ways to maximize cross-study comparability: high Fletcher index (mean of 1, 2 and 4 kHz; primary outcome relevant to speech perception), lower frequency (mean of 1 and 2 kHz) and higher frequency (mean of 4 and 8 kHz). Multivariable logistic regression examined how losses vary by age, sex and neighbourhood disadvantage. Results On high Fletcher index, 27.3% had bilateral and 23.8% unilateral thresholds >15 dB hearing level (HL) (slight or worse), and 4.9% had bilateral and 6.3% unilateral thresholds >25 dB HL (mild or worse). Bilateral higher frequency losses were more common than lower frequency losses for thresholds >15 dB HL (30.9% vs. 26.4%) and >25 dB HL (11.0% vs. 4.6%). Age increased the risk of bilateral speech and higher frequency losses (all P for trend 25 dB HL. Although sex was not associated with speech and lower frequency losses, men were more likely to have bilateral higher frequency losses (e.g. >15 dB HL: odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.5–3.2, P Conclusions Both slight and mild hearing loss show high and rising prevalence across mid-life. This offers opportunities to prevent progression to reduce the profound later burden of age-related hearing loss.

Background: Understanding early-life relationships between the Ideal Cardiovascular Health (ICVH) score and vascular phenotypes could inform likely effectiveness and timing of cardiovascular disease prevention strategies. We aimed to describe associations between ICVH scores and vascular phenotypes in 11- to 12-year-old children and their parents. Methods and results: Cross-sectional ICVH scores (range 0–7, higher indicating better health), derived by summing dichotomized metrics for cholesterol, glucose, blood pressure (BP), body mass index (BMI), diet, physical activity and smoking, were constructed for 1235 adults (89% female, mean age 43 years) and 1028 children (48% female, 12 years). The median scores were 4 and 5 for adults and children respectively. Child ICVH scores were associated with parent scores (0.18 higher child score per additional point in parent's score, 95% CI 0.12 to 0.22, P Conclusion: Few Australian children and even fewer parents have ideal cardiovascular health. Lower ICVH scores were associated with adverse adult vascular phenotypes and adverse child vascular function. Family-based interventions optimizing ICVH metrics may delay onset and progression of subclinical atherosclerosis and later cardiovascular disease.

Refereed/Peer-reviewed Background/objectives: Modelling genetic pre-disposition may identify children at risk of obesity. However, most polygenic scores (PGSs) have been derived in adults, and lack validation during childhood. This study compared the utility of existing largescale adult-derived PGSs to predict common anthropometric traits (body mass index (BMI), waist circumference, and body fat) in children and adults, and examined whether childhood BMI prediction could be improved by combining PGSs and non-genetic factors (maternal and earlier child BMI) Subjects/methods: Participants (n = 1365 children, and n = 2094 adults made up of their parents) were drawn from the Longitudinal Study of Australian Children. Children were weighed and measured every two years from 0–1 to 12–13 years, and adults were measured or self-reported measurements were obtained concurrently (average analysed). Participants were genotyped from blood or oral samples, and PGSs were derived based on published genome-wide association studies. We used linear regression to compare the relative utility of these PGSs to predict their respective traits at different ages. Results: BMI PGSs explained up to 12% of child BMI z-score variance in 10–13 year olds, compared with up to 15% in adults. PGSs for waist circumference and body fat explained less variance (up to 8%). An interaction between BMI PGSs and puberty (p =0.001–0.002) suggests the effect of some variants may differ across the life course. Individual BMI measures across childhood predicted 10–60% of the variance in BMI at 12–13 years, and maternal BMI and BMI PGS each added 1–9% above this Conclusion: Adult-derived PGSs for BMI, particularly those derived by modelling between-variant interactions, may be useful for predicting BMI during adolescence with similar accuracy to that obtained in adulthood. The level of precision presented here to predict BMI during childhood may be relevant to public health, but is likely to be less useful for individual clinical purposes.

