Plasma retinol, carotene and vitamin E concentrations and lung function in a crocidolite-exposed cohort from Wittenoom, Western Australia: a cohort study

BACKGROUND: Increased rates of death from asbestos related diseases have been reported for people previously employed in the mining and milling operations at Wittenoom (Western Australia), and people who lived in the nearby town, where they were environmentally exposed to crocidolite. METHODS: Annual measurements of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and plasma concentrations of retinol, carotene and vitamin E have been made since 1992. Mixed effects models were used to examine the associations between lung function and the plasma vitamin levels of retinol, carotene and vitamin E. RESULTS: After adjusting for potential confounders, higher plasma retinol and carotene concentrations were significantly associated with higher levels of lung function at entry into the study, while vitamin E concentrations were associated with lower entry lung function. Retinol was associated with a less steep decline of lung function over time, while carotene concentrations were associated with an increased decline of lung function over time and vitamin E levels were not associated with changes of lung function over time. CONCLUSION: These results support a beneficial relationship between plasma concentrations of retinol on the levels and rates of change of lung function, while showing no such consistent beneficial effect for plasma levels of beta-carotene or vitamin E

Identifying vulnerable population groups: On-time infant vaccination coverage in Australia

Introduction Immunisation coverage is a good measure of immunisation program effectiveness. Coverage of the 3-dose infant schedule in Australia assessed at age 12 months is >90%. Timeliness is an important goal for population immunity, but on-time coverage of the 2-4-6 month schedule and coverage in specific populations is rarely reported. Objectives and Approach We conducted a retrospective population-based cohort study of 1.9 million Australian births, 1996-2012 (approximately 42% of Australia’s population). Individual data from state-held birth and perinatal records were combined with Commonwealth-held immunisation and death records, through probabilistic linkage. We assessed on-time coverage across 13 demographic and perinatal characteristics of diphtheria-tetanus-pertussis vaccines (DTP) defined as vaccination 14 days prior to the scheduled due date, to 30 days afterwards. Results On-time DTP vaccination coverage in non-Aboriginal infants was 88.1% for the 2-month dose, 82.0% for 4-month dose, and 76.7% for 6-month dose; 3-dose coverage was 91.3% when assessed at 12 months. On-time DTP coverage for Aboriginal infants was 77.0%, 66.5%, and 61.0%; 3-dose coverage at 12 months was 79.3%. Appreciable differences in on-time coverage were observed across population subgroups. On-time coverage in non-Aboriginal infants born to mothers with ≥3 previous pregnancies was 62.5% for the 6-month dose (47.9% for Aboriginal infants); up to 23.5% lower than for first-borns. Infants born to mothers who smoked during pregnancy had coverage 8.7-10.3% lower than infants born to non-smoking mothers for the 4- and 6-month dose. A linear relationship was apparent with increasing socio-economic disadvantage and decreasing on-time coverage. Conclusion/Implications On-time vaccination coverage of the 2-4-6 month schedule is only 50-60% across specific population subgroups representing a significant avoidable public health risk. Australian Aboriginal infants, multiparous mothers, and those who are socio-economically disadvantaged are key groups most likely to benefit from targeted programs addressing vaccine timeliness

Seasonal trivalent influenza vaccination during pregnancy and the incidence of stillbirth: population-based retrospective cohort study

Concern for the safety to the fetus is a commonly cited reason for vaccine refusal during pregnancy. Results from this investigation support the safety of seasonal influenza vaccination during pregnancy and suggest seasonal influenza vaccination may be protective against stillbirth

Dietary patterns and markers for the metabolic syndrome in Australian adolescents

Background and Aims: Overweight and other risk factors for cardiovascular disease (CVD) as well as their clustering, or the metabolic syndrome, are increasingly prevalent among children and adolescents. We examined dietary patterns, CVD risk factors, and the clustering of these risk factors, in 1139 14 year olds living in Western Australia. Methods and Results: Usual dietary intake was assessed with a food frequency questionnaire. Two dietary patterns, ‘Western’ and ‘Healthy’, were identified using factor analysis. Associations between these dietary patterns and BMI, waist circumference, systolic blood pressure, fasting levels of serum glucose, insulin, total cholesterol, HDL C, LDL C, triglycerides and insulin resistance were assessed using ANOVA. Cluster analysis identified a high risk group (the “high risk metabolic cluster’) with features akin to adult metabolic syndrome. Belonging to the high risk metabolic cluster was examined in relation to dietary patterns using logistic regression, adjusting for aerobic fitness and socio demographic factors. Higher ‘Western’ dietary pattern scores were associated with greater odds for the ‘high risk metabolic cluster’ (p for trend =0.02) and greater mean values for total cholesterol (p for trend=0.03), waist circumference (p for trend=0.03) and BMI (p for trend =0.02) in girls, but not boys. Scores for the ‘Healthy’ dietary pattern were not related to the ‘high risk metabolic cluster but were inversely associated with serum glucose in boys and girls (p for trend=0.01 and 0.04, respectively) and were positively associated with HDL C in boys (p for trend=0.02). Conclusions: Dietary patterns are associated with CVD risk factors and the clustering of these risk factors in adolescence

Linking pharmacy dispensing data to other administrative health datasets to measure the compliance and effectiveness of RSV immunoprophylaxis

