Utilising surface-level data to explore surface, tooth, individual and family influence on the aetiology of hypomineralised second primary molars

OBJECTIVES: Hypomineralised second primary molars (HSPM) are common developmental enamel defects. The aims of this study were to use surface-level data to explore the clustering of HSPM at four levels (family, child, tooth, surface). METHODS: This study of 172 twin pairs was nested within the Peri/postnatal Epigenetic Twin Study. HSPM was measured by standardised oral examinations at age 6 years. Multilevel logistic regression models were fitted to assess the correlation structure of surface level data and variation in HSPM. The associations between surface level risk factors and HSPM were then explored using the multilevel logistic regression model using the best fitting correlation structure. RESULTS: The prevalence of HSPM was 68 (19.8%) children, with a total of 141 (10.3%) teeth and 264 tooth surfaces (6.3%) affected. Multilevel models revealed that a hierarchical structure accounting for correlation at the family, child and tooth level best accounted for the variation in HSPM. The estimated variances from the best fitting model (Model 3) were largest at the family level (12.27, 95% CI 6.68, 22.51) compared with 5.23 at the child level and 1.93 at the tooth level. Application of regression analysis utilising this three-level correlation structure identified tooth/surface level factors in addition to the previously identified familial and individual risk factors for HSPM. CONCLUSION: In addition to familial (environmental and genetic) and unique child-level factors, the aetiology of HSPM is likely to be influenced by local tooth-level factors

Neighbourhood socioeconomic circumstances, adiposity and cardiometabolic risk measures in children with severe obesity

Background: It has recently been shown that neighbourhood socioeconomic disadvantage in childhood is associated with obesity, hypertension, fatty liver, and type 2 diabetes in adulthood. However, it is largely unknown whether neighbourhood socioeconomic circumstances are important predictors of adiposity and associated measures in children, especially in those with severe obesity. Therefore, we evaluated the associations between neighbourhood socioeconomic factors with the severity of obesity, and related cardiometabolic risk factors in a cohort of obese children.Methods: The Childhood Overweight BioRepository of Australia (COBRA) cohort study comprises 444 children (mean age 11.1 years, mean BMI z-score 2.5). Neighbourhood socioeconomic advantage/disadvantage was evaluated based on postcode information by the national Australian Socio-Economic Indexes for Areas (SEIFA) scores. Participants/parents also completed self-administered questionnaires on neighbourhood related facilities, family education and family income.Results: In analyses adjusted for age, sex and pubertal status, SEIFA indicating neighbourhood education/occupation was negatively associated with BMI, waist circumference and body fat%. Higher family education was associated with lower BMI. Neighbourhood walkability was related to lower waist circumference. Good shopping facilities in the neighbourhood were associated with increased risk of dyslipidemia and fatty liver, and the existence of parks and playgrounds nearby was related to dyslipidemia.Conclusions: The present data suggest that neighbourhood-related issues are associated with less severe adiposity among children with established obesity. Concerning cardiometabolic risk factors, shopping facilities were related to dyslipidemia and fatty liver. These findings suggest that increased awareness and efforts are needed to diminish socioeconomic inequalities between neighbourhoods.</p

Metabolomics: population epidemiology and concordance in Australian children aged 11-12 years and their parents

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.</div

Carotid artery intima-media thickness, distensibility and elasticity: population epidemiology and concordance in Australian children aged 11-12 years old and their parents

Objectives: To 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. Design: Cross-sectional study (Child Health CheckPoint), nested within a prospective cohort study, the Longitudinal Study of Australian Children (LSAC). Setting Assessment centres in seven Australian major cities and eight selected regional towns, February 2015 to March 2016. Participants: Of 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 measures: Ultrasound 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. Results: The 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. Conclusions: We 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.</div

Childhood infection may mediate the relationship between suboptimal intrauterine growth, preterm birth, and adult cardiovascular disease

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Changes in infection-related hospitalizations in children following pandemic restrictions: an interrupted time-series analysis of total population data

