ORCID Profile
0000-0002-6581-3657
Current Organisation
Florey Institute of Neuroscience and Mental Health
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 29-04-2019
DOI: 10.1111/JPC.14436
Abstract: The burden of wheezing illnesses in Australian infants has not been documented since the success of initiatives to reduce maternal cigarette smoking. We aimed to determine the incidence of wheeze and related health-care utilisation during the first year of life among a contemporary Australian birth cohort. A birth cohort of 1074 infants was assembled between 2010 and 2013. Parents completed questionnaires periodically. Several non-exclusive infant respiratory disease phenotypes were defined, including any wheeze, wheeze with shortness of breath and recurrent wheeze. Skin prick testing was performed to determine atopic wheeze. Health-care utilisation for respiratory disease was determined from questionnaires and hospital medical records. Retention to 1 year was 840/1074 (83%). The incidence of any wheeze was 51.8% (95% confidence interval (CI) 48.3-55.2%), wheeze with shortness of breath 20.6% (95% CI 17.9-23.5), recurrent wheeze 19.4% (95% CI 16.8-22.2) and atopic wheeze 6% (95% CI 4.6-7.8). Respiratory illness resulted in primary health-care utilisation in 82.2% (95% CI 79.3-84.8) of participants and hospital presentation in 8.8% (95% CI 7.2-10.6). Maternal smoking during pregnancy was uncommon (15.7%) and was not associated with wheeze or health resource utilisation. Male gender, familial atopy and asthma and smaller household size were associated with a higher incidence of wheeze. The incidence of wheezing illness among Australian infants remains high despite relatively low rates of maternal smoking during pregnancy. The majority of the health-care burden is borne by primary health-care services. Further research is required to inform novel prevention strategies.
Publisher: American Diabetes Association
Date: 23-12-2008
DOI: 10.2337/DC08-1638
Abstract: To examine how fitness in both childhood and adulthood is associated with adult obesity and insulin resistance. A prospective cohort study set in Australia in 2004–2006 followed up a cohort of 647 adults who had participated in the Australian Schools Health and Fitness Survey in 1985 and who had undergone anthropometry and cardiorespiratory fitness assessment during the survey. Outcome measures were insulin resistance and obesity, defined as a homeostasis model assessment index above the 75th sex-specific percentile and BMI ≥30 kg/m2, respectively. Lower levels of child cardiorespiratory fitness were associated with increased odds of adult obesity (adjusted odds ratio [OR] per unit decrease 3.0 [95% CI 1.6–5.6]) and insulin resistance (1.7 [1.1–2.6]). A decline in fitness level between childhood and adulthood was associated with increased obesity (4.5 [2.6–7.7]) and insulin resistance (2.1 [1.5–2.9]) per unit decline. A decline in fitness from childhood to adulthood, and by inference a decline in physical activity, is associated with obesity and insulin resistance in adulthood. Programs aimed at maintaining high childhood physical activity levels into adulthood may have potential for reducing the burden of obesity and type 2 diabetes in adults.
Publisher: Wiley
Date: 06-2022
DOI: 10.1111/PAI.13810
Abstract: Children born to larger households have less allergic disease. T regulatory cell (Treg) development may be a relevant mechanism, but this has not been studied longitudinally. We aim to (i) describe how prenatal and postnatal environmental factors are associated with Treg development and (ii) investigate whether serial Treg measures predict allergic outcomes at 1 year of age. A birth cohort ( n = 1074) with information on prenatal and postnatal early life factors. Both naïve Treg (nTreg) and activated Treg (aTreg) cell populations (as a proportion of CD4 + T cells) were available in 463 infants at birth (cord blood), 600 at 6 months, and 675 at 12 months. 191 infants had serial measures. Measures of allergic status at 12 months were polysensitization (sensitization to 2 or more allergens), clinically proven food allergy, atopic eczema, and atopic wheeze. Infants born to larger households (3 or more residents) had higher longitudinal nTreg proportions over the first postnatal year with a mean difference (MD) of 0.67 (95% CI 0.30–1.04)%. Higher nTreg proportions at birth were associated with a reduced risk of infant allergic outcomes. Childcare attendance and breastfeeding were associated with higher longitudinal nTreg proportions (MD 0.48 (95% CI 0.08–0.80)%. Multiple prenatal and postnatal microbial factors are associated with nTreg and aTreg development. Larger household size was associated with higher nTreg at birth which in turn was associated with reduced allergic sensitization and disease at 12 months of age.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-08-2016
Publisher: Elsevier BV
Date: 08-2007
DOI: 10.1016/J.JNEUROIM.2007.06.012
Abstract: We measured the levels of IFNgamma, TNFalpha, Il-4 and Il-10 produced by mitogen-stimulated peripheral blood mononuclear cells (PBMC) from healthy people, and those with the relapse/remitting form of multiple sclerosis. Blood was taken in summer and winter. Healthy people had a summer excess of Il-4, Il-10 and TNFalpha, and a winter excess of IFNgamma. Untreated MS cases had a summer excess of Il-10, whereas those treated with Interferon-beta had lower levels of all cytokines, and displayed no seasonal effect.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JNS.2014.12.022
Abstract: Alterations in peripheral blood mononuclear cell (PBMC) cytokine production have been found in multiple sclerosis (MS) compared to healthy controls. We have previously found that stimulated PBMC-produced TNF-α and IFN-γ modulated MS relapse risk, such that raised TNF-α was protective, while raised IFN-γ increased relapse risk. To assess whether SNPs within genes for relevant cytokines and their receptors modulate the associations of TNF-α and IFN-γ with relapse, thus providing additional information about these cytokine effects and the roles of these genes in MS. Prospective cohort of 91 participants with relapsing-remitting MS and cytokine and genotype data. SNPs (N=361) within a window of 10 kb around each cytokine/cytokine receptor gene (N=84) were selected for analysis. Predictors of PBMC cytokines were evaluated by multilevel mixed-effects linear regression. Predictors of relapse were evaluated by Cox proportional hazards regression. Bonferroni correction was used to adjust for multiple testing thus p<1.39 × 10(-4) was defined as significant. In iduals of GG genotype of rs3218295 (within the gene IL2RB) demonstrated a significant protective effect of TNF-α on relapse while those of GA/AA genotype showed a significant positive association (pinteraction=5.04 × 10(-5)). Carriers of CC genotype of rs522807 (3' region of TNFRSF1B) and the AA genotype of rs25879 (5' region of IL3) showed a strong association between IFN-γ and increased relapse risk (pinteraction=8.21 × 10(-5) and 1.70 × 10(-5), respectively). Our results show novel modulation of TNF-α and IFN-γ associations with relapse by SNPs in major cytokines. These findings suggest the potential for these genes and/or their products as potential therapeutic targets in MS.
Publisher: Elsevier BV
Date: 09-2016
Publisher: Wiley
Date: 03-04-2008
Publisher: Cold Spring Harbor Laboratory
Date: 13-10-2023
Publisher: BMJ
Date: 13-01-2011
DOI: 10.1136/BMJ.C7249
Abstract: To investigate the association between change in daily step count and both adiposity and insulin sensitivity and the extent to which the association between change in daily step count and insulin sensitivity may be mediated by adiposity. Population based cohort study. Tasmania, Australia. 592 adults (men (n=267), mean age 51.4 (SD 12.2) years women (n=325), mean age 50.3 (12.3) years) who participated in the Tasmanian component of the national AusDiab Study in 2000 and 2005. Body mass index, waist to hip ratio, and HOMA insulin sensitivity at follow-up in 2005. Over the five year period, the daily step count decreased for 65% (n=382) of participants. Having a higher daily step count in 2005 than in 2000 was independently associated with lower body mass index (0.08 (95% confidence interval 0.04 to 0.12) lower per 1000 steps), lower waist to hip ratio (0.15 (0.07 to 0.23) lower), and greater insulin sensitivity (1.38 (0.14 to 2.63) HOMA units higher) in 2005. The mean increase in HOMA units fell to 0.34 (-0.79 to 1.47) after adjustment for body mass index in 2005. Among community dwelling, middle aged adults, a higher daily step count at five year follow-up than at baseline was associated with better insulin sensitivity. This effect seems to be largely mediated through lower adiposity.
Publisher: BMJ
Date: 09-2008
Abstract: To examine whether the inverse association between birth weight and blood pressure varies by skin pigmentation and/or related genotypes. 671 children from a predominantly caucasian birth cohort were followed-up to adolescence (mean (SD) age 14.4 (0.64)). Data on birth weight, socioeconomic status, maternal antenatal smoking, adolescent blood pressure and polymorphisms of candidate genes were obtained and analysed by multiple linear regression. An increase in birth weight of 1 kg was associated with an non-significant difference in adolescent systolic blood pressure of -0.53 mm Hg (95% CI -1.72 to 0.66) per kg after adjustment for child age and cohort entry criteria. The inverse association between birth weight and systolic blood pressure was stronger for those with darker skin (> or =2% melanin) (difference in effect, p = 0.02), those with more copies of the C allele of corticotropin-releasing hormone (CRH) +T1273C (p = 0.06), and those with more copies of the short (< or =236 bp) form of the 11beta-HSD2{CA}n(repeat) microsatellite (p = 0.03). These findings add to the evidence that cortisol-related pathways may account for at least part of the observed birth weight-blood pressure associations.
Publisher: S. Karger AG
Date: 2018
DOI: 10.1159/000487506
Abstract: b i Background: /i /b Lipid metabolism is vital to fetal development and cardiometabolic health and the final weeks of gestation are known to be a time of intense metabolic activity. New techniques such as lipidomics allow investigation of a complex lipidomic profile in infants. b i Objectives: /i /b This research aimed to (1) describe variations in lipidomic profile in late preterm and term infants and (2) compare variations to an adult lipidomic profile with known clinical implications. b i Methods: /i /b The Barwon Infant Study ( i n /i = 1,074) is a population-derived pre-birth cohort study. The lipidomic profile of cord blood was measured by liquid chromatography-mass spectrometry in 225 participants and the association between gestational age and lipidomic profile was investigated using multiple linear regression adjusting for birth weight, exposure to labour, and infant sex. Patterns of association with gestational age across the lipidomic profile were compared with associations between body mass index (BMI) and lipidomic profile observed among adults in the San Antonia Family Heart Study ( i n /i = 994). b i Results: /i /b Gestational age was independently associated with the abundances of 39% of lipid species. Variations in the lipidomic profile with increasing gestational age were comparable to some variations observed in association with increasing BMI among adults. b i Conclusion: /i /b There is a strong relationship between gestational age and the cord blood lipid profile at birth, providing further evidence for the importance of metabolic changes of late gestation. A number of the variations in the lipid profile with increasing gestational age are analogous to differences observed in the adult lipid profile with an increasing BMI.
Publisher: Wiley
Date: 06-1998
DOI: 10.1046/J.1440-1754.1998.00225.X
Abstract: In March 1997 a multidisciplinary forum was convened by the National SIDS Council of Australia to review recent evidence concerning risk factors of sudden infant death syndrome (SIDS) and to revise and refine the current guidelines for reducing the risk of SIDS. The forum provided an assessment of the evidence for recommendations to reduce the risk of SIDS using an evidence-based process. Strong evidence has now accumulated that the intervention c aigns to reduce prone sleeping during infancy have been followed by SIDS rate declines. Recent data indicate that the supine position is not associated with an increase in significant morbidity outcomes and provides greater protection for SIDS than the side position, which may be unstable. Covering of the baby's head by bedding is strongly related to SIDS. The infant's sleeping environment should be carefully set up to ensure that the baby's head, including the face, cannot be obstructed during sleep. Parental smoking is strongly associated with SIDS. Structural supportive interventions for parental smoking cessation are required. Bedsharing increases the risk of SIDS amongst smokers and the data are currently not sufficient to provide complete reassurance to nonsmoking parents that bedsharing is safe. Infants should be maintained in a comfortable temperature zone. The evidence for a protective effect of breast-feeding is conflicting, so breast-feeding cannot be promoted strongly as reducing the risk of SIDS. Immunisation has not been associated with SIDS. Parents and carers should be aware of the current guidelines. Health professionals should also be aware of the evidence on which the current recommendations are based. Effective health education programmes should lead to a further decline in SIDS mortality in Australia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1995
Publisher: Wiley
Date: 09-2003
DOI: 10.1046/J.1440-1754.2003.00209.X
Abstract: To measure the prevalence of respiratory symptoms and atopic disease in Aboriginal and Torres Strait Islander (indigenous) and non-indigenous children in the Australian Capital Territory (ACT). A two-stage questionnaire survey of children in the ACT with stage two completed for children identified by parents as having respiratory symptoms or asthma in the first stage cross-sectional survey. Participants in the study were: (i) all new entrant primary schoolchildren aged 4-6 years in 1999, 2000 and 2001, 217 being indigenous children and 10 604 being non-indigenous children (80% of eligible) and (ii) Year 1-6 primary schoolchildren in 2000, with 216 being indigenous children and 14 202 being non-indigenous children (52% of eligible). Respiratory symptoms (including recent wheeze and parent-reported asthma) and other factors were measured by parental questionnaire. Indigenous kindergarten children had more recent wheeze (21%, odds ratio (OR) 1.4 95% confidence interval (CI) 1.0-2.0)) and parent-reported asthma (24%, OR 1.8 95% CI 1.3-2.5) than non-indigenous children (both 15%). However, indigenous children had less eczema (25%, OR 0.7 95% CI 0.5-0.9) and hayfever (14%, OR 0.7 95% CI 0.5-1.0) than non-indigenous children (32% and 19%, respectively). Among children with respiratory symptoms, the symptom severity did not differ between groups, but indigenous children were exposed to more environmental tobacco smoke (ETS) (63%, OR 3.5 95% CI 2.1-5.9) than non-indigenous children (32%). Indigenous children in the ACT have more respiratory morbidity but less of the atopic diseases of hayfever and eczema than non-indigenous children. Whether the respiratory morbidity represents 'asthma' or results from increased ETS exposure is unclear and needs to be further explored.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2013
DOI: 10.1038/PR.2013.6
Abstract: Cardiovascular disease (CVD) is the leading cause of death worldwide and originates in early life. The exact mechanisms of this early-life origin are unclear, but a likely mediator at the molecular level is epigenetic dysregulation of gene expression. Epigenetic factors have thus been posited as the likely drivers of early-life programming of adult-onset diseases. This review summarizes recent advances in epidemiology and epigenetic research of CVD risk in children, with a particular focus on twin studies. Classic twin studies enable partitioning of phenotypic variance within a population into additive genetic, shared, and nonshared environmental variances, and are invaluable in research in this area. Longitudinal cohort twin studies, in particular, may provide important insights into the role of epigenetics in the pathogenesis of CVD. We describe candidate gene and epigenome-wide association studies (EWASs) and transgenerational epigenetic inheritance of CVD, and discuss the potential for evidence-based interventions. Identifying epigenetic changes associated with CVD-risk biomarkers in children will provide new opportunities to unravel the underlying biological mechanism of the origins of CVD and enable identification of those at risk for early-life interventions to alter the risk trajectory and potentially reduce CVD incidence later in life.
Publisher: Elsevier BV
Date: 04-2200
Publisher: Wiley
Date: 09-2011
DOI: 10.1046/J.1365-2222.2001.01163.X
Abstract: Home gas appliance use has been associated with child respiratory illness but prospective data on the relationship between infant exposure and the development of child allergic disease has not been readily available. (a) To determine if home gas appliance use is associated with increased risk of house dust mite (HDM) sensitization. (b) To examine whether any association between current home gas use and airway obstruction is influenced by HDM sensitization. an 8-year follow-up birth cohort study of children born during 1988 and 1989. a population-based s le (n = 498) of children who participated in the Tasmanian Infant Health Survey (TIHS) and resided in Northern Tasmania in 1997 (84% of eligible children). (a) Skin prick test reaction to nine allergens, including Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1). (b) Spirometric lung function indices, including forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). The relative risk for home gas appliance use at 1 month of age and HDM sensitization was 1.98 (1.04, 3.79) in a cohort analysis with confounder matching. Current home gas use was also associated with HDM sensitization (ARR 1.73 (1.43, 2.76)). Current home gas use was related to a stronger (P = 0.006) reduction in the FEV(1) : FVC ratio among HDM-sensitive children (adjusted difference - 6.2% (- 10.0 to - 2.4)) than non-HDM-sensitive children (adjusted difference - 0.3% (- 2.5 to 1.8)). Indoor pollutants from gas combustion may increase the likelihood of initial sensitization to HDM and play a role in the development of atopic asthma. HDM-sensitized children may be more vulnerable to indoor pollutant-induced airway obstruction. The ability of this study to detect such effects may partly reflect unflued gas appliance use among this s le.
Publisher: Cold Spring Harbor Laboratory
Date: 20-01-2023
DOI: 10.1101/2023.01.19.23284578
Abstract: The recent COVID-19 crisis highlighted the inadequacy of human forecasting. We aim to leverage human prediction markets with real-time machine weighting of likely higher accuracy trades to improve performance. The crowd sourced Almanis prediction market longitudinal platform (n=1822) and Next Generation Social Science (NGS2) platform (n=103) were utilised. A 43-feature model predicted top quintile relative Brier accuracy scores in two out-of-s le datasets (p both ×10 −9 ). Trades graded as high machine accuracy quality vs. other trades had a greater AUC temporal gain from before to after trade. Hybrid human-machine forecasts had higher accuracy than human forecasts alone, particularly when the two systems disagreed by 5% or more for binary event prediction: the hybrid system demonstrating substantial AUC gains of 13.2%, p=1.35×10 −14 and 13.8%, p=0.003 in the out-of-s le Almanis B and NGS2 datasets respectively. When discordant, the hybrid model was correct for COVID-19 event occurrence 72.7% of the time vs 27.3% for human-only models, p=0.007. This net classification benefit was replicated in the separate Almanis B dataset, p=2.4×10 −7 . Real-time machine classification followed by weighting human trades according to likely accuracy improves collective forecasting performance. Implementation may allow improved anticipation of and response to emerging risks and improved human collective efforts generally. Human-machine hybrid approaches have been identified as a new frontier for event prediction and decision making in the artificial intelligence and collective human intelligence fields. For the first time, we present the successful development and validation of a human-machine hybrid prediction market approach and demonstrate its superior accuracy when compared to prediction markets based on human forecasting alone. The advantages of this new hybrid system are demonstrated in the context of COVID-19-related event prediction.
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: SAGE Publications
Date: 11-2013
Publisher: Oxford University Press (OUP)
Date: 19-11-2008
DOI: 10.1111/J.1753-4887.2008.00126.X
Abstract: Current or recent low vitamin D status (or proxy measures such as dietary intake or ambient ultraviolet radiation) is linked to several chronic diseases, including osteoporosis, cancers, and cardiovascular and autoimmune diseases. Low prenatal vitamin D status may also increase susceptibility to such diseases in later life via specific target organ effects and/or through changes to the developing immune system. Maternal vitamin D supplementation during pregnancy could be an important public health measure to decrease risk of a range of chronic diseases, but further research is required to clarify beneficial and adverse effects of high prenatal vitamin D.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.JACI.2014.12.1933
Abstract: The diagnosis of food allergy (FA) can be challenging because approximately half of food-sensitized patients are asymptomatic. Current diagnostic tests are excellent makers of sensitization but poor predictors of clinical reactivity. Thus oral food challenges (OFCs) are required to determine a patient's risk of reactivity. We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes. Genome-wide DNA methylation (DNAm) profiling was performed on blood mononuclear cells from volunteers who had undergone objective OFCs, concurrent skin prick tests, and specific IgE tests. Fifty-eight food-sensitized patients (aged 11-15 months) were assessed, half of whom were clinically reactive. Thirteen nonallergic control subjects were also assessed. Reproducibility was assessed in an additional 48 s les by using methylation data from an independent population of patients with clinical FA. Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes. Diagnostic scores were derived from these 96 methylation sites, and cutoffs were determined in a sensitivity analysis. Methylation biomarkers outperformed allergen-specific IgE and skin prick tests for predicting OFC outcomes. FA status was correctly predicted in the replication cohort with an accuracy of 79.2%. DNAm biomarkers with clinical utility for predicting food challenge outcomes are readily detectable in blood. The development of this technology in detailed follow-up studies will yield highly innovative diagnostic assays.
Publisher: Wiley
Date: 16-12-2014
DOI: 10.1111/APA.12457
Abstract: Atherosclerosis is a chronic inflammatory process that begins in early life. Improved identification of markers of early atherosclerosis via neonatal aortic intima-media thickness (aIMT) measurement may allow the development of interventions to prevent or reduce later cardiovascular disease. Using aIMT, studies have shown that antenatal factors such as intra-uterine growth retardation, prematurity, maternal factors and inflammation are associated with early cardiovascular changes.
Publisher: Springer Science and Business Media LLC
Date: 10-07-2019
DOI: 10.1038/S41467-019-10703-1
Abstract: Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preecl sia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preecl tic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4 + T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preecl sia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preecl sia and immune development in offspring.
Publisher: Frontiers Media SA
Date: 08-06-2018
Publisher: Wiley
Date: 19-05-2015
DOI: 10.1111/PPE.12193
Publisher: Hindawi Limited
Date: 29-03-2011
DOI: 10.1111/J.1399-5448.2010.00693.X
Abstract: Higher birthweight is associated with increased type 1 diabetes mellitus (T1DM) risk, but the contribution of higher adiposity or lean mass is unclear. In this Tasmanian infant cohort, early upper respiratory infection has been associated with higher asthma risk. Eligible infants represented one-fifth of live births in Tasmania, 1988-1995. Hospital interview data (day 6) were obtained on 96.3% (10 628/11 040), home (5 wk) visit data (38 d) on 92.9% (9876/10 628) of those, then a phone (12 wk) interview (87 d). Tricep and subscapular skinfold measures and upper arm circumference were recorded at the first two interviews. T1DM cases (n = 26) arising from the age of 16 or under in Tasmania from 1988 to 2006 were ascertained. Higher birthweight [adjusted odds ratio (AOR) 2.82 (95% CI 1.31-6.09)], lean mid-upper arm circumference [AOR 1.76 (95% CI 1.16-2.66)], not skinfold measures, were associated with T1DM risk. Children with an early upper respiratory tract infection by 5-wk visit [AOR 2.74 (95% CI 1.19-6.32)] or ear infection by 12-wk interview [AOR 3.44 (95% CI 1.00-11.79)] were also at higher risk. Putative markers of altered microbial exposure such as resident density were not associated with T1DM risk but the effect of increasing birth order on T1DM risk differed for older (AOR 0.41, p = 0.02) than young mother (AOR 2.45, p = 0.01) difference in effect, p = 0.001. In this cohort, early upper respiratory tract infection was associated with T1DM risk, as had been previously found for asthma, consistent with immunoinflammatory upregulation. Using the detailed anthropometric measures available, the link between higher birthweight and T1DM did not appear to reflect increased adiposity.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JAIP.2019.05.057
Abstract: Cashew is a common cause of tree nut allergy in children. To date there have been few studies of diagnostic tests for cashew allergy, and positive predictive values (PPVs) for cashew as well as other tree nuts are largely extrapolated from studies of peanut allergy. How relevant these cutoffs are for cashew has not been formally explored. We aimed to establish skin prick test (SPT) wheal sizes that correlated to 95% PPV for a positive food challenge for cashew. We included all cashew oral food challenges (OFCs) conducted as part of the HealthNuts (n = 108 age, 4-6 years) and SchoolNuts (n = 37 age, 10-14 years) studies, both recruited from the community (population cohort). A second cohort of all cashew OFCs conducted at the Royal Children's Hospital (RCH) allergy center (n = 343) (2011-2016) and a private allergy clinic based at RCH (n = 43) was included via electronic medical record review (clinic cohort). The 95% PPV for cashew SPT was calculated for both cohorts. Among the population cohort (n = 145), 62% of cashew OFCs were positive compared with 20% of the clinic cohort (n = 386). The SPT cutoff for 95% PPV derived from the population cohort was 10 mm (95% confidence interval [CI], 7.5-12.0). For the clinic cohort, the 95% PPV was 14 mm (95% CI, 9.5-unknown). An SPT wheal size of 8 mm had a PPV of 89% (95% CI, 79-95) in the population cohort and 62% (95% CI, 45-78) in the clinic cohort. A higher SPT wheal size may be more appropriate than the commonly used 8 mm cutoff to guide clinical decisions around when to perform OFC for cashew.
Publisher: Wiley
Date: 29-11-2019
DOI: 10.1111/JPC.14695
Abstract: To investigate the relationship between factors which influence external microbial exposures (FEMEs), previously identified to be protective or to increase the risk of the development of allergic disease, and cognition and behaviour in infants 2 years of age in an Australian population. The Barwon Infant Study is a birth cohort (n = 1074) in Victoria, Australia. Comprehensive questionnaire, clinical and biological measures were collected at multiple time oints. Multiple linear regression was used to evaluate the associations between 56 FEMEs and 3 outcomes cognition (Bayley Scales of Infant and Toddler Development (BAYLEY-III)) (n = 667, mean (standard deviation) age = 2.45 (0.14) years), internalising and externalising behaviour (Child Behavior Checklist) (n = 666, mean (standard deviation) age = 2.45 (0.14) years). Overall, there were no consistent patterns or dose response found within an outcome nor across all three outcomes, although there was some evidence for in idual associations. Breastfeeding and child care were associated with higher cognitive scores (adjusted mean difference (95% confidence interval) = 3.20 (0.23-6.17) and 0.68 (0.12-1.24), respectively), and increasing sibling number was associated with lower internalising behaviour (adjusted mean difference (95% confidence interval) = -4.13 (-6.34, -1.91)). In contrast to allergic disease, there was an absence of epidemiological evidence to support the association between these FEMEs and cognition and behaviour. Direct investigations into the relationship between exposures which influence gut-microbial composition and cognition and behaviour are now needed.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Wiley
Date: 11-2018
DOI: 10.1111/PPE.12519
Abstract: Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological s les. Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological s les potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in s le size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.
Publisher: Wiley
Date: 12-1991
DOI: 10.1111/J.1440-1754.1991.TB00415.X
Abstract: The most recent data from the cohort and case-control studies of SIDS and prone position recently reported from Tasmania are reviewed. The cohort analysis was based on 4103 infants born between 1 January 1988 and 1 December 1990 assessed as being at high risk at birth, of whom 29 later died of SIDS. A matched analysis which controlled for infant birthweight and maternal age indicated that prone sleeping position was associated with an increased risk of SIDS (OR 3.92, 95% Cl [1.37-11.24]). The case-control study was based on all (n = 55) Tasmanian SIDS death from October 1989 to April 1991 and matched live controls. The unadjusted odds ratio for prone position and SIDS was 5.04 (95% Cl [2.29-11.11]). The population attributable risk percentage, based on the high risk cohort data, was 0.38 (95% Cl [0.35-0.41]), suggesting that a significant reduction in SIDS incidence might occur if the prevalence of the prone sleeping position in the infant population were reduced. Other factors which may be important for the development of any public health interventions to reduce SIDS based on these findings are discussed.
Publisher: Wiley
Date: 04-2003
DOI: 10.1034/J.1399-3038.2003.00023.X
Abstract: Our aim was to examine the relative importance of family size on sensitization to two different allergens: ryegrass and house dust mite (HDM), using a mutually exclusive classification for allergen-specific sensitization. An 8-year follow-up birth cohort study of children born between 1988-89 was conducted. The follow-up s le consisted of 498 children residing in Northern Tasmania in 1997 (84% of eligible). Outcome measures included skin prick test (SPT) reaction to nine aeroallergens and parental questionnaire. Family size was defined as sibling number in 1997. Children with a positive SPT to either Der p or Der f house dust mite but not ryegrass were classified as HDM-exclusive (n = 84). Children with a positive SPT to ryegrass but not HDM were classified as ryegrass-exclusive (n = 43). Family size was associated with reduced ryegrass-exclusive sensitization [AOR 0.57 (0.39, 0.84) per increase in sibling number] but not HDM-exclusive sensitization [AOR 0.97 (0.77,1.23)]. The difference in the family size effect on these sensitization outcomes was significant (p = 0.02). Similarly, family size tended to be associated with reduced asthma among ryegrass-exclusive sensitized children [AOR 0.45 (0.18,1.12)] but not HDM-exclusive sensitized children [(AOR 1.46(0.80-2.65)]. Large family size was strongly associated with reduced sensitization for ryegrass allergens but not HDM allergens using mutually exclusive sensitization categories. If this difference is confirmed in other studies, the contrasting effect of family size may reflect differences between these allergens with regard to level or timing of early life exposure, differences in allergen -specific potentiation for sensitization or unidentified confounding. The use of mutually exclusive categories for allergen sensitization will assist future work on child atopic disease.
Publisher: Wiley
Date: 30-09-2011
DOI: 10.1111/J.1399-3038.2010.01099.X
Abstract: Observations of increasing allergy prevalence with decreasing distance from the Equator and positive associations with ambient ultraviolet radiation have contributed to a growing interest in the possible role of vitamin D in the etiology of allergy. The aims of this study were to describe any latitudinal variation in the prevalence of childhood allergy in Australia and to evaluate, in parallel, the in idual associations between ultraviolet radiation (UVR)- and vitamin D-related measures and hayfever asthma and both conditions. Participants were population-based controls who took part in a multicenter case-control study, aged 18-61 yr and resident in one of four study regions ranging in latitude from 27°S to 43°S. Data were derived from a self-administered questionnaire, interview and examination by a research officer and biologic s ling. Latitude and longitude coordinates were geocoded from participants' residential locations and climatic data were linked to postcodes of current residence. Stored serum was analyzed for 25-hydroxyvitamin D concentrations and silicone rubber casts of the skin were used as an objective measure of cumulative actinic damage. There was an inverse latitude gradient for asthma (a 9% decrease per increasing degree of latitude) however, this pattern did not persist after adjusting for average daily temperature. There was no association between any of the UVR- or vitamin D-related measures and childhood asthma, but greater time in the sun in winter between the ages 6-15 yr was associated with an increase in the odds of having hayfever [adjusted odds ratios (OR) 1.29 95% CI 1.01-1.63]. Oral supplementation with cod liver oil in childhood increased the odds of a history of having both asthma and hayfever (2.87 1.00-8.32). Further investigation of the possible role of early vitamin D supplementation in the development of allergy is warranted. Our results also suggest that solar exposure during childhood may be important in allergic sensitization. Plausible explanations, including biologic mechanisms, exist for both observations.
Publisher: Walter de Gruyter GmbH
Date: 2017
Abstract: Vitamin D deficiency has been associated with adverse health outcomes. We examined genetic and environmental determinants of serum 25(OH)D The study s le consisted of 322 healthy Australian children (predominantly Caucasians) who provided a venous blood s le. A parental interview was conducted and skin phototype and anthropometry measures were assessed. Concentrations of 25(OH)D Deseasonalised log 25(OH)D Environmental factors and genetic factors contributed to both vitamin D metabolite concentrations. The intriguing finding that the higher ambient UVR contributed to higher 1,25(OH)
Publisher: Elsevier BV
Date: 07-2014
Publisher: Cold Spring Harbor Laboratory
Date: 02-12-2021
DOI: 10.1101/2021.12.02.21267173
Abstract: The risk of adult onset cardiovascular and metabolic (cardiometabolic) disease accrues from early life. Infection is ubiquitous in infancy and induces inflammation, a key cardiometabolic risk factor, but the relationship between infection, inflammation, and metabolic profiles in early childhood remains unexplored. We investigated relationships between infection and plasma metabolomic and lipidomic profiles at age 12 months, and mediation of these associations by inflammation. Matched infection, metabolomics and lipidomics data were generated from 555 infants in a pre-birth longitudinal cohort. Infection data from birth to 12 months were parent-reported (total infections at age 1, 3, 6, 9, and 12 months), inflammation markers (high-sensitivity C-reactive protein, hsCRP) glycoprotein acetyls GlycA) were quantified at 12 months. Metabolic profiles were 12-month plasma nuclear magnetic resonance metabolomics (228 metabolites) and liquid-chromatography/mass-spectrometry lipidomics (776 lipids). Associations were evaluated with multivariable linear regression models. Frequent infant infections were associated with adverse metabolomic (elevated inflammation markers, triglycerides, phenylalanine, and lower HDL cholesterol, apolipoprotein A1, and omega-3 fatty acids) and lipidomic profiles (elevated phosphatidylethanolamines and lower hexosylceramides, trihexosylceramides, and cholesteryl esters). Similar, more marked, profiles were observed with higher GlycA, but not hsCRP. GlycA, but not hsCRP, mediated a substantial proportion of the relationship between infection and metabolome/lipidome. Infants with a greater infection burden from birth to 12 months had pro-inflammatory and pro-atherogenic plasma metabolomic/lipid profiles, indicative of heightened risk of cardiovascular disease, obesity, and type 2 diabetes in adults. These findings suggest potentially modifiable pathways linking early life infection and inflammation with subsequent cardiometabolic risk. The establishment work and infrastructure for the BIS was provided by the Murdoch Children’s Research Institute (MCRI), Deakin University and Barwon Health. Subsequent funding was secured from National Health and Medical Research Council of Australia (NHMRC), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O’Brien Memorial Asthma Foundation, the Our Women’s Our Children’s Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Minderoo Foundation, the Ilhan Food Allergy Foundation, GMHBA, Vanguard Investments Australia Ltd, and the Percy Baxter Charitable Trust, Perpetual Trustees. In-kind support was provided by the Cotton on Foundation and CreativeForce. The study sponsors were not involved in the collection, analysis, and interpretation of data writing of the report or the decision to submit the report for publication. Research at MCRI is supported by the Victorian Government’s Operational Infrastructure Support Program. This work was also supported by NHMRC Senior Research Fellowships (1008396 to ALP 1064629 to DB 1045161 to RS), NHMRC Investigator Grants to ALP (1110200) and DB (1175744), NHMRC-A*STAR project grant (1149047). TM is supported by an MCRI ECR Fellowship. SB is supported by the Dutch Research Council (452173113).
Publisher: Springer Science and Business Media LLC
Date: 20-08-2015
DOI: 10.1038/GENE.2015.32
Abstract: A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) s les. Discovery s le sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95% CI=0.52-1.60, P=0.75). This was similarly observed in the replication s le. There was evidence for genotype-by-sex interaction (Pinteraction=0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.
Publisher: Oxford University Press (OUP)
Date: 12-04-2013
DOI: 10.1093/AJE/KWS361
Abstract: Inconsistent evidence exists regarding the association between work-related factors and risk of multiple sclerosis (MS). We examined the association between occupational exposures and risk of a first clinical diagnosis of central nervous system demyelination (FCD), which is strongly associated with progression to MS, in a matched case-control study of 276 FCD cases and 538 controls conducted in Australia (2003-2006). Using a personal residence and work calendar, information on occupational history and exposure to chemicals and animals was collected through face-to-face interviews. Few case-control differences were noted. Fewer cases had worked as professionals (≥6 years) than controls (adjusted odds ratio (AOR) = 0.60, 95% confidence interval (CI): 0.37, 0.96). After further adjustment for number of children, cases were more likely to have ever been exposed to livestock than controls (AOR = 1.54, 95% CI: 1.03, 2.29). Among women, there was an increase in FCD risk associated with 10 or more years of exposure to livestock (AOR = 2.78, 95% CI: 1.22, 6.33) or 6 or more years of farming (AOR = 2.00, 95% CI: 1.23, 3.25 also adjusted for number of children). Similar findings were not evident among men. Thus, farming and exposure to livestock may be important factors in the development of FCD among women, with this finding further revealed after the confounding effect of parity or number of children is considered.