Introduction Respiratory Syncytial Virus (RSV) causes considerable morbidity in children. RSV vaccines are in development, but the only current preventive measure is immunoprophylaxis with monoclonal antibody, palivizumab. Australia has no uniform palivizumab guidelines. In Western Australia palivizumab is licensed for use in high risk children but compliance and effectiveness is unknown. Objectives and Approach We conducted a retrospective cohort study using palivizumab data from multiple pharmacy dispensing datasets which had been linked with routine laboratory, hospital morbidity, emergency department presentations, deaths and perinatal data for a cohort of infants admitted to Level 3 Neonatal Intensive Care Units (NICU) between 2002 and 2013. We identified palivizumab eligible infants as those who were extremely premature (<28 weeks gestation) with bronchopulmonary dysplasia and/or who identified as Indigenous and were NICU inpatients during the annual winter RSV season (May-October). We describe the use of palivizumab in infants that did and did not fit the eligibility criteria. Results The NICU cohort included 24,367 infants, of which 1754 had at least 1 RSV-confirmed infection before age 5 years. A total of 686 (2.8%) cohort infants were eligible for palivizumab. Palivizumab dispensing data were amalgamated from 5 pharmacy datasets. Overall, 173 of the palivizumab eligible infants (25.2%) had at least 1 palivizumab dose (27% 1 dose, 34% 2 doses, 28% 3 doses and 11% 4 or more doses). From 2011 when palivizumab guidelines were formalised, 143 (75%) had at least 1 dose. Compliance with at least 1 palivizumab dose was highest in 2011 (84.9%). From 2002-2013, 98 infants were given palivizumab outside eligibility criteria (33% 1 dose, 33% 2 doses, 34% 3 or more doses) with annual use increasing since 2008. Conclusion/Implications This is the first time pharmacy dispensing data have been linked to other datasets to measure use and effectiveness. Compliance with palivizumab guidelines was high from 2011. These data will be used to measure the effectiveness of palivizumab against RSV-confirmed infections and respiratory infection-related hospitalisations up to age 5 years

A screening tool to identify risk for bronchiectasis progression in children with cystic fibrosis

BACKGROUND: The marked heterogeneity in cystic fibrosis (CF) disease complicates the selection of those most likely to benefit from existing or emergent treatments. OBJECTIVE: We aimed to predict the progression of bronchiectasis in preschool children with CF. METHODS: Using data collected up to 3 years of age, in the Australian Respiratory Early Surveillance Team for CF cohort study, clinical information, chest computed tomography (CT) scores, and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5–6. RESULTS: Follow‐up at 5–6 years was available in 171 children. Bronchiectasis prevalence at 5–6 was 134/171 (78%) and median bronchiectasis score was 3 (range 0–12). The internally validated multivariate model retained eight independent predictors accounting for 37% (adjusted R (2)) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life, and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% confidence interval [CI], 6.3–27) with positive and negative predictive values of 80% (95% CI, 72%–86%) and 77% (95% CI, 69%–83%), respectively. CONCLUSION: Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high‐risk patient selection for interventional trials. The unexplained variability in disease progression at individual patient levels remains high, limiting the use of this model as a clinical prediction tool

Mode of birth and risk of infection-related hospitalisation in childhood: A population cohort study of 7.17 million births from 4 high-income countries

BACKGROUND: The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates. METHODS AND FINDINGS: We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available. CONCLUSIONS: In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children

Background: Antigen-specific IgE binds the Fcε receptor I (FcεRI) expressed on several types of immune cells, including dendritic cells (DCs). Activation of FcεRI on DCs in atopics has been shown to modulate immune responses that potentially contribute to asthma development. However, the extent to which DC subsets differ in FcεRI expression between atopic children with or without asthma is currently not clear. This study aimed to analyse the expression of FcεRI on peripheral blood mononuclear cells (PBMCs) from atopic children with and without asthma, and non-atopic/non-asthmatic age-matched healthy controls. Methods: We performed multiparameter flow cytometry on PBMC from 391 children across three community cohorts and one clinical cohort based in Western Australia. Results: We confirmed expression of FcεRI on basophils, monocytes, plasmacytoid and conventional DCs, with higher proportions of all cell populations expressing FcεRI in atopic compared to non-atopic children. Further, we observed that levels of FcεRI expression were elevated across plasmacytoid and conventional DC as well as basophils in atopic asthmatic compared to atopic non-asthmatic children also after adjusting for serum IgE levels. Conclusion: Our data suggest that the expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children. Given the significant immune modulatory effects observed as a consequence of FcεRI expression, this altered expression pattern is likely to contribute to asthma pathology in children

Prenatal stress and risk of behavioral morbidity from age 2 to 14 years: The influence of the number, type, and timing of stressful life events

The maternal experience of stressful events during pregnancy has been associated with a number of adverse consequences for behavioral development in offspring, but the measurement and interpretation of prenatal stress varies among reported studies. The Raine Study recruited 2900 pregnancies and recorded life stress events experienced by 18 and 34 weeks’ gestation along with numerous sociodemographic data. The mother’s exposure to life stress events was further documented when the children were followed-up in conjunction with behavioral assessments at ages 2, 5, 8, 10, and 14 years using the Child Behavior Checklist. The maternal experience of multiple stressful events during pregnancy was associated with subsequent behavioral problems for offspring. Independent (e.g., death of a relative, job loss) and dependent stress events (e.g., financial problems, marital problems) were both significantly associated with a greater incidence of mental health morbidity between age 2 and 14 years. Exposure to stressful events in the first 18 weeks of pregnancy showed similar associations with subsequent total and externalizing morbidity to events reported at 34 weeks of gestation. These results were independent of postnatal stress exposure. Improved support for women with chronic stress exposure during pregnancy may improve the mental health of their offspring in later life