Paediatrics (RCH) - Research Publications

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    The effect of adverse and positive experiences on inflammatory markers in Australian and UK children
    Priest, N ; Guo, S ; Gondek, D ; Lacey, RE ; Burgner, D ; Downes, M ; Slopen, N ; Goldfeld, S ; Moreno-Betancur, M ; Kerr, JA ; Cahill, S ; Wake, M ; Juonala, M ; Lycett, K ; O'Connor, M (ELSEVIER, 2022-12)
    BACKGROUND: The relationship between childhood adversity and inflammation is well-established. Examination of positive experiences can provide a more complete understanding of intervention opportunities. We investigated associations of adverse and positive experiences, and their intersection, with inflammation in children and adolescents. 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 repeatedly (LSAC: 0-11 years; ALSPAC: 0-15 years). Outcomes: Inflammation quantified by high sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA) (LSAC: 11-12 years; ALSPAC: 15.5 years). Analyses: Linear regression on the log-transformed outcomes estimated the relative difference in inflammatory markers with adverse/positive experiences, adjusting for socio-demographics and concurrent positive/adverse experiences, respectively. RESULTS: Most associations were in the expected direction but differed in magnitude by exposure, outcome and cohort. Across both cohorts, adverse experiences were associated with up to 7.3% higher hsCRP (95% CI: -18.6%, 33.2%) and up to 2.0% higher GlycA (95% CI: 0.5%, 3.5%); while positive experiences were associated with up to 22.1% lower hsCRP (95% CI: -49.0%, 4.7%) and 1.3% lower GlycA (95% CI: -2.7%, 0.2%). In LSAC, the beneficial effect of positive experiences on inflammation was more pronounced among those with fewer concurrent adverse experiences. CONCLUSION: Across two cohorts, we found small but directionally consistent associations between adverse experiences and higher inflammation, and positive experiences and lower inflammation, particularly for GlycA. Future research should give further consideration to positive experiences to complement the current focus on adversity and inform the design and evaluation of early life interventions.
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    Data Resource Profile: Melbourne Children's LifeCourse initiative (LifeCourse)
    O'Connor, M ; Moreno-Betancur, M ; Goldfeld, S ; Wake, M ; Patton, G ; Dwyer, T ; Tang, MLK ; Saffery, R ; Craig, JM ; Loke, J ; Burgner, D ; Olsson, CA ; Investigators, LC (OXFORD UNIV PRESS, 2022-10-13)
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    No obvious impact of caesarean delivery on childhood allergic outcomes: findings from Australian cohorts
    Liao, Z ; Lamb, KE ; Burgner, D ; Ranganathan, S ; Miller, JE ; Koplin, JJ ; Dharmage, SC ; Lowe, AJ ; Ponsonby, A-L ; Tang, MLK ; Allen, KJ ; Wake, M ; Peters, RL (BMJ PUBLISHING GROUP, 2020-07)
    BACKGROUND AND OBJECTIVE: As caesarean delivery and childhood allergy continue to rise, their inter-relationships may change. We examined whether caesarean delivery predicts allergic disease and impaired lung function in two contemporary harmonised population-based cohorts. METHODS: Parent-reported asthma and eczema data were drawn from two prospective Australian infant cohorts, HealthNuts (n=5276, born 2006-2010) and the Longitudinal Study of Australian Children (LSAC, n=5107, born 2003-2004) at age 6-7 years, and spirometric lung function from LSAC's Child Health CheckPoint (n=1756) at age 11-12 years. Logistic regression estimated associations between delivery mode and current asthma and eczema at 6-7 years, and linear regression examined lung function at 11-12 years. Models were adjusted for potential confounding factors. RESULTS: Complete case analysis included 3135 HealthNuts and 3654 LSAC children (32.2% and 30.9% born by caesarean, respectively). An association was evident between caesarean delivery and asthma at age 6-7 years in HealthNuts (adjusted OR (aOR) 1.25, 95% CI 1.00 to 1.57) but not in LSAC (aOR 1.05, 95% CI 0.86 to 1.28), while neither study showed clear associations with eczema (HealthNuts: aOR 1.09, 95% CI 0.88 to 1.35; LSAC: aOR 0.89, 95% CI 0.69 to 1.15). Spirometric lung function parameters at age 11-12 years were similar by delivery mode. Associations were not modified by duration of breast feeding, maternal history of asthma/eczema, childcare attendance, number of older siblings or pet exposure. CONCLUSIONS: In two unselected populations using harmonised protocols, the likely association of caesarean delivery with developing childhood allergy was small.
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    Balancing time use for children's fitness and adiposity: Evidence to inform 24-hour guidelines for sleep, sedentary time and physical activity
    Dumuid, D ; Wake, M ; Burgner, D ; Tremblay, MS ; Okely, AD ; Edwards, B ; Dwyer, T ; Olds, T ; Bergman, P (PUBLIC LIBRARY SCIENCE, 2021-01-19)
    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 p<0.001). Optimal time use differed for fitness and adiposity. While both maximized MVPA and minimized sedentary time, optimal fitness 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.