Publisher: Springer Science and Business Media LLC
Date: 08-08-2020
DOI: 10.1038/S41430-019-0476-Z
Abstract: The evidence for diet as a risk factor for multiple sclerosis (MS) is inconclusive. We examined the associations between fish consumption and risk of a first clinical diagnosis of central nervous system demyelination (FCD), a common precursor to MS. The 2003-2006 Ausimmune Study was a case-control study examining environmental risk factors for FCD, with participants recruited from four regions of Australia and matched on age, sex, and study region. Dietary intake data were collected using a food frequency questionnaire. We used conditional logistic regression models to test associations between fish consumption (total, tinned, grilled, and fried) and risk of FCD (249 cases and 438 controls), adjusting for history of infectious mononucleosis, smoking, serum 25-hydroxyvitamin D concentrations, socio-economic status, omega-3 supplement use, dietary under-reporting, and total energy intake. Higher total fish consumption (per 30 g/day, equivalent to two serves/week) was associated with an 18% reduced risk of FCD (AOR 0.82 95% CI 0.70, 0.97). While we found no statistically significant associations between grilled and fried fish consumption and risk of FCD, higher tinned fish consumption (per 30 g/day) was associated with a 41% reduced risk of FCD (AOR 0.59 95% CI 0.39, 0.89). Tinned fish is predominantly oily, whereas grilled and fried fish are likely to be a combination of oily and white types. Oily fish is high in vitamin D and very long chain polyunsaturated omega-3 fatty acids, both of which may be beneficial in relation to MS.
Publisher: Wiley
Date: 09-08-2021
DOI: 10.1111/ALL.15022
Abstract: Bacille Calmette‐Guérin (BCG) vaccine could play a role in counteracting the rising prevalence of atopic diseases, through its beneficial off‐target effects. We aimed to determine whether neonatal BCG vaccination reduces the incidence of eczema in infants. Randomized controlled trial with 1272 infants allocated to receive BCG‐Denmark or no BCG at birth. The primary outcome was the 12‐month incidence of eczema based on 3‐monthly questionnaires. Eczema was also assessed at a 12‐month clinic visit. ClinicalTrial.gov: NCT01906853. The 12‐month eczema incidence was 32.2% in the BCG group compared with 36.6% in the control group (adjusted risk difference (aRD) −4.3%, 95% CI −9.9% to 1.3%, multiple imputation model). In addition, comparing infants in the BCG group with the control group, 15.7% vs. 19.2% had eczema lesions at the 12‐month visit (aRD −3.5%, 95% CI −8.0% to 1.0%) 35.7% vs. 39.0% reported using topical steroids (aRD −3.3, 95% CI −9.2 to 2.7) and 7.3% vs. 10.2% had severe eczema scores (aRD −3.0%, 95% CI −8.8% to 2.7%). In 344 high‐risk infants (two atopic parents), the 12‐month eczema incidence was 35.3% in the BCG group compared with 46.8% in the control group (aRD −11.5%, 95% CI −21.9% to −1.2% number needed to treat 8.7, 95% CI 4.6 to 83.3). There is insufficient evidence to recommend neonatal BCG vaccination in all infants for the prevention of eczema in the first year of life however, a modest beneficial effect was observed among high‐risk infants. A single dose of BCG‐Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.
Publisher: BMJ
Date: 18-07-2014
Abstract: The interplay between genes and environmental factors on multiple sclerosis (MS) clinical course has been little studied. We conducted a prospective cohort study of 141 participants with relapsing-remitting MS (RRMS) and genotype data followed from 2002 to 2005 and examined genes in the vitamin D metabolism and vitamin D receptor (VDR)/retinoid X receptor (RXR) transcription factor formation pathway. Gene-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis. Genetic predictors of 25-hydroxyvitamin D (25(OH)D) were evaluated by multilevel mixed-effects linear regression. Significance threshold was adjusted by Bonferroni correction for the number of genes evaluated. The relationship between 25(OH)D and hazard of relapse was significantly different for different alleles of two intronic single nucleotide polymorphisms (SNPs) (rs908742 in PRKCZ and rs3783785 in PRKCH) in the protein kinase C (PKC) family genes (p(interaction)=0.001, p(adj)=0.021, respectively). Two other intronic SNPs (rs1993116 in CYP2R1and rs7404928 in PRKCB) were significantly associated with lower levels of 25(OH)D (p(interaction)=0.001, p(adj)=0.021, respectively). A cumulative effect of multiple 'risk' genotypes on 25(OH)D levels and hazard of relapse was observed for the significant SNPs (p(trend)=7.12×10(-6) for 25(OH)D levels, p(trend)=8.86×10(-6) for hazard of relapse). Our data support the hypothesis that gene-vitamin D interactions may influence MS clinical course and that the PKC family genes may play a role in the pathogenesis of MS relapse through modulating the association between 25(OH)D and relapse.
Publisher: Elsevier BV
Date: 04-2013
Publisher: Cambridge University Press (CUP)
Date: 17-12-2019
DOI: 10.1017/S2040174419000849
Abstract: Gut bacteria from the genus Prevotella are found in high abundance in faeces of non-industrialised communities but low abundance in industrialised, Westernised communities. Prevotella copri is one of the principal Prevotella species within the human gut. As it has been associated with developmental health and disease states, we sought to (i) develop a real-time polymerase chain reaction (PCR) to rapidly determine P. copri abundance and (ii) investigate its abundance in a large group of Australian pregnant mothers. The Barwon Infant Study is a pre-birth cohort study ( n = 1074). Faecal s les were collected from mothers at 36 weeks gestation. Primers with a probe specific to the V3 region of P. copri 16S rRNA gene were designed and optimised for real-time PCR. Universal 16S rRNA gene primers lified pan-bacterial DNA in parallel. Relative abundance of P. copri was calculated using a 2 -Δ Ct method. Relative abundance of P. copri by PCR was observed in 165/605 (27.3%) women. The distribution was distinctly bimodal, defining women with substantial ( n = 115/165, 69.7%) versus very low P. copri expression ( n = 50/165, 30.3%). In addition, abundance of P. copri by PCR correlated with 16S rRNA gene MiSeq sequencing data ( r 2 = 0.67, P 0.0001, n = 61). We have developed a rapid and cost-effective technique for identifying the relative abundance of P. copri using real-time PCR. The expression of P. copri was evident in only a quarter of the mothers, and either at substantial or very low levels. PCR detection of P. copri may facilitate assessment of this species in large, longitudinal studies across multiple populations and in various clinical settings.
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000166602
Abstract: i Background: /i Monthly variation in multiple sclerosis (MS) relapses has been found. The relationship between seasonal environmental factors, infections, serum vitamin D [25(OH)D] and MS relapses is undetermined. i Methods: /i We prospectively followed a population-based cohort of relapsing-remitting (RR) MS patients in Southern Tasmania for a mean 2.3 years (January 2002–April 2005). Associations between monthly ambient environmental factors, estimated serum 25(OH)D, upper respiratory tract (URT) infections and relapse rates were examined using weighted Pearson’s correlation and linear regression. i Results: /i Of 199 definite MS patients, 142 had RRMS. The lowest relapse rate of 0.5 per 1,000 days (95% CI: 0.2–1.3) occurred in February (mid-late summer) versus the March–January RR of 1.1 per 1,000 days (95% CI: 0.9–1.3 p = 0.018, weighted regression). Monthly relapse rates correlated with: (1) prior erythemal ultraviolet radiation (EUV): lagged 1.5 months, r = –0.32, p = 0.046 (2) URT infection rate: no lag, r = 0.39, p = 0.014 (3) 25(OH)D: no lag, r = –0.31, p = 0.057. The association between URT infections and relapses was reduced after adjustment for monthly EUV. i Conclusions: /i Relapse rates were inversely associated with EUV and serum 25(OH)D levels and positively associated with URT infections. The demonstrated lag between EUV but not 25(OH)D and relapse rates is consistent with a role for EUV-generated 25(OH)D in the alteration of relapse rates. Future work on the association between URT infections and relapses should be considered in the context of ultraviolet radiation and vitamin D.
Publisher: BMJ
Date: 30-03-2011
Publisher: SAGE Publications
Date: 06-09-2016
Abstract: There is substantial evidence that stress increases multiple sclerosis disease activity, but limited evidence on its association with the onset of multiple sclerosis. To examine the association between stressful life events and risk of first demyelinating event (FDE). This was a multicentre incident case–control study. Cases ( n = 282 with first diagnosis of central nervous system (CNS) demyelination, including n = 216 with ‘classic FDE’) were aged 18–59 years. Controls without CNS demyelination ( n = 558) were matched to cases on age, sex and study region. Stressful life events were assessed using a questionnaire based on the Social Readjustment Rating Scale. Those who suffered from a serious illness in the previous 12 months were more likely to have an FDE (odds ratio (OR) = 2.35 (1.36, 4.06), p = 0.002), and when we limited our reference group to those who had no stressful life events, the magnitude of effect became stronger (OR = 5.41 (1.80, 16.28)). The total stress number and stress load were not convincingly associated with the risk of an FDE. Cases were more likely to report a serious illness in the previous 12 months, which could suggest that a non-specific illness provides an additional strain to an already predisposed immune system.
Publisher: SAGE Publications
Date: 13-05-2013
Abstract: Lifestyle factors prior to a first clinical demyelinating event (FCD), a disorder often preceding the development of clinically definite multiple sclerosis (MS), have not previously been examined in detail. Past tobacco smoking has been consistently associated with MS. This was a multicentre incident case-control study. Cases ( n = 282) were aged 18–59 years with an FCD and resident within one of four Australian centres (from latitudes 27°S to 43°S), from 1 November 2003 to 31 December 2006. Controls ( n = 558) were matched to cases on age, sex and study region, without CNS demyelination. Exposures measured included current and past tobacco and marijuana, alcohol and beverage use, physical activity patterns, blood pressure and physical anthropometry. A history of smoking ever was associated with FCD risk (AOR 1.89 (95%CL 1.82, 3.52)). Marijuana use was not associated with FCD risk after adjusting for confounders such as smoking ever but the estimates were imprecise because of a low prevalence of use. Alcohol consumption was common and not associated with FCD risk. No case-control differences in blood pressure or physical anthropometry were observed. Past tobacco smoking was positively associated with a risk of FCD but most other lifestyle factors were not. Prevention efforts against type 2 diabetes and cardiovascular disease by increasing physical activity and reducing obesity are unlikely to alter MS incidence, and more targeted c aigns will be required.
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.AJO.2010.06.028
Abstract: To examine the relationship of birth weight with ocular measures in a Caucasian twin population. Cross-sectional study of 1498 twins (308 monozygotic and 441 dizygotic pairs) aged between 5 to 80 years participating in the Australian Twins Eye Study. All participants underwent ophthalmic examination including bilateral cycloplegic autorefraction, keratometry, interpupillary distance (IPD), central corneal thickness, intraocular pressure (IOP), and retinal photography. Birth weight and gestation were obtained from a self-administered questionnaire. A subset of the twins also participated in the Tasmanian Infant Health Study (288) and the Childhood Blood Pressure Study (184), which collected data on birth parameters allowing for verification of data. Linear mixed models were used for the main analysis. Both the within-pair (β(w) 0.27, 95% confidence interval [CI] 0.15, 0.38 mm per kg increase in birth weight, P < .001) and between-pair associations (β(B) 0.22, 95% CI 0.08, 0.35, P = .002) of birth weight with axial length were significant and of similar magnitude (difference in effect, P = .56), after adjusting for relevant confounders. In contrast, birth weight was negatively associated with corneal curvature (β(w) -0.82, 95% CI -1.09, -0.55 diopters per kg increase β(B) -0.69, 95% CI -0.98, -0.41, both P < .001). These associations remained significant within dizygotic and monozygotic pairs. Refraction, anterior chamber depth, IPD, IOP, and optic disc parameters are unrelated to birth weight. Consistent with previous studies in singleton children, lower birth weight is associated with shorter axial length and more curved corneas in this twin study. This also adds new insights into the emmetropization process.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-01-2016
DOI: 10.1126/SCITRANSLMED.AAD4322
Abstract: Infants who develop food allergy display hyperresponsive innate immunity at birth that promotes nonclassical T H 2 differentiation.
Publisher: Springer Science and Business Media LLC
Date: 28-06-2023
DOI: 10.1007/S00394-023-03186-W
Abstract: Maternal dietary choline has a central role in foetal brain development and may be associated with later cognitive function. However, many countries are reporting lower than recommended intake of choline during pregnancy. Dietary choline was estimated using food frequency questionnaires in pregnant women participating in population-derived birth cohort, the Barwon Infant Study (BIS). Dietary choline is reported as the sum of all choline-containing moieties. Serum total choline-containing compounds (choline-c), phosphatidylcholine and sphingomyelin were measured using nuclear magnetic resonance metabolomics in the third trimester. The main form of analysis was multivariable linear regression. The mean daily dietary choline during pregnancy was 372 (standard deviation (SD) 104) mg/day. A total of 236 women (23%) had adequate choline intake (440 mg/day) based on the Australian and New Zealand guidelines, and 27 women (2.6%) took supplemental choline ( $$\\ge$$ ≥ 50 mg/dose) daily during pregnancy. The mean serum choline-c in pregnant women was 3.27 (SD 0.44) mmol/l. Ingested choline and serum choline-c were not correlated ( R 2 ) = − 0.005, p = 0.880. Maternal age, maternal weight gain in pregnancy, and a pregnancy with more than one infant were associated with higher serum choline-c, whereas gestational diabetes and environmental tobacco smoke during preconception and pregnancy were associated with lower serum choline-c. Nutrients or dietary patterns were not associated with variation in serum choline-c. In this cohort, approximately one-quarter of women met daily choline recommendations during pregnancy. Future studies are needed to understand the potential impact of low dietary choline intake during pregnancy on infant cognition and metabolic intermediaries.
Publisher: American Academy of Pediatrics (AAP)
Date: 06-2016
Abstract: Swaddling is a traditional practice of wrapping infants to promote calming and sleep. Although the benefits and risks of swaddling in general have been studied, the practice in relation to sudden infant death syndrome remains unclear. The goal of this study was to conduct an in idual-level meta-analysis of sudden infant death syndrome risk for infants swaddled for sleep. Additional data on sleeping position and age were provided by authors of included studies. Observational studies that measured swaddling for the last or reference sleep were included. Of 283 articles screened, 4 studies met the inclusion criteria. There was significant heterogeneity among studies (I2 = 65.5% P = .03), and a random effects model was therefore used for analysis. The overall age-adjusted pooled odds ratio (OR) for swaddling in all 4 studies was 1.58 (95% confidence interval [CI], 0.97–2.58). Removing the most recent study conducted in the United Kingdom reduced the heterogeneity (I2 = 28.2% P = .25) and provided a pooled OR (using a fixed effects model) of 1.38 (95% CI, 1.05–1.80). Swaddling risk varied according to position placed for sleep the risk was highest for prone sleeping (OR, 12.99 [95% CI, 4.14–40.77]), followed by side sleeping (OR, 3.16 [95% CI, 2.08–4.81]) and supine sleeping (OR, 1.93 [95% CI, 1.27–2.93]). Limited evidence suggested swaddling risk increased with infant age and was associated with a twofold risk for infants aged & months. Heterogeneity among the few studies available, imprecise definitions of swaddling, and difficulties controlling for further known risks make interpretation difficult. Current advice to avoid front or side positions for sleep especially applies to infants who are swaddled. Consideration should be given to an age after which swaddling should be discouraged.
Publisher: Oxford University Press (OUP)
Date: 17-02-2021
DOI: 10.1093/IJE/DYAA174
Abstract: This commentary provides a practical perspective on epidemiological analysis within a single high-dimensional study of moderate size to consider a causal question. In this setting, non-causal confounding is important. This occurs when a factor is a determinant of outcome and the underlying association between exposure and the factor is non-causal. That is, the association arises due to chance, confounding or other bias rather than reflecting that exposure and the factor are causally related. In particular, the influence of technical processing factors must be accounted for by pre-processing measures to remove artefact or to control for these factors such as batch run. Work steps include the evaluation of alternative non-causal explanations for observed exposure-disease associations and strategies to obtain the highest level of causal inference possible within the study. A systematic approach is required to work through a question set and obtain insights on not only the exposure-disease association but also the multifactorial causal structure of the underlying data where possible. The appropriate inclusion of molecular findings will enhance the quest to better understand multifactorial disease causation in modern observational epidemiological studies.
Publisher: Wiley
Date: 08-1997
DOI: 10.1111/J.1440-1754.1997.TB01608.X
Abstract: To examine the relationship between infant and parental characteristics and parental report of infant cyanosis and also hospital admission for apnoea/cyanosis. A prospective cohort study was conducted. It involved the one-fifth of Tasmanian live births who were assessed, using a perinatal score, as being at higher risk of sudden infant death syndrome (SIDS). From 1 May 1988 to 30 April 1993, 6213 infants (89% of eligible infants) participated in the hospital (4 days postnatal age) and home interview (5 weeks postnatal age). Data on usual sleep position and infant history of cyanosis were collected at home interview. Hospital admission records for apnoea/cyanosis in the first year of life were linked to data on cohort infants in Southern Tasmania. Several factors were related to parental reports of cyanosis, with strong associations observed for very premature infants < 28 weeks (adjusted odds ratio [AOR] 6.06, 95% confidence interval [2.47, 14.85]), history of fits (AOR 5.59 [2.35, 13.13]) and the administration of antihistamine medication during the first month of life (AOR 3.03 [1.12, 8.18]). The median age at hospital admission was 7 weeks postnatal age. A family history of asthma, a history of fits, a history of turning blue while feeding or trouble breathing while feeding were associated with parental reports of cyanosis, breathing difficulties and also with hospital admission for apnoea/cyanosis. Other factors such as prematurity, maternal smoking, bottle feeding and a history of fever were significantly related to the infant history of cyanosis but not to hospital admission. This may partly reflect the low incidence rate (1.37%) for hospitalization for apnoea/cyanosis in the first year of life among these cohort infants. Several infant and parental characteristics are associated with increased risk of infant apnoea/cyanosis in this study but further population-based work with a larger group of infants hospitalised for apnoea/cyanosis should be conducted. The finding of an association between the administration of antihistamine medication and infant cyanosis highlights the possibility of adverse side-effects if antihistamine medication is administered to young infants.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2020
Publisher: Springer Science and Business Media LLC
Date: 22-09-2010
Publisher: Wiley
Date: 09-03-2017
DOI: 10.1002/BRB3.670
Publisher: Cambridge University Press (CUP)
Date: 22-05-2014
DOI: 10.1017/S2040174414000282
Abstract: Childhood cardiovascular risk factors affect vascular function long before overt cardiovascular disease. Twin studies provide a unique opportunity to examine the influence of shared genetic and environmental influences on childhood cardiovascular function. We examined the relationship between birth parameters, markers of adiposity, insulin resistance, lipid profile and blood pressure and carotid–femoral pulse wave velocity (PWV), a validated non-invasive measure of arterial stiffness in a healthy cohort of school-aged twin children. PWV was performed on a population-based birth cohort of 147 twin pairs aged 7–11 years. Fasting blood s les, blood pressure and adiposity measures were collected concurrently. Mixed linear regression models were used to account for twin clustering, within- and between-twin pair associations. There were positive associations between both markers of higher adiposity, insulin resistance, elevated triglycerides and PWV, which remained significant after accounting for twin birth-set clustering. There was a positive association between both diastolic and mean arterial blood pressure and PWV in within-pair analysis in dizygotic, but not monozygotic twins, indicating genetic differences evident in dizygotic not monozygotic twins may affect these associations. Increased blood pressure, triglycerides and other metabolic markers are associated with increased PWV in school-aged twins. These results support both the genetic and environmental contribution to higher PWV, as a marker of arterial stiffness, and reiterate the importance of preventing metabolic syndrome from childhood.
Publisher: Wiley
Date: 28-05-2013
DOI: 10.1111/CEA.12048
Abstract: A variety of hypotheses have been proposed to explain the recently described increase in food allergy among children living in developed countries. In this study, we summarize the emerging risk factors for IgE-mediated food allergy in early life, and then review the evidence for and against an association between low vitamin status (VDS) and food allergy. We consider whether each of the epidemiological variables that have been associated with food allergy may also be associated with VDS and argue that future studies must adequately account for the potential relationships between risk factors for food allergy and VDS, and must also discriminate between vitamin D derived by sun exposure, diet and oral supplementation.
Publisher: Wiley
Date: 02-2010
DOI: 10.1002/ANA.21849
Publisher: Springer Science and Business Media LLC
Date: 19-11-2008
DOI: 10.1038/EJCN.2008.55
Abstract: We tested the hypothesis that the relationship between maternal 25-hydroxyvitamin D (25-(OH)D) and offspring birth size differs according to offspring vitamin D receptor (VDR) genotype (Apa1, Bsm1, Fok1 or Taq1). Mothers of 354 singleton babies had serum 25-(OH)D concentration measured at 28-30 weeks of gestation and consented to measurement of their babies soon after birth. DNA was extracted from the babies' Guthrie cards. There was evidence of effect modification by infant FokI genotype. Babies of deficient mothers had lower birth weight with FF or Ff, but not ff genotype (P-value for interaction after adjustment for potential confounding factors=0.02), but thicker subscapular and suprailiac skinfolds with ff, but not FF or Ff genotype (P=0.008 and 0.02, respectively). S le size was insufficient to investigate effect modification by the other VDR polymorphisms. These preliminary findings suggest that studies of maternal vitamin D status and birth size may need to take VDR genotype into account.
Publisher: Wiley
Date: 04-2003
DOI: 10.1046/J.1365-2222.2003.01642.X
Abstract: Higher house dust mite (HDM) allergen exposure during infancy has been associated with increased HDM sensitization. Infant bedding has been associated with the accumulation of varying levels of HDM. Prospective data on the relationship between infant bedding and the development of HDM sensitization has not been previously examined. To determine if particular types of bedding used in infancy are associated with increased risk of house dust mite sensitization in childhood. A population-based s le (n = 498) of children born in 1988 or 1989, and who were resident in Northern Tasmania in 1997, participated in this study. These children were part of a birth cohort study (1988-95), the Tasmanian Infant Health Survey. Data on infant underbedding and mattresses was available on 460 and 457 children, respectively. The main outcome measure was HDM sensitization defined as a skin prick test (SPT) reaction of 3 mm or more to the allergens of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. The use of either sheepskin underbedding or plastic mattress covers in infancy was associated with an increased risk of sensitization to HDM allergens at age 8 years. The adjusted risk ratio (RR) for sensitization to HDM with sheepskin in infancy was 2.27 (95% CI: 1.14, 4.55), P = 0.020. The adjusted RR for sensitization to HDM with the use of plastic mattress covers in infancy was 2.06 (95% CI: 1.22, 3.51), P = 0.007. The use of a foam mattress in infancy was not related to subsequent HDM sensitization. Infant's bedding plays a role in the development of HDM sensitization in childhood. Intervention studies to examine mite allergen levels and the role of underbedding on the development of HDM sensitization are required.
Publisher: Cambridge University Press (CUP)
Date: 22-11-2012
DOI: 10.1017/THG.2012.114
Abstract: The Peri ostnatal Epigenetic Twins Study (PETS) is a longitudinal cohort of 250 pairs of Australian twins and their mothers, who were recruited mid-way through pregnancy from January 2007 to September 2009. The study is centered on the developmental origins of health and disease paradigm (DOHaD) in which an adverse intrauterine environment predisposes the in idual to complex disease in later life by reducing growth in utero and adversely altering developmental plasticity. Data concerning diet and lifestyle were collected from mothers during pregnancy, and s les of plasma and serum taken at 28 weeks’ gestation. We attended 75% of all births, at which time we collected multiple biological s les including placenta, cord blood, and neonatal cheek cells, the latter from 91% of pairs. Chorionicity was recorded and zygosity was determined by DNA testing where necessary. Approximately 40% of the twins are monozygotic, two-thirds of which are dichorionic. Twins were seen again at 18 months of age and repeat blood and cheek swabs taken where possible. Studies of gene expression and the epigenetic marks of DNA methylation have so far revealed that twins exhibit a wide range of epigenetic discordance at birth, that one-third of the epigenome changes significantly between birth and 18 months shared (maternal) environment, genetic factors, and non-shared intrauterine environment contribute to an increasing proportion of epigenetic variation at birth, respectively, and affect tissues differently, and that within-pair birth weight discordance correlates with epigenetic discordance in genes associated with lipid metabolism, supporting an epigenetic mechanism for DOHaD.
Publisher: Bentham Science Publishers Ltd.
Date: 02-07-2015
DOI: 10.2174/1389557515666150519111328
Abstract: Studies from several countries have reported an association between latitudes further from the equator and proxy markers of food allergy prevalence. As latitudes further from the equator are associated with lower sun exposure and vitamin D status (VDS), it has been proposed that low VDS may be a risk factor for food allergy. A range of basic science evidence supports the biological plausibility of this hypothesis and recent work has identified a cross sectional association between low VDS and challenge proven food allergy in infants. Overall, however, the evidence regarding the relationship between VDS and food allergy remains controversial and the limited longitudinal data are discouraging. In this review we consider the evidence for and against low VDS as a risk factor for food allergy and discuss the possibility that other factors (including genetic variables) may contribute to the inconsistent nature of the available observational evidence. We then discuss whether genetic and/or environmental factors may modify the potential influence of VDS on food allergy risk. Finally, we argue that given the rising burden of food allergy, the balance of available evidence regarding the potential relevance of VDS to this phenomenon, and the inherent limitations of the existing observational data, there is a compelling case for conducting randomised clinical trials of vitamin D supplementation for the prevention of food allergy during early life.
Publisher: Oxford University Press (OUP)
Date: 13-10-2006
DOI: 10.1111/J.1365-2249.2006.03235.X
Abstract: Higher sibling exposure is associated with a reduced risk of asthma and other T helper 2 (Th2)-type disorders, possibly through a beneficial effect of higher infection load. The effect on Th1 disorders such as multiple sclerosis (MS) is less clear. Here we examine the association between asthma and MS, taking into account early life sibling exposure. A population-based case–control study in Tasmania, Australia based on 136 cases of magnetic resonance imaging (MRI)-confirmed MS and 272 community controls, matched on sex and year of birth. Study measures include cumulative exposure to total, older or younger siblings by age 6 years, history of doctor-diagnosed asthma and serological IgG responses to herpes viruses. MS cases were more likely (P = 0·02) than controls to have asthma which began before age of onset of MS symptoms compared to the corresponding age for controls. The absence of younger sibling exposure by age 6 years potentiated (P = 0·04) the association between asthma and MS. Compared to those with younger sibling exposure and no asthma, the adjusted odds ratio for MS for those with asthma and no younger sibling exposure was 7·22 (95% CI: 2·52, 20·65). Early life sibling exposure was associated with altered IgG serological responses to Epstein–Barr virus (EBV) and herpes simplex virus 1 (HSV1) in adulthood. Reduced early life sibling exposure appeared to contribute to the excess of asthma among MS cases by the time of MS onset. MS development may reflect factors that relate to a general immuno-inflammatory up-regulation of immune activity as well as disease specific factors. The link between early life sibling exposure and the immune response to herpes group viral antigens is consistent with a protective role for early life infections.
Publisher: SAGE Publications
Date: 18-02-2010
Abstract: Increasing prevalence and variable geographic patterns of occurrence of multiple sclerosis suggest an environmental role in causation. There are few descriptive, population-level, data on whether such variability applies to first demyelinating events (FDEs). We recruited 216 adults (18—59 years), with a FDE between 1 November 2003 and 31 December 2006 in a multi-center incident case-control study in four locations on the south-eastern and eastern seaboard of Australia, spanning latitudes 27° south to 43° south. Population denominators were obtained from the Australian Bureau of Statistics censuses of 2001 and 2006. Age and sex adjusted FDE incidence rates increased by 9.55% (95% confidence interval (CI) 7.37—11.78, p 0.001) per higher degree of latitude. The incidence rate gradient per higher degree of latitude varied by gender (male: 14.69% (95% CI 9.68—19.94, p 0.001) female 8.13% (95% CI 5.69—10.62, p 0.001)) and also by the presenting FDE type: optic neuritis 11.39% (95% CI 7.15—15.80, p 0.001) brainstem/cerebellar syndrome 9.47% (95% CI 5.18—13.93, p 0.001) and spinal cord syndrome 5.36% (95% CI 1.78—9.06, p = 0.003). Differences in incidence rate gradients were statistically significant between males and females ( p = 0.02) and between optic neuritis and spinal cord syndrome ( p = 0.04). The male to female ratio varied from 1 : 6.7 at 27° south to 1 : 2.5 at 43° south. The study establishes a positive latitudinal gradient of FDE incidence in Australia. The latitude-related factor(s) influences FDE incidence variably according to subtype and gender, with the strongest influence on optic neuritis presentations and for males. These descriptive case analyses show intriguing patterns that could be important for understanding the etiology of multiple sclerosis.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.MSARD.2019.101486
Abstract: Due to the considerable burden of multiple sclerosis (MS)-related symptoms and the need to identify effective interventions to prevent disease progression, various nutraceutical interventions have been trialed as adjunctive treatments. The aim of this review was to investigate the efficacy and safety of nutraceutical interventions for clinical and biological outcomes in people with MS. In accordance with PRISMA reporting guidelines, a systematic literature search was conducted using three electronic literature databases. Risk of bias was assessed using the Jadad scale. Thirty-seven randomized controlled trials, investigating fourteen nutraceuticals, were included in the review. Trials that investigated alpha lipoic acid (n = 4/6), ginkgo biloba (n = 3/5), vitamin A (n = 2/2), biotin (n = 1/2), carnitine (n = 1/2), green tea (n = 1/2), coenzyme Q10 (n = 1/1), probiotics (n = 1/1), curcumin (n = 1/1), Andrographis paniculata (n = 1/1), ginseng (n = 1/1), and lemon verbena (n = 1/1) were reported to improve biological (e.g. MRI brain volume change, antioxidant capacity) and/or clinical (e.g. fatigue, depression, Expanded Disability Status Scale) outcomes in multiple sclerosis compared to control. However, most trials were relatively small (average study s le size across included studies, n = 55) and there were few replicate studies per nutraceutical to validate the reported results. Furthermore, some nutraceuticals (e.g. green tea and inosine) should be used with caution due to reported adverse events. Risk of bias across most studies was low, with 31 studies receiving a score between 4 and 5 (out of 5) on the Jadad Scale. The existing literature provides preliminary support for the use of a number of nutraceutical interventions in MS. However, sufficiently powered long-term trials are required to expand the currently limited literature and to investigate unexplored nutraceuticals that may target relevant pathways involved in MS such as the gut microbiome and mitochondrial dysfunction. Prospero ID: CRD42018111736.
Publisher: Elsevier BV
Date: 05-1991
DOI: 10.1016/0140-6736(91)92917-Q
Abstract: Studies of the link between prone sleeping position and sudden infant death syndrome have been criticised on grounds of recall bias and for not taking into account possible confounding effects. To avoid recall bias and to allow measurement of important biological factors a prospective cohort study of the cause of sudden infant death syndrome (SIDS) is being conducted. The infants included are those at high risk of the syndrome as assessed by a perinatal score. Of the 3110 members of the cohort born between January, 1988, and end of March, 1990, 23 infants later died of SIDS. Sleep position information was available for 15 of these. Matched analysis to control for the confounding effects of infant birthweight and maternal age indicated that prone sleeping position was associated with an increased risk of SIDS (OR 4.47 95% Cl [1.30-15.43]). The findings are strengthened by the results of a concurrent retrospective case-control study of 42 SIDS cases in which the prone position was also associated with an increased risk of SIDS (unadjusted OR 3.45 [1.59-7.49]).
Publisher: Wiley
Date: 08-2010
Abstract: Vitamin D is important for bone health, as well as an increasing number of other health outcomes. Here we discuss the evidence relating to vitamin D in pregnancy, from preconception to the perinatal period. During pregnancy extra calcium required for fetal skeletal growth is attained by both maternal bone resorption and increased absorption from dietary sources, necessitating increased maternal vitamin D. Many women have low vitamin D status during pregnancy and may require supplementation, although optimal serum levels and intake required to achieve those levels is not yet well defined. Evidence from animal studies, with some supportive human evidence, suggests that fertility may be impaired in mothers with low vitamin D. During pregnancy, maintaining vitamin D and calcium levels may decrease the risks of pre-ecl sia, while gestational diabetes mellitus appears to be more common in those with low vitamin D status, although there is insufficient evidence of causality. The evidence in relation to increased risks of bacterial vaginosis and caesarean section similarly requires confirmation in carefully designed observational and experimental studies. This review outlines the emerging evidence that maternal vitamin D status during pregnancy is important for the health of the mother and offspring across a range of possible health outcomes.
Publisher: Wiley
Date: 17-01-2019
DOI: 10.1111/ALL.14159
Abstract: A few studies have investigated the antecedents and outcomes of infants who demonstrate IgE sensitization to foods that they clinically tolerate. Improved understanding of this sensitized-tolerant phenotype may inform strategies for the prevention of food allergy. In an Australian birth cohort (n = 1074), assembled using an unselected antenatal s ling frame, participants were categorized as nonsensitized (NS), sensitizedtolerant (ST), or food allergic (FA) based on skin prick testing and food challenge at 12 months of age. Environmental exposures were recorded throughout. Cord blood regulatory T-cell populations were measured at birth. Subsequent childhood allergic disease was assessed by parent report, clinical examination, and repeat skin prick testing. The covariates of interest varied between NS (n = 698), ST (n = 27), and FA (n = 61) groups as follows, suggesting that across these measures, the ST group was more similar to the NS than the FA group: family history of eczema NS 44.6%, ST. 44.6%, FA 65.6% pet ownership at 12 months: NS 71.5%, ST 81.5%, FA 45.8% eczema during the first 12 months: NS 19%, ST 32%, FA 64% and aeroallergen sensitization at 4 years: NS 19.1%, ST 28.6%, FA 44.4%. At birth, a higher proportion of activated regulatory T cells was associated with ST (OR = 2.89, 95% CI 1.03-8.16, P = .045). Food-sensitized-tolerance in infancy appears to be associated with a similar pattern of exposures, immunity, and outcomes to nonsensitized infants. In addition, we found some evidence that an elevated proportion of activated regulatory T cells at birth was specific to the sensitized-tolerant infants, which may be relevant to suppression of clinical disease.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.JACI.2019.07.032
Abstract: Randomized controlled trials demonstrate that timely introduction of peanut to infants reduces the risk of peanut allergy. However, much debate remains regarding how to best achieve earlier peanut introduction at the population level. Our previous study in 2007-2011 (HealthNuts, n = 5300) indicated that few infants were consuming peanut in the first year. Australian infant feeding guidelines were updated in 2016 to recommend introducing peanut before 12 months for all infants. There were no data available on the subsequent effect on peanut introduction or peanut reactions. We sought to assess the consequences of a nonscreening approach to allergenic food introduction in a population-based s le of infants in their first year of life. EarlyNuts is a population-based, cross-sectional study of 12-month-old infants in Melbourne, Australia, recruited by using an identical s ling frame and methods to HealthNuts (72% response rate vs 73% response rate in HealthNuts). We report here on the first 860 participants recruited between November 2016 and October 2018. Most infants (88.6% 95% CI, 86.1% to 90.7%) had introduced peanut by 12 months (median age, 6 months), an increase from 28.4% (95% CI, 27.2% to 29.7%) in the HealthNuts study. By 12 months, the majority of these (76.4%) had consumed peanut more than 4 times, and 28% were eating peanut more than once per week. Preliminary results on parent-reported reactions show that 4.0% of those consuming peanut by 12 months had possible IgE-mediated reactions. There has been a striking shift toward earlier peanut introduction, with a 3-fold increase in peanut introduction by age 1 year in 2018 compared with 2007-2011.
