Paediatrics (RCH) - Research Publications
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ItemVitamin D insufficiency in the first 6 months of infancy and challenge-proven IgE-mediated food allergy at 1 year of age: a case-cohort study(WILEY, 2017-08)BACKGROUND: Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. OBJECTIVE: To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. METHODS: In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D3 (25(OH)D3 ) levels among infants with food allergy vs a random subcohort (n = 274). The primary exposures were VDI (25(OH)D3 <50 nM) at birth and 6 months of age. Ambient UVR and time in the sun were combined to estimate UVR exposure dose. IgE-mediated food allergy status at 1 year was determined by formal challenge. Binomial regression was used to examine associations between VDI, UVR exposure dose and food allergy and investigate potential confounding. RESULTS: Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. CONCLUSIONS: There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required.
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ItemThe association between higher maternal pre-pregnancy body mass index and increased birth weight, adiposity and inflammation in the newborn(WILEY, 2018-01)BACKGROUND: Excess adiposity and adiposity-related inflammation are known risk factors for cardiovascular disease in adults; however, little is known regarding the determinants of adiposity-related inflammation at birth. OBJECTIVES: The aim of this study was to investigate the association between maternal pre-pregnancy BMI and newborn adiposity and inflammation. METHODS: Paired maternal (28-week gestation) and infant (umbilical cord) blood samples were collected from a population-derived birth cohort (Barwon Infant Study, n = 1074). Data on maternal comorbidities and infant birth anthropomorphic measures were compiled, and infant aortic intima-media thickness was measured by trans-abdominal ultrasound. In a selected subgroup of term infants (n = 161), matched maternal and cord lipids, high-sensitivity C-reactive protein (hsCRP) and maternal soluble CD14 were measured. Analysis was completed by using pairwise correlation and linear regression. Because of their non-normal distribution, pathology blood measures were log transformed prior to analysis. RESULTS: Maternal pre-pregnancy BMI was positively associated with increased birth weight (mean difference 17.8 g per kg m-2 , 95% CI 6.6 to 28.9; p = 0.002), newborn mean skin-fold thickness (mean difference 0.1 mm per kg m-2 , 95% CI 0.0 to 0.1; p < 0.001) and cord blood hsCRP (mean difference of 4.2% increase in hsCRP per kg m-2 increase in pre-pregnancy BMI, 95% CI 0.6 to 7.7%, p = 0.02), but not cord blood soluble CD14. Inclusion of maternal hsCRP as a covariate attenuated the associations between pre-pregnancy BMI and both newborn skin-fold thickness and cord blood hsCRP. CONCLUSION: Higher maternal pre-pregnancy BMI is associated with increased newborn adiposity and inflammation. These associations may be partially mediated by maternal inflammation during pregnancy.
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ItemSocioeconomic Position Is Associated With Carotid Intima-Media Thickness in Mid-Childhood: The Longitudinal Study of Australian Children(WILEY, 2017-08)BACKGROUND: Lower socioeconomic position (SEP) predicts higher cardiovascular risk in adults. Few studies differentiate between neighborhood and family SEP or have repeated measures through childhood, which would inform understanding of potential mechanisms and the timing of interventions. We investigated whether neighborhood and family SEP, measured biennially from ages 0 to 1 year onward, was associated with carotid intima-media thickness (IMT) at ages 11 to 12 years. METHODS AND RESULTS: Data were obtained from 1477 families participating in the Child Health CheckPoint study, nested within the Longitudinal Study of Australian Children. Disadvantaged family and neighborhood SEP was cross-sectionally associated with thicker maximum carotid IMT in separate univariable linear regression models. Associations with family SEP were not attenuated in multivariable analyses, and associations with neighborhood SEP were attenuated only in models adjusted for family SEP. The difference in maximum carotid IMT between the highest and lowest family SEP quartile measured at ages 10 to 11 years was 10.7 μm (95% CI, 3.4-18.0; P=0.004), adjusted for age, sex, pubertal status, passive smoking exposure, body mass index, blood pressure, and arterial lumen diameter. In longitudinal analyses, family SEP measured as early as age 2 to 3 years was associated with maximum carotid IMT at ages 11 to 12 years (difference between highest and lowest quartile: 8.5 μm; 95% CI, 1.3-15.8; P=0.02). No associations were observed between SEP and mean carotid IMT. CONCLUSIONS: We report a robust association between lower SEP in early childhood and carotid IMT in mid-childhood. Further investigation of mechanisms may inform pediatric cardiovascular risk assessment and prevention strategies.