Parental preconception exposures to built and natural outdoor environments could influence pregnancy and birth outcomes either directly, or via a range of health-related behaviours and conditions. However, there is no existing review summarising the evidence linking natural and built characteristics, such as air and noise pollution, walkability, greenness with pregnancy and birth outcomes. Therefore, the planned scoping review aims to collate and map the published literature on parental preconception exposures to built and natural outdoor environments and adverse pregnancy and birth outcomes. We will search electronic databases (MEDLINE, EMBASE, Scopus) to identify studies for inclusion. Studies will be included if they empirically assess the relationship between maternal and paternal preconception exposures to physical natural and built environment features that occur outdoors in the residential neighbourhood and adverse pregnancy and birth outcomes. Two reviewers will independently screen titles and abstracts, and then the full text. Data extraction and assessment of study quality will be performed by one researcher and checked by a second researcher. Results will be summarised in a narrative synthesis, with additional summaries presented as tables and figures. The scoping review will be disseminated via a peer-reviewed publication, at academic conferences, and published on a website.

Background Many current research needs can only be addressed using very large cohorts. In such studies, traditional one-on-one phone, face-to-face, or paper-based engagement may not be feasible. The only realistic mechanism for maintaining engagement and participation at this scale is via digital methods. Given the substantial investment being made into very large birth cohort studies, evidence for optimal methods of participant engagement, participation, and retention over sustained periods without in-person contact from researchers is paramount. Objective This study aims to provide an overview of systematic reviews and meta-analyses evaluating alternative strategies for maximizing participant engagement and retention rates in large-scale studies using digital methods. Methods We used a rapid review method by searching PubMed and Ovid MEDLINE databases from January 2012 to December 2019. Studies evaluating at least 1 e-engagement, participation, or retention strategy were eligible. Articles were screened for relevance based on preset inclusion and exclusion criteria. The methodological quality of the included reviews was assessed using the AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews 2) measurement tool, and a narrative synthesis of the data was conducted. Results The literature search yielded 19 eligible reviews. Overall, 63% (n=12) of these reviews reported on the effectiveness of e-engagement or participation promotion strategies. These evaluations were generally not conducted within very large observational digital cohorts. Most of the contributing reviews included multipurpose cohort studies (with both observational and interventional elements) conducted in clinical and research settings. Email or SMS text message reminders, SMS text messages or voice notifications, and incentives were the most commonly used design features to engage and retain participants. For parental outcomes, engagement-facilitation interventions influenced uptake and behavior change, including video feedback, goal setting, and intensive human facilitation and support. Participant-stated preferences for content included new knowledge, reminders, solutions, and suggestions about health issues presented in a clear, short, and personalized way. Perinatal and postpartum women valued self-monitoring and personalized feedback. Digital reminders and multiple SMS text messages were specific strategies that were found to increase adherence to medication and clinic attendance, respectively. Conclusions This review adds to the growing literature evaluating methods to optimize engagement and participation that may apply to large-scale studies using digital methods; it is promising that most e-engagement and participation promotion strategies appear to be effective. However, these reviews canvassed relatively few strategies, suggesting that few alternative strategies have been experimentally evaluated. The reviews also revealed a dearth of experimental evidence generated within very large observational digital cohort studies, which may reflect the small number of such studies worldwide. Thus, very large studies may need to proactively build in experimental opportunities to test engagement and retention approaches to enhance the success of their own and other large digital contact studies.

In this population-based cohort of 1179 children 11 to 12 years of age, equivalent benefits to adiposity and HRQoL were associated with different changes (trade-offs) in activities. BACKGROUND Understanding equivalence of time-use trade-offs may inform tailored lifestyle choices. We explored which time reallocations were associated with equivalent changes in children’s health outcomes. METHODS Participants were from the cross-sectional Child Health CheckPoint Study (N = 1181; 11–12 years; 50% boys) nested within the population-based Longitudinal Study of Australian Children. Outcomes were adiposity (bioelectrical impedance analysis, BMI and waist girth), self-reported health-related quality of life (HRQoL; Pediatric Quality of Life Inventory), and academic achievement (standardized national tests). Participants’ 24-hour time use (sleep, sedentary behavior, light physical activity, and moderate-to-vigorous physical activity [MVPA]) from 8-day 24-hour accelerometry was regressed against outcomes by using compositional log-ratio linear regression models. RESULTS Children with lower adiposity and higher HRQoL had more MVPA (both P < .001) and sleep (P = .002; P = .008), and less sedentary time (P = .02; P = .001) and light physical activity (P < .001; P = .04), each relative to remaining activities. Children with better academic achievement had more sedentary time (P = .03) and less light physical activity (P = .006), each relative to remaining activities. A 0.1 standardized decrease in adiposity was associated with either 55 minutes more sleep, 89 minutes less sedentary time, 34 minutes less light physical activity, or 19 minutes more MVPA. A 0.1 standardized increase in HRQoL was associated with either 64 minutes more sleep, 65 minutes less sedentary time, 72 minutes less light physical activity, or 29 minutes more MVPA. CONCLUSIONS Equivalent differences in outcomes were associated with several time reallocations. On a minute-for-minute basis, MVPA was 2 to 6 times as potent as sleep or sedentary time.