Publisher: Cambridge University Press (CUP)
Date: 2014
DOI: 10.1017/ERM.2014.5
Abstract: Autoimmune disease manifests in numerous forms, but as a disease group is relatively common in the population. It is complex in aetiology, with genetic and environmental determinants. The involvement of gene variants in autoimmune disease is well established, and evidence for significant involvement of the environment in various disease forms is growing. These factors may act independently, or they may interact, with the effect of one factor influenced by the presence of another. Identifying combinations of genetic and environmental factors that interact in autoimmune disease has the capacity to more fully explain disease risk profile, and to uncover underlying molecular mechanisms contributing to disease pathogenesis. In turn, such knowledge is likely to contribute significantly to the development of personalised medicine, and targeted preventative approaches. In this review, we consider the current evidence for gene–environment (G–E) interaction in autoimmune disease. Large-scale G–E interaction research efforts, while well-justified, face significant practical and methodological challenges. However, it is clear from the evidence that has already been generated that knowledge on how genes and environment interact at a biological level will be crucial in fully understanding the processes that manifest as autoimmunity.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2006
DOI: 10.1158/1055-9965.EPI-05-0969
Abstract: Background: Measurement of past sun exposure through recall by adults has the potential for measurement error. We aimed to investigate aspects of validity and reliability of self-reported past sun exposure. Methods: A population-based case-control study was conducted in Tasmania on 136 cases with multiple sclerosis and 272 age- and sex-matched community controls. Repeat interviews on 52 cases and 52 controls were done on average 11 weeks after the initial interview. Sun exposure was assessed by questionnaire and lifetime calendar. Other measurements included serum 25-hydroxyvitamin D, actinic damage, and skin phenotype. Results: There was an association between recent sun exposure and serum vitamin D (time in the sun: r = 0.22, P & 0.01 activities outside: r = 0.31, P & 0.01 for controls) and between lifetime sun exposure and actinic damage [correlation between 0.34 (P & 0.01) and 0.17 (P = 0.01) for controls]. The test-retest weighted κ statistic of self-reported sun exposure ranged from 0.43 to 0.74. Recall of childhood/adolescent sun exposure by standardized questioning was no less reproducible than recall of recent adult sun exposure and no less reliable when made with the calendar method. Comparing the questionnaire and calendar method, the measures of childhood/adolescent sun exposure had a similar predictive validity for multiple sclerosis. Conclusions: The results of this study provide further evidence that adults are able to recall past sun exposure with shown validity and reliability and present information about the possible reasons for the good reliability of recalled sun exposure measures. (Cancer Epidemiol Biomarkers Prev 2006 (8):1538–44)
Publisher: Wiley
Date: 07-1999
DOI: 10.1046/J.1365-3016.1999.00194.X
Abstract: Following evidence that prone sleeping is causally related to sudden infant death syndrome (SIDS), intervention c aigns to avoid prone sleeping in many countries have led to a large reduction in SIDS and total infant mortality. The supine position has been recommended for healthy infants in several countries. The objective of this report was to determine how usual sleep position at 1 month relates to morbidity indicators at 1 month and 12 weeks and to SIDS and postneonatal mortality using a prospective population-based live birth cohort in Tasmania, Australia. Eligible infants were the one-fifth of Tasmanian live births at higher risk of SIDS using a perinatal score. From 1 January 1988 to 31 December 1995, 9826 (89% of eligible) infants participated in the home interview. Fifty-three eligible infants died of SIDS, 51 (96%) with hospital interview data and 35 (81% of those eligible for home visit) with home visit data. The main outcome measures were SIDS, postneonatal mortality and parentally reported infant morbidity. The postneonatal mortality rates (cases per 1000 live births) by usual sleep position at 1 month of age were supine 1.60 [95% CI 0.04, 8.87], side 2.87 [1.79, 4.35], prone 10.27 [5.62, 17.18] and other (including no usual position) 6.37 [0.16, 34.98]. None of the study infants who slept supine died of SIDS at a later time. Of 25 morbidity indicators studied, only noisy breathing was increased for supine compared with side-sleeping babies. In this study, there was no evidence to suggest that supine sleeping at 1 month of age was associated with an increase in important short-term morbidity or postneonatal mortality. These findings provide further support for the recent recommendations of the American Academy of Pediatrics that healthy infants should preferably sleep in the supine position.
Publisher: SAGE Publications
Date: 09-2015
DOI: 10.1177/154431671503900301
Abstract: Distinguishing pathological from physiological relationships between vessel size and aortic intima-media thickness (aIMT) is an important challenge, especially in growing children. We examined the relationship between childhood vessel diameter and aIMT and assessed common analytic approaches used to address this relationship. We analyzed aIMT in two population-derived cohorts 6-week-old infants and 19-year-olds. We simulated datasets in which we assumed a simple physiological relationship between vessel diameter and aIMT, and then superimposed possible pathological effects on aIMT (a) intrauterine growth retardation, (b) macrosomia and (c) both intrauterine growth retardation and macrosomia. Using simulated datasets and cohorts, we evaluated analytic strategies including those in which the relationship between vessel diameter and aIMT was (a) ignored, (b) adjusted for by iding aIMT by weight, or (c) adjusted for using varying regression techniques. aIMT was found to increase in proportion to vessel diameter in both cohorts (138 μm/mm at 6 weeks and 52 μm/mm at 19 years of age). Simply iding aIMT by weight produced negative associations with weight across all datasets. By contrast, adjusting for vessel diameter as a covariate enabled accurate distinction of the direction of the association between aIMT and weight in all simulated datasets. These results were replicated in the cohort studies for both aIMT and carotid intima-media thickness. There is a physiological relationship between vessel diameter and aIMT. Simply iding aIMT by weight may lead to incorrect assumptions regarding the relationship between weight and aIMT. However, the physiological relationship is appropriately estimated by including vessel diameter as a covariate in regression.
Publisher: European Respiratory Society (ERS)
Date: 06-1996
DOI: 10.1183/09031936.96.09071356
Abstract: The predictive value of parental questionnaire responses for exercise-induced bronchoconstriction in childhood asthma has not been fully clarified. The aim of this study was to compare exercise-induced bronchial hyperresponsiveness in 7 year old children with parental responses to core questions in the International Study of Asthma and Allergies in Childhood (ISAAC) study. A cross-sectional study was conducted on 191 (91% of eligible) children from seven randomly selected schools in Southern Tasmania. Study measurements included a parental questionnaire and exercise challenge testing, using a recently validated 6 min free-running protocol. The response to exercise was assessed using forced expiratory volume in one second (FEV1) measurement. The median percentage fall in FEV1 was significantly higher in children whose parents responded positively to ISAAC questions on a history of wheeze (p = 0.0031) or asthma (p = 0.0005), recent wheeze (p = 0.0005), sleep disturbance due to wheeze (p = 0.0005), or exercise-induced wheeze (p = 0.0015). Receiver operating characteristic (ROC) curve analysis showed exercise-induced bronchial hyperresponsiveness to be a good indicator of current asthma status. Using a 12% or greater fall in FEV1 postexercise as a positive test response, the exercise challenge had sensitivity and specificity estimates for current asthma and exercise-induced wheeze of (0.58 and 0.77) and (0.60 and 0.77), respectively. In conclusion, the respiratory response to exercise was consistent with parental responses to the ISAAC questionnaire in a population-based s le of 7 year old children. These findings will assist interpretation of large ISAAC studies in terms of asthma prevalence.
Publisher: Elsevier BV
Date: 12-2002
DOI: 10.1016/S0300-483X(02)00257-3
Abstract: This review examines the epidemiological evidence that suggests ultraviolet radiation (UVR) may play a protective role in three autoimmune diseases: multiple sclerosis, insulin-dependent diabetes mellitus and rheumatoid arthritis. To date, most of the information has accumulated from population studies that have studied the relationship between geography or climate and autoimmune disease prevalence. An interesting gradient of increasing prevalence with increasing latitude has been observed for at least two of the three diseases. This is most evident for multiple sclerosis, but a similar gradient has been shown for insulin-dependent diabetes mellitus in Europe and North America. Seasonal influences on both disease incidence and clinical course and, more recently, analytical studies at the in idual level have provided further support for a possible protective role for UVR in some of these diseases but the data are not conclusive. Organ-specific autoimmune diseases involve Th1 cell-mediated immune processes. Recent work in photoimmunology has shown ultraviolet B (UVB) can specifically attenuate these processes through several mechanisms which we discuss. In particular, the possible contribution of an UVR-induced increase in serum vitamin D (1,25(OH)2D3) levels in the beneficial immunomodulation of these diseases is discussed.
Publisher: BMJ
Date: 02-1996
DOI: 10.1136/JECH.50.1.40
Abstract: To document changes in smoking style around infants over time and to identify factors associated with the smoking hygiene of mothers and others. A population based cohort study. Population based, involving 22% of live births in Tasmania, Australia. From 1 May 1988 to 30 April, 1993, 6109 infants and their mothers (89% of eligible infants) participated in the hospital and home interview of the cohort study. Infants eligible for cohort entry were those assessed at birth to be at a higher risk of SIDS. The overall proportion of mothers who smoked during pregnancy and postnatally did not decline. Increasing trends were found for mothers and others not smoking in the same room as baby or while holding or feeding the baby, significant over the five year period. Good smoking hygiene (mother not smoking in the same room as baby) was positively associated with--first birth (OR = 1.74 (1.30, 2.33)), low birth weight (1.69 (1.27, 2.23)), being born after 1 May 1991 (1.67 (1.33, 2.11)), and private health insurance status (1.39 (1.02, 1.90)). Good smoking hygiene was negatively associated with maternal smoking during pregnancy (0.50 (0.31, 0.80)), intention to bottle feed (0.62 (0.49, 0.78)), the level of maternal postnatal smoking, increasing numbers of smokers in the household, and parents cohabiting but unmarried. A similar analysis was conducted for other household residents who smoked. Changes in maternal smoking prevalence have been small. The exposure of infants to tobacco smoke postnatally has decreased significantly, although a large proportion of infants are still exposed to tobacco smoke. The identification of the above parental and infant factors associated with good smoking hygiene should be useful for health education planning.
Publisher: BMJ
Date: 12-2015
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1093/JN/NXZ089
Abstract: The evidence associating diet and risk of multiple sclerosis (MS) is inconclusive. The aim of this study was to investigate associations between a Mediterranean diet and risk of a first clinical diagnosis of central nervous system demyelination (FCD), a common precursor to MS. We used data from the 2003-2006 Ausimmune Study, an Australian multicenter, case-control study examining environmental risk factors for FCD, with participants matched on age, sex, and study region (282 cases, 558 controls 18-59 y old 78% female). The alternate Mediterranean diet score (aMED) was calculated based on data from a food-frequency questionnaire. We created a modified version of the aMED (aMED-Red) where ∼1 daily serving (65 g) of unprocessed red meat received 1 point. All other components remained the same as aMED. Conditional logistic regression (254 cases, 451 controls) was used to test associations between aMED and aMED-Red scores and categories and risk of FCD, adjusting for history of infectious mononucleosis, serum 25-hydroxyvitamin D concentrations, smoking, education, total energy intake, and dietary underreporting. There was no statistically significant association between aMED and risk of FCD [per 1-SD increase in aMED score: adjusted odds ratio (aOR): 0.89 95% CI: 0.75, 1.06 P = 0.181]. There was evidence of a nonlinear relation between aMED-Red and risk of FCD when a quadratic term was used (P = 0.016). Compared with the lowest category of aMED-Red, higher categories were significantly associated with reduced risk of FCD, corresponding to a 37% (aOR: 0.63 95% CI: 0.41, 0.98 P = 0.039), 52% (aOR: 0.48 95% CI: 0.28, 0.83 P = 0.009), and 42% (aOR: 0.58 95% CI: 0.35, 0.96 P = 0.034) reduced risk of FCD in categories 2, 3, and 4, respectively. A Mediterranean diet, including unprocessed red meat, was associated with reduced risk of FCD in this Australian adult population. The addition of unprocessed red meat to a Mediterranean diet may be beneficial for those at high risk of MS.
Publisher: Springer Science and Business Media LLC
Date: 16-10-2023
Publisher: Springer Science and Business Media LLC
Date: 03-2014
DOI: 10.1038/507169B
Publisher: BMJ
Date: 02-1992
DOI: 10.1136/JECH.46.1.33
Abstract: This paper examines the relationship between season, age, and the sudden infant death syndrome (SIDS). It provides a theoretical model for the pathogenesis of SIDS and uses it as a framework to consider risk factor mechanism. A case series analysis was used to examine season and age in relation to SIDS and seasonal pattern and age at death distribution of perinatal risk factors. The source population for the SIDS cases in this study was all live births in the state of Tasmania, Australia, 1975 to 1987 inclusive. Cases were all infants born 1975 to 1987 who died of SIDS on whom birth notification information was available (n = 348). The live birth cohort 1980-87 (n = 55,944) was used as the control population for risk factor identification. The median ages of death for spring, summer, autumn, and winter born infants were 115, 103.5, 91 and 78 days. Spring and summer born infants died at a significantly older median age than winter born infants. The month of birth distribution of SIDS cases did not alter significantly from a uniform, nonseasonal distribution (p greater than 0.25) but month of death was seasonally distributed (p less than 0.01). Premature and low birthweight infants died at an older median age (p less than 0.05) than term and non-low-birthweight infants. An excess of male infant deaths and infant deaths to older mothers occurred during winter (p less than 0.05). The pathogenesis of SIDS can be represented as a biphasic model with three pathways of risk factor operation. In this study, season influenced the age at death of SIDS infants. We propose that risk factors with a strong seasonal distribution are likely to be operating in the postnatal period.
Publisher: Wiley
Date: 24-05-2019
DOI: 10.1002/IJC.32388
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-07-2011
Publisher: MDPI AG
Date: 21-04-2022
DOI: 10.3390/IJMS23094601
Abstract: Environmental factors can accelerate telomere length (TL) attrition. Shortened TL is linked to attention deficit/hyperactivity disorder (ADHD) symptoms in school-aged children. The onset of ADHD occurs as early as preschool-age, but the TL-ADHD association in younger children is unknown. We investigated associations between infant TL and ADHD symptoms in children and assessed environmental factors as potential confounders and/or mediators of this association. Relative TL was measured by quantitative polymerase chain reaction in cord and 12-month blood in the birth cohort study, the Barwon Infant Study. Early life environmental factors collected antenatally to two years were used to measure confounding. ADHD symptoms at age two years were evaluated by the Child Behavior Checklist Attention Problems (AP) and the Attention Deficit/Hyperactivity Problems (ADHP). Associations between early life environmental factors on TL or ADHD symptoms were assessed using multivariable regression models adjusted for relevant factors. Telomere length at 12 months (TL12), but not at birth, was inversely associated with AP (β = −0.56 95% CI (−1.13, 0.006) p = 0.05) and ADHP (β = −0.66 95% CI (−1.11, −0.21) p = 0.004). Infant secondhand smoke exposure at one month was independently associated with shorter TL12 and also higher ADHD symptoms. Further work is needed to elucidate the mechanisms that influence TL attrition and early neurodevelopment.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.JACI.2015.05.051
Abstract: There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels. We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk. From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype high, the GG genotype). Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7 95% CI, 0.2-2.0 P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6 95% CI, 1.5-106.6), particularly in those with the GG genotype. Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy.
Publisher: Wiley
Date: 06-1998
DOI: 10.1046/J.1365-2222.1998.00307.X
Abstract: High exposure to house dust mite allergen during the first year of life has been found to increase the risk of subsequent asthma and mite sensitization. Environmental factors, home construction and cleaning methods used are associated with levels of dust mites in the home. To investigate determinants of levels of Der p 1 and Der f 1 mite allergens in homes of infants in southern Tasmania. Dust s les were collected from 72 homes of infants participating in the Tasmanian Infant Health Survey (TIHS). The Der p 1 and Der f 1 allergen concentrations in these s les were measured. The TIHS interviewers obtained information from the mothers of the infants via a questionnaire, observed specified aspects of the home environment, and took readings of bedroom temperature and humidity. The effect of each item on allergen concentration in dust from bedroom floors was examined in a variety of ways. Those items which in this study appeared to be significantly related to allergen concentrations plus items which in other studies have been found to be related to allergen concentrations were then investigated further in multivariate models. Der p 1 allergen concentration (microg/g) and density (microg/m2) in dust from bedroom floors were found to be related to several home environment factors. In the univariate analyses, indoor humidity, 24 h maximum temperature, number of residents and a combination of floor covering and cleaning methods appeared to have a significant effect on allergen levels. These factors remained important in the multivariate model except that indicators for mould in the bathroom and drying washing on an outside line replaced indoor humidity. Features related to home d ness, the number of residents and floor covering and cleaning were major determinants of Der p 1 levels in the bedrooms studied.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/565160
Abstract: The incidence of gestational diabetes is increasing worldwide, exposing large numbers of infants to hyperglycaemia whilst in utero . This exposure may have a long-term negative impact on the cardiovascular health of the offspring. Novel methods to assess cardiovascular status in the neonatal period are now available—including measuring arterial intima-media thickness and retinal photography. These measures will allow researchers to assess the relative impact of intrauterine exposures, distinguishing these from genetic or postnatal environmental factors. Understanding the long-term impact of the intrauterine environment should allow the development of more effective health policy and interventions to decrease the future burden of cardiovascular disease. Initiating disease prevention aimed at the developing fetus during the antenatal period may optimise community health outcomes.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.JSBMB.2014.10.012
Abstract: Juvenile idiopathic arthritis (JIA) is a leading cause of childhood-onset disability. Although epistasis (gene-gene interaction) is frequently cited as an important component of heritability in complex diseases such as JIA, there is little compelling evidence that demonstrates such interaction. PTPN2, a vitamin D responsive gene, is a confirmed susceptibility gene in JIA, and PTPN2 has been suggested to interact with vitamin D pathway genes in type 1 diabetes. We therefore, tested for evidence of epistasis amongst PTPN2 and the vitamin D pathway genes GC, VDR, CYP24A1, CYP2R1, and DHCR7 in two independent JIA case-control s les (discovery and replication). In the discovery s le (318 cases, 556 controls), we identified evidence in support of epistasis across six gene-gene combinations (e.g., GC rs1155563 and PTPN2 rs2542151, ORint=0.45, p=0.00085). Replication was obtained for three of these combinations. That is, for GC and PTPN2, CYP2R1 and VDR, and VDR and PTPN2, similar epistasis was observed using the same SNPs or correlated proxies in an independent JIA case-control s le (1008 cases, 9287 controls). Using SNP data imputed across a 4 MB region spanning each gene, we obtained highly significant evidence for epistasis amongst all 6 gene-gene combinations identified in the discovery s le (p-values ranging from 5.6×10(-9) to 7.5×10(-7)). This is the first report of epistasis in JIA risk. Epistasis amongst PTPN2 and vitamin D pathway genes was both demonstrated and replicated.
Publisher: Wiley
Date: 27-08-2010
DOI: 10.1002/GEPI.20511
Abstract: Complex diseases are likely to be caused by the interplay of genetic and environmental factors. Despite this, gene-disease associations are frequently investigated using models that focus solely on a marginal gene effect, ignoring environmental factors entirely. Failing to take into account a gene-environment interaction can weaken the apparent gene-disease association, leading to loss in statistical power and, potentially, inability to identify genuine risk factors. If a gene-environment interaction exists, therefore, a joint analysis allowing the effect of the gene to differ between groups defined by the environmental exposure can have greater statistical power than a marginal gene-disease model. However, environmental data are subject to measurement error. Substantial losses in statistical power for detecting gene-environment interactions can arise from measurement error in the environmental exposure. It is unclear, however, what effect measurement error may have on the power of the joint analysis. We consider the potential benefits, in terms of statistical power, of collecting concurrent environmental data within large cohorts in order to enhance gene detection. We further consider whether these benefits remain in the presence of misclassification in both the gene and the environmental exposure. We find that when an effect of the gene is apparent only in the presence of the environmental exposure, the joint analysis has greater power than a marginal gene-disease analysis. This comparative increase in power remains in the presence of likely levels of misclassification of either the gene or environmental exposure.
Publisher: The American Association of Immunologists
Date: 15-02-2021
Abstract: Vitamin D has shown immune-modulatory effects but mostly in in vitro and animal studies. Regulatory T cells (Treg) are important for a balanced immune system. The relationship between vitamin D on the number of circulating neonatal Treg is unclear. We sought to investigate the association between maternal and neonatal vitamin D metabolites and cord blood (CB) Treg subsets. In a cohort of Australian infants (n = 1074), recruited using an unselected antenatal s ling frame, 158 mother–infant pairs had data on the following: 1) 25-hydroxyvitamin D3 (25(OH)D3) measures in both maternal peripheral blood (28- to 32-wk gestation) and infant CB 2) proportions (percentage of CD4+ T cells) of CB Treg subsets (CD4+CD45RA+ FOXP3low naive Treg, and CD4+CD45RA− FOXP3high activated Treg [aTreg]) and 3) possible confounders, including maternal personal UV radiation. Multiple regression analyses were used. The median 25(OH)D3 was 85.4 and 50.7 nmol/l for maternal and CB s les, respectively. Higher maternal 25(OH)D3 levels were associated with increased CB naive Treg (relative adjusted mean difference [AMD] per 25 nmol/l increase: 5% 95% confidence interval [CI]: 1–9%), and aTreg (AMD per 25 nmol/l increase: 17% 95% CI: 6–28%). Furthermore, a positive association between CB 25(OH)D3 levels and CB aTreg (AMD per 25 nmol/l increase: 29% 95% CI: 13–48%) was also evident. These results persisted after adjustment for other factors such as maternal personal UV radiation and season of birth. 25(OH)D3, may play a role in the adaptive neonatal immune system via induction of FOXP3+ Tregs. Further studies of immune priming actions of antenatal 25(OH)D3 are warranted.
Publisher: S. Karger AG
Date: 19-10-2017
DOI: 10.1159/000448680
Abstract: b i Background: /i /b Vitamin D deficiency is linked to adverse childhood health outcomes, yet data on the distribution and quantifiable determinants of neonatal 25-hydroxyvitamin D sub /sub (25OHD) concentration, a vitamin D biomarker, are limited. b i Objective: /i /b Our aim was to identify determinants of neonatal 25OHD concentration, measured using neonatal dried blood spots (DBS). b i Methods: /i /b A total of 259 ethnically erse children aged 0-16 years born in Victoria, Australia, were recruited. Data included maternal sun exposure, skin type, 25OHD concentration on stored neonatal DBS, and genotypes at the target genes. Associations were investigated using multiple linear regression models. b i Results: /i /b The median 25OHD concentration was 29.2 nmol/l (IQR 18.0-47.4). Measured 25OHD was nmol/l in almost half of the neonatal s le. Ambient ultraviolet radiation (UVR) 6 weeks before birth was the strongest predictor of neonatal 25OHD, accounting for 23% of its variation. A further 10% was explained by infant genetic variants at i GC /i (rs2282679), the gene encoding the vitamin D binding protein, and i DHCR7 /i (rs12785878), a gene required for synthesis of 7-dehydrocholesterol, a precursor to 25OHD. DBS age explained 7%, and patterns of maternal sun exposure and clothing choices accounted for 4%. A child's skin colour was strongly associated with i GC /i gene variants and not independent of these variants in predicting 25OHD. The final model explained 43% of the total variance in neonatal 25OHD concentration. b i Conclusion: /i /b Maternal lifestyle factors and infant genetic variants predict neonatal 25OHD levels the importance of maternal UVR exposure in late pregnancy is highlighted.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-04-2010
Publisher: American Public Health Association
Date: 12-2005
Abstract: Objectives. We investigated the role of infant bedding items, as part of a composite bedding environment, in the development of childhood wheezing. Methods. This prospective cohort investigation involved 863 children who participated in an infant survey in 1988 and an asthma study in Tasmania, Australia, in 1995. The derived 3 composite infant bedding categories corresponded to increasing numbers of house dust mite (HDM)–rich bedding items used. Outcomes measured included recent and frequent wheezing. Results. Composite infant bedding used was associated with recent wheezing. Effects increased at increasing levels of HDM–rich bedding items used. Effects were further enhanced by home environmental factors of bedroom heating, recent bedroom painting, and absence of bedroom carpeting. When any 2 or more of these environmental factors were present, a strong dose–response relationship was evident. Conclusions. Our results show that bedding exposures in infancy are prospectively associated with childhood wheezing and that home environmental conditions may modify this association.
Publisher: Oxford University Press (OUP)
Date: 05-10-2005
DOI: 10.1093/JNCI/DJI307
Publisher: Hogrefe Publishing Group
Date: 06-2017
DOI: 10.1024/0301-1526/A000630
Abstract: Abstract. Background: Carotid intima-media thickness (CIMT), an ultrasonographic marker of cardiovascular risk, is increasingly used in adults and children. The choice of specific images used to quantify CIMT from a cine sequence is often based on image quality rather than on a consistent point in the cardiac cycle. This methodological study quantified the imprecision that may be introduced by variation of CIMT during the cardiac cycle. Probands and methods: Data from four-year-olds, 11 to 12-year-olds, and adults (n=30 each age group) were selected retrospectively from two population-derived studies. Far wall CIMT of the right common carotid artery was measured at end-diastole and peak systole using standardized protocols. All images were analysed using semi-automated edge-detection software. Results: In all age groups CIMT varied significantly during the cardiac cycle and was largest at end-diastole. The mean difference in CIMT between end-diastole and peak systole was greater in four-year-olds (38 μm 95 % confidence interval (CI) 33 to 43 μm) and 11 to 12-year-olds (31 μm CI 26 to 36 μm) than in adults (18 μm CI 16 to 22 μm). Carotid IMT increased by 8.8 % (CI 7.7 to 9.8 %), 6.9 % (CI 5.8 to 8.1 %), and 3.8 % (CI 3.1 to 4.5 %) between minimum and maximum arterial diameter in four-year-olds, 11 to 12-year-olds, and adults, respectively. The greatest variation in CIMT during the cardiac cycle was observed in children (up to 14 %). Conclusions: Inconsistent timing of CIMT measurement during the cardiac cycle is an avoidable source of imprecision, especially in children, in whom inter-in idual differences are smallest. As CIMT is largest at end-diastole, this is the most appropriate time point for consistent and comparable measurements to be made.
Publisher: Springer Science and Business Media LLC
Date: 29-11-2007
Abstract: A high ponderal index at birth has been associated with later obesity and it has been suggested that intervention to prevent obesity and its sequela should consider the antenatal period. In this context, we investigated the association between maternal nutrition and birth anthropometry. We analyzed data on 1040 mother-infant pairs collected during the Tasmanian Infant Health Survey (TIHS), Tasmania, 1988-1989. Maternal dietary intake during pregnancy was measured by food frequency questionnaire (FFQ) applied soon after birth. Outcomes of interest were birth weight, birth length, head circumference, ponderal index, head circumference -to-ponderal index ratio, placenta-to-birth weight ratio and head circumference-to-birth length index. In multiple regression model, an increase of 10 g of absolute protein intake/day was associated with a reduction in birth weight of 17.8 g (95% CI: -32.7, -3.0 P=0.02). Protein intake was also associated negatively with ponderal index (beta=-0.01 95% CI: -0.02, -0.00 P=0.01). A 1 % increase in carbohydrate intake resulted in a 1% decline in placental weight relative to birth weight. Higher protein intake in the third trimester was associated with a reduced ponderal index among large birth weight infants but not low birth weight infants. This raises the possibility that any effect of high protein in altering infant anthropometry at birth may involve changes in body composition and future work to examine how a high-protein diet influences body composition at birth is warranted.
Publisher: Oxford University Press (OUP)
Date: 10-2021
DOI: 10.1093/BRAINCOMMS/FCAB288
Abstract: Our inability to reliably predict disease outcomes in multiple sclerosis remains an issue for clinicians and clinical trialists. This study aims to create, from available clinical, genetic and environmental factors a clinical–environmental–genotypic prognostic index to predict the probability of new relapses and disability worsening. The analyses cohort included prospectively assessed multiple sclerosis cases (N = 253) with 2858 repeated observations measured over 10 years. N = 219 had been diagnosed as relapsing-onset, while N = 34 remained as clinically isolated syndrome by the 10th-year review. Genotype data were available for 199 genetic variants associated with multiple sclerosis risk. Penalized Cox regression models were used to select potential genetic variants and predict risk for relapses and/or worsening of disability. Multivariable Cox regression models with backward elimination were then used to construct clinical–environmental, genetic and clinical–environmental–genotypic prognostic index, respectively. Robust time-course predictions were obtained by Landmarking. To validate our models, Weibull calibration models were used, and the Chi-square statistics, Harrell’s C-index and pseudo-R2 were used to compare models. The predictive performance at diagnosis was evaluated using the Kullback–Leibler and Brier (dynamic) prediction error (reduction) curves. The combined index (clinical–environmental–genotypic) predicted a quadratic time-dynamic disease course in terms of worsening (HR = 2.74, CI: 2.00–3.76 pseudo-R2=0.64 C-index = 0.76), relapses (HR = 2.16, CI: 1.74–2.68 pseudo-R2 = 0.91 C-index = 0.85), or both (HR = 3.32, CI: 1.88–5.86 pseudo-R2 = 0.72 C-index = 0.77). The Kullback–Leibler and Brier curves suggested that for short-term prognosis (≤5 years from diagnosis), the clinical–environmental components of disease were more relevant, whereas the genetic components reduced the prediction errors only in the long-term (≥5 years from diagnosis). The combined components performed slightly better than the in idual ones, although their prognostic sensitivities were largely modulated by the clinical–environmental components. We have created a clinical–environmental–genotypic prognostic index using relevant clinical, environmental, and genetic predictors, and obtained robust dynamic predictions for the probability of developing new relapses and worsening of symptoms in multiple sclerosis. Our prognostic index provides reliable information that is relevant for long-term prognostication and may be used as a selection criterion and risk stratification tool for clinical trials. Further work to investigate component interactions is required and to validate the index in independent data sets.
Publisher: Public Library of Science (PLoS)
Date: 04-11-2015
Publisher: Elsevier BV
Date: 2018
Publisher: Informa UK Limited
Date: 04-2020
DOI: 10.1080/07420528.2020.1740724
Abstract: Experimental evidence suggests that perinatal light imprinting of circadian clocks and systems may affect downstream physiology and cancer risk in later life. For humans, the predominant circadian stimulus is the daily light-dark cycle. Herein, we explore associations between perinatal photoperiod characteristics (photoperiod: duration of daylight as determined by time-of-year and location) and childhood cancer risk. We use pooled data on 182,856 mothers and babies from prospective birth cohorts in six countries (Australia, Denmark, Israel, Norway, UK, USA) within the International Childhood Cancer Cohort Consortium (I4C). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In line with predicted differential dose-responses, restricted cubic splines indicate a potential non-linear, non-monotonic relationship between perinatal mean daily photoperiod (0-24 h) and childhood cancer risk. In a restricted analysis of 154,121 in iduals who experienced third trimester photoperiods exclusively within the 8-16-h range, the relative risk of developing childhood cancer decreased by 9% with every hour increase in third trimester mean daily photoperiod [HR: 0.91 (95%CIs: 0.84-0.99)]. In conclusion, in this first study of perinatal photoperiod and childhood cancer, we detected an inverse ["protective"] linear association between third trimester mean daily photoperiod and childhood cancer risk in the 8-16-h set of the total study population. Limited statistical power impeded the investigation of risks with in iduals exposed to more extreme photoperiods. Future studies are needed to confirm differential photoperiod-associated risks and further investigations into the hypothesized circadian imprinting mechanism are warranted.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.JACI.2013.11.019
Abstract: It is unknown whether population infant feeding practices have changed since recently revised Australian allergy guidelines removed recommendations to delay allergenic solids. We sought to determine whether updated 2008 guidelines were associated with changes in feeding practice and to determine whether sociodemographic factors influenced this response. In a population-based, cross-sectional study (HealthNuts) of 5276 infants recruited between 2007 and 2011 in Melbourne, Australia, parents reported on infant feeding practices. Multinomial logistic regression was used to investigate the associations between recruitment year and feeding practices and whether these associations were modified by sociodemographic factors. Compared with participants recruited in 2007-2009, those recruited in 2009-2011 were more likely to introduce solids at age 4 months (adjusted multinomial odds ratio [aMOR], 1.21 95% CI, 1.02-1.45 P = .032) and less likely to introduce solids at age 6 months (aMOR, 0.80 95% CI, 0.69-0.92 P = .002), egg after 6 months (aMOR, 0.82 95% CI, 0.71-0.94 P = .004), and peanut after 12 months (aMOR, 0.70 95% CI, 0.49-0.98 P = .037). Although parents recruited in 2009-2011 were less likely to formula feed (aMOR, 0.84 95% CI, 0.72-0.98 P = .023), formula-fed infants were more likely to be given a partially hydrolyzed formula (aMOR, 1.37 95% CI, 1.12-1.70 P = .003). These changes were significantly stronger among families with a higher socioeconomic status and those without a family history of allergies. Updated national allergy guidelines are associated with reduced delay in introduction of solids, egg, and peanut and an increase in partially hydrolyzed formula use among formula-fed infants. Higher socioeconomic status and absence of family history of allergies were associated with better uptake of feeding guidelines.
Publisher: Wiley
Date: 26-10-2018
DOI: 10.1002/IJC.31635
Abstract: The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 10
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.ANNEPIDEM.2014.01.001
Abstract: In the field of epidemiology, much attention has been given to the reduction of random or systematic errors in study design, analysis, and reporting. This article reviews relevant literature on group work processes. The review orients attention toward optimizing group work processes to enhance group decision making and optimize the conduct of epidemiologic work in the era of team science. The review contrasts interactive open group work with group aggregate work. We define the latter as occurring without member to member communication. The impacts of group characteristics on process issues are examined. Group characteristics such as purpose, modality, size, and member incentives are shown to influence the likely optimal group structure for varying tasks. Open group work allows rapid communication and interactive feedback as well as the emergence of a collective intelligence above that of the in idual members. However, productivity may be limited by large open group size and the multiple dyads of communication, limiting cognitive ersity and human resource capital. Furthermore, group-level biases and bias may be introduced within the group. Little quantitative work on these issues has been conducted in the epidemiologic work setting, but recent experimental research in other areas of science and management indicates that structured protocols to support dynamic group work can improve group decisions. The merit of often highly accurate group aggregate approaches, with parallel independent in idual inputs such as crowd sourcing is becoming increasingly recognized. We outline several ex les in recent medical research. We outline principles that should be explicitly considered when setting up new work groups in epidemiology and recommend that further work on these issues be conducted.
