Paediatrics (RCH) - Research Publications

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    Fat-Soluble Vitamers: Parent-Child Concordance and Population Epidemiology in the Longitudinal Study of Australian Children
    Arachchige, GRP ; Pook, CJ ; Jones, B ; Coe, M ; Saffery, R ; Wake, M ; Thorstensen, EB ; O'Sullivan, JM (MDPI, 2022-12)
    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.
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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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    Your best day: An interactive app to translate how time reallocations within a 24-hour day are associated with health measures
    Dumuid, D ; Olds, T ; Wake, M ; Rasmussen, CL ; Pedisic, Z ; Hughes, JH ; Foster, DJR ; Walmsley, R ; Atkin, AJ ; Straker, L ; Fraysse, F ; Smith, RT ; Neumann, F ; Kenett, RS ; Mork, PJ ; Bennett, D ; Doherty, A ; Stanford, T ; Harezlak, J (PUBLIC LIBRARY SCIENCE, 2022-09-07)
    Reallocations of time between daily activities such as sleep, sedentary behavior and physical activity are differentially associated with markers of physical, mental and social health. An individual's most desirable allocation of time may differ depending on which outcomes they value most, with these outcomes potentially competing with each other for reallocations. We aimed to develop an interactive app that translates how self-selected time reallocations are associated with multiple health measures. We used data from the Australian Child Health CheckPoint study (n = 1685, 48% female, 11-12 y), with time spent in daily activities derived from a validated 24-h recall instrument, %body fat from bioelectric impedance, psychosocial health from the Pediatric Quality of Life Inventory and academic performance (writing) from national standardized tests. We created a user-interface to the compositional isotemporal substitution model with interactive sliders that can be manipulated to self-select time reallocations between activities. The time-use composition was significantly associated with body fat percentage (F = 2.66, P < .001), psychosocial health (F = 4.02, P < .001), and academic performance (F = 2.76, P < .001). Dragging the sliders on the app shows how self-selected time reallocations are associated with the health measures. For example, reallocating 60 minutes from screen time to physical activity was associated with -0.8 [95% CI -1.0 to -0.5] %body fat, +1.9 [1.4 to 2.5] psychosocial score and +4.5 [1.8 to 7.2] academic performance. Our app allows the health associations of time reallocations to be compared against each other. Interactive interfaces provide flexibility in selecting which time reallocations to investigate, and may transform how research findings are disseminated.
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    Improving Cohort-Hospital Matching Accuracy through Standardization and Validation of Participant Identifiable Information
    Hu, YJ ; Fedyukova, A ; Wang, J ; Said, JMM ; Thomas, N ; Noble, E ; Cheong, JLY ; Karanatsios, B ; Goldfeld, S ; Wake, M (MDPI, 2022-12)
    Linking very large, consented birth cohorts to birthing hospitals clinical data could elucidate the lifecourse outcomes of health care and exposures during the pregnancy, birth and newborn periods. Unfortunately, cohort personally identifiable information (PII) often does not include unique identifier numbers, presenting matching challenges. To develop optimized cohort matching to birthing hospital clinical records, this pilot drew on a one-year (December 2020-December 2021) cohort for a single Australian birthing hospital participating in the whole-of-state Generation Victoria (GenV) study. For 1819 consented mother-baby pairs and 58 additional babies (whose mothers were not themselves participating), we tested the accuracy and effort of various approaches to matching. We selected demographic variables drawn from names, DOB, sex, telephone, address (and birth order for multiple births). After variable standardization and validation, accuracy rose from 10% to 99% using a deterministic-rule-based approach in 10 steps. Using cohort-specific modifications of the Australian Statistical Linkage Key (SLK-581), it took only 3 steps to reach 97% (SLK-5881) and 98% (SLK-5881.1) accuracy. We conclude that our SLK-5881 process could safely and efficiently achieve high accuracy at the population level for future birth cohort-birth hospital matching in the absence of unique identifier numbers.
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    Multi-omics analysis from archival neonatal dried blood spots: limitations and opportunities
    Zhuang, Y-J ; Mangwiro, Y ; Wake, M ; Saffery, R ; Greaves, RF (WALTER DE GRUYTER GMBH, 2022-08-26)
    Newborn screening (NBS) programs operate in many countries, processing millions of dried bloodspot (DBS) samples annually. In addition to early identification of various adverse health outcomes, these samples have considerable potential as a resource for population-based research that could address key questions related to child health. The feasibility of archival DBS samples for emerging targeted and untargeted multi-omics analysis has not been previously explored in the literature. This review aims to critically evaluate the latest advances to identify opportunities and challenges of applying omics analyses to NBS cards in a research setting. Medline, Embase and PubMed databases were searched to identify studies utilizing DBS for genomic, proteomic and metabolomic assays. A total of 800 records were identified after removing duplicates, of which 23 records were included in this review. These papers consisted of one combined genomic/metabolomic, four genomic, three epigenomic, four proteomic and 11 metabolomic studies. Together they demonstrate that the increasing sensitivity of multi-omic analytical techniques makes the broad use of NBS samples achievable for large cohort studies. Maintaining the pre-analytical integrity of the DBS sample through storage at temperatures below -20 °C will enable this important resource to be fully realized in a research capacity.