Scope: B vitamers are co-enzymes involved in key physiological processes including energy production, one-carbon, and macronutrient metabolism. Studies profiling B vitamers simultaneously in parent–child dyads are scarce. Profiling B vitamers in parent–child dyads enables an insightful determination of gene–environment contributions to their circulating concentrations. We aimed to characterise: (a) parent–child dyad concordance, (b) generation (children versus adults), (c) age (within the adult subgroup (age range 28–71 years)) and (d) sex differences in plasma B vitamer concentrations in the CheckPoint study of Australian children. Methods and Results: 1166 children (11 ± 0.5 years, 51% female) and 1324 parents (44 ± 5.1 years, 87% female) took part in a biomedical assessment of a population-derived longitudinal cohort study: The Growing Up in Australia’s Child Health CheckPoint. B vitamer levels were quantified by UHPLC/MS-MS. B vitamer levels were weakly concordant between parent–child pairs (10–31% of variability explained). All B vitamer concentrations exhibited generation-specificity, except for flavin mononucleotide (FMN). The levels of thiamine, pantothenic acid, and 4-pyridoxic acid were higher in male children, and those of pantothenic acid were higher in male adults compared to their female counterparts. Conclusion: Family, age, and sex contribute to variations in the concentrations of plasma B vitamers in Australian children and adults.

BackgroundOne size rarely fits all in population health. Differing outcomes may compete for best allocations of time. Among children aged 11–12 years, we aimed to (1) describe optimal 24-hour time use for diverse physical, cognitive/academic and well-being outcomes, (2) pinpoint the ‘Goldilocks Day’ that optimises all outcomes and (3) develop a tool to customise time-use recommendations.MethodsIn 2004, the Longitudinal Study of Australian Children recruited a nationally-representative cohort of 5107 infants with biennial follow-up waves. We used data from the cross-sectional Child Health CheckPoint module (2015–2016, n=1874, 11–12 years, 51% males). Time use was from 7-day 24-hour accelerometry. Outcomes included life satisfaction, psychosocial health, depressive symptoms, emotional problems, non-verbal IQ; vocabulary, academic performance, adiposity, fitness, blood pressure, inflammatory biomarkers, bone strength. Relationships between time use and outcomes were modelled using compositional regression.ResultsOptimal daily durations varied widely for different health outcomes (sleep: 8.3–11.4 hours; sedentary: 7.3–12.2 hours; light physical activity: 1.7–5.1 hours; moderate-to-vigorous physical activity (MVPA): 0.3–2.7 hours, all models p≤0.04). In general, days with highest physical activity (predominantly MVPA) and low sedentary time were optimal for physical health, while days with highest sleep and lowest sedentary time were optimal for mental health. Days with highest sedentary time and lowest physical activity were optimal for cognitive health. The overall Goldilocks Day had 10 hours 21 min sleep, 9 hours 44 min sedentary time, 2 hours 26 min light physical activity and 1 hour 29 min MVPA. Our interactive interface allows personalisation of Goldilocks Days to an individual’s outcome priorities.Conclusion‘Goldilocks Days’ necessitate compromises based on hierarchies of priorities for health, social and economic outcomes.