Publisher: Oxford University Press (OUP)
Date: 27-10-2021
DOI: 10.1093/IJE/DYAB228
Publisher: AMPCo
Date: 12-2011
DOI: 10.5694/MJA11.10493
Publisher: Oxford University Press (OUP)
Date: 14-02-2008
DOI: 10.1093/IJE/DYN029
Abstract: Asthma prevalence has declined in some countries over the past 10 years. Most reports have been based on population surveys conducted at two points of time in a given location. Comparisons across countries and time periods can be limited by differences in study methodology or disease diagnostics in different communities. Here, we examined trends in asthma prevalence using serial annual data and further examine the importance of country of birth. The source population has children aged 4-6 commencing school in the Australian Capital Territory from 2000 to 2005 inclusive. Over 80% of these children and their families completed a health questionnaire on asthma, other atopic disease and respiratory symptoms using some questions from the International Study of Asthma and Allergies in Childhood (n = 22 882). Current asthma has been previously validated against physician assessment in this setting. The prevalence of current asthma declined (P < 0.001) but eczema ever increased (P < 0.001) from 2000 to 2005. The asthma decline was predominantly linear in form, and accompanied by a reduction in night cough and shortness of breath but not recent wheeze. Compared with Australian-born children, children from New Zealand and the United Kingdom had a similar prevalence of asthma, hay fever and eczema history. However, children born in other countries, such as Asia, generally had a lower prevalence of these disorders. The temporal trends for atopic disorders or respiratory symptoms did not differ for overseas-born compared with Australian-born children. The decline in current asthma prevalence from 2000 to 2005 was linear in form and appeared uncoupled from trends in child eczema. Country of birth was associated with marked variation in atopic disorder prevalence. The similar temporal trends for Australian vs overseas-born children indicate that the factors underlying the asthma prevalence decline are unlikely to be only in the pre-natal period.
Publisher: Wiley
Date: 24-11-2020
DOI: 10.5694/MJA2.50427
Abstract: To investigate blood lead levels in an Australian birth cohort of children to identify factors associated with higher lead levels. Cross-sectional study within the Barwon Infant Study, a population birth cohort study in the Barwon region of Victoria (1074 infants, recruited June 2010 - June 2013). Data were adjusted for non-participation and attrition by propensity weighting. Blood lead was measured in 523 of 708 children appraised in the Barwon Infant Study pre-school review (mean age, 4.2 years SD, 0.3 years). Blood lead concentration in whole blood (μg/dL). The median blood lead level was 0.8 μg/dL (range, 0.2-3.7 μg/dL) the geometric mean blood lead level after propensity weighting was 0.97 μg/dL (95% CI, 0.92-1.02 μg/dL). Children in houses 50 or more years old had higher blood lead levels (adjusted mean difference [AMD], 0.13 natural log units 95% CI, 0.02-0.24 natural log units P = 0.020), as did children of families with lower household income (per $10 000, AMD, -0.035 natural log units 95% CI, -0.056 to -0.013 natural log units P = 0.002) and those living closer to Point Henry (inverse square distance relationship P = 0.002). Associations between hygiene factors and lead levels were evident only for children living in older homes. Blood lead levels in our pre-school children were lower than in previous Australian surveys and recent surveys in areas at risk of higher exposure, and no children had levels above 5 μg/dL. Our findings support advice to manage risks related to exposure to historical lead, especially in older houses.
Publisher: Massachusetts Medical Society
Date: 05-08-1993
Publisher: Springer Science and Business Media LLC
Date: 17-01-2012
DOI: 10.1038/IJO.2011.261
Abstract: To examine the maternal and neonatal factors associated with offspring adiposity and the role of birth and placental weight as potential mediators in such associations. The Tasmanian Infant Health Survey was a prospective cohort study conducted between 1988 and 1995 in Australia to investigate the cause of Sudden Infant Death Syndrome. This large infant cohort provides measurement of skinfolds on 7945 mothers and their offspring. Participants included singletons born ≥37 weeks gestation who were at high risk of sudden infant death syndrome identified through a composite score that included birth weight, maternal age, neonatal gender, season of birth, duration of second-stage labor and intention to breastfeed. Neonatal adiposity was assessed from skinfold measurements of the subscapular (SSF) and triceps folds (TSF) taken at birth. Maternal early-pregnancy body mass index (BMI) was calculated from self-reported height and weight. Neonatal data were extracted from birth records. Data relating to other environmental exposures were obtained from questionnaires administered when neonates were ∼4-days old. In multivariable models, higher maternal adiposity, increasing maternal age, gestation age, delivery by Caesarian section and female gender were associated with larger SSF independent of placental and birth weight (P<0.001). Maternal age and delivery by Caesarian section were significantly associated with larger TSF, whereas gestational age and male gender were associated with thinner TSF independent of placental and birth weight. Higher early-pregnancy BMI, maternal weight gain, maternal age, parity and gestational age were significantly associated with larger placental and birth weight. Smoking during pregnancy was associated with smaller birth weight but not with placental weight. In addition to birth weight, maternal adiposity and placental weight were important additional factors associated with neonatal adiposity.
Publisher: SAGE Publications
Date: 07-08-2019
Abstract: The evidence associating diet and risk of multiple sclerosis is inconclusive. We investigated associations between dietary patterns and risk of a first clinical diagnosis of central nervous system demyelination, a common precursor to multiple sclerosis. We used data from the 2003–2006 Ausimmune Study, a case–control study examining environmental risk factors for a first clinical diagnosis of central nervous system demyelination, with participants matched on age, sex and study region. Using data from a food frequency questionnaire, dietary patterns were identified using principal component analysis. Conditional logistic regression models ( n = 698, 252 cases, 446 controls) were adjusted for history of infectious mononucleosis, serum 25-hydroxyvitamin D concentrations, smoking, race, education, body mass index and dietary misreporting. We identified two major dietary patterns – healthy (high in poultry, fish, eggs, vegetables, legumes) and Western (high in meat, full-fat dairy low in wholegrains, nuts, fresh fruit, low-fat dairy), explaining 9.3% and 7.5% of variability in diet, respectively. A one-standard deviation increase in the healthy pattern score was associated with a 25% reduced risk of a first clinical diagnosis of central nervous system demyelination (adjusted odds ratio 0.75 95% confidence interval 0.60, 0.94 p = 0.011). There was no statistically significant association between the Western dietary pattern and risk of a first clinical diagnosis of central nervous system demyelination. Following healthy eating guidelines may be beneficial for those at high risk of multiple sclerosis.
Publisher: Frontiers Media SA
Date: 02-2018
Publisher: American Association for Cancer Research (AACR)
Date: 11-2009
DOI: 10.1158/1055-9965.EPI-09-0191
Abstract: Past sun exposure is linked to a wide range of disease outcomes but is difficult to measure accurately. Silicone skin casts measure skin damage, but some studies show that age rather than sun exposure is the most important determinant of cast score. We examined skin damage scores from silicone casts of the back of the hand in a large adult s le (n = 534) with a broad range of past cumulative UV radiation (UVR) doses. Participants were ages 18 to 61 years and resided in one of four locations down the eastern Australian seaboard, spanning 27-43°S. Data were collected by questionnaire and during a nurse-led interview and examination. Silicone casts were graded from 1 to 6, where higher score represents greater damage. Higher skin damage score was associated with lighter skin pigmentation [adjusted odds ratio (AOR), 4.51 95% confidence interval (95% CI), 2.33-8.75], fairer natural hair color, particularly red hair (AOR, 11.31 95% CI, 4.08-31.36), and blue/gray eyes (AOR, 1.72 95% CI, 1.14-2.59). Higher cumulative UVR dose, particularly before age 18 years, was associated with higher skin damage score (AOR, 2.06 95% CI, 1.15-2.67 per 1,000 KJ/m2), as was number of sunburns, even after adjustment for cumulative UVR dose (AOR, 2.86 95% CI, 1.50-5.43 for & sunburns ever compared with no sunburns ever). Silicone casts of the dorsum of the hand provide a measure of cumulative UVR dose and number of sunburns over the lifetime, which persists after adjustment for chronological age. They can be used as an objective measure of cumulative past sun exposure in epidemiologic studies, but other determinants of skin damage, such as skin pigmentation, should be concurrently evaluated. (Cancer Epidemiol Biomarkers Prev 2009 (11):2887–94)
Publisher: Hindawi Limited
Date: 13-06-2013
DOI: 10.1111/ANE.12155
Abstract: Insufficient sun exposure and vitamin D deficiency have both been associated with increased risk of multiple sclerosis (MS). Depressi on, anxiety, fatigue and cognitive impairment are prevalent and disabling symptoms in MS. Our objective was to examine the associations between personal sun exposure and serum 25-hydroxyvitamin D (25(OH)D), and depression, anxiety, fatigue and cognition. A total of 198 participants with multiple sclerosis were followed prospectively for an average of 2.3 years. Assessments of serum 25(OH)D, sun exposure, depression, anxiety and fatigue were carried out biannually cognition was assessed annually. Personal reported sun exposure was inversely associated with depression scores (β -0.26 (95%CI -0.40, -0.12) P ≤ 0.001) and fatigue scores (β -0.65 (95%CI -1.23, -0.07) P = 0.028). Only high levels of 25(OH)D (>80 nm) were inversely associated depression scores (β -0.64 (95%CI -1.15, -0.13) P = 0.015), but this was not significant after adjustment for reported sun exposure. No associations were seen between reported sun exposure or serum 25(OH)D levels and anxiety or cognition scores. We found that higher levels reported sun exposure, rather than 25(OH)D levels, were associated with less depressive symptoms and levels of fatigue. The role of UV or light therapy will need to be evaluated in randomized controlled trials to confirm an effect on these symptoms in MS.
Publisher: Wiley
Date: 23-02-2009
DOI: 10.1111/J.1398-9995.2009.01970.X
Abstract: The period of immune programming during early life presents a critical window of opportunity for the prevention of allergic diseases. There is mounting evidence that inappropriate immune programming may involve disruption of specific epigenetic modifications (switches) at immune-related genes. This novel area of research has great potential, as epigenetic changes are known to be sensitive to environmental factors and may therefore provide a mechanistic link for the observed association between specific environmental cues, faulty immune development, and the risk of allergic disease. In addition, the dynamic and potentially reversible nature of epigenetic modifications offers potentially novel targets for therapeutic and/or preventative interventions. We review the evidence that (1) failure to up-regulate the interferon gamma (IFNgamma) response during infancy is an important determinant of the risk of allergic disease, (2) expression of the IFNgamma gene in naïve T-cells is regulated by epigenetic mechanisms, and (3) failure to up-regulate IFNgamma gene expression of naïve T-cells associated with low early life microbial exposure. Taken together, these lines of evidence suggest that low microbial exposure during early life increases the risk of allergic disease by reducing demethylation (activation) of the IFNgamma gene of naive T-cells.
Publisher: Cambridge University Press (CUP)
Date: 04-04-2016
DOI: 10.1017/S0954579416000183
Abstract: Maternal mental health during pregnancy has been linked to health outcomes in progeny. Mounting evidence implicates fetal “programming” in this process, possibly via epigenetic disruption. Maternal mental health has been associated with glucocorticoid receptor methylation (nuclear receptor subfamily 3, group C, member 1 [ NR3C1 ]) in the neonate however, most studies have been small ( n 100) and have failed to control for multiple testing in the statistical analysis. The Barwon Infant Study is a population-derived birth cohort with antenatal recruitment. Maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale and psychological distress using the Perceived Stress Scale. NR3C1 cord blood methylation levels were determined using Sequenom MassArray for 481 participants. Maternal psychological distress and anxiety were associated with a small increase in neonate NR3C1 methylation at specific CpG sites, thus replicating some previous findings. However, associations were only nominally significant and did not remain after correction for the number of CpG sites and exposures investigated. As the largest study to explore the relationship between maternal well-being and offspring NR3C1 cord blood methylation, our results highlight the need for caution when interpreting previous findings in this area. Future studies must ensure they are adequately powered to detect the likely small effect sizes while controlling for multiple testing.
Publisher: Wiley
Date: 03-2002
DOI: 10.1034/J.1398-9995.2002.1S3234.X
Abstract: Synthetic bedding has been associated with increased child wheeze and also higher allergen levels in several studies. We aimed to examine whether the association between synthetic bedding and adverse respiratory outcomes was more evident among skin-prick test (SPT) positive children. A cross-sectional survey involving a population s le of 758 (81% of eligible) school children aged 8-10 years from randomly selected schools in the Australian Capital Territory in 1999. Parental questionnaires for ISAAC respiratory symptoms and child bedding were obtained. SPT results of 10 common allergens were available on 722 of the subjects (77% of those eligible). Synthetic pillow or quilt use was termed synthetic upper bedding. Synthetic quilt use was associated with asthma (Adjusted Odds Ratio 1.67 (1.05, 2.65)), recent wheeze (AOR 1.63 (1.03, 2.59)) and allergic rhinoconjunctivitis (AOR 2.11 (1.33, 3.34)) among SPT-positive children. However, these associations were not apparent for SPT-negative children. Similarly, increasing synthetic upper bedding use was associated with more than 12 episodes of wheeze among SPT-positive children (AOR 1.69 (1.08, 2.64), P=0.02, per category) but not SPT-negative children (AOR 0.77 (0.26, 2.21), P=0.6, per category). The apparent association between synthetic upper bedding and adverse respiratory outcomes was evident among SPT-positive but not SPT-negative children. Prospective intervention studies that aim to examine the effect of upper bedding composition on child asthma among SPT-positive children are required.
Publisher: Oxford University Press (OUP)
Date: 30-06-2008
DOI: 10.1093/AJE/KWN142
Abstract: Vitamin D receptor (VDR) gene polymorphisms may be associated with risk of developing type 1 diabetes mellitus (T1DM), but reports have been conflicting. The authors reexamined population-based case-control studies on selected VDR polymorphisms and T1DM to investigate whether variation in reported associations could be partly explained by differences in ambient winter ultraviolet radiation (UVR) levels. A meta-analysis of 16 studies from 19 regions (midwinter UVR range, 1.0-133.8 mW/m(2)) was conducted. The association between winter UVR and the log odds ratio was examined by meta-regression. For FokI and BsmI, the log odds ratio for the association between the F and B alleles and T1DM increased as regional winter UVR increased (p = 0.039 and p = 0.036, respectively). The association between the TaqI T allele and T1DM was reduced with increasing winter UVR (p = 0.040). Low winter regional UVR was associated with a higher proportion of controls carrying BsmI and ApaI uppercase alleles and a lower proportion of controls carrying TaqI uppercase alleles. These findings strengthen the case that VDR variants are involved in the etiology of T1DM. They suggest that environmental UVR may influence the association between VDR genotype and T1DM risk. Further work on VDR polymorphisms and T1DM should concomitantly examine the roles of past UVR exposure and vitamin D status.
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.JACI.2013.05.038
Abstract: Ninety-five percent positive predictive values (PPVs) provide an invaluable tool for clinicians to avoid unnecessary oral food challenges. However, 95% PPVs specific to infants, the age group most likely to present for diagnosis of food allergy, are limited. We sought to develop skin prick test (SPT) and allergen-specific IgE (sIgE) thresholds with 95% PPVs for challenge-confirmed food allergy in a large population-based cohort of 1-year-old infants with challenges undertaken irrespective of SPT wheal size or previous history of ingestion. HealthNuts is a population-based, longitudinal food allergy study with baseline recruitment of 1-year-old infants. Infants were recruited from council-run immunization sessions during which they underwent SPTs to 4 allergens: egg, peanut, sesame, and cow's milk/shrimp. Any infant with a detectable SPT response was invited to undergo oral food challenge and sIgE testing. Five thousand two hundred seventy-six infants participated in the study. Peanut SPT responses of 8 mm or greater (95% CI, 7-9 mm), egg SPT responses of 4 mm or greater (95% CI, 3-5 mm), and sesame SPT responses of 8 mm or greater (95% CI, 5-9 mm) had 95% PPVs for challenge-proved food allergy. Peanut sIgE levels of 34 kUA/L or greater (95% CI, 14-48 kUA/L) and egg sIgE levels of 1.7 kUA/L or greater (95% CI, 1-3 kUA/L) had 95% PPVs for challenge-proved food allergy. Results were robust when stratified on established risk factors for food allergy. Egg SPT responses and sIgE levels were poor predictors of allergy to egg in baked goods. These 95% PPVs, which were generated from a unique dataset, are valuable for the diagnosis of food allergy in young infants and were robust when stratified across a number of different risk factors.
Publisher: Wiley
Date: 29-04-2022
DOI: 10.1111/CEA.14146
Abstract: Probiotic and Peanut Oral Immunotherapy (PPOIT) is effective at inducing sustained unresponsiveness (SU) at end-of-treatment and this effect persists up to four years post-treatment, referred to as persistent SU. We sought to evaluate (i) how PPOIT altered peanut-specific humoral immune indices, and (ii) how such longitudinal indices relate to persistent SU. Longitudinal serum lasma levels of whole peanut- and peanut component- (Ara-h1, -h2, -h3, -h8, -h9) specific-IgE (sIgE) and specific-IgG4 (sIgG4) antibodies were measured by ImmunoCAP and salivary peanut-specific-IgA (sIgA) by ELISA in children (n=62) enrolled in the PPOIT-001 randomised trial from baseline (T0) to 4-years post-treatment (T5). Multivariate regression analyses of log-transformed values were used for point-in-time between group comparisons. Generalised estimating equations (GEE) were used for longitudinal comparisons between groups. PPOIT was associated with changes in sIgE and sIgG4 over time. sIgE levels were significantly reduced post-treatment [T5, PPOIT v.s. Placebo ratio of geometric mean (GM): Ara-h1 0.07, p=0.008 Ara-h2 0.08, p=0.007 Ara-h3 0.15, p=0.021]. sIgG4 levels were significantly increased by end-of-treatment (T1, PPOIT v.s. Placebo ratio of GM: Ara-h1 3.77, p=0.011 Ara-h2 17.97, p<0.001 Ara-h3 10.42, p<0.001) but levels in PPOIT group decreased once treatment was stopped and returned to levels comparable with Placebo group by T5. Similarly, salivary peanut sIgA increased during treatment, as early as 4 months of treatment (PPOIT v.s. Placebo, ratio of GM: 2.04, p=0.014), then reduced post-treatment. PPOIT was associated with broad reduction in peanut specific humoral responses which may mediate the clinical effects of SU that persists to 4-years post-treatment.
Publisher: Oxford University Press (OUP)
Date: 23-12-2019
DOI: 10.1093/HMG/DDZ287
Abstract: Despite the many advances made in the diagnosis and management of preecl sia, this syndrome remains a leading cause of maternal mortality and life-long morbidity, as well as adverse fetal outcomes. Successful prediction and therapeutic intervention require an improved understanding of the molecular mechanisms, which underlie preecl sia pathophysiology. We have used an integrated approach to discover placental genetic and epigenetic markers of preecl sia and validated our findings in an independent cohort of women. We observed the microRNA, MIR138, to be upregulated in singleton preecl tic placentas however, this appears to be a female infant sex-specific effect. We did not identify any significant differentially methylated positions (DMPs) in singleton pregnancies, indicating that DNA methylation changes in mild forms of the disease are likely limited. However, we identified infant sex-specific preecl sia-associated differentially methylated regions among singletons. Disease-associated DMPs were more obvious in a limited s ling of twin pregnancies. Interestingly, 2 out of the 10 most significant changes in methylation over larger regions overlap between singletons and twins and correspond to NAPRT1 and ZNF417.
Publisher: SAGE Publications
Date: 23-10-2018
Abstract: Transition probabilities are the engine within many health economics decision models. However, the probabilities of progression of disability due to multiple sclerosis (MS) have not previously been estimated in Australia. To estimate annual probabilities of changing disability levels in Australians with relapsing-remitting MS (RRMS). Combining data from Ausimmune/Ausimmune Longitudinal (2003–2011) and Tasmanian MS Longitudinal (2002–2005) studies ( n = 330), annual transition probabilities were obtained between no/mild (Expanded Disability Status Scale (EDSS) levels 0–3.5), moderate (EDSS 4–6.0) and severe (EDSS 6.5–9.5) disability. From no/mild disability, 6.4% (95% confidence interval (CI): 4.7–8.4) and 0.1% (0.0–0.2) progressed to moderate and severe disability annually, respectively. From moderate disability, 6.9% (1.0–11.4) improved (to no/mild state) and 2.6% (1.1–4.5) worsened. From severe disability, 0.0% improved to moderate and no/mild disability. Male sex, age at onset, longer disease duration, not using immunotherapies greater than 3 months and a history of relapse were related to higher probabilities of worsening. We have estimated probabilities of changing disability levels in Australians with RRMS. Probabilities differed between various subgroups, but due to small s le sizes, results should be interpreted with caution. Our findings will be helpful in predicting long-term disease outcomes and in health economic evaluations of MS.
Publisher: Wiley
Date: 04-04-2017
DOI: 10.1111/ALL.13143
Abstract: A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions. To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy. We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery s le) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these in iduals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent s le group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components. SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery s le (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also. We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.
Publisher: BMJ
Date: 05-2015
Abstract: Altered reactivity of peripheral blood mononuclear cells (PBMC) and their production of cytokines may affect multiple sclerosis (MS) clinical course. We assessed the relationship of stimulated PBMC-produced IFN-γ, TNF-α, IL-4 and IL-10 in modulating relapse risk using a prospective cohort with established relapsing-remitting MS. Cytokine production from PBMCs taken in summer and winter was measured by ELISA. Predictors of cytokines assessed by multilevel mixed-effects linear regression. Predictors of relapse assessed by survival analysis. Increasing IFN-γ was associated with increasing relapse risk, while increasing TNF-α reduced relapse risk after adjusting for IFN-γ. IL-10 and IL4 were not consistently associated with relapse risk. IFN-γ's effects on relapse were greatly attenuated by immunomodulatory therapies, by summer season and by higher serum vitamin D, whereas TNF-α's inverse association with relapse was only present in these circumstances. The TNF-α inverse association with relapse was only present among persons carrying the wild-type of the functional SNP rs1800693 in TNFRSF1A that has been previously associated with MS risk. We found strong effects of IFN-γ and TNF-α on relapse risk, these differing by immunomodulatory therapy, season, and serum vitamin D, as well as by genotype. These results indicate altered reactivity of immune cells modulate MS disease.
Publisher: American Medical Association (AMA)
Date: 26-01-2005
Abstract: The "hygiene hypothesis" has implicated sibship as a marker of infection load during early life and suggests that exposure or reexposure to infections can influence the developing immune system. Viral infection has also been implicated in the pathogenesis of multiple sclerosis (MS). To evaluate whether exposure to infant siblings in early life is associated with the risk of MS, and to explore the possible mechanism for any apparent protective effect, including altered Epstein-Barr virus (EBV) infection patterns. Population-based case-control study in Tasmania, Australia, from 1999 to 2001 based on 136 cases of magnetic resonance imaging-confirmed MS and 272 community controls, matched on sex and year of birth. Risk of MS by duration of contact with younger siblings aged less than 2 years in the first 6 years of life. Increasing duration of contact with a younger sibling aged less than 2 years in the first 6 years of life was associated with reduced MS risk (adjusted odds ratios [AORs]: <1 infant-year, 1.00 [reference] 1 to <3 infant-years, 0.57 [95% confidence interval {CI}, 0.33-0.98] 3 to or =5 infant-years, 0.12 [95% CI, 0.02-0.88] test for trend, P = .002). A history of exposure to infant siblings was associated with a reduced IgG response to EBV among controls. Controls with at least 1 infant-year contact had a reduced risk of infectious mononucleosis and a reduced risk of very high composite EBV IgG titers (AOR, 0.33 95% CI, 0.11-0.98) compared with other controls. The inverse association between higher infant contact and MS was independent of EBV IgG titer. Higher infant sibling exposure in the first 6 years of life was associated with a reduced risk of MS, possibly by altering childhood infection patterns and related immune responses.
Publisher: Wiley
Date: 28-05-2013
DOI: 10.1111/CEA.12092
Abstract: Socio-demographic predictors for the development of clinically observed, infantile eczema have not been formally examined in a large population-based study. Few studies of eczema risk factors have included current, objective eczema outcomes as well as parent-reported history. We aimed to measure the population prevalence of infantile eczema using novel s ling methodology, and identify socio-demographic risk factors for eczema in the first year of life. A population-based cross-sectional study of infantile allergy (the HealthNuts study, n = 4972, response rate 74.1%) was conducted from 2008-2011 in Melbourne, Australia. Infants were examined for current eczema at age 12 months (mean 12.7, SD 0.7). Parents provided information about the infants' history of eczema and demographic factors. Factors associated with eczema were modelled using multinomial logistic regression. The population prevalence of observed eczema at 12 months was 20.3% (95% CI 19.0, 21.5), while cumulative prevalence for parent-reported eczema was 28.0% (95% CI 26.7, 29.4). The strongest predictors of eczema were maternal eczema and asthma (multinomial (M)-OR 1.7, P < 0.001, and M-OR 1.4, P = 0.007), male sex (M-OR 1.4, P < 0.001), and East Asian ethnicity (M-OR 1.6, P < 0.001) with over 80% of infants with all risk factors exhibiting eczema. East Asian parents, particularly recent migrants, reported fewer allergies than other parents. Approximately, one in three infants developed eczema by 12 months of age. East Asian infants are at increased risk of eczema despite their parents having lower rates of allergy than non-Asian parents. Gene-environment interactions may explain the differential effect seen in this minority group.
Publisher: Springer Science and Business Media LLC
Date: 07-2019
Publisher: Elsevier BV
Date: 08-2002
Abstract: This review documents and assesses recent trends in sudden infant death syndrome. We review medical literature, Internet resources, and national governmental data. A striking reduction in SIDS incidence of more than 50% has been observed in various countries after interventions, particularly during the early 1990s, to reduce the prevalence of prone infant sleeping. A reduction in postneonatal mortality has accompanied these lower rates. Evaluation studies from several countries indicate that the SIDS rate drop is largely attributable to a decline in the proportion of babies sleeping prone. Within countries, the SIDS rate decline has not occurred to the same extent for different ethnic and socio-economic groups. Future public health activities must aim to address this issue. In the post-intervention era, the relative importance of the risk factors of side compared to supine sleeping and soft bedding near the infant's airway have become more evident. Recent death scene data indicate that a substantial proportion of the remaining SIDS deaths could be avoided by supine sleeping and by providing a safe sleeping environment for all infants.
Publisher: S. Karger AG
Date: 28-10-2010
DOI: 10.1159/000252973
Abstract: i Background: /i Intrauterine exposure to alcohol may affect cardiovascular development, increasing risk of cardiovascular malformations. Intrauterine exposure to light maternal alcohol intake has been reported to affect human umbilical arterial contractility, and adult sheep exposed in utero have had altered cerebrovascular reactivity. In human adults, alcohol intake affects arterial stiffness. i Objectives: /i We investigated whether intrauterine exposure to alcohol was associated with childhood pulse wave velocity (PWV), a measure of arterial stiffness. i Methods: /i On postnatal day 4, mothers of 147 twin pairs born in Tasmania from 1991 to 1993 reported alcohol intake during each trimester of pregnancy. At 9 years, child PWV was assessed over carotid-femoral and femoral-dorsalis pedis arterial segments by applanation tonometry. i Results: /i Carotid-femoral PWV was 0.2 m/s (95% CI 0.06, 0.4) higher (indicating stiffer vessels) in children whose mothers drank alcohol in the 2nd trimester rather than abstained, after adjusting for potential confounding factors. A similar effect was not seen for femoral-dorsalis pedis PWV. Findings were independent of child blood pressure which correlated strongly with PWV. Alcohol intake varied little between trimesters, so it was not possible to assess the effect of timing of exposure. i Conclusions: /i Carotid-femoral PWV in adults is predictive of cardiovascular morbidity and mortality. The degree of continuity between childhood and adulthood PWV is unknown, but as we found an association between prenatal alcohol exposure and carotid-femoral PWV at 9 years, a permanent change in vessel wall structure or function is possible. These findings need to be confirmed in other and larger cohorts, and mechanistic animal studies are needed.
Publisher: Wiley
Date: 02-06-2019
DOI: 10.1111/ALL.13822
Abstract: In previous studies, deficits in regulatory T-cell (Treg) number and function at birth have been linked with subsequent allergic disease. However, longitudinal studies that account for relevant perinatal factors are required. The aim of this study was to investigate the relationship between perinatal factors, naïve Treg (nTreg) over the first postnatal year and development of food allergy. In a birth cohort (n = 1074), the proportion of nTreg in the CD4 A higher proportion of nTreg at birth, larger birth size and male sex was each associated with higher nTreg in infancy. Exposure to labour, as compared to delivery by prelabour Caesarean section, was associated with a transient decrease nTreg. Infants that developed food allergy had decreased nTreg at birth, and the labour-associated decrease in nTreg at birth was more evident among infants with subsequent food allergy. Mode of birth was not associated with risk of food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food allergy. The proportion of nTreg at birth is a major determinant of the proportion present throughout infancy, highlighting the importance of prenatal immune development. Exposure to the inflammatory stimulus of labour appears to reveal differences in immune function among infants at risk of food allergy.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JACI.2017.02.019
Abstract: The HealthNuts study previously reported interim prevalence data showing the highest prevalence of challenge-confirmed food allergy in infants internationally. However, population-derived prevalence data on challenge-confirmed food allergy and other allergic diseases in preschool-aged children remain sparse. This study aimed to report the updated prevalence of food allergy at age 1 year from the whole cohort, and to report the prevalence of food allergy, asthma, eczema, and allergic rhinitis at age 4 years. HealthNuts is a population-based cohort study with baseline recruitment of 5276 one-year-old children who underwent skin prick test (SPT) to 4 food allergens and those with detectable SPT results had formal food challenges. At age 4 years, parents completed a questionnaire (81.3% completed) and those who previously attended the HealthNuts clinic at age 1 year or reported symptoms of a new food allergy were invited for an assessment that included SPT and oral food challenges. Data on asthma, eczema, and allergic rhinitis were captured by validated International Study of Asthma and Allergies in Childhood questionnaires. The prevalence of challenge-confirmed food allergy at age 1 and 4 years was 11.0% and 3.8%, respectively. At age 4 years, peanut allergy prevalence was 1.9% (95% CI, 1.6% to 2.3%), egg allergy was 1.2% (95% CI, 0.9% to 1.6%), and sesame allergy was 0.4% (95% CI, 0.3% to 0.6%). Late-onset peanut allergy at age 4 years was rare (0.2%). The prevalence of current asthma was 10.8% (95% CI, 9.7% to 12.1%), current eczema was 16.0% (95% CI, 14.7% to 17.4%), and current allergic rhinitis was 8.3% (95% CI, 7.2% to 9.4%). Forty percent to 50% of this population-based cohort experienced symptoms of an allergic disease in the first 4 years of their life. Although the prevalence of food allergy decreased between age 1 year and age 4 years in this population-based cohort, the prevalence of any allergic disease among 4-year-old children in Melbourne, Australia, is remarkably high.
Publisher: Hindawi Limited
Date: 03-06-2014
DOI: 10.1111/ANE.12268
Abstract: Among the environmental factors associated with multiple sclerosis (MS) causation, some of the strongest associations are with Epstein-Barr virus (EBV), and to a lesser extent human herpesvirus 6 (HHV6). Associations with clinical course are less conclusive, however. We evaluated serum anti-EBV-EA-R IgG and anti-HHV6 IgM, and EBV and HHV6 viral load (VL) for their associations with relapse, disability, and progression in disability in a prospective cohort of 198 participants with clinically definite MS. Anti-EBV-EA-R IgG was detected in 81.8% of cases at study entry, and titers remained essentially unchanged during the study. Anti-HHV6 IgM was detected in only one participant, and EBV-VL (29%) and HHV6-VL (1.8%) were detected in a minority of s les, and where detected levels were low. Our previously demonstrated association between anti-HHV6 IgG and relapse hazard was not affected by adjustment for parameters of reactivation. We found no evidence that any of the viral markers were associated with disability or progression in disability. In relation to relapse, only EBV-VL was positively associated, although this was strongly influenced by a single in idual. Using a prospective cohort design, we found no convincing evidence that reactivation parameters of EBV or HHV6 were associated with subsequent MS relapse hazard or progression in disability, confirming previous findings, and indicating that herpesvirus reactivation is not an important driver of relapse or disability in this established MS population.
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000442203
Abstract: b i Background: /i /b Multiple sclerosis (MS) patients may be at an increased risk of comorbidities due to the debilitating and chronic nature of the disease. An increased understanding of comorbidities and disease course in MS may provide new insights and enhance MS management. We aimed at investigating the frequency of comorbidities and their associations with clinical disability and relapse in MS. b i Methods: /i /b A prospective cohort of 198 MS patients was followed during 2002-2005 and queried about specific doctor-diagnosed comorbidities. In Australia, the MS cohort was compared to the 2007 general population with regard to the prevalence of comorbidities. Multilevel mixed-effects linear regression was used to assess the difference in subsequent disability between those who reported comorbidities and those who did not. The association of comorbidities with the hazard of relapse was assessed using survival analysis. b i Results: /i /b The age-standardised prevalence of hypertension, dyslipidaemia, asthma, psoriasis, eczema and anaemia was significantly higher in the MS cohort compared to that in the general Australian population. The level of disability (Multiple Sclerosis Severity Score) in those who reported overweight/obesity (β: 0.76 (95% CI 0.04-1.48), p = 0.037), or dyslipidaemia (β: 1.05 (95% CI 0.07-2.02), p = 0.036) was significantly higher compared to those who did not report these comorbidities, even after adjustment for potential confounders. There were no significant associations between comorbidities and change in disability. For relapse analyses, rheumatoid arthritis and anaemia were associated with more than threefold (hazard ratio, HR 3.70 (95% CI 1.80-7.58), p 0.001) and twofold (HR 2.04 (95% CI 1.11-3.74), p = 0.022) increased risk of subsequent relapse respectively. b i Conclusions: /i /b The prevalence of some comorbidities was higher in MS patients and associated with greater disability and relapse risk. Treatment of these comorbidities in patients with MS has the potential to improve disease course and help in the understanding of the prognosis and outcomes of MS.
Publisher: Wiley
Date: 08-1992
DOI: 10.1111/J.1440-1754.1992.TB02731.X
Abstract: This report examines the thermal environment during last sleep of a control population to investigate how the thermal environment of the infant's bedroom varies by season, external temperature and by certain maternal and infant characteristics. Two age-matched control infants were chosen for each case, one of which was also matched on birthweight. The home visits were not pre-arranged and were matched on climatic conditions, time of year and time period of day for the index case. The initial response rate for controls (n = 108) was 86%. Although there was a large amount of variation in the infant thermal environment, thermal insulation correlated with room temperature (r = -0.44, P = 0.0001) and external temperature (r = -0.30, P = 0.002). The thermal environment of the infant, as defined by excess thermal insulation for room temperature, did not vary by indoor or outdoor temperature, but higher average values were observed in teenage mothers (mean difference = 2.7 tog [95% Cl = 0.3, 5.2]), infants who slept in an adult bed (mean difference = 2.6 tog [-0.1, 5.4]) and infants with an illness (mean difference = 0.8 tog [-0.3, 1.9]). There was a tendency for the thermal environment of infants to be higher and more variable during winter, supporting previous hypotheses that paradoxical overheating may occur in some infants during winter. Further work is required to provide a set of recommendations on the optimal thermal conditions for post-neonatal infants.