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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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    Modifiable Early Childhood Risk Factors for Obesity at Age Four Years
    Malihi, Z ; Portch, R ; Hashemi, L ; Schlichting, D ; Wake, M ; Morton, S ; Fa'alili-Fidow, J ; Mensah, F ; Olds, T ; Carr, PA ; Kingi, TK ; Grant, CC ; Denny, S (MARY ANN LIEBERT, INC, 2021-04-01)
    Background: Childhood obesity is associated with an increased risk of adult obesity and related chronic disease. Our aim was to identify modifiable exposures that are independently associated with obesity in the preschool age group. Methods: A prospective cohort study of 5734 children in New Zealand with anthropometric measurements was completed at age 4.5 years. The modifiable exposures of interest, measured at age 9 months and 2 years, were: food security during infancy; and, at age 2 years, screen time; sleep duration; and takeaway food and soft drink intake. The risk of obesity independently associated with each exposure was determined using Binomial and Poisson regression and described using adjusted risk ratios (RRs) and 95% confidence intervals (CIs), after controlling for confounding variables including gender, ethnicity, birth weight, and mother's age. The probability of obesity given cumulative exposures to the four risk factors and the population attributable fraction (PAF) were estimated. Results: Lower food security during infancy (1 hour/day; RR = 1.22; 95% CI : 1.01-1.48), shorter sleep duration (≤11.5 hours/day; RR = 1.30; 95% CI : 1.05-1.61), and weekly to daily consumption of takeaway/soft drink (RR = 1.25, 95% CI : 1.00-1.57) were independently associated with an increased risk of obesity at age 4.5 years. The cumulative PAF for childhood obesity was 42.9%, under an ideal scenario where all risk factors were eliminated. Conclusion: Exposure to modifiable factors by age 2 years is associated with obesity at age 4.5 years. Interventions to prevent childhood obesity need to be effective during infancy.
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    The role of Australian clinical quality registries in pregnancy care: A scoping review
    Campion, TSD ; Daly, JO ; Wake, M ; Ahern, S ; Said, JM (WILEY, 2022-08)
    BACKGROUND: Pregnancy represents a time of increased morbidity and mortality for women and their infants. Clinical quality registries (CQRs) collect, analyse and report key healthcare quality indicators for patient cohorts to improve patient care. There are limited data regarding existing CQRs in pregnancy. This scoping review aimed to: (1) identify Australian CQRs specific to pregnancy care and describe their general characteristics; and (2) outline their aims and measured outcomes METHODS: The scoping review was undertaken according to Joanna Briggs Institute guidelines. CQRs were identified using a systematic approach from publications (Ovid MEDLINE, PubMed, Google Scholar), peer consultation, the Australian register of clinical registries and web searches. Details surrounding general characteristics, aims and outcomes were collated. RESULTS: We identified two primary sources of information about pregnancy care. (1) Six CQRs are specific to pregnancy (Australia and New Zealand twin-twin transfusion syndrome registry, Australian Pregnancy Register for women with epilepsy and those taking anti-epileptic drugs, National Register of Antipsychotic Medication in Pregnancy, Australasian Maternity Outcomes Surveillance System, Neonatal Alloimmune Thrombocytopaenia Registry and the Diabetes in Pregnancy clinical register). (2) Fourteen observational cohort studies were facilitated by non-pregnancy-specific CQRs where a subsection of patients underwent pregnancy. CONCLUSIONS: Australian CQRs currently report varied information regarding some selected conditions during pregnancy and offer therapeutic and epidemiological insight into their care. Further research into their effectiveness is warranted. We note the lack of a CQR spanning the common problems of pregnancy in general, where significant health, service and economic gains are possible.
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    Association of in utero antibiotic exposure on childhood ear infection trajectories: Results from a national birth cohort study
    Hu, YJ ; Wang, J ; Harwell, J ; Wake, M (WILEY, 2021-07)
    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.
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    Potential indirect impacts of the COVID-19 pandemic on children: a narrative review using a community child health lens
    Goldfeld, S ; O'Connor, E ; Sung, V ; Roberts, G ; Wake, M ; West, S ; Hiscock, H (WILEY, 2022-04-18)
    ▪In this narrative review, we summarise the vast and burgeoning research on the potential and established indirect impacts on children of the COVID-19 pandemic. We used a community child health lens to organise our findings and to consider how Australia might best respond to the needs of children (aged 0-12 years). ▪We synthesised the literature on previous pandemics, epidemics and natural disasters, and the current COVID-19 pandemic. We found clear evidence of adverse impacts of the COVID-19 pandemic on children that either repeated or extended the findings from previous pandemics. ▪We identified 11 impact areas, under three broad categories: child-level factors (poorer mental health, poorer child health and development, poorer academic achievement); family-level factors that affect children (poorer parent mental health, reduced family income and job losses, increased household stress, increased abuse and neglect, poorer maternal and newborn health); and service-level factors that affect children (school closures, reduced access to health care, increased use of technology for learning, connection and health care). ▪There is increasing global concern about the likely disproportionate impact of the current pandemic on children experiencing adversity, widening existing disparities in child health and developmental outcomes. ▪We suggest five potential strategy areas that could begin to address these inequities: addressing financial instability through parent financial supplements; expanding the role of schools to address learning gaps and wellbeing; rethinking health care delivery to address reduced access; focusing on prevention and early intervention for mental health; and using digital solutions to address inequitable service delivery.