OBJECTIVES: To examine the contribution of early life factors and preschool- and school-aged language abilities to children’s 11-year language and academic outcomes. METHODS: Participants (N = 839) were from a prospective community cohort study of 1910 infants recruited at 8 to 10 months of age. Early life factors included a combination of child (prematurity, birth weight), family (socioeconomic disadvantage, family history of language difficulties), and maternal factors (education, vocabulary, and age). Language (standardized assessment of receptive and expressive skills) and academic (national assessment) outcomes at 11 years were predicted by using a series of multivariable regression models. RESULTS: Early life factors explained 11% to 12% of variance in language scores at 11 years. The variance explained increased to 47% to 64% when language scores from 2 to 7 years were included. The largest increase in variance explained was with 4-year language scores. The same early life factors explained 13% to 14% of academic scores at 11 years, with increases to 43% to 54% when language scores from 2 to 11 years were included. Early life factors adequately discriminated between children with typical and low language scores but were much better discriminators of children with typical and low academic scores. When earlier language scores were added to models then the area under the curve increased to 0.9 and above. CONCLUSIONS: Children’s language outcomes at 11 years are accurately predicted by their 4-year language ability and their academic outcomes at 11 years are predicted by early family and home environment factors. Children with low language abilities at 11 years consistently performed more poorly on national assessments of literacy and numeracy.

Aim: To examine associations between patterns of language use and early adolescent well-being. Methods: Participants were 1763 Australian 11- to 12-year-olds in the Child Health CheckPoint. Six patterns of language use were identified from a writing activity using Linguistic Inquiry and Word Count and factor analysis: Acting in the present and future, Positive emotion, Gender and relationships, Self-aware, Inquisitive and time focused, and Confident. Well-being measures represented a spectrum from negatively to positively framed psychosocial health. Associations between language use and well-being were estimated using linear regression adjusted for age, sex and social disadvantage. Results: Positive emotion (high emotional tone, positive emotion) was associated with better general well-being (standardised regression coefficient (SRC) 0.05; 95% confidence interval 0.00 to 0.11; p = 0.04), life satisfaction (0.06; 0.01 to 0.11; p = 0.03), psychosocial health (0.07; 0.02 to 0.12; p = 0.01) and quality of life (QoL) (0.06; 0.01 to 0.11; p = 0.02). Similarly, Self-aware (high first person singular pronouns, authentic, low clout) was associated with better general well-being, life satisfaction and psychosocial health (SRC 0.05, 0.09, 0.08), but Confident (high clout, first person plural pronouns, affiliation) was associated with worse life satisfaction, psychosocial health and QoL (SRC −0.06, −0.09, −0.06). Conclusion: If replicated in ‘real-world’ settings (e.g., social media), language patterns could provide naturalistic insights into early adolescents’ well-being. Refereed/Peer-reviewed

Study Objectives Sleep plays an important role in cardiometabolic health. Although the importance of considering sleep as a multidimensional construct is widely appreciated, studies have largely focused on individual sleep characteristics. The association between actigraphy-derived sleep profiles and cardiometabolic health in healthy adults and children has not been examined. Methods This study used 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 nondominant wrist for 7 days and sleep characteristics (period, efficiency, timing, and variability) were derived from raw actigraphy data. Actigraphy-derived sleep profiles of 1,043 Australian children aged 11–12 years and 1,337 adults were determined using K-means cluster analysis. The association between cluster membership and biomarkers of cardiometabolic health (blood pressure, body mass index, apolipoproteins, glycoprotein acetyls, composite metabolic syndrome severity score) were assessed using Generalized Estimating Equations, adjusting for geographic clustering, with sex, socioeconomic status, maturity stage (age for adults, pubertal status for children), and season of data collection as covariates. Results Four actigraphy-derived sleep profiles were identified in both children and adults: short sleepers, late to bed, long sleepers, and overall good sleepers. The overall good sleeper pattern (characterized by adequate sleep period time, high efficiency, early bedtime, and low day-to-day variability) was associated with better cardiometabolic health in the majority of comparisons (80%). Conclusion Actigraphy-derived sleep profiles are associated with cardiometabolic health in adults and children. The overall good sleeper pattern is associated with more favorable cardiometabolic health.