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.JACI.2013.11.032
Abstract: There is a paucity of data examining the natural history of and risk factors for egg allergy persistence, the most common IgE-mediated food allergy in infants. We aimed to assess the natural history of egg allergy and identify clinical predictors for persistent egg allergy in a population-based cohort. The HealthNuts study is a prospective, population-based cohort study of 5276 infants who underwent skin prick tests to 4 allergens, including egg. Infants with a detectable wheal were offered hospital-based oral food challenges (OFCs) to egg, irrespective of skin prick test wheal sizes. Infants with challenge-confirmed raw egg allergy were offered baked egg OFCs at age 1 year and follow-up at age 2 years, with repeat OFCs to raw egg. One hundred forty infants with challenge-confirmed egg allergy at age 1 year participated in the follow-up. Egg allergy resolved in 66 (47%) infants (95% CI, 37% to 56%) by 2 years of age however, resolution was lower in children with baked egg allergy at age 1 year compared with baked egg tolerance (13% and 56%, respectively adjusted odds ratio, 5.27 95% CI, 1.36-20.50 P = .02). In the subgroup of infants who were tolerant to baked egg at age 1 year, frequent ingestion of baked egg (≥5 times per month) compared with infrequent ingestion (0-4 times per month) increased the likelihood of tolerance (adjusted odds ratio, 3.52 95% CI, 1.38-8.98 P = .009). Mutation in the filaggrin gene was not associated with the resolution of either egg allergy or egg sensitization at age 2 years. Phenotyping of egg allergy (baked egg tolerant vs allergic) should be considered in the management of this allergy because it has prognostic implications and eases dietary restrictions. Randomized controlled trials for egg oral immunotherapy should consider stratifying at baseline by the baked egg subphenotype to account for the differential rate of tolerance development.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/10253890701379023
Abstract: Perception of stress with consequent activation of a neuroendocrine cascade causes changes in immune function that may be bi-directional, with alterations in basal levels of biological parameters outside the optimal range. In this cross-sectional study of 302 healthy persons (males 56.3%, females 43.7%) aged 41-46 years, higher stress levels, as assessed by questionnaire measures of recurrent and recent perceived stress, were associated with a 4-fold greater risk of having a high compared to mid-range serum neopterin concentration, indicating activation of cellular immune mechanisms [adjusted odds ratio, OR (95% confidence intervals, CI): Low stress=1.00 (reference group) Medium stress=4.13 (1.51, 11.29) High stress=4.63, (1.35, 15.83), p for trend=0.01]. Higher stress levels were associated with a 3-fold greater risk of having signs of humoral immune activation, as indicated by salivary IgA concentration [high compared to mid-range salivary IgA: Low stress=1.00 (reference group) Medium stress=1.06 (0.48, 2.34) High stress=3.62 (1.26, 10.39), p for trend=0.02], but also a 4-fold greater risk of humoral immune depression [low compared to mid-range IgA: Low stress=1.00 (reference group) Medium stress=1.72 (0.74, 3.99) High stress=4.38 (1.47, 13.00), p for trend=0.02]. In conclusion, in this cross-sectional study, higher stress levels were associated with higher serum neopterin and both elevated and depressed salivary IgA levels. These findings emphasise the importance of considering that stress may have bi-directional effects on immune mechanisms, and are consistent with an activational effect of chronic, perceived stress on cellular immunity, and a bi-directional effect on IgA levels, one aspect of humoral immunity.
Publisher: eLife Sciences Publications, Ltd
Date: 03-04-2022
Publisher: Oxford University Press (OUP)
Date: 06-2009
DOI: 10.1002/IBD.20842
Abstract: The incidence of Crohn's disease (CD) with onset before age 16 has increased. Several perinatal characteristics have been associated with CD. Our objective was to examine the temporal change in CD incidence by period of birth and the extent that this could be attributed to perinatal characteristics associated with higher CD risk. A record linkage study was conducted utilizing the perinatal records of Victorian births 1983-1998 inclusive and a state-based CD registry. Proportional hazards models were used to investigate the perinatal factors in relation to the onset of CD by age 16. Further, a nested case control study was conducted to examine the association between sibling exposure and CD risk. The CD incidence rate for births 1983-1998 was 2.01 (95% confidence interval [CI] 1.79, 2.27) per 100,000 child-years. A birth cohort effect was demonstrated, with higher CD risk for 1992-1998 versus 1983-1991 births (hazard ratio [HR] 1.56 95% CI 1.18, 2.06). Perinatal characteristics associated with higher CD risk included urban location, higher socioeconomic status, married mother, a congenital abnormality and delivery by elective cesarean section. Sibling exposure during the first 6 years of life was not associated with CD risk. The increased CD incidence among more recent births was not accounted for by changes in these measured perinatal factors. The temporal increase in CD incidence documented for births up to 1990 has continued for children born after 1991 and was not accounted for by temporal changes in the measured perinatal factors.
Publisher: eLife Sciences Publications, Ltd
Date: 10-05-2022
DOI: 10.7554/ELIFE.75170
Abstract: The risk of adult onset cardiovascular and metabolic (cardiometabolic) disease accrues from early life. Infection is ubiquitous in infancy and induces inflammation, a key cardiometabolic risk factor, but the relationship between infection, inflammation, and metabolic profiles in early childhood remains unexplored. We investigated relationships between infection and plasma metabolomic and lipidomic profiles at age 6 and 12 months, and mediation of these associations by inflammation. Matched infection, metabolomics, and lipidomics data were generated from 555 infants in a pre-birth longitudinal cohort. Infection data from birth to 12 months were parent-reported (total infections at age 1, 3, 6, 9, and 12 months), inflammation markers (high-sensitivity C-reactive protein [hsCRP] glycoprotein acetyls [GlycA]) were quantified at 12 months. Metabolic profiles were 12-month plasma nuclear magnetic resonance metabolomics (228 metabolites) and liquid chromatography/mass spectrometry lipidomics (776 lipids). Associations were evaluated with multivariable linear regression models. In secondary analyses, corresponding inflammation and metabolic data from birth (serum) and 6-month (plasma) time points were used. At 12 months, more frequent infant infections were associated with adverse metabolomic (elevated inflammation markers, triglycerides and phenylalanine, and lower high-density lipoprotein [HDL] cholesterol and apolipoprotein A1) and lipidomic profiles (elevated phosphatidylethanolamines and lower trihexosylceramides, dehydrocholesteryl esters, and plasmalogens). Similar, more marked, profiles were observed with higher GlycA, but not hsCRP. GlycA mediated a substantial proportion of the relationship between infection and metabolome/lipidome, with hsCRP generally mediating a lower proportion. Analogous relationships were observed between infection and 6-month inflammation, HDL cholesterol, and apolipoprotein A1. Infants with a greater infection burden in the first year of life had proinflammatory and proatherogenic plasma metabolomic/lipidomic profiles at 12 months of age that in adults are indicative of heightened risk of cardiovascular disease, obesity, and type 2 diabetes. These findings suggest potentially modifiable pathways linking early life infection and inflammation with subsequent cardiometabolic risk. The establishment work and infrastructure for the BIS was provided by the Murdoch Children’s Research Institute (MCRI), Deakin University, and Barwon Health. Subsequent funding was secured from National Health and Medical Research Council of Australia (NHMRC), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O’Brien Memorial Asthma Foundation, the Our Women’s Our Children’s Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Minderoo Foundation, the Ilhan Food Allergy Foundation, GMHBA, Vanguard Investments Australia Ltd, and the Percy Baxter Charitable Trust, Perpetual Trustees. In-kind support was provided by the Cotton On Foundation and CreativeForce. The study sponsors were not involved in the collection, analysis, and interpretation of data writing of the report or the decision to submit the report for publication. Research at MCRI is supported by the Victorian Government’s Operational Infrastructure Support Program. This work was also supported by NHMRC Senior Research Fellowships to ALP (1008396) DB (1064629) and RS (1045161) , NHMRC Investigator Grants to ALP (1110200) and DB (1175744), NHMRC-A*STAR project grant (1149047). TM is supported by an MCRI ECR Fellowship. SB is supported by the Dutch Research Council (452173113).
Publisher: Springer Science and Business Media LLC
Date: 09-06-2015
DOI: 10.1038/SREP11063
Abstract: Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease of childhood. We recently showed that DNA methylation at the gene encoding the pro-inflammatory cytokine interleukin-32 ( IL32 ) is reduced in JIA CD4+ T cells. To extend this finding, we measured IL32 methylation in CD4+ T-cells from an additional s le of JIA cases and age- and sex-matched controls and found a reduction in methylation associated with JIA consistent with the prior data (combined case-control dataset: 25.0% vs 37.7%, p = 0.0045). Further, JIA was associated with reduced IL32 methylation in CD8+ T cells (15.2% vs 25.5%, p = 0.034), suggesting disease-associated changes to a T cell precursor. Additionally, we measured regional SNPs, along with CD4+ T cell expression of total IL32 and the γ and β isoforms. Several SNPs were associated with methylation. Two SNPs were also associated with JIA and we found evidence of interaction such that methylation was only associated with JIA in minor allele carriers (e.g. rs10431961 p interaction = 0.011). Methylation at one measured CpG was inversely correlated with total IL32 expression (Spearman r = −0.73, p = 0.0009), but this was not a JIA-associated CpG. Overall, our data further confirms that reduced IL32 methylation is associated with JIA and that SNPs play an interactive role.
Publisher: BMJ
Date: 07-2004
Publisher: Springer Science and Business Media LLC
Date: 24-03-2020
DOI: 10.1038/S41467-020-14552-1
Abstract: In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella , a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort ( n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal s les shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri . Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri .
Publisher: MDPI AG
Date: 23-03-2010
DOI: 10.3390/NU2030389
Publisher: Wiley
Date: 10-1990
DOI: 10.1111/J.1365-3016.1990.TB00670.X
Abstract: A statutory 'Notification of Birth' form, containing obstetric and perinatal information, has been routinely collected for Tasmanian deliveries since 1974. For the period 1980 to 1984, birth notification data was collected for over 99% of Tasmanian deliveries. This data was examined for the 130 cases of sudden infant death syndrome (SIDS) that occurred from 1980 to 1984 and for 610 controls. It was then used to construct an at-birth scoring system to predict infants at higher risk of SIDS in the postneonatal period. A predictive model of the relative risk of SIDS was developed by fitting a binomial/logistic generalised linear model to the binary 1980-1984 case control data with birth variables used as predictors. The final predictive model contained five variables (maternal age, infant sex, birth weight, month of birth and feeding practice) and had a sensitivity of 62% and specificity of 73%. The model was then tested on independent birth cohorts from 1985 and 1986 and found to have a sensitivity of 47% and specificity of 77%. The risk of SIDS in the group of infants classified as high risk was 7.9 per 1000 live births and in the group at low risk it was 2.5 per 1000 live births. In addition, the model predicted 74% of neonatal deaths occurring during these 2 years. This compares well with other predictive models developed elsewhere. The predictive model will be used to identify infants at high risk for SIDS in a prospective cohort study.
Publisher: Wiley
Date: 29-09-2009
DOI: 10.1002/ART.24790
Abstract: This ecological study describes and quantifies the association between ambient ultraviolet (UV) radiation levels, including daily winter vitamin D effective UV radiation levels and the incidence of the 3 antineutrophil cytoplasmic antibody-associated vasculitides (AAVs): Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS). Latitudinal variation in occurrence of the AAVs, especially WG, has been previously reported. For other autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus, inverse associations with latitude are hypothesized to indicate a causative role for low UV radiation exposure, possibly acting via vitamin D status. Published epidemiologic studies provided data on incident cases, total population of study regions, age-specific incidence rates, and study location. From these data and online age-specific population data, we calculated crude incidence rates, the expected number of cases (to control for possible age confounding), and measures of ambient UV radiation. Negative binomial regression models were used to calculate the incidence rate ratio (IRR) for a 1,000 joules/m(2) increase in ambient UV radiation. The incidence of WG and CSS increased with increasing latitude and decreasing ambient UV radiation, with a stronger and more consistent effect across different UV radiation measures for WG, e.g., for average daily ambient clear sky erythemal UV radiation (WG: IRR 0.64 [95% confidence interval (95% CI) 0.44-0.94], P = 0.02 CSS: IRR 0.67 [95% CI 0.43-1.05], P = 0.08 MPA: IRR 1.16 [95% CI 0.92-1.47], P = 0.22). There was no apparent latitudinal variation in MPA incidence. Our findings are consistent with a protective immunomodulatory effect of ambient UV radiation on the onset of WG and CSS. We discuss possible mechanisms, including the effect of vitamin D on the immune system.
Publisher: BMJ
Date: 10-1998
DOI: 10.1136/ADC.79.4.328
Abstract: To document the relation between sibling number and atopic disease, and to assess the contribution of possible confounding factors to the protective effect of siblings in relation to asthma and hay fever. Cross sectional survey by parental questionnaire in Tasmania, Australia, on 6378 children (92% of those eligible) who reached 7 years of age during 1995. Exercise challenge lung function testing was conducted on 428 children. Analyses reported were conducted on singleton births only (n = 6158). The prevalences of a history of asthma ever, hay fever, and eczema were 27%, 19%, and 22%, respectively. Asthma and hay fever, but not eczema, were inversely related to sibling number, with evidence of a dose-response trend. The mean age at onset for asthma or wheezy breathing decreased as the number of siblings increased. The inverse association between sibling number and asthma or hay fever persisted after adjustment for several confounders, such as parental smoking or breast feeding, but did not persist after adjustment for household size in 1995. The protective effect of high sibling number could not be separated from household size at age 7, and it appears to be operating after birth and influences the age at onset of asthma symptoms. Further work to increase knowledge of how the protective effect of the presence of siblings works might have important implications for the understanding of the pathogenesis of asthma.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.CLINBIOCHEM.2015.04.014
Abstract: In widely used protocols for the collection and isolation of cord blood mononuclear cells, investigators are left with substantial volumes of diluted plasma which could be used for other measurements. The aim of this study was to ascertain the validity of umbilical cord blood (UCB) diluted plasma s les for vitamin D, A and E analysis compared to UCB serum s les. Twenty UCB matched s les of diluted plasma and serum were collected. The s les were analysed by two liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods on two separate occasions. The results of 25(OH)D3 obtained by the two laboratories demonstrated close agreement with a mean difference of 0.14nmol/L [95% confidence interval (95% CI), -6.8 to 7.1]. Both methods demonstrate close agreement for 25(OH)D3 in UCB serum versus diluted UCB plasma mean difference 2.2nmol/L [95% CI, -9.5 to 13.9] and 4.1nmol/L [95% CI, -14.5 to 6.1] for the results from Lab A and Lab B, respectively. Vitamin A was quantified by Lab A in UCB serum and diluted UCB plasma mean difference 0.07μmol/L [95% CI, -0.41 to 0.28]. Results of 25(OH)D3 epimer and vitamin E in the diluted UCB plasma were below the limit of quantification, and could not be compared with UCB serum. Diluted UCB plasma can be used for the quantification of retinol and 25(OH)D3 by LC-MS/MS. By contrast, quantification of 25(OH)D3 epimer and vitamin E in diluted UCB plasma is not supported by this study due to limitations in analytical sensitivity.
Publisher: Wiley
Date: 26-06-2015
DOI: 10.1002/ART.39129
Abstract: Susceptibility to juvenile idiopathic arthritis (JIA) is presumed to be determined by both genes and environment. However, the environmental factors remain largely unknown. The hygiene hypothesis suggests that exposure to siblings, as a marker of exposure to microbes in early life, may protect against the development of later immune disorders. Some prior evidence suggests this may also be true for JIA. The present study was undertaken to test this hypothesis in detail. We conducted a comprehensive analysis of the role of sibling exposure in JIA risk within the Childhood Arthritis Risk Factor Identification Study JIA case-hospital control s le (302 cases and 676 controls) from Victoria, Australia. We found that, compared to being an only child, having any siblings was protective against JIA, with an adjusted odds ratio (OR) of 0.46 (95% confidence interval [95% CI] 0.28-0.74) (P = 0.001). The protective association appeared to increase with increasing number of siblings (e.g., for ≥3 siblings, adjusted OR 0.25 [95% CI 0.13-0.48], P < 0.001). A protective association of siblings was also observed when we considered cumulative sibling years by age 6 (e.g., for ≥3 years of exposure versus no exposure, adjusted OR 0.49 [95% CI 0.30-0.79], P = 0.003). We also compared cases to a second control s le (n = 341) collected from the community and weighted to represent the child population of Victoria. Data remained supportive of an association between sibling exposure and protection against JIA, particularly for exposure to younger siblings. Increased exposure to siblings is associated with a reduced risk of disease in our s le. This suggests that increased microbial exposure in childhood may confer protection against the development of JIA.
Publisher: Frontiers Media SA
Date: 21-03-2019
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.MEHY.2008.01.033
Abstract: Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy.
Publisher: BMJ
Date: 19-02-2019
Abstract: To investigate whether lipid-related or body mass index (BMI)–related common genetic polymorphisms modulate the associations between serum lipid levels, BMI and disability progression in multiple sclerosis (MS). The association between disability progression (annualised Expanded Disability Status Scale (EDSS) change over 5 years, ΔEDSS) and lipid-related or BMI-related genetic polymorphisms was evaluated in a longitudinal cohort (n=184), diagnosed with MS. We constructed a cumulative genetic risk score (CGRS) of associated polymorphisms (p .05) and examined the interactions between the CGRS and lipid levels (measured at baseline) in predicting ΔEDSS. All analyses were conducted using linear regression. Five lipid polymorphisms (rs2013208, rs9488822, rs17173637, rs10401969 and rs2277862) and one BMI polymorphism (rs2033529) were nominally associated with ΔEDSS. The constructed lipid CGRS showed a significant, dose-dependent association with ΔEDSS (p trend =1.4×10 −6 ), such that participants having ≥6 risk alleles progressed 0.38 EDSS points per year faster compared with those having ≤3. This CGRS model explained 16% of the variance in ΔEDSS. We also found significant interactions between the CGRS and lipid levels in modulating ΔEDSS, including high-density lipoprotein (HDL p interaction =0.005) and total cholesterol:high-density lipoprotein ratio (TC:HDL p interaction =0.030). The combined model (combination of CGRS and the lipid parameter) explained 26% of the disability variance for HDL and 27% for TC:HDL. In this prospective cohort study, both lipid levels and lipid-related polymorphisms in idually and jointly were associated with significantly increased disability progression in MS. These results indicate that these polymorphisms and tagged genes might be potential points of intervention to moderate disability progression.
Publisher: Frontiers Media SA
Date: 19-02-2019
Publisher: Wiley
Date: 11-2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-08-2023
DOI: 10.1212/WNL.0000000000207489
Abstract: In multiple sclerosis (MS), accelerated aging of the immune system (immunosenescence) may be associated with disease onset or drive progression. DNA methylation (DNAm) is an epigenetic factor that varies among lymphocyte subtypes, and cell-specific DNAm is associated with MS. DNAm varies across the life span and can be used to accurately estimate biological age acceleration, which has been linked to a range of morbidities. The objective of this study was to test for cell-specific epigenetic age acceleration (EAA) in people with MS. This was a case-control study of EAA using existing DNAm data from several independent previously published studies. Data were included if .idat files from Illumina 450K or EPIC arrays were available for both a case with MS and an age-matched and sex-matched control, from the same study. Multifactor statistical modeling was performed to assess the primary outcome of EAA. We explored the relationship of EAA and MS, including interaction terms to identify immune cell-specific effects. Cell-sorted DNA methylation data from 3 independent datasets were used to validate findings. We used whole blood DNA methylation data from 583 cases with MS and 643 non-MS controls to calculate EAA using the GrimAge algorithm. The MS group exhibited an increased EAA compared with controls (approximately 9 mths, 95% CI 3.6–14.4), p = 0.001). Statistical deconvolution showed that EAA is associated with MS in a B cell–dependent manner ( β int = 1.7, 95% CI 0.3–2.8), p = 0.002), irrespective of B-cell proportions. Validation analysis using 3 independent datasets enriched for B cells showed an EAA increase of 5.1 years in cases with MS compared with that in controls (95% CI 2.8–7.4, p = 5.5 × 10 −5 ). By comparison, there was no EAA difference in MS in a T cell–enriched dataset. We found that EAA was attributed to the DNAm surrogates for Beta-2-microglobulin (difference = 47,546, 95% CI 10,067–85,026 p = 7.2 × 10 −5 ), and smoking pack-years (difference = 8.1, 95% CI 1.9–14.2, p = 0.002). This study provides compelling evidence that B cells exhibit marked EAA in MS and supports the hypothesis that premature B-cell immune senescence plays a role in MS. Future MS studies should focus on age-related molecular mechanisms in B cells.
Publisher: Elsevier BV
Date: 10-2013
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.JAUT.2015.12.006
Abstract: MicroRNAs (miRNAs) regulate T cell development and function and the disruption of miRNAs in natural regulatory CD4(+) FOXP3(+) T cells (nTreg) leads to autoimmune disease in mice. To investigate miRNA expression in relation to autoimmune disease risk in humans we sequenced them in purified CD4(+) T cell subsets from in iduals at high risk of type 1 diabetes (pre-T1D), as well as other healthy in iduals. Differences in miRNA expression patterns were observed between specific T cell subsets and, within subsets, between pre-T1D and healthy in iduals. Compared to healthy, naive CD4(+) T cells in pre-T1D displayed 32 differentially expressed miRNAs, potentially a template for altered miRNA expression in effector memory T cells in T1D. Naive nTreg in pre-T1D displayed two differentially expressed miRNAs, Let-7c and miR-15a. In contrast, nTreg activated in vivo displayed a large number of differentially expressed miRNAs, revealing a pro-inflammatory and FOXP3-repressive signature. Differential expression of specific miRNAs was also a signpost to altered T cell function. For ex le, in pre-T1D, increased expression of miR-26a in nTreg activated in vivo or in vitro was associated with decreased expression of its target, the histone methyltransferase EZH2. Chemical inhibition of EZH2 decreased the number of activated naïve nTreg and their expression of nTreg signature genes FOXP3 and TIGIT. Our findings demonstrate that miRNAs differentially expressed in CD4(+) T cell subsets are markers of risk and T cell dysfunction in T1D.
Publisher: Springer Science and Business Media LLC
Date: 29-03-2016
DOI: 10.1038/TP.2016.32
Abstract: Compelling evidence suggests that maternal mental health in pregnancy can influence fetal development. The imprinted genes, insulin-like growth factor 2 ( IGF2 ) and H19, are involved in fetal growth and each is regulated by DNA methylation. This study aimed to determine the association between maternal mental well-being during pregnancy and differentially methylated regions (DMRs) of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn offspring. Maternal depression, anxiety and perceived stress were assessed at 28 weeks of pregnancy in the Barwon Infant Study ( n =576). DNA methylation was measured in purified cord blood mononuclear cells using the Sequenom MassArray Platform. Maternal anxiety was associated with a decrease in average ICR methylation (Δ=−2.23% 95% CI=−3.68 to −0.77%), and across all six of the in idual CpG units in anxious compared with non-anxious groups. Birth weight and sex modified the association between prenatal anxiety and infant methylation. When stratified into lower (⩽3530 g) and higher ( g) birth weight groups using the median birth weight, there was a stronger association between anxiety and ICR methylation in the lower birth weight group (Δ=−3.89% 95% CI=−6.06 to −1.72%), with no association in the higher birth weight group. When stratified by infant sex, there was a stronger association in female infants (Δ=−3.70% 95% CI=−5.90 to −1.51%) and no association in males. All the linear regression models were adjusted for maternal age, smoking and folate intake. These findings show that maternal anxiety in pregnancy is associated with decreased IGF2 / H19 ICR DNA methylation in progeny at birth, particularly in female, low birth weight neonates. ICR methylation may help link poor maternal mental health and adverse birth outcomes, but further investigation is needed.
Publisher: Springer Science and Business Media LLC
Date: 15-11-2012
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JSBMB.2013.01.011
Abstract: Vitamin D deficiency is common and implicated in risk of several human diseases. Evidence on the relative quantitative contribution of environmental, genetic and phenotypic factors to vitamin D status (assessed by the serum concentration of 25-hydroxyvitamin D, 25(OH)D) in free-living populations is sparse. We conducted a cross-sectional study of 494 Caucasian adults aged 18-61years, randomly selected from the Australian Electoral Roll according to groups defined by age, sex and region (spanning 27°-43°South). Data collected included personal characteristics, sun exposure behaviour, biomarkers of skin type and past sun exposure, serum 25(OH)D concentration and candidate single nucleotide polymorphisms. Ambient ultraviolet radiation (UVR) levels in the month six weeks before blood s ling best predicted vitamin D status. Serum 25(OH)D concentration increased by 10nmol/L as reported time in the sun doubled. Overall, 54% of the variation in serum 25(OH)D concentration could be accounted for: 36% of the variation was explained by sun exposure-related factors 14% by genetic factors (including epistasis) and 3.5% by direct measures of skin phenotype. Novel findings from this study are demonstration of gene epistasis, and quantification of the relative contribution of a wide range of environmental, constitutional and genetic factors to vitamin D status. Ambient UVR levels and time in the sun were of prime importance but it is nonetheless important to include the contribution of genetic factors when considering sun exposure effects. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
Publisher: Elsevier BV
Date: 10-2023
Publisher: SAGE Publications
Date: 14-02-2013
Abstract: Gene–environment interactions may shed light on the mechanisms underlying multiple sclerosis (MS). We pooled data from two case-control studies on incident demyelination and used different methods to assess interaction between HLA-DRB1*15 (DRB1-15) and history of infectious mononucleosis (IM). In iduals exposed to both factors were at substantially increased risk of disease (OR=7.32, 95% CI=4.92–10.90). In logistic regression models, DRB1-15 and IM status were independent predictors of disease while their interaction term was not (DRB1-15*IM: OR=1.35, 95% CI=0.79–2.23). However, interaction on an additive scale was evident (Synergy index=2.09, 95% CI=1.59–2.59 excess risk due to interaction=3.30, 95%CI=0.47–6.12 attributable proportion due to interaction=45%, 95% CI=22–68%). This suggests, if the additive model is appropriate, the DRB1-15 and IM may be involved in the same causal process leading to MS and highlights the benefit of reporting gene–environment interactions on both a multiplicative and additive scale.
Publisher: BMJ
Date: 20-03-2017
Abstract: To investigate the prospective associations between adiposity and lipid-related variables and conversion to multiple sclerosis (MS), time to subsequent relapse and progression in disability. A cohort of 279 participants with a first clinical diagnosis of central nervous system demyelination was prospectively followed to 5-year review. Height, weight, waist and hip circumference were measured, and serum s les taken for measurement of lipids and apolipoproteins. Survival analysis was used for conversion to MS and time to relapse, and linear regression for annualised change in disability (Expanded Disability Status Scale). Higher body mass index (BMI adjusted HR (aHR): 1.22 (1.04 to 1.44) per 5 kg/m Higher levels of adiposity, non-HDL and TC/HDL ratio were prospectively associated with a higher rate of disability progression, and higher adiposity and triglycerides were associated with relapse but not with conversion to MS. Improving the lipid profile and losing weight into the healthy range could reduce the accumulation of disability.
Publisher: SAGE Publications
Date: 21-07-2016
Abstract: We examined the combined effect of having multiple key risk factors and the interactions between the key risk factors of multiple sclerosis (MS). We performed an incident case-control study including cases with a first clinical diagnosis of central nervous system demyelination (FCD) and population-based controls. Compared to those without any risk factors, those with one, two, three, and four or five risk factors had increased odds of being an FCD case of 2.12 (95% confidence interval (CI), 1.11–4.03), 4.31 (95% CI, 2.24–8.31), 7.96 (95% CI, 3.84–16.49), and 21.24 (95% CI, 5.48–82.40), respectively. Only HLA-DR15 and history of infectious mononucleosis interacted significantly on the additive scale (Synergy index, 3.78 p = 0.03). The five key risk factors jointly accounted for 63.8% (95% CI, 43.9–91.4) of FCD onset. High anti-EBNA IgG was another important contributor. A high proportion of FCD onset can be explained by the currently known risk factors, with HLA-DR15, ever smoking and low cumulative sun exposure explaining most. We identified a significant interaction between HLA-DR15 and history of IM in predicting an FCD of CNS demyelination, which together with previous observations suggests that this is a true interaction.
Publisher: Informa UK Limited
Date: 2000
DOI: 10.3109/02770900009090816
Abstract: The aim of this cross-sectional study was to describe the role of asthma, asthma severity, and medication usage in bone mineralization of prepubertal children. Asthma severity, medication usage, and physical activity were assessed by questionnaire and objective measures in 330 children. Bone densitometry and body composition were measured by dual-energy x-ray absorptiometry. Asthma ever was reported by 110 subjects (33%). A diagnosis of asthma was not associated with any deficit in bone mass, whereas usage of inhaled corticosteroids (ICS) in the last year (but not past use) was associated with deficits in bone in the total body (only after adjustment for confounders), particularly for doses of > or =400 microg/day. These observations support current recommendations with regard to ICS usage in children, but require confirmation in longitudinal studies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-06-2012
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.JACI.2012.01.056
Abstract: Measurement of whole peanut-specific IgE (sIgE) is often used to confirm sensitization but does not reliably predict allergy. Ara h 2 is the dominant peanut allergen detected in 90% to 100% of patients with peanut allergy and could help improve diagnosis. We sought to determine whether Ara h 2 testing might improve the accuracy of diagnosing peanut allergy and therefore circumvent the need for an oral food challenge (OFC). Infants from the population-based HealthNuts study underwent skin prick tests to determine peanut sensitization and subsequently underwent a peanut OFC to confirm allergy status. In a stratified random s le of 200 infants (100 with peanut allergy and 100 with peanut tolerance), whole peanut sIgE and Ara h 2 sIgE levels were quantified by using fluorescence enzyme immunoassay. By using the previously published 95% positive predictive value of 15 kU(A)/L for whole peanut sIgE, a corresponding specificity of 98% (95% CI, 93% to 100%) was found in this study cohort. At the equivalent specificity of 98%, the sensitivity of Ara h 2 sIgE is 60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut allergy compared with only 26% correctly identified by using whole peanut sIgE. We report that when using a combined approach of plasma sIgE testing for whole peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of OFCs required is reduced by almost two thirds. Ara h 2 plasma sIgE test levels provide higher diagnostic accuracy than whole peanut plasma sIgE levels and could be considered a new diagnostic tool to distinguish peanut allergy from peanut tolerance, which might reduce the need for an OFC.
Publisher: Springer Science and Business Media LLC
Date: 04-2009
DOI: 10.1007/S00415-009-0120-2
Abstract: Multiple sclerosis has a variable disease course. The contribution of modifiable lifestyle factors to disease course has not been well studied, although one cohort has reported that smoking is associated with conversion to secondary progressive MS course and another that smoking is not. We conducted a prospective cohort study of people with MS in Southern Tasmania from 2002 to 2004 with 78% (203/259) of eligible participating and 198 with one or more reviews and confirmed MS. The cohort had a high retention rate (90% (183/203)). The median follow-up time was 909 days. Smoking data were collected at baseline and six-monthly reviews. Clinical disability assessments were conducted annually in conjunction with a real time clinical notification system for relapses. A repeated measures analysis and other statistical methods were used. Cumulative pack-years (p-y) smoked after cohort entry was associated with an increase in longitudinal MSSS (p < 0.001). Relative to the 0 pack years (p-y) category (in the year prior to the MSSS measure) those in the 0 to 1 p-y category had an adjusted mean difference in MSSS of 0.34 (95% CI 0.28, 0.66) those in the 1 to 2 p-y category had a 0.41 (95% CI -0.03, 0.85) increase and those in the 2 or more p-y category had a 0.99 (95% CI 0.41, 1.58) increase in MSSS. Similar results were found using a variety of statistical approaches or EDSS as a clinical outcome. Smoking during the cohort period was not associated with relapse (cumulative pack years smoked after cohort entry, HR 0.94 (0.69, 1.26) per pack year). A better understanding of the mechanisms underlying smoking and multiple sclerosis, particularly progressive forms of the disease, may provide new insights for the eventual goal of better treatment and prevention of multiple sclerosis.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.JNS.2014.02.038
Abstract: There is increasing evidence that serum lipids and apolipoproteins may be associated with multiple sclerosis (MS) clinical course. To investigate the associations between serum lipids, apolipoproteins, body mass index and relapse in MS. A prospective cohort of 141 participants with relapsing-remitting MS was followed from 2002 to 2005. Serum lipid and apolipoprotein levels were measured biannually, and body mass index at baseline. The association with hazard of relapse was assessed using survival analysis. Neither body mass index nor any of the lipid-related measures were associated with the hazard of relapse. Serum lipid profile and body mass index are not associated with the hazard of relapse in MS.
Publisher: Public Library of Science (PLoS)
Date: 17-04-2018
Publisher: Wiley
Date: 23-02-2017
DOI: 10.1111/ALL.13122
Abstract: 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. To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D 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. 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.
Publisher: Wiley
Date: 26-03-2018
DOI: 10.1002/SIM.7650
Abstract: Paediatric respiratory researchers have widely adopted the multiple-breath washout (MBW) test because it allows assessment of lung function in unsedated infants and is well suited to longitudinal studies of lung development and disease. However, a substantial proportion of MBW tests in infants fail current acceptability criteria. We hypothesised that a model-based approach to analysing the data, in place of traditional simple empirical summaries, would enable more efficient use of these tests. We therefore developed a novel statistical model for infant MBW data and applied it to 1197 tests from 432 in iduals from a large birth cohort study. We focus on Bayesian estimation of the lung clearance index, the most commonly used summary of lung function from MBW tests. Our results show that the model provides an excellent fit to the data and shed further light on statistical properties of the standard empirical approach. Furthermore, the modelling approach enables the lung clearance index to be estimated by using tests with different degrees of completeness, something not possible with the standard approach. Our model therefore allows previously unused data to be used rather than discarded, as well as routine use of shorter tests without significant loss of precision. Beyond our specific application, our work illustrates a number of important aspects of Bayesian modelling in practice, such as the importance of hierarchical specifications to account for repeated measurements and the value of model checking via posterior predictive distributions.
Publisher: Wiley
Date: 07-01-2019
DOI: 10.1002/CCR3.1928
Publisher: Massachusetts Medical Society
Date: 06-01-1994
Publisher: SAGE Publications
Date: 25-07-2014
Abstract: The modulating effects of the multiple sclerosis (MS) risk-associated single-nucleotide polymorphisms (SNPs) on MS clinical course are not well established. The objective of this paper is to investigate whether known MS risk-associated SNPs were associated with clinical course, and whether these SNPs modified the 25(OH)D-relapse association. Using a prospective cohort of 141 participants with relapsing–remitting MS and genotype data followed between 2002 and 2005, genotype-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis, and genetic predictors of 25(OH)D and disability progression were evaluated by multilevel mixed-effects linear regression. While no SNP reached statistical significance after multiple testing, five SNPs were associated with relapse, with significant cumulative genotype risk effects and two demonstrated significant allele dose-response. Two SNPs altered the 25(OH)D-relapse association with significant allele dose-response. Five SNPs modified levels of 25(OH)D, with significant cumulative genotype ‘risk’ effect, and three demonstrated significant allele dose-response. We found no consistent evidence for an association between any SNPs and disability. Our study provides evidence for an association between known MS risk-associated SNPs and relapse. Our findings indicate gene-environment interactions may be an important mechanism on MS clinical course, and provide support for the role of vitamin D in MS relapse.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-10-2011
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.JAIP.2017.10.019
Abstract: The risk of developing asthma in those with early food allergy is unknown, particularly when early life food allergy has resolved. To understand whether challenge-proven food allergy in infancy increases the risk of asthma at age 4 years, using data from a population-based cohort. A total of 5,276 12-month-old infants were recruited using a population-based s ling frame. Infants underwent skin prick test to egg, peanut, and sesame and those with a detectable skin prick test result had oral food challenges. At age 4 years, food challenges were repeated to determine persistence or resolution of food allergy. The association between food allergy and doctor-diagnosed asthma was examined using binomial regression in 2,789 participants. Children with food allergy at age 1 year had an increased risk of asthma (1 food allergy: relative risk [RR], 1.69 95% CI, 1.29-2.21 2 or more food allergies: RR, 2.76 95% CI, 1.94-3.92). The risk of asthma was highest in children with food allergy and coexistent eczema in infancy (RR, 2.87 95% CI, 2.22-3.70). Transient food allergy and persistent food allergy were both associated with an increased risk of asthma (transient egg allergy: RR, 1.92 95% CI, 1.46-2.51 persistent egg allergy: RR, 2.60 95% CI, 1.76-3.85). Asthma at age 4 years is twice as common in those with challenge-proven food allergy at age 1 year, irrespective of whether the food allergy subsequently resolves. Children with 2 or more food allergies and those with coexistent eczema were almost 3 times as likely to develop asthma compared with those with no food allergies.