BACKGROUND: Infectious diseases are a leading cause of hospitalization during childhood. The various mitigation strategies implemented to control the coronavirus disease (COVID-19) pandemic could have additional, unintended benefits for limiting the spread of other infectious diseases and their associated burden on the health care system. METHODS: We conducted an interrupted time-series analysis using population-wide hospitalization data for the state of Victoria, Australia. Infection-related hospitalizations for children and adolescents (aged <18 years, total source population ∼1.4 million) were extracted using pre-defined International Classification of Diseases 10th Revision Australian Modification (ICD-10-AM) codes. The change in weekly hospitalization rates (incidence rate ratio, IRR) for all infections following the introduction of pandemic-related restrictions from 15 March 2020 was estimated. RESULTS: Over 2015-19, the mean annual incidence of hospitalization with infection among children less than 18 years was 37 per 1000 population. There was an estimated 65% (95% CI 62-67%) reduction in the incidence of overall infection-related hospitalizations associated with the introduction of pandemic restrictions. The reduction was most marked in younger children (at least 66% in those less than 5 years of age) and for lower respiratory tract infections (relative reduction 85%, 95% CI 85-86%). CONCLUSIONS: The wider impacts of pandemic mitigation strategies on non-COVID-19 infection-related hospitalizations are poorly understood. We observed marked and rapid decreases in hospitalized childhood infection. In tandem with broader consequences, sustainable measures, such as improved hand hygiene, could reduce the burden of severe childhood infection post-pandemic and the social and economic costs of hospitalization.Isobel M F Todd, Jessica E Miller, Stacey L Rowe, David P Burgner, Sheena G Sulliva

Trained Innate Immunity as a Novel Mechanism Linking Infection and the Development of Atherosclerosis

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Maternal chorioamnionitis and postneonatal respiratory tract infection in ex-Preterm infants

Objective: To assess whether exposure to histologically confirmed chorioamnionitis (ie, histologic chorioamnionitis [HCA]) is associated with altered risk of infection-related hospitalization (IRH) during the first 24 months of life in very preterm infants. Study design: This single-center retrospective cohort study analyzed data on 1218 infants born at <30 weeks gestational age (GA). Semiquantitative placental histology, obstetric, and neonatal data were extracted from hospital databases and linked with discharge diagnoses on rehospitalization until age 24 months from statewide statutory data. The associations between HCA and overall and clinical categories of IRH were analyzed by Cox proportional hazards regression with left-truncated failure times. Results: Mean GA was 27 weeks, and HCA was present in 577 placentas (47.4%). Among the 1088 infants surviving until the birth-related discharge, 684 (62.9%) of had at least 1 IRH by age 24 months, of whom 287 included a diagnosis of acute lower respiratory tract infection (ALRTI). Following adjustment for sex, birth weight z-score, GA, early-onset sepsis, late-onset sepsis, previous antibiotic use, age at birth-related discharge, and chronic lung disease, HCA was associated with a 32% increased risk of hospitalization with ALRTI (HR, 1.32; 95% CI, 1.02-1.70; P = .033). There was no association with infection overall or with other infection categories. Conclusions: HCA is associated with a significantly increased risk of hospitalization with ALRTI that is independent of known risk factors, including chronic lung disease

Trained Immunity: Linking Obesity and Cardiovascular Disease across the Life-Course?

Obesity, a chronic inflammatory disease, is the most prevalent modifiable risk factor for cardiovascular disease. The mechanisms underlying inflammation in obesity are incompletely understood. Recent developments have challenged the dogma of immunological memory occurring exclusively in the adaptive immune system and show that the innate immune system has potential to be reprogrammed. This innate immune memory (trained immunity) is characterized by epigenetic and metabolic reprogramming of myeloid cells following endogenous or exogenous stimulation, resulting in enhanced inflammation to subsequent stimuli. Trained immunity phenotypes have now been reported for other immune and non-immune cells. Here, we provide a novel perspective on the putative role of trained immunity in mediating the adverse cardiovascular effects of obesity and highlight potential translational pathways

A twin study of body mass index and dental caries in childhood

Sub-optimal nutrition and dental caries are both common with significant short and long-term implications for child health and development. We applied twin statistical methods to explore the relationship between body mass index (BMI) and dental caries. We measured BMI at 18 months and six years of age and cumulative dental caries experience at six years in 344 twin children. Dental caries in primary teeth was categorised into 'any' or 'advanced' and BMI was analysed as both a continuous and categorical variable. Statistical analyses included multiple logistic regression using generalized estimating equations and within/between-pair analyses. There was no association between BMI and 'any' dental caries experience at either time-point, neither overall nor in within/between pair analyses. However, 'advanced' dental caries at six years was associated with a within-pair difference in BMI of -0.55 kg/m2 (95% CI -1.00, -0.11, p = 0.015). A within-pair increase of 1 kg/m2 in BMI was associated with a lower within-pair risk of advanced dental caries (OR 0.68, 95% CI 0.52, 0.90, p = 0.007). These findings reveal a possible causal relationship between lower BMI and dental caries. As dental outcomes were only measured at one time point, the direction of this potentially causal relationship is unclear