Aims To investigate relationships between takeaway food and sugar-sweetened beverage (SSB) consumption with cardiometabolic phenotypes during childhood and mid-adulthood. Method Design: Cross-sectional Child Health CheckPoint within the national population-representative Longitudinal Study of Australian Children. Participants: 1838 children (mean age 11.5 years; 49.1% female) and 1846 adults (mean age 43.7 years; 87.6% female). Exposures: Self-reported takeaway food and SSB consumption (‘frequent’: ≥ weekly). Outcomes: Functional (pulse wave velocity (PWV), blood pressure (BP)) and structural (carotid intima-media thickness, retinal microvascular calibre) preclinical cardiovascular phenotypes; lipids (total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides). Analysis: Linear regression (exposure: takeaway or SSB consumption, individually or together) adjusted for age, sex and socio-economic position; and mediation analysis for body mass index (BMI). Results Associations were small among children (standardized mean difference (SMD) ≤0.15). In adults, associations were stronger with functional, but not structural, cardiovascular phenotypes and lipids, particularly for frequent takeaway food consumption (e.g. PWV (0.20 m/s; 95% confidence interval (CI) 0.03 to 0.37); systolic (3.3 mmHg; 95% CI 1.3 to 5.3) and diastolic BP (1.4 mmHg; 95% CI 0.2 to 2.6); LDL (0.10 mmol/L; 95% CI 0.02 to 0.18); HDL (−0.14 mmol/L; 95% CI −0.19 to −0.10) and triglycerides (0.30 mmol/L; 95% CI 0.12 to 0.48)]. BMI mediated associations between takeaway food consumption and PWV, BP, HDL and TG (proportion of mediation 34% to 75%), while mediation effects were smaller for SSB consumption. Conclusions Frequent takeaway food consumption in adults was associated with adverse blood lipids and vascular function (mainly via BMI). Lack of strong associations in children highlights opportunities for prevention.

Aim Most prescribed medicines during pregnancy are antibiotics, with unknown effects on a fetus and on the infant's acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections. Methods Design and participants: The Longitudinal Study of Australian Children birth cohort recruited a nationally-representative sample of 5107 infants in 2004. Measures Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1-6). Analysis Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. Results A total of 4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: 'consistently low' (86.2%), 'moderate to low' (5.6%), 'low to moderate' (6.7%) and 'consistently high' (1.4%). Antibiotic use in pregnancy was associated with children following 'consistently high' (adjusted odds ratio 2.04, 95% confidence interval 1.08-3.88, P = 0.03) and 'moderate to low' (adjusted odds ratio 1.78, 95% confidence interval 1.25-2.53, P = 0.001) trajectories. Conclusions Antibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for the study of potential mechanisms underlying these associations.

Obesity is characterized by heightened inflammation, and both phenotypes are associated with hearing loss. We aimed to determine if inflammation mediates the associations between obesity and hearing ability in mid-childhood and mid-life.Participants: 1165 11- to 12-year-old children and 1316 parents in the population-based cross-sectional Child Health CheckPoint within the Longitudinal Study of Australian Children. Adiposity measures: Body mass index (BMI) classified as normal, overweight and obesity; waist-to-height ratio (WHtR) classified as0.5 and ≥0.5; fat mass index. Inflammatory biomarkers: Serum glycoprotein A (GlycA); high-sensitivity C-reactive protein (hsCRP). Audiometry: Composite high Fletcher Index (mean threshold of 1, 2, 4 kHz) in the better ear.Causal mediation analysis decomposed a 'total effect' (obesity on hearing status) into 'indirect' effect via a mediator (eg GlycA, hsCRP) and 'direct' effect via other pathways, adjusting for age, sex and socioeconomic position.Compared to adults with BMI within the normal range, those with obesity had hearing thresholds 1.9 dB HL (95% CI 1.0-2.8) higher on the high Fletcher Index; 40% of the total effect was mediated via GlycA (indirect effect: 0.8 dB HL, 95% CI 0.1-1.4). Children with obesity had hearing thresholds 1.3 dB HL (95% CI 0.2-2.5) higher than those with normal BMI, of which 67% (indirect effect: 0.9 dB HL, 95% CI 0.4-1.4) was mediated via GlycA. Similar mediation effects were noted using other adiposity measures. Similar but less marked mediation effects were observed when hsCRP was used as the inflammatory biomarker (6-23% in adults and 23-33% in children).Inflammation may play an important mediating role in the modest hearing reductions associated with obesity, particularly in children. These findings offer insights into possible mechanisms and early prevention strategies for hearing loss.