Publisher: Wiley
Date: 03-2009
DOI: 10.1111/J.1440-1754.2008.01436.X
Abstract: To describe parent-reported prevalence and management of peanut and nut allergy in school entrant children. A population-based, cross-sectional study in the Australian National Capital. Out of 3851 children, parents reported 127 had a strong allergic reaction to peanuts and 19 to other nuts ever. Nut allergy ever prevalence was 3.8% (95% confidence interval 3.2-4.4%), and of peanut allergy ever 3.3% (2.8-3.9%). Children with nut allergy were more likely to have a general practitioner (odds ratio 2.64, 1.16-6.03), hay fever (3.78, 2.67-5.36), eczema (4.54, 3.15-6.56) and wheeze in the last 12 months (3.19, 2.22-4.59) and have been breastfed (2.68, 1.26-5.77) than those who did not. At follow up of 109 children with parent-reported allergy (75% response), 70% had diagnostic test-confirmed sensitisation, 32% had been prescribed an adrenalin autoinjector (6% had used one) and 46% were not eating peanut. Increasing severity of reported symptoms following consumption of peanut was associated with an increasing likelihood of recommended management. Based on parent report, the projected estimated diagnostic test-confirmed prevalence of peanut sensitisation was 2.4% (1.9%, 3.0%) for the entire s le. Among a highly representative s le of children at school entry, 1 in 30 parents reported their child to have a strong allergic reaction to nuts and over 1 in 50 are estimated to have diagnostic test-confirmed peanut sensitisation, based on parent report.
Publisher: European Respiratory Society (ERS)
Date: 06-1996
DOI: 10.1183/09031936.96.09071335
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) profoundly impacts hemostasis and microvasculature. In the light of the dilemma between thromboembolic and hemorrhagic complications, in the present paper, we systematically investigate the prevalence, mortality, radiological subtypes, and clinical characteristics of intracranial hemorrhage (ICH) in coronavirus disease (COVID-19) patients. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the literature by screening the PubMed database and included patients diagnosed with COVID-19 and concomitant ICH. We performed a pooled analysis, including a prospectively collected cohort of critically ill COVID-19 patients with ICH, as part of the PANDEMIC registry (Pooled Analysis of Neurologic Disorders Manifesting in Intensive Care of COVID-19). Our literature review revealed a total of 217 citations. After the selection process, 79 studies and a total of 477 patients were included. The median age was 58.8 years. A total of 23.3% of patients experienced the critical stage of COVID-19, 62.7% of patients were on anticoagulation and 27.5% of the patients received ECMO. The prevalence of ICH was at 0.85% and the mortality at 52.18%, respectively. ICH in COVID-19 patients is rare, but it has a very poor prognosis. Different subtypes of ICH seen in COVID-19, support the assumption of heterogeneous and multifaceted pathomechanisms contributing to ICH in COVID-19. Further clinical and pathophysiological investigations are warranted to resolve the conflict between thromboembolic and hemorrhagic complications in the future.
Publisher: Elsevier BV
Date: 08-2002
DOI: 10.1016/S1011-1344(02)00331-7
Abstract: Recent advances have enabled quite accurate estimations of cutaneous melanin density by spectrophotometry using reflectance of light at wavelengths 400 and 420 nm. Our purpose was to assess the effect of body hair and seasonal variation at the upper inner arm and buttock on measurements of melanin density. We estimated melanin density of 104 volunteers at 3-monthly intervals over 12 months both before and after shaving. Removing body hair at the upper inner arm had no effect, but substantially reduced melanin estimates at the buttock in men. Significant seasonal variation was only observed at the upper inner arm, with highest readings in summer-autumn. In case-control studies, misclassification due to body hair at the buttock and seasonal variation at the upper inner arm could affect the observed odds ratio substantially. However, both sources of error can be reduced by careful attention to key aspects of study design.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-02-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2018
Publisher: SAGE Publications
Date: 11-09-2016
Abstract: There is contradictory evidence for a role of dietary fat in risk of multiple sclerosis (MS). To examine the association between usual fat intake (total, saturated, monounsaturated (MUFA), polyunsaturated (PUFA), omega-3 and omega-6) and risk of a first clinical diagnosis of CNS demyelination (FCD). Multi-centre incident case-control study in four regions of Australia during 2003–2006. Cases were aged 18–59 years and had a FCD controls were matched to a case on age, sex and location. Dietary data were collected using a validated food frequency questionnaire. In 267 cases and 517 controls with dietary data, higher intake (per g/day) of omega-3 PUFA (adjusted odds ratio, AOR=0.61 (95% CI 0.40–0.93)), and particularly that derived from fish (AOR=0.54 (95% CI 0.31–0.93)) rather than from plants (AOR=0.75 (95% CI 0.39–1.43)) was associated with a decreased risk of FCD. Total fat intake and intake of other types of fat were not associated with FCD risk. There was a significant decrease in FCD risk with higher intake of omega-3 PUFA, particularly that originating from fish. There was no evidence to indicate that the intake of other types of dietary fat or fat quantity in the previous 12 months was associated with an altered risk of FCD.
Publisher: Wiley
Date: 29-03-2016
DOI: 10.1111/CEA.12699
Abstract: Asian infants born in Australia are three times more likely to develop nut allergy than non-Asian infants, and rates of challenge-proven food allergy in infants have been found to be unexpectedly high in metropolitan Melbourne. To further investigate the risk factors for nut allergy, we assessed the whole-of-state prevalence distribution of parent-reported nut allergy in 5-year-old children entering school. Using the 2010 School Entrant Health Questionnaire administered to all 5-year-old children in Victoria, Australia, we assessed the prevalence of parent-reported nut allergy (tree nut and peanut) and whether this was altered by region of residence, socio-economic status, country of birth or history of migration. Prevalence was calculated as observed proportion with 95% confidence intervals (CI). Risk factors were evaluated using multivariable logistic regression and adjusted for appropriate confounders. Parent-reported nut allergy prevalence was 3.1% (95% CI 2.9-3.2) amongst a cohort of nearly 60 000 children. It was more common amongst children of mothers with higher education and socio-economic index and less prevalent amongst children in regional Victoria than in Melbourne. While children born in Australia to Asian-born mothers (aOR 2.67, 95% CI 2.28-3.27) were more likely to have nut allergy than non-Asian children, children born in Asia who subsequently migrated to Australia were at decreased risk of nut allergy (aOR 0.1, 95% CI 0.03-0.31). Migration from Asia after the early infant period appears protective for the development of nut allergy. Additionally, rural regions have lower rates of nut allergy than urban areas.
Publisher: American Diabetes Association
Date: 17-06-2011
DOI: 10.2337/DC10-2386
Abstract: To investigate pedometer-measured physical activity (PA) in 2000 and change in PA over 5 years with subsequent risk of dysglycemia by 2005. This prospective cohort study in Tasmania, Australia, analyzed 458 adults with normal glucose tolerance and a mean (SD) age of 49.7 (12.1) years in 2000. Variables assessed in 2000 and 2005 included PA, by pedometer and questionnaire, nutrient intake, and other lifestyle factors. Incident dysglycemia was defined as the development of impaired fasting glucose or impaired glucose tolerance revealed by oral glucose tolerance testing in 2005, without type 2 diabetes. Incident dysglycemia developed in 26 participants during the 5-year period. Higher daily steps in 2000 were independently associated with a lower 5-year risk of incident dysglycemia (adjusted odds ratio [AOR] 0.87 [95% CI 0.77–0.97] per 1,000-step increment). Higher daily steps in 2005, after controlling for baseline steps in 2000 (thus reflecting change in steps over 5 years), were not associated with incident dysglycemia (AOR 1.02 [0.92–1.14]). Higher daily steps in 2000 were also associated with lower fasting blood glucose, but not 2-h plasma glucose by 2005. Further adjustment for BMI or waist circumference did not remove these associations. Among community-dwelling adults, a higher rate of daily steps is associated with a reduced risk of incident dysglycemia. This effect appears to be not fully mediated through reduced adiposity.
Publisher: SAGE Publications
Date: 21-04-2009
Abstract: Multiple studies have provided evidence for an association between reduced sun exposure and increased risk of multiple sclerosis (MS), an association likely to be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we examine whether the vitamin D receptor ( VDR), an integral component of this pathway, influences MS risk in a population-based s le where winter sun exposure in early childhood has been found to be an important determinant of MS risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and 235 controls, and associations with MS and past sun exposure were examined by logistic regression. No significant univariate associations between the polymorphisms, rs11574010 ( Cdx-2A G), rs10735810 ( Fok1T C), or rs731236 ( Taq1C T) and MS risk were observed. However, a significant interaction was observed between winter sun exposure during childhood, genotype at rs11574010, and MS risk ( P = 0.012), with the ‘G’ allele conferring an increased risk of MS in the low sun exposure group (≤2 h/day). No significant interactions were observed for either rs10735810 or rs731236, after stratification by sun exposure. These data provide support for the involvement of the VDR gene in determining MS risk, an interaction likely to be dependent on past sun exposure.
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 2002
Abstract: The contribution of atopy to childhood asthma has been debated. We aimed to examine the relationship between atopy and asthma, taking into account differences in respiratory symptoms and disease severity. A cross-sectional asthma survey involving the following: (1) a population s le of 758 (81% of eligible) school children aged 8 to 10 years from randomly selected schools in the Australian Capital Territory in 1999, and (2) a hospital-based s le of 78 (70% of eligible) children attending the hospital for asthma. Skin-prick test results to 10 common aeroallergens were available on 722 children and 77 children, respectively. Baseline spirometry was obtained on a subset of school children (n = 515, 78% of eligible). The association between atopy and wheeze by wheeze frequency over the past year was as follows: no episodes (odds ratio [OR], 1.00 [reference]), 1 to 3 episodes (OR, 3.27 95% confidence interval [CI], 2.15 to 4.97), 4 to 12 episodes (OR, 3.44 95% CI, 1.75 to 6.75), and > 12 episodes (OR, 8.70 95% CI, 3.07 to 24.55), with a higher population attributable fraction (PAF) for > 12 episodes (75%) than 1 to 3 episodes (49%). Atopy was moderately related to asthma ever (OR, 2.09 95% CI, 1.52 to 2.85 PAF, 33%) but strongly related to 1999 hospital attendance for asthma (OR, 16.95 95% CI, 6.76 to 42.48 PAF, 89%). Adjustment for child age, gas heater use, and maternal smoking near the child did not materially alter these findings. The clinical features of frequent wheeze or hospital asthma attendance are largely attributable to atopy, but infrequent wheeze or a history of asthma ever are not. Atopic children are overrepresented in the severe range of the asthma spectrum.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2003
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JAIP.2017.03.013
Abstract: Infant feeding in the first postnatal year of life has an important role in an infant's risk of developing food allergy. Consumer infant feeding advice is erse and lacks consistency. The Australian Infant Feeding Summit was held with the aim of achieving national consensus on the wording of guidelines for infant feeding and allergy prevention. Two meetings were hosted by the Centre for Food and Allergy Research, the Australasian Society of Clinical Immunology and Allergy, and the Australian National Allergy Strategy. The first meeting of 30 allergy researchers, clinicians, and consumers assessed the evidence. The second consensus meeting involved 46 expert stakeholders including state and federal health care agencies, consumers, and experts in allergy, infant feeding, and population health. Partner stakeholders agreed on consensus wording for infant feeding advice: CONCLUSIONS: Consensus was achieved in a context in which there is a high prevalence of food allergy. Guidelines for other countries are being updated. Provision of consistent wording related to infant feeding to reduce food allergy risk will ensure clear consumer advice.
Publisher: eLife Sciences Publications, Ltd
Date: 04-02-2022
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JAIP.2018.08.038
Abstract: Overall early exposure to allergenic foods in the infant's diet is a new strategy for preventing food allergy to that allergen, but the optimal timing of exposure for different allergens is not known. We aimed to examine the relationship between exposure to cow's milk protein in the first 3 months of life and risk of cow's milk allergy at age 12 months. HealthNuts is a longitudinal population-based food allergy study that recruited 5,276 twelve-month-old infants. Skin prick testing to cow's milk was conducted on the second half of the cohort (n = 2,715) and sensitization defined as a wheal ≥2 mm. Cow's milk allergy was defined as a parent-reported reaction to cow's milk consistent with IgE-mediated allergy together with evidence of sensitization. Early exposure to cow's milk protein was captured through parental questionnaire administered at 1 year of age and defined as consumption of cow's milk-based infant formula during the first 3 months of life. Forty-two percent of infants were exposed to cow's milk in the first 3 months of life (n= 1,977/4,712) and 87% of these infants were also breastfed. Early exposure to cow's milk protein was associated with a reduced risk of cow's milk sensitization (adjusted odds ratio [aOR] 0.44, 95% confidence interval [CI] 0.23-0.83), parent-reported reactions to cow's milk (aOR 0.44, 95% CI 0.29-0.67), and cow's milk allergy (aOR 0.31, 95% CI 0.10-0.91) at age 12 months. Age at exposure to cow's milk protein was not associated with the risk of other food allergies. Exposure to cow's milk protein in the first 3 months of life was associated with a reduced risk of cow's milk allergy. These findings are from an observational study and clinical trials are warranted to further assess this association before any recommendations to infant feeding guidelines can be made.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.JACI.2016.04.011
Abstract: A recent randomized trial (the Learning Early About Peanut Allergy [LEAP] study) provided evidence that earlier dietary peanut introduction reduces peanut allergy prevalence in high-risk infants. However, questions remain as to how to identify and target the "at-risk" population to facilitate timely introduction of peanut. We sought to use population-based infant peanut allergy data to understand feasibility and implications of implementing the LEAP trial intervention. Using the HealthNuts study cohort (n = 5276) of 1-year-old infants, we explored the impact of using various criteria to identify infants at high risk of developing peanut allergy, and the implications of skin prick test (SPT) screening before peanut introduction. Screening all infants with early onset eczema and/or egg allergy could require testing 16% of the population and would still miss 23% of peanut allergy cases 29% of screened infants would require clinical follow-up because of being SPT-positive. Around 11% of high-risk infants were excluded from the LEAP study because of an SPT wheal size of more than 4 mm to peanut at baseline data from the HealthNuts study suggest that 80% of these would be peanut allergic on food challenge. There were no life-threatening events among either low- or high-risk infants whose parents chose to introduce peanut at home in the first year of life, or in 150 peanut-allergic infants during hospital-based challenges. Based on this large epidemiological study, a population program aiming to identify and screen all infants at risk of peanut allergy would pose major cost and logistic challenges that need to be carefully considered. Further research might be required to provide data for low-risk infants.
Publisher: American Public Health Association
Date: 03-2003
Abstract: Objectives. We sought to quantify the effect of good smoking hygiene on infant risk of respiratory tract infection in the first 12 months of life. Methods. A cohort of 4486 infants in Tasmania, Australia, was followed from birth to 12 months of age for hospitalization with respiratory infection. Case ascertainment was 98.2%. Results. Relative to the infants of mothers who smoked postpartum but never in the same room with their infants, risk of hospitalization was 56% (95% confidence interval [CI] = 13%, 119%) higher if the mother smoked in the same room with the infant, 73% (95% CI = 18%, 157%) higher if the mother smoked when holding the infant, and 95% (95% CI = 28%, 298%) higher if the mother smoked while feeding the infant. Conclusions. Parents who smoke should not smoke with their infants present in the same room.
Publisher: Oxford University Press (OUP)
Date: 07-04-2017
DOI: 10.1093/IJE/DYW042
Abstract: The maternal and infant microbiome may influence infant cardiovascular risk through immune programming. The maternal vagino-enteric microbiome is often s led for group B streptococcus (GBS) colonization during pregnancy. Our aim was to investigate the association between maternal GBS colonization, intrapartum antibiotics, antenatal pet exposure and infant aortic intima-media thickness (aIMT), an intermediate vascular phenotype, and whether this association varied by mode of delivery. The Barwon Infant Study is a population-derived pre-birth cohort. Perinatal data were collected on participants. Women were tested for vagino-enteric group B streptococcus (GBS) colonization during third trimester. Six-week infant aIMT was measured by trans-abdominal ultrasound. Adjustment for confounders included maternal age, pre-pregnancy body mass index (BMI), smoking, socioeconomic status, gestational diabetes, length of gestation, infant sex, birthweight and aortic internal diameter. Data were available on 835 mother-infant pairs. Of these, 574 (69%) women delivered vaginally of those, 129 (22%) were GBS-colonized and of these women, 111 (86%) received prophylactic intrapartum antibiotics. An association between maternal GBS colonization and infant aIMT was observed among those delivered vaginally (β = 19.5 µm, 95% CI 9.5, 29.4 P < 0.0001) but not by Caesarean section ( P for interaction = 0.02). A similar pattern was seen for intrapartum antibiotics. There was a negative association between antenatal pet exposure and aIMT observed in those delivered vaginally. Maternal GBS colonization and intrapartum antibiotics were associated with increased infant aIMT in those delivered vaginally, whereas antenatal pet exposure was associated with decreased aIMT. These data suggest that differences in early life microbial experience may contribute to an increased cardiovascular risk.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JPEDS.2016.08.064
Abstract: To evaluate the associations between breastfeeding duration, age at solids introduction, and their interaction in relation to infant (age 9-15 months) above normal body mass index (BMI). Cross-sectional, population-based study with 3153 infants from Melbourne (2007-2011). Above normal BMI (z score > 2, equivalent to >97.7th percentile) defined using the World Health Organization standard. Both longer duration of full and any (full or partial) breastfeeding were associated with lower odds of above normal BMI (eg, aOR, 0.37 [95% CI, 0.22-0.60] for full breastfeeding 4-5 months versus 0-1 months). Compared with introduction of solids at 5-6 months, both early and delayed introduction were associated with increased odds of above normal BMI (aOR for 4 months, 1.75 [95% CI, 1.10-2.80] and for ≥7 months, 2.64 [95% CI, 1.26-5.54] versus 6 months). Such associations differ by breastfeeding status at 4 months (interaction P = .08). Early introduction of solids was associated with increased odds of above normal BMI in both infants fully or partially breastfed for ≥4 months (aOR, 3.66 95% CI, 1.41-9.51) and those breastfed for <4 months (aOR, 3.11 95% CI, 1.39-6.97). Introduction of solids at ≥7 months was associated with increased odds of above normal BMI (aOR, 5.79 95% CI, 1.91-17.49) among infants breastfed for <4 months only. Introduction of solids at 5-6 months, compared with either early or delayed introduction, is associated with decreased odds of above normal BMI at 1 year of age, regardless of infants' breastfeeding status at 4 months. These results may have implications for public health guidelines with regard to recommendations about the optimal timing of the introduction of solid foods in infancy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1994
DOI: 10.1097/00001648-199405000-00012
Abstract: We examined the negative relation between temperature and the sudden infant death syndrome (SIDS) in 22 communities in seven countries. We estimated the percentage increase in SIDS rate for a 1 degree C drop in climatic temperature. The relation differed substantially among communities. In New Zealand and Australia (10 communities), the association was consistently strong in Europe (seven communities), it varied from strong to weak and in the USA (five communities), it was moderate or weak. We postulate that low climatic temperature indirectly increases the incidence of SIDS, particularly in countries where outdoor climatic temperature modifies the indoor temperature and clothing habits.
Publisher: BMJ
Date: 20-11-2010
Abstract: Hobart, Tasmania, has been the site of two major studies of multiple sclerosis (MS) frequency, in 1951-1961 and 1971-1981. Since then, there have been no studies of MS frequency in Hobart. Using a prevalent cohort of 226 cases in 2001 and 265 in 2009, the authors undertook a two-stage survey of MS frequency in Hobart. Combined with the published data from the two preceding studies, the authors conducted a time-trend analysis of MS epidemiology over 1951-2009. The age-standardised prevalence in 2001 was 96.6/100 000, and 99.6/100 000 in 2009, a significant increase from the 1961 prevalence of 32.5/100 000 (p<0.001). Female prevalence increased over each time point male prevalence increased between 1961 and 2001 but was unchanged thereafter. Incidence over 2001-2009 was 3.7/100 000, significantly increased from the 1951-1961 incidence of 2.2/100 000 (p=0.004), though the majority of this was between 1951-1961 and 1971-1981. Mortality fell by half from 2.4/100 000 in 1951-1959 to 1.0/100 000 in 2001-2009-this decreased mortality and an older cohort contribute to the increase in prevalence. Neither prevalence (p=0.48) nor incidence (p=0.18) sex ratios changed significantly between 1951 and 2009. Between 1951 and 2009, the age-standardised prevalence of MS in Hobart increased threefold, and the incidence nearly doubled. Part of the increase in prevalence was due to an increased longevity, decreased mortality and increased incidence. Differences in patterns by birthplace may be explained by the Australian assisted-migration programme of 1945-1981. These data do not demonstrate the strong and significant changes in sex ratio observed elsewhere.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2014
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.PBIOMOLBIO.2006.02.019
Abstract: Exposure to ultraviolet radiation (UVR) is associated with both adverse and beneficial health effects. While many of the adverse effects of excessive exposure are well known, the adverse effects of insufficient UVR exposure are less clear-cut, but may include a heightened risk of several cancers and autoimmune disorders as well as of bone diseases such as rickets, osteomalacia and osteoporosis. Although some of the postulated beneficial effects of UVR exposure may occur through the maintenance of adequate levels of vitamin D, it is not clear that this can account for all of these effects. We briefly review the epidemiological literature with respect to vitamin D, UVR exposure and autoimmune diseases. We further outline alternative pathways, whereby UVR could alter the risk of development of some cancers and autoimmune disorders, independent of effects on vitamin D synthesis. Recognition of the beneficial effects of UVR exposure has led to a reconsideration of sun avoidance policies. It is important to recognize that all of the beneficial effects of UVR exposure may not occur only through UVR-induced vitamin D synthesis. Thus maintaining current sun avoidance policies while supplementing food with vitamin D may not be sufficient to avoid the risks of insufficient exposure to UVR.
Publisher: American Academy of Pediatrics (AAP)
Date: 05-2004
Abstract: Objective. Synthetic quilt use has been associated with increased childhood wheeze in previous studies. Our aim was to examine whether the adverse effect of synthetic quilt use on frequent wheeze differed by usual sleep position. Design, Setting, and Participants. A population-based cross-sectional study of 6378 (92% of those eligible) 7-year-olds in Tasmania, Australia, was conducted in 1995. Exercise-challenge lung function was obtained on a subset of 414 children from randomly selected schools. Exposure Measures. Child bedding including pillow and overbedding composition and usual sleep position by parental questionnaire. Outcome Measures. Frequent wheeze (& wheeze episodes over the past year), using the International Study of Asthma and Allergies in Childhood parental questionnaire, and baseline and postexercise forced expiratory volume in 1 second lung-function measures. Results. Frequent wheeze (n = 117) was positively associated with synthetic quilts, synthetic pillows, electric blankets, and sleeping in a bottom bunk bed but did not vary by sleep position. In a nested case-control analysis, the association between synthetic quilt use and frequent wheeze differed by sleep position. Among children who slept supine, synthetic (versus feather) quilt use was associated with frequent wheeze (adjusted odds ratio: 2.37 [1.08, 5.23]). However, among nonsupine sleepers, overlying synthetic quilt use was not associated with frequent wheeze (adjusted odds ratio: 1.06 [0.60, 1.88]). This difference in quilt effect by sleep position was highly significant. Similarly, synthetic quilt use was associated with lower postexercise forced expiratory volume in 1 second measures among supine but not nonsupine sleeping children. Conclusion. An increasing focus on the bedding environment immediately adjacent to the nose and mouth is required for respiratory disorders provoked by bedding, such as child asthma characterized by frequent wheeze.
Publisher: Wiley
Date: 10-10-2019
DOI: 10.1111/APA.14932
Abstract: We investigated the effect of early-life factors, namely sex, delivery mode, feeding method and antibiotic exposure, on antibody responses to routine vaccinations administered during the first year of life. One and seven months after the primary course of routine vaccines and 1 month after routine vaccines at 12 months of age, antibodies against 26 vaccine antigens were measured in 398 healthy infants. The geometric mean concentration (GMC) of antibodies (adjusted for effect modifiers with multiple linear regression) and the seroprotection rate for each vaccine were compared for each early-life factor. Sex had an influence on GMCs. Antibody concentrations were significantly lower at 7 months of age in females for tetanus and filamentous haemagglutinin and at 13 months of age for pertactin. In contrast, at 13 months of age, antibody concentrations were significantly higher in females for polio type 3, pneumococcal serotype 6A and measles. Sex did not have an influence on seroprotection rates. Delivery mode, feeding method and antibiotic exposure did not exert a substantial influence on vaccine antibody concentrations. There is a difference between males and females in the humoral response to routine vaccinations in the first year of life.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.NEURO.2016.05.011
Abstract: Accumulating evidence, from animal models and human observational studies, implicates the in utero (and early postnatal) environment in the 'programming' of risk for a variety of adverse outcomes and health trajectories. The modern environment is replete with man-made compounds such as plastic product chemicals (PPC), including phenols and phthalates. Evidence from several human cohorts implicates exposure to these chemicals in adverse offspring neurodevelopment, though a direct causal relationship has not been firmly established. In this review we consider a potential causal pathway that encompasses epigenetic human variation, and how we might test this mechanistic hypothesis in human studies. In the first part of this report we outline how PPCs induce epigenetic change, focusing on the brain derived neurotrophic factor (BDNF) gene, a key regulator of neurodevelopment. Further, we discuss the role of the epigenetics of BDNF and other genes in neurodevelopment and the emerging human evidence of an association between phthalate exposure and adverse offspring neurodevelopment. We discuss aspects of epidemiological and molecular study design and analysis that could be employed to strengthen the level of human evidence to infer causality. We undertake this using an exemplar recent research ex le: maternal prenatal smoking, linked to methylation change at the aryl hydrocarbon receptor repressor (AHRR) gene at birth, now shown to mediate some of the effects of maternal smoking on birth weight. Characterizing the relationship between the modern environment and the human molecular pathways underpinning its impact on early development is paramount to understanding the public health significance of modern day chemical exposures.
Publisher: Elsevier BV
Date: 30-05-2008
Publisher: BMJ
Date: 03-1995
DOI: 10.1136/ADC.72.3.204
Abstract: Intervention to avoid the prone sleeping position during infancy has occurred in various countries after evidence that it increases the risk of sudden infant death syndrome (SIDS). This study examined cohort data to determine if correlates of the prone position differed by period of birth, before intervention (1 May 1988 to 30 April 1991) compared with after intervention (1 May 1991 to 30 April 1992). The usual prone sleeping position was more closely associated with the following factors after intervention: teenage motherhood, low maternal education, paternal unemployment, unmarried motherhood, non-specialist antenatal care, not reading books to prepare for a baby, poor smoking hygiene, and bottle feeding. For ex le, the association of usual prone position with being unmarried shown by the odds ratio (95% confidence interval) was 0.54 (0.47 to 0.63) in the period before intervention and 1.92 (1.18 to 3.15) in the period after intervention. The alteration in correlates of the prone position reported here provide an ex le to support the theoretical concept that well known 'modifiable' risk factors for disease tend to be associated with each other in both populations and in iduals. This phenomenon was not evident in the population before intervention, that is, before the prone sleeping position became a well known SIDS risk factor.
Publisher: American Medical Association (AMA)
Date: 08-03-1995
Publisher: Wiley
Date: 27-07-2017
DOI: 10.1111/JPC.13616
Abstract: The aim of this study was to describe antibiotic exposure in Australian infants during the first year of life, focusing on antibiotic class, indication, risk factors associated with exposure and comparison with international counterparts. The Barwon Infant Study is a birth cohort study (n = 1074) with an unselected antenatal s ling frame from a large regional centre in Victoria, Australia. Longitudinal data on infection and medication were collected at 1, 3, 6, 9 and 12 months by parental questionnaire and from general practitioner and hospital records. Predictors of questionnaire non-completion were identified. A total of 660 infants with complete serial data were comprehensively examined. Antibiotic exposure was calculated as (i) antibiotic prescriptions and (ii) antibiotic days-exposed per person-year. Mean antibiotic prescription rate was 0.92 prescriptions (95% confidence interval (CI), 0.83-1.02) per person-year, with the highest rates in those aged <1 month (1.50 (95% CI, 1.09-1.91) per person-year). A total of 50.0% of infants were exposed to at least one antibiotic in their first year of life. Increasing number of siblings was associated with increased antibiotic exposure. Penicillin with extended spectrum (365 of 661 antibiotic prescriptions, 52.6%) and cephalosporins (12.0%) were the most frequently prescribed antibiotics. One fifth of antibiotics were prescribed for respiratory tract infections and bronchiolitis. Australian infants in this large population-based study are exposed to considerably more antibiotics than the majority of their international counterparts. Interventions aimed at addressing avoidable prescribing by medical practitioners and modifiable risk factors associated with antibiotic exposure may reduce antibiotic use.
Publisher: Portland Press Ltd.
Date: 04-02-2016
DOI: 10.1042/CS20150685
Abstract: Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth and early cardiovascular parameters. Increased aortic intima-media thickness (aortic IMT) is an intermediate phenotype of early atherosclerosis. The aim of the present study was to investigate the relationship between weight and adiposity at birth, postnatal growth and aortic IMT. The Barwon Infant Study (n=1074 mother–infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic IMT was measured by trans-abdominal ultrasound at 6 weeks of age (n=835). After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (β=19.9 μm/kg, 95%CI 11.1, 28.6 P& .001) and birth skinfold thickness (β=6.9 μm/mm, 95%CI 3.3, 10.5 P& .001) were associated with aortic IMT at 6 weeks. The association between birth skinfold thickness and aortic IMT was independent of birth weight. In addition, greater postnatal weight gain was associated with increased aortic IMT, independent of birth weight and age at time of scan (β=11.3 μm/kg increase, 95%CI 2.2, 20.3 P=0.01). Increased infant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic IMT. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2007
DOI: 10.1007/S00415-006-0315-8
Abstract: Adequate 25(OH)D levels are required to prevent adverse effects on bone health. Population-based data on factors associated with 25(OH)D levels of people with MS have been lacking. To examine the prevalence and determinants of vitamin D insufficiency in a population-based s le of MS cases and controls, and to compare 25(OH)D status between MS cases and controls, taking into account case disability. We conducted a population based case-control study in Tasmania, Australia (latitude 41-43 degrees S) on 136 prevalent cases with MS confirmed by magnetic resonance imaging and 272 community controls, matched on sex and year of birth. Measurements included serum 25(OH)D, sun exposure, skin type, dietary vitamin D intake and disability including EDSS. A high prevalence of vitamin D insufficiency was found in MS cases and controls. Among MS cases, increasing disability was strongly associated with lower levels of 25(OH)D and with reduced sun exposure. Cases with higher disability (EDSS > 3) were more likely to have vitamin D insufficiency than controls (OR = 3.07 (1.37, 6.90) for 25(OH)D </= 40 nmol/l), but cases with low disability were not (OR = 0.87 (0.41, 1.86)). The strong associations between disability, sun exposure and vitamin D status indicate that reduced exposure to the sun, related to higher disability, may contribute to the high prevalence of vitamin D insufficiency found in this population-based MS case s le. Active detection of vitamin D insufficiency among people with MS and intervention to restore vitamin D status to adequate levels should be considered as part of the clinical management of MS.
Publisher: Wiley
Date: 07-09-2012
DOI: 10.1111/ALL.12015
Abstract: Although egg allergy is the most common food allergy in infants and young children, risk factors for egg allergy remain largely unknown. This study examined the relationship between environmental and demographic factors and egg allergy in a population-based infant cohort. In a study of 5276 infants (HealthNuts), infants underwent skin prick testing (SPT) to egg white at 12 months of age. Questionnaire data on relevant exposures were obtained. 699/873 (80%) infants eligible for oral food challenge (detectable wheal on SPT) attended for formal assessment of egg allergy status 453 had confirmed egg allergy (positive challenge and SPT ≥ 2 mm). Associations between environmental and demographic factors and egg allergy were investigated using multivariable logistic regression. Children with older siblings and those with a pet dog at home were less likely to develop egg allergy by 1 year of age (adjusted OR [aOR], 0.72 95% CI, 0.62, 0.83 per sibling and aOR, 0.72 95% CI, 0.52, 0.99, respectively). Caesarean section delivery, antibiotic use in infancy, childcare attendance and maternal age were not associated with egg allergy. History of allergic disease in an immediate family member and having parents born in East Asia were strong risk factors for infantile egg allergy (aOR, 1.82 95% CI, 1.40, 2.36 and aOR, 3.30 95% CI, 2.45, 4.45, respectively). Exposure in the first year of life to siblings and dogs may decrease the risk of subsequent egg allergy. Infants with a family history of allergy and those with parents born in East Asia are at increased risk of egg allergy.
Publisher: Oxford University Press (OUP)
Date: 15-03-1993
DOI: 10.1093/OXFORDJOURNALS.AJE.A116723
Abstract: Based on information from two studies of sudden infant death syndrome (SIDS) from 1988-1991 in Tasmania, Australia, prospective and retrospective maternal responses to an identical set of questions were compared for 27 cases and 25 controls. There was good agreement on demographic factors, maternal obstetric history, parental smoking, and infant feeding practices. Reported changes in sleep habits were slightly greater for cases, and further work is needed to determine if this reflects recall bias or real changes during early infant life. Case mother reports regarding family history of disease and infant bedding were more discrepant, suggesting recall bias and supporting prospective collection of this information.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2018
DOI: 10.1007/S10072-017-3177-1
Abstract: Despite extensive studies focusing on the changes in expression of microRNAs (miRNAs) in multiple sclerosis (MS) compared to healthy controls, few studies have evaluated the association of genetic variants of miRNAs with MS clinical course. We investigated whether a functional polymorphism in the MS associated miR-146a gene predicted clinical course (hazard of conversion to MS and of relapse, and annualized change in disability), using a longitudinal cohort study of persons with a first demyelinating event followed up to their 5-year review. We found the genotype (GC+CC) of rs2910164 predicted relapse compared with the GG genotype (HR=2.09 (95% CI 1.42, 3.06), p=0.0001), as well as a near-significant (p=0.07) association with MS conversion risk. Moreover, we found a significant additive interaction between rs2910164 and baseline anti-EBNA-1 IgG titers predicting risk of conversion to MS (relative excess risk due to interaction [RERI] 2.39, p=0.00002) and of relapse (RERI 1.20, p=0.006). Supporting these results, similar results were seen for the other EBV-correlated variables: anti-EBNA-2 IgG titers and past history of infectious mononucleosis. There was no association of rs2910164 genotype for disability progression. Our findings provide evidence for miR-146a and EBV infection in modulating MS clinical course.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2020
DOI: 10.1038/S41366-019-0472-3
Abstract: Leptin regulates satiety and energy homoeostasis, and plays a key role in placentation in pregnancy. Previous studies have demonstrated regulation of leptin gene (LEP) expression and/or methylation in placenta and cord blood in association with early life exposures, but most have been small and have not considered the influence of genetic variation. Here, we investigated the relationship between maternal factors in pregnancy, infant anthropometry and LEP genetic variation with LEP promoter methylation at birth and 12 months of age. LEP methylation was measured in cord (n = 877) and 12-month (n = 734) blood in the Barwon Infant Study, a population-based pre-birth cohort. Infant adiposity at birth and 12-months was measured as triceps and subscapular skinfold thickness. Cross-sectional regression tested associations of methylation with pregnancy and anthropometry measures, while longitudinal regression tested if birth anthropometry predicted 12-month LEP methylation levels. Male infants had lower LEP methylation in cord blood (-2.07% average methylation, 95% CI (-2.92, -1.22), p < 0.001). Genetic variation strongly influenced DNA methylation at a single CpG site, which was also negatively associated with birth weight (r = -0.10, p = 0.003). Pre-ecl sia was associated with lower cord blood methylation at another CpG site (-6.06%, 95% CI (-10.70, -1.42), p = 0.01). Gestational diabetes was more modestly associated with methylation at two other CpG units. Adiposity at birth was associated with 12-month LEP methylation, modified by rs41457646 genotype. There was no association of LEP methylation with 12-month anthropometric measures. Infant sex, weight, genetic variation, and exposure to pre-ecl sia and gestational diabetes, are associated with LEP methylation in cord blood. Infant adiposity at birth predicts 12-month blood LEP methylation in a genotype-dependent manner. These findings are consistent with genetics and anthropometry driving altered LEP epigenetic profile and expression in infancy. Further work is required to confirm this and to determine the long-term impact of altered LEP methylation on health.