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    The "Goldilocks Day" for Children's Skeletal Health: Compositional Data Analysis of 24-Hour Activity Behaviors
    Dumuid, D ; Simm, P ; Wake, M ; Burgner, D ; Juonala, M ; Wu, F ; Magnussen, CG ; Olds, T (WILEY, 2020-12)
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    Associations of retinal microvascular caliber with large arterial function and structure: A population-based study of 11 to 12 year-olds and midlife adults
    Liu, M ; Lycett, K ; Wong, TY ; Grobler, A ; Juonala, M ; He, M ; Dwyer, T ; Burgner, D ; Wake, M (WILEY, 2020-08)
    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.
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    Plasma B Vitamers: Population Epidemiology and Parent-Child Concordance in Children and Adults
    Andraos, S ; Jones, B ; Wall, C ; Thorstensen, E ; Kussmann, M ; Cameron-Smith, D ; Lange, K ; Clifford, S ; Saffery, R ; Burgner, D ; Wake, M ; O'Sullivan, J (MDPI, 2021-03)
    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.
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    Population epidemiology and concordance for plasma amino acids and precursors in 11-12-year-old children and their parents
    Andraos, S ; Lange, K ; Clifford, SA ; Jones, B ; Thorstensen, EB ; Wake, M ; Burgner, DP ; Saffery, R ; O'Sullivan, JM (NATURE PORTFOLIO, 2021-02-11)
    Amino acid (AA) concentrations are influenced by both exogenous (e.g. diet, lifestyle) and endogenous factors (e.g. genetic, transcriptomic, epigenetic, and metabolomic). Fasting plasma AA profiles in adulthood are predictive of diabetes risk over periods of up to 12 years. Data on AA profiles in cross-generational cohorts, including individuals from shared gene-environment settings are scarce, but would allow the identification of the contribution of heritable and environmental factors characterising the levels of circulating AAs. This study aimed to investigate parent-child (familial dyad) concordance, absolute differences between generations- (children versus adults), age- (in adults: 28-71 years), and sex-dependent differences in plasma AA concentrations. Plasma AA concentrations were measured by UHPLC/MS-MS in 1166 children [mean (SD) age 11 (0.5) years, 51% female] and 1324 of their parents [44 (5.1) years, 87% female]. AA concentrations were variably concordant between parents and their children (5-41% of variability explained). Most AA concentrations were higher in adults than children, except for the non-essential AAs arginine, aspartic acid, glutamine, hydroxy-proline, proline, and serine. Male adults and children typically had higher AA concentrations than females. The exceptions were alanine, glutamine, glycine, hydroxy-proline, serine, and threonine in girls; and glycine and serine in women. Age, sex, and shared familial factors are important determinants of plasma AA concentrations.
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    Trimethylamine N-oxide (TMAO) Is not Associated with Cardiometabolic Phenotypes and Inflammatory Markers in Children and Adults
    Andraos, S ; Jones, B ; Lange, K ; Clifford, SA ; Thorstensen, EB ; Kerr, JA ; Wake, M ; Saffery, R ; Burgner, DP ; M O'Sullivan, J (OXFORD UNIV PRESS INC, 2021-01)
    BACKGROUND: Trimethylamine N-oxide (TMAO) is a diet- and microbiome-derived metabolite and a proposed biomarker of adverse cardiometabolic outcomes. TMAO studies have mainly been conducted in individuals with cardiometabolic disease, and studies in population-derived samples are limited. OBJECTIVE: We aimed to investigate the associations between plasma TMAO concentrations and its precursors [carnitine, choline, betaine, and dimethylglycine (DMG)] with metabolic syndrome (MetS) scores, preclinical cardiovascular phenotypes, and inflammatory biomarkers (i.e. high-sensitivity C-reactive protein and serum glycoprotein acetyls) in a population-derived cohort of children and their parents. METHODS: The concentrations of TMAO and its precursors were quantified using UHPLC coupled with tandem MS (UHPLC/MS-MS) in 1166 children (mean age 11 y ± 0.5 y, 51% female) and 1324 adults (44 y ± 5.1 y, 87% female) participating in The Growing Up in Australia's Child Health CheckPoint Study. We developed multivariable fractional polynomial models to analyze associations between TMAO, its precursors, MetS (adjusted for sex and age), and cardiovascular phenotypes (adjusted for sex, age, BMI, household income, and the urinary albumin to creatinine ratio). Pearson's correlations were computed to identify associations between TMAO, its precursors, and inflammatory biomarkers. RESULTS: The concentrations of TMAO precursors, but not TMAO itself, were associated with MetS, cardiovascular phenotypes, and inflammatory biomarkers in children and adults. CONCLUSIONS: TMAO precursors, but not TMAO itself, were associated with adverse cardiometabolic and inflammatory phenotypes in children and adults. TMAO precursor concentrations may better reflect cardiovascular health and inflammatory status within the wider population. Replication in other population settings and mechanistic studies are warranted.
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    Sleep and cardiometabolic risk: a cluster analysis of actigraphy-derived sleep profiles in adults and children
    Matricciani, L ; Paquet, C ; Fraysse, F ; Grobler, A ; Wang, Y ; Baur, L ; Juonala, M ; Nguyen, MT ; Ranganathan, S ; Burgner, D ; Wake, M ; Olds, T (OXFORD UNIV PRESS INC, 2021-07)
    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.