BackgroundMost prescribed medicines during pregnancy are antibiotics, with unknown effects on a foetus and on the infant’s acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections.MethodsDesign & Participants: The Longitudinal Study of Australian Children (LSAC) birth cohort recruited a nationally-representative sample of 5107 infants in 2004. Measures: Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1 to 6). Analysis: Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. Results4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: “consistently low” (86.2%), “moderate to low” (5.6%), “low to moderate” (6.7%) and “consistently high” (1.4%). Antibiotic use in pregnancy was associated with children following “consistently high” (aOR 2.06, 95% CI 1.09 to 3.91, p=0.03) and “moderate to low” (aOR 1.78, 95% CI 1.25 to 2.53, p=0.001) trajectories.ConclusionsAntibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for study of potential mechanisms underlying these associations.

Background Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities. Methods Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years. Results For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian’s agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles. We consider governance, ethical and shared trial oversight, and expectations that trials will adhere to the best practice of the day. Conclusions Children and younger adults can access fewer trials than older adults. Integrating trials into mega-cohorts should improve health and well-being by generating faster, larger-scale evidence on a longer and/or broader horizon than previously possible. GenV will explore the limits and details of this approach over the coming years.

BACKGROUND Many current research needs can only be addressed using very large cohorts. In such studies, traditional one-on-one phone, face-to-face, or paper-based engagement may not be feasible. The only realistic mechanism for maintaining engagement and participation at this scale is via digital methods. Given the substantial investment being made into very large birth cohort studies, evidence for optimal methods of participant engagement, participation, and retention over sustained periods without in-person contact from researchers is paramount. OBJECTIVE This study aims to provide an overview of systematic reviews and meta-analyses evaluating alternative strategies for maximizing participant engagement and retention rates in large-scale studies using digital methods. METHODS We used a rapid review method by searching PubMed and Ovid MEDLINE databases from January 2012 to December 2019. Studies evaluating at least 1 e-engagement, participation, or retention strategy were eligible. Articles were screened for relevance based on preset inclusion and exclusion criteria. The methodological quality of the included reviews was assessed using the AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews 2) measurement tool, and a narrative synthesis of the data was conducted. RESULTS The literature search yielded 19 eligible reviews. Overall, 63% (n=12) of these reviews reported on the effectiveness of e-engagement or participation promotion strategies. These evaluations were generally not conducted within very large observational digital cohorts. Most of the contributing reviews included multipurpose cohort studies (with both observational and interventional elements) conducted in clinical and research settings. Email or SMS text message reminders, SMS text messages or voice notifications, and incentives were the most commonly used design features to engage and retain participants. For parental outcomes, engagement-facilitation interventions influenced uptake and behavior change, including video feedback, goal setting, and intensive human facilitation and support. Participant-stated preferences for content included new knowledge, reminders, solutions, and suggestions about health issues presented in a clear, short, and personalized way. Perinatal and postpartum women valued self-monitoring and personalized feedback. Digital reminders and multiple SMS text messages were specific strategies that were found to increase adherence to medication and clinic attendance, respectively. CONCLUSIONS This review adds to the growing literature evaluating methods to optimize engagement and participation that may apply to large-scale studies using digital methods; it is promising that most e-engagement and participation promotion strategies appear to be effective. However, these reviews canvassed relatively few strategies, suggesting that few alternative strategies have been experimentally evaluated. The reviews also revealed a dearth of experimental evidence generated within very large observational digital cohort studies, which may reflect the small number of such studies worldwide. Thus, very large studies may need to proactively build in experimental opportunities to test engagement and retention approaches to enhance the success of their own and other large digital contact studies.