Publisher: Elsevier BV
Date: 02-1996
DOI: 10.1111/J.1467-842X.1996.TB01336.X
Abstract: The decision about whether the findings from analytical epidemiological studies can be extrapolated to another setting is an important one. We discuss some of the issues involved in the process of generalisation. A critical systematic qualitative approach should be used. This involves an assessment of the internal validity of the study and of the nature of the study base. The study subject matter and choice of epidemiologic measure should be considered. A study base similar to the target population is essential if the study is descriptive or if there is concern about effect modifiers whose effects cannot be predicted. In addition, data from quantitative tests of study findings in different populations should be considered.
Publisher: Informa UK Limited
Date: 10-2009
Publisher: Springer Science and Business Media LLC
Date: 18-03-2013
Publisher: Cold Spring Harbor Laboratory
Date: 14-06-2022
DOI: 10.1101/2022.06.08.22275892
Abstract: Prenatal phthalate exposure has previously been linked to the development of autism spectrum disorder (ASD). However, the underlying biological mechanisms remain unclear. We investigated whether maternal and child central carbon metabolism is involved as part of the Barwon Infant Study, a population-based birth cohort of 1074 Australian children. We estimated phthalate daily intakes using third-trimester urinary phthalate metabolite concentrations and other relevant indices. The metabolome of maternal serum in the third trimester, cord blood at birth and child plasma at 1 year were measured by nuclear magnetic resonance. We used the Small Molecule Pathway Database and principal component analysis to construct composite metabolite scores reflecting metabolic pathways. ASD symptoms at 2 and 4 years were measured by subscales of the Child Behavior Checklist and the Strengths and Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) associations between higher prenatal di(2-ethylhexyl) phthalate (DEHP) levels and increased activity in maternal non-oxidative energy metabolism pathways, specifically non-oxidative pyruvate metabolism and the Warburg Effect, and (ii) associations between increased activity in these pathways and increased offspring ASD symptomology at 2 and 4 years of age. Mediation analyses suggested that part of the mechanism by which higher prenatal DEHP exposure influences the development of ASD symptoms in early childhood is through a maternal metabolic shift in pregnancy towards non-oxidative energy pathways, which are inefficient compared to oxidative metabolism. Interventions targeting maternal metabolic activity in pregnancy may be beneficial in reducing the potential risk to the developing fetus.
Publisher: Wiley
Date: 19-02-2013
DOI: 10.1111/PHP.12044
Abstract: Spatio-temporal patterns in sun exposure underlie variations in skin cancer incidence and vitamin D deficiency, indicate effectiveness of sun protection programs and provide insights into future health risks. From 558 adults across four regions of Australia (Brisbane (27°S), Newcastle (33°S), Geelong and the Western Districts of Victoria (37°S) and Tasmania (43°S)), we collected: self-report data on time-in-the-sun from age 6 years natural skin color and ethnicity silicone skin casts (for cumulative skin damage) and serum for vitamin D status. Ambient ultraviolet radiation (UVR) at the location of residence, with time-in-the-sun, was used to calculate a "UVR dose" for each year of life. In iduals maintained their ranking compared to their peers for time-in-the-sun in summer compared to winter and across ages (Spearman rho 0.24-0.84, all P < 0.001). Time-in-the-sun decreased with age in all birth cohorts, and over calendar time. Summer time-in-the-sun increased with increasing latitude (P < 0.001). Seasonal variation in vitamin D status had greater litude and vitamin D deficiency increased with increasing latitude. Temporal patterns are consistent with effectiveness of sun protection programs. Higher relative time-in-the-sun persists from childhood through adulthood. Lower summer time-in-the-sun in the warmest location may have implications for predictions of UVR-related health risks of climate change.
Publisher: SAGE Publications
Date: 22-06-2013
Abstract: Anxiety, depression and fatigue are commonly reported by persons with multiple sclerosis (PwMS). We estimated the prevalence of each factor in a representative s le of PwMS, and in subgroups defined by age, sex and disease duration, at cohort entry and over time. We further examined whether and how these factors clustered together. A population-based longitudinal cohort of 198 PwMS was followed 6-monthly for 2.5 years. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety (cut-point >7) and depression (>7) and the Fatigue Severity Scale (FSS) to measure fatigue (≥5). At cohort entry, prevalence of anxiety was 44.5% (95%CI 37-51%), depression 18.5% (95%CI 12.6-23.4%), and fatigue 53.7% (95%CI 47-61%). Fatigue was more common in males than females (RR 1.29, p=0.01), with attenuation of the effect after adjustment for Expanded Disability Status Scale (adjusted RR 1.18, p=0.13). Prevalence of anxiety (but not depression or fatigue) decreased by 8.1% per year of cohort observation (RR 0.92, 95%CI 0.86-0.98, p=0.009), with the effect more pronounced in women (14.6%, RR 0.85, 95%CI 0.79-0.93, - 0.05). All three factors occurred contemporaneously at cohort entry in a higher proportion of the cohort than expected by chance (p<0.001). Anxiety, depression and fatigue are common in PwMS and tend to cluster together. The findings are important for clinical management of PwMS and to the exploration of possible shared causal biological pathways.
Publisher: Wiley
Date: 08-2001
DOI: 10.1046/J.1365-2222.2001.01168.X
Abstract: Nitrogen dioxide (NO(2)) or home gas appliance use has been inconsistently associated with adverse respiratory outcomes in childhood. (i) To examine the contribution of home gas appliance type and personal NO(2) exposure. (ii) To examine the relationship between NO(2) exposure and child lung function and respiratory history. (iii) To assess whether these relationships vary by house dust mite sensitization status. A cross-sectional survey of 344 children (71% of the eligible group) with a mean age of 9.1 years from four randomly selected schools in the Australian Capital Territory from July to September 1999. Study measurements included a parental questionnaire, NO(2) exposure by passive gas s lers, skin prick testing for 10 aeroallergens and lung function at rest and after cold air challenge. Total NO(2) exposure was low with a mean concentration of 10.1 ppb. No associations were found between NO(2) exposure or gas appliance use and asthma, wheeze or baseline lung function. Personal NO(2) exposure was associated with a reduction in forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) after cold air challenge (adjusted difference - 0.12% (- 0.23% to - 0.01%) per 1 ppb increase). After exclusion of children who had home heating changed because of asthma, gas heater use was also significantly associated with a reduction in this measure (adjusted difference - 2.0% (- 3.7% to - 0.2%)). There was some evidence that these reductions were greater among the non-mite-sensitized children. The effect of low-level NO(2) exposure on these respiratory outcomes was not marked. The possible effect of low-level NO(2) exposure on non-specific bronchial reactivity requires confirmation. Future studies on NO(2) and respiratory health should include measures of house dust mite sensitization and bronchial hyper-responsiveness.
Publisher: Wiley
Date: 19-02-2013
DOI: 10.1111/PHP.12043
Abstract: Our aim was to examine the association between ethnicity, phenotype, sun behavior and other characteristics, and constitutive and relative facultative skin pigmentation. A total of 191 participants were recruited, with a mean age of 7.6 years (SD 3.4), during 2009-2011 from Maternal and Child Health Centres (MCHC) and schools in Melbourne, Australia. Parental questionnaire data were obtained on sun behavior and examination consisted of noting the child's natural skin, hair and eye color, ethnicity, nevi count and spectrophotometric melanin density (MD). Constitutive skin pigmentation was estimated from buttock MD. Relative facultative skin pigmentation was estimated by hand compared with buttock absorption. Ethnicity, hair color and skin color were associated with constitutive and facultative skin pigmentation on univariate analysis. Higher ambient ultraviolet radiation (UVR) in the past month, greater freckling, greater nevi and increased sun exposure over the past year were related to darker facultative skin pigmentation. Sun exposure over the life course was not. The two skin charts accounted for 39.7% and 21.4% of buttock MD, respectively. Relative facultative skin pigmentation is associated with recent UVR levels, not life-course sun exposure. Relative facultative skin pigmentation may not be a useful measure of sun exposure over the early life course. Skin color charts can be used to assess constitutive skin pigmentation if spectrophotometry is not available.
Publisher: Wiley
Date: 20-12-2016
Abstract: Patients presenting with clinically isolated syndrome (CIS) may proceed to clinically definite multiple sclerosis (CDMS). Midsagittal corpus callosum area (CCA) is a surrogate marker for callosal atrophy, and can be obtained from a standard MRI study. This study explores the relationship between CCA measured at CIS presentation (baseline) and at 5 years post presentation, with conversion from CIS to CDMS. The association between CCA and markers of disability progression is explored. Corpus callosum area was measured on MRI scans at presentation and 5-year review following diagnosis of a first demyelinating event, or evidence of progressive MS, in 143 participants in the Ausimmune/AusLong Study. Relationships between CCA (at baseline and follow-up) and clinical outcomes were assessed. Mean CCA at baseline study was 6.63 cm Baseline CCA obtained from standard MRI protocols may be compared with subsequent MRI examinations as a surrogate for neurodegeneration and cerebral atrophy in patients with MS. This study demonstrates an association between CCA and disability in in iduals presenting with CIS who convert to MS.
Publisher: Frontiers Media SA
Date: 20-03-2018
Publisher: Springer Science and Business Media LLC
Date: 08-02-2023
DOI: 10.1038/S41430-023-01271-1
Abstract: Consumption of ultra-processed foods (UPFs) has been linked to risk of chronic diseases, with scant evidence in relation to multiple sclerosis (MS). We tested associations between UPF consumption and likelihood of a first clinical diagnosis of central nervous system demyelination (FCD) (267 cases, 508 controls), a common precursor to MS. We used data from the 2003–2006 Ausimmune Study and logistic regression with full propensity score matching for age, sex, region of residence, education, smoking history, body mass index, physical activity, history of infectious mononucleosis, dietary misreporting, and total energy intake. Higher UPF consumption was statistically significantly associated with an increased likelihood of FCD (adjusted odds ratio = 1.08 95% confidence interval = 1.0,1.15 p = 0.039), representing an 8% increase in likelihood of FCD per one energy-adjusted serving/day of UPFs. Higher intakes of UPF were associated with increased likelihood of FCD in this Australian cohort. Nutrition education and awareness of healthy eating patterns may benefit those at high risk of FCD.
Publisher: Wiley
Date: 03-06-2013
DOI: 10.1111/PAI.12085
Abstract: It has been postulated that ultraviolet ray exposure in childhood might influence the development of allergic disease. We examined whether reported sun exposure during childhood or in adolescence is related to the occurrence of atopy or allergic disease. Population-based longitudinal cohort study with sixteen-year follow-up (N = 415). Subjects were recruited at birth as part of an infant health study. The reported daily duration of sun exposure in the summer months was recorded at 8 and 16 yrs of age. Allergen sensitization and the presence of eczema, asthma, and rye grass positive rhinitis were recorded at age 16. Reported sun exposures of more than 4 h per day during summer holidays in adolescence were associated with reduced eczema and rhinitis but not inhalant allergen sensitization or asthma risk. Thus, higher sun exposure during summer holidays and summer weekends in adolescence was associated with significantly reduced eczema (test of trend p-value = 0.001 summer holidays test of trend p-value = 0.003 summer weekends) and rye grass positive rhinitis (test of trend p-value = 0.03 summer holidays test of trend p-value = 0.02 summer weekends). Sun exposure at adolescence or age 8 was not related to inhalant allergen sensitization. There was no association between serum 25(OH)D levels at adolescence with either inhalant allergen sensitization or allergic disease and adjustment for serum 25(OH)D levels did not alter these findings. Increased sun exposure during summer holidays in adolescence was associated with reduced eczema and rhinitis risk, independently of measured vitamin D levels but no difference in inhalant allergen sensitization or asthma. The beneficial effects of sun exposure on allergic disease may operate independently from vitamin D or an effect on allergen sensitization.
Publisher: Wiley
Date: 04-06-2013
DOI: 10.1111/OBR.12047
Abstract: To evaluate the effectiveness of school-based physical activity interventions on fitness, adiposity and cardiometabolic outcomes among schoolchildren. Medline, Embase, EBSCOhost CINAHL and ERIC databases were searched up to October 2012. intervention delivered at school with controls having no intervention or usual physical education classes participants aged 5-18 years outcomes spanning some or all of the above. We assessed levels of evidence for identified trials based on methodological quality and s le size. Dose of the interventions (a total summary measure of intensity, frequency and duration) were considered. Eighteen randomized controlled trials (RCTs, total participants = 6,207) were included, of which six were large, higher quality trials with high dose of the intervention. The intervention was consistent in increasing fitness with large, higher quality studies and high dose of intervention providing strong evidence. Dose of school-based physical activity is an important determinant of trial efficiency. Some large, higher quality RCTs provided strong evidence for interventions to decrease skin-fold thickness, increase fitness and high-density lipoprotein cholesterol. Evidence for body mass index, body fat and waist circumference, blood pressure and triglycerides, low-density lipoprotein cholesterol and total cholesterol remain inconclusive and require additional higher quality studies with high dose of interventions to provide conclusive evidence.
Publisher: Elsevier BV
Date: 06-2002
DOI: 10.1016/S0895-4356(01)00519-4
Abstract: Feather bedding has been inversely associated with child wheeze and also with house dust mite (HDM) allergen levels. We conducted a cross-sectional analysis of the childhood component of a birth cohort study. Our aim was to examine the relation between feather bedding and HDM sensitization and airway disease. A total of 498 children (84% of eligible) residing in Northern Tasmania in 1997 who were eligible for the Tasmanian Infant Health Survey at birth in 1988 or 1989 participated. Outcome measures included atopic sensitization to Dermatophagoides farinae or Dermatophagoides pteronyssinus allergens, spirometric lung function, and child respiratory symptoms using questions from the ISAAC study. HDM sensitization was strongly associated with frequent wheeze (more than 12 episodes of wheeze compared with no wheeze in the past year) (rate ratio [RR], 19.61 confidence interval [CI], 6.94-55.56) but only weakly associated with asthma ever (RR, 1.65 CI, 1.30-2.09). Feather quilt use was associated with reduced HDM sensitization (adjusted RR [ARR], 0.60 CI, 0.45-0.80) and also reduced frequent wheeze episodes over the past year (ARR, 0.24 CI, 0.07-0.86). The reduction in wheeze was more evident among HDM-sensitized children. These findings are consistent with the possible mechanisms for feather bedding of a reduction in initial HDM sensitization and an improvement in respiratory symptoms among HDM-sensitized children. However, prospective studies are required to fully exclude selection bias.
Publisher: Wiley
Date: 13-11-2017
DOI: 10.1111/ALL.13330
Abstract: We previously reported that probiotic and peanut oral immunotherapy (PPOIT) was effective at inducing sustained unresponsiveness compared with placebo in a double-blind, placebo-controlled randomized trial. This study evaluated the impact of PPOIT on health-related quality of life (HRQL). Fifty-one participants (PPOIT 24 placebo 27) from the PPOIT trial completed Food Allergy Quality of Life Questionnaire (FAQLQ-PF) and Food Allergy Independent Measure (FAIM) at pre-treatment, end-of-treatment and 3 months after end-of-treatment. A total of 42 participants (20 PPOIT 22 placebo) completed measures at 12 months post-treatment. Changes over time in PPOIT and placebo groups were examined by repeated-measures analysis of variance and paired t tests. Probiotic and peanut oral immunotherapy was associated with significant improvement in FAQLQ-PF (F = 3.63, P = .02), with mean difference 0.8 at 3 months post-treatment (P = .05) and 1.3 at 12 months post-treatment (P = .005), exceeding the 0.5 minimal clinically important difference for FAQLQ-PF. For FAIM, mean difference was 0.5 (P = .03) at 3 months and 0.4 (P = .04) at 12 months post-treatment. In placebo group, post-treatment FAQLQ and FAIM remained unchanged from pretreatment. Improvement in FAQLQ-PF and FAIM scores related specifically to acquisition of sustained unresponsiveness rather than to receiving PPOIT treatment or participation in the trial. Probiotic and peanut oral immunotherapy has a sustained beneficial effect on psychosocial impact of food allergy at 3 and 12 months after end-of-treatment. Treatment was not associated with reduced HRQL relative to baseline in either PPOIT or placebo groups, indicating that PPOIT was well tolerated and psychological well-being was not negatively impacted. Improved HRQL was specifically associated with acquisition of sustained unresponsiveness.
Publisher: Wiley
Date: 2012
DOI: 10.1111/J.1445-5994.2011.02471.X
Abstract: Measuring serum 25(OH)D concentration is common in clinical practice despite the questionable reliability of assays. The aim of the present study was to examine agreement in 25(OH)D concentrations measured by different assays and laboratories, and consider related clinical implications. Serum s les from 813 participants in the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study) were assayed for 25(OH)D concentration. Duplicate s les from subsets of subjects were sent to different laboratories, two using DiaSorin Liaison (Laboratory A and B) and one using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS - selected here as the nominal gold standard). Pairwise within-assay (both within-laboratory and between-laboratories) and between-assay agreement was examined using Deming regression and Bland-Altman plots. Common 25(OH)D cut-points for classification of vitamin D deficiency were used to compare the different assays. 25(OH)D concentrations measured using Liaison were substantially lower at Laboratory A than at Laboratory B (mean bias -11.60 nmol/L, 95% limits of agreement -46.39, 23.18). Both Liaison assays returned much lower 25(OH)D concentrations than LC-MS/MS (mean bias up to -26.05 nmol/L, 95% limits of agreement of -13.21, 65.31). For Laboratory A participants, 46% (355/765) were classified as vitamin D deficient (25(OH)D <50 nmol/L) using Liaison compared with 17% (128/765) using LC-MS/MS. For Laboratory B participants, the respective figures were 36% (76/209) and 20% (41/209). Hence, between 1-in-5 and 1-in-3 participants were misclassified as 'deficient'. Bias and variability in 25(OH)D measurements sufficient to affect significantly clinical decision-making were found both between-laboratories and between-assays. The adoption of common standards to allow assay calibration is required urgently.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.CHEMOSPHERE.2019.124631
Abstract: There is an interdisciplinary interface between analytical chemistry and epidemiology studies with respect to the design, execution, and analysis of environmental epidemiology cohorts and studies. Extracting meaningful results linking chemical exposure to human health outcomes begins at study design and spans the entire workflow. Here we discuss analytical experimental design from an exposure science perspective, and propose a reporting checklist for the design of human biomonitoring studies. We explain key analytical chemistry concepts of blanks and limits of reporting and present a case series of plastic product chemical exposure in prenatal urine specimens from the Barwon Infant Study.
Publisher: Wiley
Date: 19-11-2019
DOI: 10.1111/ALL.13572
Abstract: IgE-mediated egg allergy presents as one of the most common food allergies in children. Measurement of egg white specific IgE (sIgE) levels in serum or skin prick test has been shown to be a poor predictor of clinical allergy to raw egg white, and also to baked or cooked egg. Recent developments in component resolved diagnostic (CRD) technology have enabled us to improve the way in which we diagnose and predict peanut allergy by examining IgE specificity to in idual peptides. We aimed to investigate whether egg CRD could improve current methods to diagnose various egg allergy phenotypes as well as predict the development of tolerance to egg. Using the HealthNuts cohort of food challenge-proven egg allergic and egg-sensitized and egg-tolerant, age-matched 12-month infants with longitudinal follow-up at 2 and 4 years (n = 451), we measured serum egg white, Gal d 1, 2, 3 and 5 sIgE using ImmunoCAP. Gal d 1 sensitization increased the risk of persistent egg allergy by 2.5-fold. The production of sIgE to all four egg allergens (Gal d 1, 2, 3 or 5) increased the risk of having persistent raw egg allergy fourfold (OR 4.19 (95% CI: 1.25-14.07). We did not find any improvements of using Gal d 1, 2, 3 or 5 to diagnose current egg allergy compared to egg white sIgE. Sensitization to multiple egg allergens Gal d 1, 2, 3 or 5 may be a prognostic marker that could be useful for patient management and identifying in iduals at risk of developing persistent egg allergy.
Publisher: BMJ
Date: 26-03-2013
DOI: 10.1136/BMJ.F1675
Publisher: Wiley
Date: 2008
DOI: 10.1002/PDS.1593
Abstract: Long-term immunomodulatory drug (IMD) treatment is now common in multiple sclerosis (MS). However, predictors of adherence are not well understood past studies lacked lifestyle factors such as alcohol use and predictors of missed doses have not been evaluated. We examined both levels of non-adherence-stopping IMD and missing doses. This longitudinal prospective study followed a population-based cohort (n = 199) of definite MS patients in Southern Tasmania (January 2002 to April 2005, source population 226 559) every 6 months. Baseline factors (demographic, clinical, psychological and cognitive) affecting adherence were examined by logistic regression and a longitudinal analysis (generalized estimating equation (GEE)). Of the 97 patients taking an IMD (mean follow-up = 2.4 years), 73% (71/97) missed doses, with 1 in 10 missing > 10 doses in any 6-month period. Missed doses were positively associated with alcohol amount consumed per session (p = 0.008). A history of missed doses predicted future missed doses (p < 0.0005). Over one-quarter (27/97) stopped their current IMD, which was associated with lower education levels (p = 0.032) and previous relapses (p = 0.05). No cognitive or psychological test predicted adherence. There were few strong predictors of missed doses, although people with MS consuming more alcoholic drinks per session are at a higher risk of missing doses. Divergent factors influenced the two levels of non-adherence indicating the need for a multifaceted approach to improving IMD adherence. In addition, missed doses should be assessed and incorporated into clinical trial design and clinical practice as poor adherers could impact on clinical outcomes.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.MSARD.2016.08.015
Abstract: There exists inconsistent evidence regarding animals including pets as risk factors for the development of Multiple Sclerosis (MS). We investigated the association between farm animals and pets as possible environmental factors in MS development. Population based case-control study with 136 clinically definite MS cases and 272 controls randomly chosen from the community matched on sex and age. Data was collected from both questionnaire and a lifetime calendar detailing residence, occupation and pet/animal exposure over the course of participant's lives. Exposure to farming, livestock, specific farm animals and remoteness of residence showed no significant association with MS risk. Exposure to cats prior to disease onset was associated with a greater risk of MS (Adjusted Odds Ratio 2.46 (1.17-5.18)) but without a clear dose-response (test for trend, p=0.76). In contrast to other literature, farming and exposure to farm animals were not associated with MS. While we identified an association between cat exposure and MS, there was no dose-response relationship, and previous studies showed inconsistent results, leaving us to conclude that there is no strong evidence that exposure to cats is associated with MS.
Publisher: Oxford University Press (OUP)
Date: 04-1999
DOI: 10.1093/OXFORDJOURNALS.AJE.A009857
Abstract: The aim of this investigation was to identify the sources of postnatal exposure to tobacco smoke at 1 month of age and to examine their relation to sudden infant death syndrome (SIDS). The Tasmanian Infant Health Survey was a prospective cohort study undertaken from 1988 to 1995. It involved 9,826 infants (89% of eligible infants) at higher risk of SIDS. Subsequently 53 eligible infants died of SIDS. Hospital interviews were available on 51 and home interviews on 35 SIDS infants. Urinary cotinine assays were conducted using gas-liquid chromatography (n = 100). Within a predictive model that explained 63% of urinary cotinine variance, the strongest predictor of cotinine and also of SIDS was maternal smoking, though the effects of prenatal and postnatal smoking could not be separated. However, for particular smoking-related behaviors, there was a discordance between prediction of cotinine concentration and prediction of risk of SIDS. If smoking mothers did not smoke in the room with the baby, the cotinine level in the infant's urine was reduced by a little more than a half (p = 0.009), but this was not associated with a reduction in SIDS risk (odds ratio = 1.09, 95% confidence interval 0.47-2.55). Similarly, the presence of other adult resident smokers was associated with a 63% increase in urinary cotinine (p = 0.047) but not with increased SIDS risk (odds ratio = 0.69, 95% confidence interval 0.34-1.40). However, the study lacked the power to detect modest effects, that is, those altering risk less than twofold.
Publisher: Wiley
Date: 29-09-2014
DOI: 10.1111/ALL.12487
Abstract: Asian infants appear to be over-represented among patients with clinical food allergy in Australia, but this has not been formally examined at the population level. Any difference in prevalence according to parental country of birth may be secondary to modifiable lifestyle factors. We aimed to quantify (i) differences in the prevalence of peanut allergy by parental country of birth and (ii) contribution of measured environmental exposures to these differences. The population-based HealthNuts study in Melbourne, Australia, screened 5276 infants (74% participation) with skin prick tests and sensitized infants underwent food challenge. Of these, 535 had a parent born in East Asia and 574 in UK/Europe. Associations between parents' country of birth and offspring peanut allergy were examined using multiple logistic regression. Compared to infants with two Australian-born parents, peanut allergy was more common among infants with parent/s born in East Asia (OR 3.4, 95% CI 2.2-5.1) but not those with parent/s born in the UK/Europe (OR 0.8, 95% CI 0.4-1.5). Paradoxically rates of allergic disease were lower among Asian parents. A higher prevalence of eczema among infants of Asian parents explained around 30% of the increase in peanut allergy, while differences in dog ownership explained around 18%. The high peanut allergy prevalence among infants of Asian-born parents appears to have occurred in a single generation and was not present among infants with parents migrating from other countries, suggesting gene-environment interactions are important. The role of eczema and microbial exposure in food allergy prevention warrants exploration.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-08-2008
DOI: 10.1212/01.WNL.0000323928.57408.93
Abstract: Low past sun exposure, fair skin type, and polymorphisms of the MC1R gene have been associated with multiple sclerosis (MS) risk. We aimed to investigate the interplay between melanocortin 1 receptor gene variants, red hair/fair skin phenotype, and past environmental sun exposure in MS. Population-based case-control study in Tasmania, Australia, involving 136 cases with MS and 272 controls randomly drawn from the community and matched on sex and year of birth. Measures included past sun exposure by calendar and questionnaire, spectrophotometric skin type, and MC1R genotype, with any MC1R Arg151Cys, Arg160Trp, or Asp294His alleles present denoted as red hair color (RHC) variant. The association between RHC variant genotype and MS was more evident for women (odds ratio 2.02 [1.15-3.54]) than for men (odds ratio 0.65 [0.27-1.57]) (difference in effect, p = 0.03). The RHC variant genotype was associated with behavioral sun avoidance. In addition, increasing summer sun exposure at ages 6 through 10 years was associated with reduced MS risk among those with no RHC variant (p = 0.03), but not among those with RHC variant genotype (p = 0.15 difference in effect, p = 0.02). Similar findings were evident for other past sun exposure measures and when the s le was restricted to women only. The interplay between red hair color variant genotype, red hair/fair skin phenotype, and multiple sclerosis (MS) is complex. The modification of past sun exposure by MC1R genotype provides further support that ultraviolet radiation or derivatives such as vitamin D may be causally related to a reduced MS risk.
Publisher: Oxford University Press (OUP)
Date: 04-1999
Publisher: eLife Sciences Publications, Ltd
Date: 02-03-2022
DOI: 10.7554/ELIFE.72779
Abstract: There is mounting evidence that in utero and early life exposures may predispose an in idual to metabolic disorders in later life and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. We studied the effect of antenatal factors such as gestational age, birth weight, and mode of birth on lipid metabolism at birth changes in the circulating lipidome in the first 4 years of life and the effect of breastfeeding in the first year of life. From this study, we aim to generate a framework for deeper understanding into factors effecting lipid metabolism in early life, to provide early interventions for those at risk of developing metabolic disorders including cardiovascular diseases. We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population-based pre-birth cohort and measured 776 distinct lipid features across 39 lipid classes using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We measured lipids in 1032 maternal serum s les at 28 weeks’ gestation, 893 cord serum s les at birth, 793, 735, and 511 plasma s les at 6, 12 months, and 4 years, respectively. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. We performed regression analyses to investigate the associations of cord serum lipid species with antenatal factors: gestational age, birth weight, mode of birth and duration of labour. The lipidome differed between mother and newborn and changed markedly with increasing child’s age. Alkenylphosphatidylethanolamine species containing LC-PUFAs increased with child’s age, whereas the corresponding lysophospholipids and triglycerides decreased. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids. Breastfeeding had a significant impact on the plasma lipidome in the first year of life, with up to 17-fold increases in a few species of alkyldiaclylglycerols at 6 months of age. This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood. This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
Publisher: Elsevier BV
Date: 07-2015
Publisher: MDPI AG
Date: 08-08-2023
Abstract: Epigenetic mechanisms can regulate how DNA is expressed independently of sequence and are known to be associated with various diseases. Among those epigenetic mechanisms, DNA methylation (DNAm) is influenced by genotype and the environment, making it an important molecular interface for studying disease etiology and progression. In this study, we examined the whole blood DNA methylation profiles of a large group of people with (pw) multiple sclerosis (MS) compared to those of controls. We reveal that methylation differences in pwMS occur independently of known genetic risk loci and show that they more strongly differentiate disease (AUC = 0.85, 95% CI 0.82–0.89, p = 1.22 × 10−29) than known genetic risk loci (AUC = 0.72, 95% CI: 0.66–0.76, p = 9.07 × 10−17). We also show that methylation differences in MS occur predominantly in B cells and monocytes and indicate the involvement of cell-specific biological pathways. Overall, this study comprehensively characterizes the immune cell-specific epigenetic architecture of MS.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-03-2012
Publisher: Wiley
Date: 04-2015
DOI: 10.14814/PHY2.12347
Publisher: Oxford University Press (OUP)
Date: 04-12-2009
DOI: 10.1093/RHEUMATOLOGY/KEP383
Abstract: Like other autoimmune diseases, including adult RA, risk of developing juvenile idiopathic arthritis (JIA) is thought to be determined by a complex combination of genetic and environmental factors. Although some predisposing JIA genes are now being identified, research aimed at identifying environmental influences lags behind most other autoimmune conditions. Here we review research to date, from which some evidence has been generated to support a role for breastfeeding, infection and maternal smoking in determining JIA risk. We also propose further hypotheses worthy of testing, based on knowledge acquired for other autoimmune diseases. These include the role of vitamin D and sun exposure, and the role of early-life infection ('the hygiene hypothesis') in determining risk. Finally, we discuss future directions including practical study designs to more comprehensively test hypotheses and provide new insight into this important area of research.
Publisher: BMJ
Date: 04-1992
DOI: 10.1136/JECH.46.2.98
Publisher: BMJ
Date: 08-1999
DOI: 10.1136/THX.54.8.664
Abstract: The timing and mechanism of the inverse association between increasing sibling number and atopic disease are not yet understood. A study was undertaken to examine how family size at birth predicts early respiratory illness, to report the association between infant respiratory illness and childhood atopic disease, and to determine whether the protective effect of large family size operates during infancy or later childhood. A prospective follow up study was carried out on 863 children (78%) of 1111 participants in the Tasmanian Infant Health Survey performed in 1988. In 1988 household size and history of respiratory illness were obtained by parental interview at home (median age 35 days) and later by telephone (median age 85 days). In 1995 asthma, hay fever, and household size were assessed by parental questionnaire in a large cross sectional survey. In 1988 increasing resident number (per resident) (adjusted odds ratio (AOR) 1.17 (95% CI 1.05 to 1.31)) and resident density (AOR 1.77 (95% CI 1.07 to 2.94)) were related to parental report of an upper respiratory tract infection (URTI) by one month of age. Children with a reported URTI by home interview were more likely to have subsequent asthma (adjusted relative risk (ARR) 1.27 (95% CI 1.05 to 1.53)). The association between lower respiratory tract infection (LRTI) at telephone interview (relative risk (RR) 1.34 (95% CI 1.02 to 1.75) and asthma was reduced after adjustment for family history of asthma (ARR 1.27 (95% CI 0.98 to 1.66)). Antibiotic use by home interview was not associated with subsequent asthma or hay fever. Indicators of family size in 1988 were associated with hay fever but not asthma but, in contrast, resident number in 1995 was inversely associated with asthma (AOR 0.82 (95% CI 0.72 to 0.92) per resident) and hay fever (AOR 0.82 (95% CI 0.71 to 0.96) per resident). Children with no siblings were at risk for current asthma, particularly if symptoms began after the age of four (RR 2.81 (95% CI 1.36 to 5.84)). The apparent protective effect of large household size and asthma could not be explained by an increase in reported early respiratory illness. The first year of life may not be the most critical time for the protective effect of large household size to be mediated in relation to asthma, but this effect occurred by the seventh year of life.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.JAUT.2017.09.010
Abstract: Juvenile idiopathic arthritis (JIA) is presumed to be driven by an adverse combination of genes and environment. Epigenetic processes, including DNA methylation, act as a conduit through which the environment can regulate gene activity. Altered DNA methylation has been associated with adult autoimmune rheumatic diseases such as rheumatoid arthritis, but studies are lacking for paediatric autoimmune rheumatic diseases including JIA. Here, we performed a genome-scale case-control analysis of CD4
Publisher: Hindawi Limited
Date: 14-10-2015
DOI: 10.1111/ANE.12315
Abstract: To investigate whether those genes involved in the vitamin D pathway modulate the relationship between 25-hydroxyvitamin D (25(OH)D) and IFN-β, the relationship between IFN-β and sun in predicting 25(OH)D, and the interaction between IFN-β and 25(OH)D in modulating relapse risk in patients with MS. Prospective cohort study of 169 participants with MS and genotype data followed 2002-2005. Gene-IFN-β and gene-IFN-β-sun interactions predicting 25(OH)D evaluated by multilevel mixed-effects linear regression. Gene-IFN-β interactions with 25(OH)D in modulating in relapse risk assessed using survival analysis. The cohort was 71.6% female and of mean age 47.8. Two-independent intronic genotyped SNPs (rs10767935 and rs5030244) in WT1 significantly modified the IFN-β-25(OH)D association after adjustment (P(interaction) = 0.001, 0.0002 P(adj) = 0.003, 0.006, respectively). There was a marked difference in the interaction between self-reported sun exposure and IFN-β in predicting 25(OH)D by level of rs10767935, although this did not reach statistical significance. No SNPs modified the interaction between IFN-β and 25(OH)D in predicting relapse. We have demonstrated that two-independent SNPs (rs10767935 and rs5030244) in WT1 modified the IFN-β-25(OH)D association in patients with MS. Some evidence was shown for a difference in the sun-IFN-β-25(OH)D association by level of rs10767935. These findings indicate that WT1 variants may play a role in altering the effects of IFN-β on vitamin D in MS.