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ItemHigher parental occupational social contact is associated with a reduced risk of incident pediatric type 1 diabetes: Mediation through molecular enteroviral indices(PUBLIC LIBRARY SCIENCE, 2018-04-17)We aimed to examine the association between parental occupational social contact and hygiene factors on type 1 diabetes (T1D) risk and possible mediation of these effects through child enteroviral infection. We interviewed 333 incident T1D cases and 660 controls from 2008-2011 in Melbourne, Australia. Enteroviral indices (ribonucleic acid by reverse transcription polymerase chain reaction and Coxsackie B virus antibody levels) in peripheral blood were measured in nested case control samples. Parent occupational social contact was assessed by the number of well or sick children, adults or animals contacted daily through work. Higher parental occupational social contact was strongly associated with reduced T1D risk with evidence of dose response (contact with the well or sick score, Adjusted odds ratio (AOR) per category: 0.73 (95% Confidence Interval (CI): 0.66, 0.81); P<0.001 or AOR 0.63 (95% CI: 0.53, 0.75); P<0.001) respectively). Nine of the ten parental social contact indices, were significant mediated through one or more enteroviral indices. The strength of association between enterovirus presence and T1D onset increased with child age (1.2 fold increase per year; P = 0.05). Lower child hand hygiene enhanced the adverse effect of low parental occupational contact with the sick; Synergy Index 5.16 (95% CI: 3.61, 7.36). The interaction between hand washing and parental occupational contact is more consistent with protection against parental enteroviral shedding than the sharing of a protective infectious agent or microbiome.
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ItemEarly-life determinants of hypoxia-inducible factor 3A gene(HIF3A) methylation: a birth cohort study(BMC, 2019-07-01)BACKGROUND: Methylation of the hypoxia-inducible factor 3α gene (HIF3A) has been linked to pregnancy exposures, infant adiposity and later BMI. Genetic variation influences HIF3A methylation levels and may modify these relationships. However, data in very early life are limited, particularly in association with adverse pregnancy outcomes. We investigated the relationship between maternal and gestational factors, infant anthropometry, genetic variation and HIF3A DNA methylation in the Barwon Infant Study, a population-based birth cohort. Methylation of two previously studied regions of HIF3A were tested in the cord blood mononuclear cells of 938 infants. RESULTS: No compelling evidence was found of an association between birth weight, adiposity or maternal gestational diabetes with methylation at the most widely studied HIF3A region. Male sex (- 4.3%, p < 0.001) and pre-eclampsia (- 5.4%, p = 0.02) negatively associated with methylation at a second region of HIF3A; while positive associations were identified for gestational diabetes (4.8%, p = 0.01) and gestational age (1.2% increase per week, p < 0.001). HIF3A genetic variation also associated strongly with methylation at this region (p < 0.001). CONCLUSIONS: Pre- and perinatal factors impact HIF3A methylation, including pre-eclampsia. This provides evidence that specific pregnancy complications, previously linked to adverse outcomes for both mother and child, impact the infant epigenome in a molecular pathway critical to several vascular and metabolic conditions. Further work is required to understand the mechanisms and clinical relevance, particularly the differing effects of in utero exposure to gestational diabetes or pre-eclampsia.
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ItemChild Health CheckPoint: cohort summary and methodology of a physical health and biospecimen module for the Longitudinal Study of Australian Children(BMJ PUBLISHING GROUP, 2019-07-04)OBJECTIVES: 'Growing Up in Australia: The Longitudinal Study of Australian Children' (LSAC) is Australia's only nationally representative children's longitudinal study, focusing on social, economic, physical and cultural impacts on health, learning, social and cognitive development. LSAC's first decade collected wide-ranging repeated psychosocial and administrative data; here, we describe the Child Health CheckPoint, LSAC's dedicated biophysical module. DESIGN, SETTING AND PARTICIPANTS: LSAC recruited a cross-sequential sample of 5107 infants aged 0-1 year and a sample of 4983 children aged 4-5 years in 2004, since completing seven biennial visits. CheckPoint was a cross-sectional wave that travelled Australia in 2015-2016 to reach LSAC's younger cohort at ages 11-12 years between LSAC waves 6 and 7. Parent-child pairs participated in comprehensive assessments at 15 Assessment Centres nationwide or, if unable to attend, a shorter home visit. MEASURES: CheckPoint's intergenerational, multidimensional measures were prioritised to show meaningful variation within normal ranges and capture non-communicable disease (NCD) phenotype precursors. These included anthropometry, physical activity, fitness, time use, vision, hearing, and cardiovascular, respiratory and bone health. Biospecimens included blood, saliva, buccal swabs (also from second parent), urine, hair and toenails. The epidemiology and parent-child concordance of many measures are described in separate papers. RESULTS: 1874 (54% of eligible) parent-child pairs and 1051 second parents participated. Participants' geographical distribution mirrored the broader Australian population; however, mean socioeconomic position and parental education were higher and fewer reported non-English-speaking or Indigenous backgrounds. Application of survey weights partially mitigates that the achieved sample is less population representative than previous waves of LSAC due to non-random attrition. Completeness was uniformly high for phenotypic data (>92% of eligible), biospecimens (74%-97%) and consent (genetic analyses 98%, accessing neonatal blood spots 97%, sharing 96%). CONCLUSIONS: CheckPoint enriches LSAC to study how NCDs develop at the molecular and phenotypic levels before overt disease emerges, and clarify the underlying dimensionality of health in childhood and mid-adulthood.