OBJECTIVES: Subgroups of children may benefit more from working memory training than others. In this study, we aimed to examine whether response to the Cogmed Working Memory Training program differed for children with low IQ and elevated attention-deficit/hyperactivity disorder, emotional and behavioral symptoms, special health care needs, or by sex. METHODS: We used data from the Memory Maestros trial, a population-based randomized controlled trial of the Cogmed program delivered at school (n = 226) compared to usual teaching (n = 226) in grade 1 children (mean age 6.9 years; SD 0.4) with low working memory. Cogmed comprises 20 to 25 sessions of 45-minute duration over 5 to 7 weeks. Children completed subtests from the Automated Working Memory Assessment to measure change in working memory from baseline to 6 months postrandomization. RESULTS: After training, improved working memory standard scores (>1 SD) from baseline to 6 months were observed for approximately one-third of the children, with more than half maintaining stable scores (within 1 SD). However, similar outcomes were observed for children receiving usual teaching. Differential effect of Cogmed versus usual teaching was evident for children with elevated hyperactivity and/or inattention, who were less likely to show improved visuospatial working memory, but not for other subgroups studied. CONCLUSIONS: Children with elevated hyperactivity and/or inattention were less likely to show clinically meaningful improvement after Cogmed; however, differential effects were not evident for children with low IQ and elevated emotional and behavioral symptoms, special health care needs, or by sex. More research is needed to determine if training can improve working memory and, if so, for whom.

Purpose Daily time spent on one activity cannot change without compensatory changes in others, which themselves may impact on health outcomes. Optimal daily activity combinations may differ across outcomes. We estimated optimal daily activity durations for the highest fitness and lowest adiposity. Methods Cross-sectional Child Health CheckPoint data (1182 11-12-year-olds; 51% boys) from the population-based Longitudinal Study of Australian Children were used. Daily activity composition (sleep, sedentary time, light physical activity [LPA], moderate-to-vigorous physical activity [MVPA]) was from 8-day, 24-hour accelerometry. We created composite outcomes for fitness (VO2max; standing long jump) and adiposity (waist-to-height ratio; body mass index; fat-to-fat-free log-ratio). Adjusted compositional models regressed activity log-ratios against each outcome. Best activity compositions (optimal time-use zones) were plotted in quaternary tetrahedrons; the overall optimal time-use composition was the center of the overlapping area. Results Time-use composition was associated with fitness and adiposity (all measures pfitness days had higher LPA (3.4 h) and shorter sleep (8.25 h), but optimal adiposity days had lower LPA (1.0 h) and longer sleep (10.9 h). Balancing both outcomes, the overall optimal time-use composition was (mean [range]): 10.2 [9.5; 10.5] h sleep, 9.9 [8.8; 11.2] h sedentary time, 2.4 [1.8; 3.2] h LPA and 1.5 [1.5; 1.5] h MVPA. Conclusion Optimal time use for children’s fitness and adiposity involves trade-offs. To best balance both outcomes, estimated activity durations for sleep and LPA align with, but for MVPA exceed, 24-h guidelines.

Objective We examined associations between retinal microvascular and large arterial phenotypes to explore relationships between the micro‐ and macro‐vasculature in childhood and midlife. Methods Participants were 1288 children (11‐12 years, 50.9% female) and 1264 adults (mean age 44 years, 87.6% female) in a cross‐sectional population‐based study. Exposures were retinal arteriolar and venular caliber quantified from retinal images. Outcomes included arterial function (pulse wave velocity; carotid arterial elasticity) and structure (carotid intima‐media thickness). Multivariable regression models were performed adjusting for age, sex, and family socioeconomic position. Results In children, one standard deviation wider arteriolar caliber was associated with slower pulse wave velocity (−0.15 SD, 95% CI −0.21, −0.09) and higher elasticity (0.13 SD, 95% CI 0.06, 0.20); per SD wider venular caliber was associated with faster pulse wave velocity (0.09 SD, 95% CI 0.03, 0.15) and lower elasticity (−0.07 SD, 95% CI −0.13, −0.01). The size of adult associations was approximately double. Wider arteriolar caliber was associated with smaller carotid intima‐media thickness (−0.09 SD, 95% CI −0.16, −0.03) in adults but not children. Venular caliber and carotid intima‐media thickness showed little evidence of association. Conclusions Narrower retinal arterioles and wider venules are associated with large arterial function as early as mid‐childhood. Associations strengthen by midlife and also extend to arterial structure, although effect sizes remain small.