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ItemA Cross-Cohort Study Examining the Associations of Metabolomic Profile and Subclinical Atherosclerosis in Children and Their Parents: The Child Health CheckPoint Study and Avon Longitudinal Study of Parents and Children(WILEY, 2019-07-16)Background High-throughput nuclear magnetic resonance profiling of circulating metabolites is suggested as an adjunct for cardiovascular risk evaluation. The relationship between metabolites and subclinical atherosclerosis remains unclear, particularly among children. Therefore, we examined the associations of metabolites with carotid intima-media thickness ( cIMT ) and arterial pulse wave velocity ( PWV ). Methods and Results Data from two independent population-based studies was examined; (1) cross-sectional associations with cIMT and PWV in 1178 children (age 11-12 years, 51% female) and 1316 parents (mean age 45 years, 87% female) from the CheckPoint study (Australia); and (2) longitudinal associations in 4249 children (metabolites at 7-8 years, PWV at 10-11 years, 52% female), and cross-sectional associations in 4171 of their mothers (mean age 48 years, cIMT data) from ALSPAC (The Avon Longitudinal Study of Parents and Children; UK ). Metabolites were measured by the same nuclear magnetic resonance platform in both studies, comprising of 69 biomarkers. Biophysical assessments included body mass index, blood pressure, cIMT and PWV . In linear regression analyses adjusted for age, sex, body mass index, and blood pressure, there was no evidence of metabolite associations in either children or adults for cIMT at a 10% false discovery threshold. In CheckPoint adults, glucose was positively, and some high-density lipoprotein-cholesterol derived measures and amino acids (glutamine, histidine, tyrosine) inversely associated with PWV. Conclusions These data suggest that in children circulating metabolites have no consistent association with cIMT and PWV once adjusted for body mass index and blood pressure. In their middle-aged parents, some evidence of metabolite associations with PWV were identified that warrant further investigation.
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ItemMetabolomics: population epidemiology and concordance in Australian children aged 11-12 years and their parents(BMJ PUBLISHING GROUP, 2019-07-04)OBJECTIVES: Nuclear 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. DESIGN: The population-based cross-sectional Child Health CheckPoint study nested within the Longitudinal Study of Australian Children. SETTING: Blood samples collected from CheckPoint participants at assessment centres in seven Australian cities and eight regional towns; February 2015-March 2016. PARTICIPANTS: 1180 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 MEASURES: 228 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. RESULTS: We 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. CONCLUSIONS: We 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.
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ItemTime-Use Patterns and Health-Related Quality of Life in Adolescents(AMER ACAD PEDIATRICS, 2017-07)OBJECTIVES: To describe 24-hour time-use patterns and their association with health-related quality of life (HRQoL) in early adolescence. METHODS: The Child Health CheckPoint was a cross-sectional study nested between Waves 6 and 7 of the Longitudinal Study of Australian Children. The participants were 1455 11- to 12-year-olds (39% of Wave 6; 51% boys). The exposure was 24-hour time use measured across 259 activities using the Multimedia Activity Recall for Children and Adolescents. "Average" days were generated from 1 school and 1 nonschool day. Time-use clusters were derived from cluster analysis with compositional inputs. The outcomes were self-reported HRQoL (Physical and Psychosocial Health [PedsQL] summary scores; Child Health Utility 9D [CHU9D] health utility). RESULTS: Four time-use clusters emerged: "studious actives" (22%; highest school-related time, low screen time), "techno-actives" (33%; highest physical activity, lowest school-related time), "stay home screenies" (23%; highest screen time, lowest passive transport), and "potterers" (21%; low physical activity). Linear regression models, adjusted for a priori confounders, showed that compared with the healthiest "studious actives" (mean [SD]: CHU9D 0.84 [0.14], PedsQL physical 86.8 [10.8], PedsQL psychosocial 79.9 [12.6]), HRQoL in "potterers" was 0.2 to 0.5 SDs lower (mean differences [95% confidence interval]: CHU9D -0.03 [-0.05 to -0.00], PedsQL physical -5.5 [-7.4 to -3.5], PedsQL psychosocial -5.8 [-8.0 to -3.5]). CONCLUSIONS: Discrete time-use patterns exist in Australian young adolescents. The cluster characterized by low physical activity and moderate screen time was associated with the lowest HRQoL. Whether this pattern translates into precursors of noncommunicable diseases remains to be determined.