Publisher: MDPI AG
Date: 29-03-2022
Abstract: The developing brain is highly sensitive to environmental disturbances, and adverse exposures can act through oxidative stress. Given that oxidative stress susceptibility is determined partly by genetics, multiple studies have employed genetic scores to explore the role of oxidative stress in human disease. However, traditional approaches to genetic score construction face a range of challenges, including a lack of interpretability, bias towards the disease outcome, and often overfitting to the study they were derived on. Here, we develop an alternative strategy by first generating a genetic pathway function score for oxidative stress (gPFSox) based on the transcriptional activity levels of the oxidative stress response pathway in brain and other tissue types. Then, in the Barwon Infant Study (BIS), a population-based birth cohort (n = 1074), we show that a high gPFSox, indicating reduced ability to counter oxidative stress, is linked to higher autism spectrum disorder risk and higher parent-reported autistic traits at age 4 years, with AOR values (per 2 additional pro-oxidant alleles) of 2.10 (95% CI (1.12, 4.11) p = 0.024) and 1.42 (95% CI (1.02, 2.01) p = 0.041), respectively. Past work in BIS has reported higher prenatal phthalate exposure at 36 weeks of gestation associated with offspring autism spectrum disorder. In this study, we examine combined effects and show a consistent pattern of increased neurodevelopmental problems for in iduals with both a high gPFSox and high prenatal phthalate exposure across a range of outcomes, including high gPFSox and high DEHP levels against autism spectrum disorder (attributable proportion due to interaction 0.89 95% CI (0.62, 1.16) p 0.0001). The results highlight the utility of this novel functional genetic score and add to the growing evidence implicating gestational phthalate exposure in adverse neurodevelopment.
Publisher: Public Library of Science (PLoS)
Date: 26-11-2013
Publisher: SAGE Publications
Date: 08-2007
Abstract: Rising multiple sclerosis incidence over the last 50 years and geographic patterns of occurrence suggest an environmental role in the causation of this multifactorial disease. Design options for epidemiological studies of environmental causes of multiple sclerosis are limited by the low incidence of the disease, possible diagnostic delay and budgetary constraints. We describe scientific and methodological issues considered in the development of the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study), which seeks, in particular, to better understand the causes of the well-known MS positive latitudinal gradient. A multicentre, case-control design down the eastern seaboard of Australia allows the recruitment of sufficient cases for adequate study power and provides data on environmental exposures that vary by latitude. Cases are persons with an incident first demyelinating event (rather than prevalent multiple sclerosis), sourced from a population base using a two tier notification system. Controls, matched on sex, age (within two years) and region of residence, are recruited from the general population. Biases common in case-control studies, eg, prevalence-incidence bias, admission-rate bias, non-respondent bias, observer bias and recall bias, as well as confounding have been carefully considered in the study design and conduct of the Ausimmune Study. Multiple Sclerosis 2007 13 : 827—839. msj.sagepub.com
Publisher: SAGE Publications
Date: 04-2004
DOI: 10.1191/1352458504MS1006OA
Abstract: Evolving information techno logy has raised the possibility of new methods of data collection in multiple sclerosis (MS) research. A n anonymous, self-report, Internet-based survey was developed, which asked people with MS their opinion on how various extrinsic factors affected their condition. From September 2001 to July 2002, a total of 2529 people completed the questionnaire. The demographic and clinical profiles of the anonymous respondents indicated that most were likely to have MS. C ommon factors reported as beneficial were cannabis, cold baths, meditation and dietar y factors. C ommon adverse factors reported were high stress, exposure to high temperatures and viral infections. There was an increasing report of high temperatures as being adverse with increasing respondent age (test for trend, P B-0.001). The adverse report of high temperatures correlated significantly with the report of strong sunlight apparently making MS worse (r =0.35, P B-0.0001). In A ustralia, high temperatur es were more likely to be reported as adverse in warmer, lower latitude regions. The association between strong sunlight as adverse and age or region did not persist after adjustment for high temperatures. Thus, this apparent adverse factor appeared to relate to solar heat, not solar light. People with MS may risk vitamin D deficiency because of sun avoidance due to heat-related fatigue or intolerance. This is of clinical significance not only for bone health but because vitamin D may have beneficial immunomodulatory properties. The present study provides new information from people with MS on factors that may influence symptoms or clinical course. This information will now be used in the design of formal epidemiological cohort studies.
Publisher: Wiley
Date: 21-05-2017
DOI: 10.1111/CEA.12942
Abstract: Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells. Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy. We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located s le of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication s le phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. IL13 rs1295686 was associated with challenge-proven food allergy in the discovery s le (P=.003 OR=1.75 CI=1.20-2.53). This association was also detected in the replication s le (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE. We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.
Publisher: Wiley
Date: 31-08-2009
DOI: 10.1111/J.1751-1097.2009.00563.X
Abstract: Fair skin pigmentation has been associated with a higher risk of type 1 diabetes mellitus (T1DM). The aim is to compare children with T1DM directly to a sibling in relation to their skin pigmentation in sun-exposed and unexposed sites, past sun exposure and methylation of the VDR gene promoter. The s le consisted of children with T1DM attending a diabetes outpatient clinic and siblings (total n=42). Cutaneous melanin density was estimated using a spectrophotometer. Parental report on past sun exposure was obtained. DNA methylation analysis of the VDR gene promoter was conducted. Matched data analysis was performed comparing each case directly to their sibling. Cases were significantly more likely to have lighter skin pigmentation at the upper arm (AOR 0.69 [95% CI: 0.52, 0.90] P=0.01). Low infant sun exposure was imprecisely associated with a two-fold increase in T1DM risk (AOR 2.43 [95% CI: 0.91, 6.51] P=0.08 for under 1 h of winter sun exposure per leisure day). The VDR gene promoter was completely unmethylated in both cases and siblings. The previously demonstrated association between light skin pigmentation and T1DM risk was evident even in this comparison across sibling pairs. Further work on past UVR exposure and related factors such as skin pigmentation is required.
Publisher: Wiley
Date: 14-08-2018
DOI: 10.1111/CEA.13235
Abstract: Asian children born in Australia have higher rates of eczema and nut allergy than non-Asian children. However, it is not known whether this country of birth differential exists for other allergies or anaphylaxis risk. We investigated the influence of maternal and child's country of birth on the prevalence of parent-reported eczema, asthma, food allergy and being diagnosed by a doctor as being "at risk of anaphylaxis." We assessed the relationship between mother and child country of birth and allergies using the 2010 School Entrant Health Questionnaire, completed for 57 005 5-year old children (85.8% response rate) in Victoria, Australia. Analyses were conducted using logistic regression with results presented as odds ratios (OR) with 95% confidence intervals (CIs). Children born in Australia to Asian-born mothers were more likely to have parent-reported food allergy (OR 2.33, 95%CI 1.96-2.77) and eczema (OR 2.04, 95%CI 1.73-2.41), but not more likely to have asthma (OR 0.87, 95% CI 0.74-1.02) than non-Asian children. By contrast, children born in Asia who subsequently migrated to Australia had a lower risk of food allergy (OR 0.33, 95%CI 0.20-0.55), eczema (OR 0.37, 95%CI 0.24-0.57) and asthma (OR 0.29, 95% CI 0.21-0.40). Patterns of anaphylaxis risk differed depending on the trigger. Compared with Australian-born non-Asian children, Australian-born Asian children were more likely to be diagnosed as being at risk of both food-induced and non-food-induced anaphylaxis. For children born in Asia, risk was lower for anaphylaxis to milk, peanut and tree nuts compared to non-Asian children, but higher for soy, wheat and non-food triggers. Patterns of allergy/anaphylaxis risk and their triggers differed according to both ethnicity and country of birth, suggesting a gene-environment factor is in play. The difference in patterns for asthma compared with other atopic diseases is surprising and warrants further exploration.
Publisher: Wiley
Date: 09-2008
DOI: 10.1038/OBY.2008.302
Abstract: We aimed to (i) determine the relative importance of childhood gain in upper body adiposity for insulin resistance (IR) and triglyceridemia (TG) (ii) examine whether the associations between adiposity and metabolic indices were more evident in those with the ACE DD genotype. We examined a birth cohort study of 292 children with measures in the neonatal period (day 4) including subscapular and triceps skinfolds repeat skinfold measures at age 8, cardiorespiratory (CR) fitness, IR by the homeostasis model assessment (HOMA) equation (HOMA-IR) and serum triglyceride (TG) concentrations and measures of ACE I/D gene variants. A multiple linear regression analysis incorporating a life course approach was undertaken. Childhood gain in upper body adiposity was positively associated with HOMA-IR and TG independently of neonatal skinfolds (P < or = 0.02). The magnitude of these associations was higher among those of the ACE DD genotype. For ex le, subscapular skinfold gain was not strongly associated with HOMA-IR or TG among those with II or ID genotype (b = 0.03, P = 0.05 b = 0.02, P = 0.18 respectively) but was positively associated among those with the DD genotype (b = 0.11, P = 0.001 b = 0.08, P = 0.003) difference in effect P = 0.05 P = 0.01 respectively. Upper body fat accumulation during childhood was positively associated with HOMA-IR and TG independently of neonatal skinfolds. Further, the stronger associations for those with the ACE DD genotype is consistent with randomised controlled trial findings that ACE inhibition is associated with a reduced risk of developing type 2 diabetes. Further work is required to confirm and extend these findings.
Publisher: Public Library of Science (PLoS)
Date: 31-12-2015
Publisher: Springer Science and Business Media LLC
Date: 10-10-2012
Abstract: Overweight and obesity are becoming increasingly prevalent problems worldwide. A number of factors in early life have been found to be associated with body composition of neonates or young children but there is limited follow-up data for adolescents. This study aims to describe associations between early nutrition and body composition in adolescents. Birth cohort study of 415 pregnant women and their offspring (mean age 16 years). Body composition including fat mass (FM) and lean body mass (LBM) of adolescents at 16 years of age was measured by dual-energy X-ray absorptiometry. Information on maternal food and nutrients intake during the third trimester of pregnancy and breastfeeding was collected by questionnaires soon after birth. A total of 264 mother-adolescents pairs were studied. Maternal antenatal meat intake was positively associated with FM of adolescents (an increase of 0.9% ortion, P 25 days was negatively associated with FM in adolescents (a decrease of 14%, P=0.01). These associations were independent of the significant association between maternal energy and macronutrient intakes during pregnancy and adolescent intakes at 16 years of age. No significant association was found between maternal dietary intake and lean mass in adolescents. Breastfeeding may have a biological effect that is beneficial for the prevention of obesity. Conversely, higher maternal meat intake during pregnancy may increase FM in adolescents.
Publisher: Elsevier BV
Date: 04-2012
Publisher: BMJ
Date: 24-01-2020
DOI: 10.1136/ARCHDISCHILD-2019-317485
Abstract: 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. 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. 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. In two unselected populations using harmonised protocols, the likely association of caesarean delivery with developing childhood allergy was small.
Publisher: S. Karger AG
Date: 2001
DOI: 10.1159/000054783
Abstract: The aim of this study was to conduct an ecological analysis of the extent to which ultraviolet radiation (UVR) levels might explain the regional variation of multiple sclerosis (MS) in Australia. MS prevalence data for six Australian regions were compared with UVR levels of the largest city in each region, with some other climatic variables and with the melanoma incidence in the same regions. A close association was found between the theoretical MS prevalence predicted from UVR levels and the actual prevalence. Furthermore, the negative correlation between UVR and MS prevalence (r = –0.91, p = 0.01) was higher than the positive correlation observed for UVR and malignant melanoma incidence (r = 0.75, p = 0.15 for males and r = 0.80, p = 0.10 for females). This study demonstrated that the regional variation in MS prevalence in the continent of Australia could be closely predicted by regional UVR levels. It is consistent with the hypothesis that UVR exposure may reduce the risk of MS possibly via T-lymphocyte-mediated immunosuppression. Analytical epidemiology studies are required to investigate this specific hypothesis.
Publisher: Wiley
Date: 03-12-2010
DOI: 10.1111/J.1365-2222.2010.03668.X
Abstract: There is considerable controversy whether maternal peanut ingestion during pregnancy might influence sensitization in later life. Objective To examine whether maternal peanut ingestion during pregnancy might increase sensitization in the offspring. A population-based longitudinal cohort study with 16 years follow-up was conducted (N=373). Subjects were recruited at birth as part of an infant health study. Maternal antenatal peanut consumption was documented at birth and peanut and rye sensitization were determined by measurement of serum-specific IgE at age 16. Peanut sensitization was common (14%). In the entire cohort (n=310), there was no association between antenatal peanut ingestion and peanut sensitization (P=0.17). However, there was a strong association between antenatal peanut ingestion and decreased risk of rye sensitization and peanut sensitization in those (n=201) without a family history (FH) of asthma (Rye OR 0.30, 95% CI 0.14-0.63, P=0.001 and Peanut OR 0.18, 95% CI 0.04-0.78, P=0.02). There was an increased risk of rye sensitization in those (n=108) with a FH of asthma and antenatal peanut ingestion (Rye OR 2.69, 95% CI 1.11-6.51 P=0.03). It was considered that these sensitizations were likely to be related to the presence of IgE antibodies to cross-reacting carbohydrate epitopes common to rye and peanut allergens. Antenatal peanut ingestion may influence the development of IgE antibody to cross-reacting carbohydrate epitopes in later life. Genetic factors may modify this association.
Publisher: Elsevier BV
Date: 08-1970
DOI: 10.1111/J.1467-842X.1997.TB01740.X
Abstract: The Centers for Disease Control in the United States have stated that studies to determine factors associated with failure to receive the first recommended dose of diphtheria-tetanus-pertussis are required. We examined an infant cohort to identify family and infant characteristics predictive of prompt first immunisation, to document changes in prompt first immunisation rates over time and to identify reasons for immunisation delay. The study s le consisted of one-fifth of live births in Tasmania at risk of sudden infant death syndrome. From 1 January 1988 to 31 December 1994, families of 8011 infants (83 per cent of eligible infants) participated in a telephone interview when the infants were a median postnatal age of 11 weeks and 3 days. Prompt immunisation was defined as the report by parents of diphtheria-tetanus-pertussis vaccination before a postnatal age of 10 weeks. The proportion of cohort infants promptly immunised increased (P < 0.0001) over time from 1988 to 1994. Prompt immunisation was associated with various characteristics of the infant and family. The proportion of infants promptly immunised decreased as birth order increased and as the interpregnancy interval between the index child and his or her immediately elder sibling decreased. After exclusion of infants not promptly immunised because of illness, birth order and interbirth interval remained significant predictors of prompt immunisation, suggesting that these factors are acting to increase immunisation delay through pathways unrelated to their potential effect on infant illness rates.
Publisher: Wiley
Date: 08-2010
DOI: 10.1002/ANA.22043
Abstract: A protective association between higher vitamin D levels and the onset of multiple sclerosis (MS) has been demonstrated however, its role in modulating MS clinical course has been little studied. We investigated whether higher levels of serum 25-hydroxyvitamin D (25-OH-D) were associated with a lower risk of relapses in people with MS. We conducted a prospective cohort study of 145 participants with relapsing-remitting MS from 2002 to 2005. Serum 25-OH-D levels were measured biannually, and the hazard of relapse was assessed using survival analysis. There was an inverse linear relationship between 25-OH-D levels and the hazard of relapse over the subsequent 6 months, with hazard ratio (HR) 0.91 (95% confidence interval [CI]: 0.85-0.97) per 10 nmol/l increase in 25-OH-D level (p = 0.006). When variation due to timing of blood collection was removed by estimating 25-OH-D at the start of each season, this association persisted, with HR 0.90 (95% CI, 0.83-0.98) per 10 nmol/l increase (p = 0.016). Taking into account the biological half-life of 25-OH-D, we estimated 25-OH-D at monthly intervals, resulting in a slightly enhanced association, with HR 0.88 (95% CI, 0.82-0.95) per 10 nmol/l increase (p = 0.001). Adjusting for potential confounders did not alter these findings. In this prospective population-based cohort study, in a cohort largely on immunomodulatory therapy, higher 25-OH-D levels were associated with a reduced hazard of relapse. This occurred in a dose-dependent linear fashion, with each 10 nmol/l increase in 25-OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25-OH-D levels by 50 nmol/l could halve the hazard of a relapse.
Publisher: Elsevier BV
Date: 2012
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.JACI.2014.11.034
Abstract: Coadministration of a bacterial adjuvant with oral immunotherapy (OIT) has been suggested as a potential treatment for food allergy. To evaluate a combined therapy comprising a probiotic together with peanut OIT. We performed a double-blind, placebo-controlled randomized trial of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 and peanut OIT (probiotic and peanut oral immunotherapy [PPOIT]) in children (1-10 years) with peanut allergy. The primary outcome was induction of sustained unresponsiveness 2 to 5 weeks after discontinuation of treatment (referred to as possible sustained unresponsiveness). Secondary outcomes were desensitization, peanut skin prick test, and specific IgE and specific IgG4 measurements. Sixty-two children were randomized and stratified by age (≤5 and >5 years) and peanut skin test wheal size (≤10 and >10 mm) 56 reached the trial's end. Baseline demographics were similar across groups. Possible sustained unresponsiveness was achieved in 82.1% receiving PPOIT and 3.6% receiving placebo (P < .001). Nine children need to be treated for 7 to achieve sustained unresponsiveness (number needed to treat, 1.27 95% CI, 1.06-1.59). Of the subjects, 89.7% receiving PPOIT and 7.1% receiving placebo were desensitized (P < .001). PPOIT was associated with reduced peanut skin prick test responses and peanut-specific IgE levels and increased peanut-specific IgG4 levels (all P < .001). PPOIT-treated participants reported a greater number of adverse events, mostly with maintenance home dosing. This is the first randomized placebo-controlled trial evaluating the novel coadministration of a probiotic and peanut OIT and assessing sustained unresponsiveness in children with peanut allergy. PPOIT was effective in inducing possible sustained unresponsiveness and immune changes that suggest modulation of the peanut-specific immune response. Further work is required to confirm sustained unresponsiveness after a longer period of secondary peanut elimination and to clarify the relative contributions of probiotics versus OIT.
Publisher: BMJ
Date: 24-08-2016
Abstract: The genetic drivers of multiple sclerosis (MS) clinical course are essentially unknown with limited data arising from severity and clinical phenotype analyses in genome-wide association studies. Prospective cohort study of 127 first demyelinating events with genotype data, where 116 MS risk-associated single nucleotide polymorphisms (SNPs) were assessed as predictors of conversion to MS, relapse and annualised disability progression (Expanded Disability Status Scale, EDSS) up to 5-year review (ΔEDSS). Survival analysis was used to test for predictors of MS and relapse, and linear regression for disability progression. The top 7 SNPs predicting MS/relapse and disability progression were evaluated as a cumulative genetic risk score (CGRS). We identified 2 non-human leucocyte antigen (HLA rs12599600 and rs1021156) and 1 HLA (rs9266773) SNP predicting both MS and relapse risk. Additionally, 3 non-HLA SNPs predicted only conversion to MS 1 HLA and 2 non-HLA SNPs predicted only relapse and 7 non-HLA SNPs predicted ΔEDSS. The CGRS significantly predicted MS and relapse in a significant, dose-dependent manner: those having ≥5 risk genotypes had a 6-fold greater risk of converting to MS and relapse compared with those with ≤2. The CGRS for ΔEDSS was also significant: those carrying ≥6 risk genotypes progressed at 0.48 EDSS points per year faster compared with those with ≤2, and the CGRS model explained 32% of the variance in disability in this study cohort. These data strongly suggest that MS genetic risk variants significantly influence MS clinical course and that this effect is polygenic.
Publisher: SAGE Publications
Date: 14-11-2011
Abstract: Background: Some of the strongest associations with MS onset are for human herpesviruses, particularly Epstein–Barr virus (EBV) and human herpesvirus 6 (HHV-6). Their role in MS clinical course is less clear, however. Methods: Prospective cohort of 198 persons with clinically definite MS, followed 2002–5, and serum s les obtained from all subjects at study entry to measure anti-HHV-6 and anti-EBV (Epstein–Barr nuclear antigen [EBNA] and viral capsid antigen [VCA]) IgG titers. Association with relapse evaluated using survival analysis association with disability rogression evaluated using linear regression or multilevel mixed-effects linear regression. Results: For the 145 persons with relapsing–remitting MS followed beyond one review, anti-HHV-6 IgG titer was positively associated with the hazard of relapse with a dose-dependent trend ( p = 0.003), not affected by adjustment for anti-EBV IgG titers, neither of which were independently associated with relapse. There was no significant association between anti-human herpesvirus IgG titers and baseline-measured disability scores, or change in disability scores however, anti-HHV-6 IgG titers were 2.8 times higher among progressive-course females than progressive-course males. Discussion: These findings suggest that, in addition to a potential etiological role in MS, HHV-6 infection or the immune response to HHV-6 antigens may have an effect on the risk of MS relapses and possibly on progressive courses of MS. The observed effect was directly related to anti-HHV-6 IgG titers and may indicate that either HHV-6 infection or factors associated with an altered humoral immune response to HHV-6 may have an effect on MS clinical course. Anti-HHV-6 IgG titer may be a useful prognostic factor in relapsing–remitting MS clinical course.
Publisher: SAGE Publications
Date: 14-05-2014
Abstract: There is accumulating data suggesting an association between serum lipids, apolipoproteins and disability in multiple sclerosis (MS). To investigate the associations between serum lipids, apolipoproteins and disability in MS. A cohort of 178 participants with clinically-definite MS in southern Tasmania, Australia were prospectively followed from 2002 – 2005, and serum s les were obtained at study entry and at each biannual review, to measure lipid profile and apolipoprotein levels. Associations with disability and annual change in disability were evaluated using linear regression and multilevel mixed-effects linear regression. In the unadjusted analyses, nearly all lipid-related variables were positively associated with Expanded Disability Status Scale (EDSS). After adjustment for confounders, total cholesterol (TC) ( p = 0.037), apolipoprotein B (ApoB) ( p = 0.003), and the apolipoprotein B to apolipoprotein A-I ratio (ApoB/ApoA-I ratio) ( p = 0.018) were independently associated with a higher EDSS. Higher body mass index (BMI) was also independently associated with higher EDSS ( p = 0.013). With the progression analysis, the total cholesterol to high density lipoprotein (HDL) ratio (TC/HDL ratio) ( p = 0.029) was prospectively associated with subsequent change in EDSS. In this prospective population-based cohort study, an adverse lipid profile was associated with high levels of MS disability and disease progression. Improving serum lipids may be beneficial for MS patients, to potentially improve clinical outcomes and vascular comorbidities.
Publisher: Public Library of Science (PLoS)
Date: 12-08-2015
Publisher: Oxford University Press (OUP)
Date: 30-03-2015
DOI: 10.1093/IJE/DYV026
Abstract: The modern environment is associated with an increasing burden of non-communicable diseases (NCDs). Mounting evidence implicates environmental exposures, experienced early in life (including in utero), in the aetiology of many NCDs, though the cellular/molecular mechanism(s) underlying this elevated risk across the life course remain unclear. Epigenetic variation has emerged as a candidate mediator of such effects. The Barwon Infant Study (BIS) is a population-derived birth cohort study (n = 1074 infants) with antenatal recruitment, conducted in the south-east of Australia (Victoria). BIS has been designed to facilitate a detailed mechanistic investigation of development within an epidemiological framework. The broad objectives are to investigate the role of specific environmental factors, gut microbiota and epigenetic variation in early-life development, and subsequent immune, allergic, cardiovascular, respiratory and neurodevelopmental outcomes. Participants have been reviewed at birth and at 1, 6, 9 and 12 months, with 2- and 4-year reviews under way. Biological s les and measures include: maternal blood, faeces and urine during pregnancy infant urine, faeces and blood at regular intervals during the first 4 years lung function at 1 month and 4 years cardiovascular assessment at 1 month and 4 years skin-prick allergy testing and food challenge at 1 year and neurodevelopmental assessment at 9 months, 2 and 4 years. Data access enquiries can be made at [www.barwoninfantstudy.org.au] or via [peter.vuillermin@deakin.edu.au].
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JACI.2018.07.038
Abstract: Longitudinal population-based data regarding tree nut allergy are limited. We sought to determine the population prevalence of tree nut allergy at age 6 years and explore the relationship between egg and peanut allergy at age 1 year and development of tree nut allergy at age 6 years. A population-based s le of 5276 children was recruited at age 1 year and followed up at age 6 years. At age 1 year, allergies to egg and peanut were determined by means of oral food challenge, and parents reported their child's history of reaction to tree nuts. Challenge-confirmed tree nut allergy was assessed at age 6 years. At age 1 year, the prevalence of parent-reported tree nut allergy was 0.1% (95% CI, 0.04% to 0.2%). Only 18.5% of infants had consumed tree nuts in the first year of life. At age 6 years, challenge-confirmed tree nut allergy prevalence was 3.3% (95% CI, 2.8% to 4.0%), with cashew the most common (2.7% 95% CI, 2.2% to 3.3%). Of children with peanut allergy only at age 1 year, 27% (95% CI, 16.1% to 39.7%) had tree nut allergy at age 6 years compared with 14% (95% CI, 10.4% to 17.9%) of those with egg allergy only and 37% (95% CI, 27.2% to 47.4%) of those with both peanut and egg allergy. Tree nut allergy is uncommon in the first year of life, likely because of limited tree nut consumption. At age 6 years, tree nut allergy prevalence is similar to peanut allergy prevalence. More than a third of children with both peanut and egg allergy in infancy have tree nut allergy at age 6 years. Understanding how to prevent tree nut allergy should be an urgent priority for future research.
Publisher: Public Library of Science (PLoS)
Date: 11-2011
Publisher: Wiley
Date: 07-2004
Publisher: Elsevier BV
Date: 05-1994
Abstract: An intervention to reduce the prevalence of the prone sleeping position during infancy was implemented in Tasmania particularly from 1991 onward. The purpose of this report is to assess the impact of public health activities in promoting avoidance of the prone infant sleeping position among cohort study participants. The prospective cohort study involved the one-fifth of Tasmanian live births who are assessed perinatally as being at higher risk for Sudden Infant Death Syndrome (SIDS). From 1 January 1988 until 30 April 1992, 5,403 infants participated in the hospital (4 days postnatal age) and home interviews (5 weeks postnatal age) (88% of eligible infants). After the finding that cohort infants who usually slept prone were at significantly greater risk for SIDS, additional questions on awareness and choice of infant sleep position were asked. The proportion of infants usually sleeping prone declined from 29.9% in the cohort prior to publication of the cohort findings (1 May 1988-30 April 1991) to 5.4% in the post publication cohort (1 May 1991-30 April 1992), RR = 0.18 (0.15, 0.22). Teenage motherhood was associated with non-awareness (RR = 2.39 (1.41, 3.24)) of an association between prone position and SIDS. After adjusting for maternal age, nonawareness remained positively associated with maternal smoking, maternal education (< Year 12), and paternal unemployment, while mothers who read books to prepare for the baby and who were married were more likely to be aware. In the period after the cohort study publication, the most common reasons given for the usual prone position were that the baby preferred that position and slept better. Public health activities to reduce the prevalence of the prone sleeping position have had a significant impact, with a dramatic reduction in the proportion of cohort infants usually sleeping prone. The identification of characteristics of nonaware mothers and the reasons for choosing a particular sleeping position will be used to maintain and improve health education in this area.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JAIP.2017.11.018
Abstract: Although food allergy has probably risen over recent decades, recent reports suggest that the prevalence of food sensitization in the general population has not changed. However, this has not been analyzed in infants at high risk of food allergy. The objective of this study was to compare the prevalence of food sensitization in high-risk infants from 2 cohorts recruited 15 years apart in the same region. This study includes 620 high-risk infants with a family history of allergy (Melbourne Atopy Cohort Study [MACS]) born 1990-1994, and a subgroup of high-risk infants from the population-based HealthNuts study (n = 3,661/5,276), born 2006-2010. Both studies undertook skin prick tests (SPT) to peanut, egg, and milk at age 12 months. A logistic regression model generated adjusted prevalences to account for differences in s ling frame. SPT ≥ 95% positive predictive values (PPVs) for food allergy were used as proxies for food allergy. The adjusted prevalence of sensitization in MACS was similar to the observed prevalence of sensitization in the high-risk subgroup of HealthNuts: 7.9% (95% confidence interval 6.8-8.9) and 7.9% (7.0-8.8) respectively for peanut, 15.0% (13.4-16.6) and 14.5% (13.4-15.7) respectively for egg, and 2.4% (1.6-3.1) and 2.6% (2.0-3.4) respectively for cow's milk. The prevalence of SPT ≥ 95% PPVs was similar between the 2 studies. The prevalence of food sensitization among high-risk infants has remained stable in Australia since the 1990s, despite the reported increase in food-related anaphylaxis in the same period. This discrepancy could be due to increased food allergy in the low-risk population, increased conversion of food sensitization to allergy, or increased number of high-risk infants. Alternatively, increased awareness or severity of reactions may have led to an apparent increase in food allergy.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.ANNEPIDEM.2009.01.024
Abstract: In this review, we describe the epidemiological work conducted by ourselves and others on prone sleep position and sudden infant death. What we have learned since 1990 is that the prone sleep position was a major component of a casual pathway that was operating in over half of the SIDS deaths that were occurring in developed countries at the end of the 1980. It has been estimated that advice to place infants supine to sleep may have saved in the order of 850 infants annually in Australia and other countries. The story of the SIDS epidemic is an ex le of the contribution that epidemiology can make to the understanding and prevention of an important public health problem.
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/01658100701486467
Abstract: To investigate the association between maternal smoking in pregnancy, early-life environment and childhood vision. Twin and triplet children enrolled in the Twins Eye Study in Tasmania underwent a comprehensive ophthalmic examination and their parents/guardians retrospectively answered a questionnaire regarding crawling, walking and other measures. A subset of these twins was also in the Tasmanian Infant Health Survey, which prospectively collected data on antenatal smoking, gestation, birth weight and other factors. The mean age of the 346 in iduals (172 multiple birth sets) at the time of examination was 9.25+/-2.4 years. Mean unaided visual acuity was 0.0 (6/6). The mean spherical equivalent was +0.87D, and decreased with increasing child age (p ) than 100'', p=0.05) and Lang test (p=0.001) and also with the presence of esotropia (p=0.02). These associations persisted after adjustment for infant postnatal smoke exposure at one month of age. Poor stereoacuity on Titmus stereo test circles was associated with late age of first crawling (RR=1.23 (1.06, 1.42) p=0.005 per month) and late age of first walking (RR 1.18 (1.05, 1.22) p=0.001 per month). Antenatal smoking was independently associated with poor stereovision and the presence of esotropia. Poor stereoacuity may be associated with delayed age at first crawling or walking.
Publisher: Wiley
Date: 13-06-2013
DOI: 10.1002/JMV.23605
Abstract: Primary infection with varicella zoster virus (VZV) occurs in immunocompromised and immunocompetent in iduals. Clinical and asymptomatic reactivation with shedding of infectious virus and viremia may occur. The prevalence of VZV viremia is unknown. The aim of this study was to detect VZV viremia and quantify VZV DNA using quantitative polymerase chain reaction (qPCR) in blood from different populations. A qPCR-based method using EvaGreen® was used to quantify VZV DNA in 491 s les, including whole blood, plasma and buffy-coat, from patients hospitalized with varicella-associated disease (Group 1, n=10) and three groups with no VZV disease: in iduals with a first clinical diagnosis of central nervous system demyelination (Group 2, n=213) with their age and sex-matched controls (Group 3, n=218) and HIV-infected in iduals (Group 4, n=50). VZV-specific IgG antibody titres were measured in Group 3. The proportion positive for viremia and mean detectable VZV DNA load (copies/ml) were: Group 1: 100% (10/10) and 4.6 × 10(6) ± 1.4 × 10(7) Group 2: 4% (9/213) and 1.5 × 10(3) ± 1.8 × 10(4) Group 3: 8% (17/218) and 1.1 × 10(3) ± 7.8 × 10(3) Group 4: 12% (6/50) and 7.7 × 10(1) ± 2.8 × 10(2) . VZV DNA load and IgG titres were not significantly correlated (Group 3 only). VZV load in Group 1 was significantly elevated compared to Groups 2-4 (P<0.001) the latter were not significantly different from each other (P=0.05). VZV genotypes from clades 1-5 were identified in Group 1. VZV DNA was detected but at low frequency and viral load in both immunocompetent and immunocompromised in iduals asymptomatic for VZV infection, compared to in iduals with active VZV infection.
Publisher: Cold Spring Harbor Laboratory
Date: 22-09-2021
DOI: 10.1101/2021.09.15.21263636
Abstract: There is mounting evidence that in utero and early life exposures may predispose an in idual to metabolic disorders in later life and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. In this study, we aim to understand the lipid metabolism in pregnancy, and from birth to four years. We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population based pre-birth cohort and measured 776 distinct lipid species across 42 lipid classes using ultra high-performance liquid chromatography (UHPLC). We measured lipids in 1032 maternal serum s les at 28 weeks’ gestation, 893 cord serum s les at birth, 793, 735, and 511 plasma s les at six, twelve months, and four years, respectively. The lipidome differed between mother and newborn and changed markedly with increasing postnatal age. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. Alkenyl-phosphatidylethanolamine species containing LC-PUFAs increased with postnatal age, whereas the corresponding lysophospholipids and triglycerides decreased. We performed regression analyses to investigate the associations of cord serum lipid species with birth factors: gestational age, birth weight, mode of birth and duration of labor. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids. There were marked changes in the plasma lipidome over the first four years of life. This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood. This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2000
DOI: 10.1097/00001648-200003000-00008
Abstract: Our aim was to examine the contribution of an infant's indoor environment to childhood asthma using prospective data. We conducted a cross-sectional asthma survey in 1995 on 92% (6,378/6,911) of 7-year-olds in Tasmania, Australia. We linked these data with data collected in 1988 as part of the Tasmanian Infant Health Survey, which was designed to investigate sudden infant death. We were able to match 863 records out of the 1,111 in the 1988 survey and the 6,378 in the 1995 survey. The former group was interviewed at home at 1 month of age. In homes where at least one adult smoked in 1988, reported infant exposure to smoking in the same room in 1988 was associated with increased asthma by 1995 (relative risk = 1.52 95% confidence interval = 1.01-2.29) after adjustment for confounders. The associations between infant exposure to environmental tobacco smoke and asthma were not consistent, however. Gas heater use in 1988 was associated with asthma (relative risk = 1.92 95% confidence interval = 1.33-2.76). Markers of aeroallergen exposure at 1 month of age were not materially associated with asthma or wheeze. In some settings, air circulation practice with regard to bedroom door closure appeared important. Poor indoor air quality may play an important role in the development of childhood asthma.
Publisher: Hindawi Limited
Date: 12-01-2016
DOI: 10.1111/ANE.12554
Abstract: Anxiety and depression are common in multiple sclerosis (MS). We evaluated the prevalence and factors associated with anxiety, depression and fatigue at the 5-year review of a longitudinal cohort study following a first clinical diagnosis of CNS demyelination (FCD). Cases with a FCD were recruited soon after diagnosis and followed annually thereafter. A variety of environmental, behavioural and clinical covariates were measured at five-year review. Anxiety and depression were measured using the Hospital Anxiety & Depression Scale (HADS), and fatigue by the Fatigue Severity Scale (FSS). Of the 236 cases, 40.2% had clinical anxiety (median HADS-A: 6.0), 16.0% had clinical depression (median HADS-D: 3.0), and 41.3% had clinical fatigue (median FSS: 4.56). The co-occurrence of all three symptoms was 3.76 times greater than expectation. Younger age, higher disability, concussion or other disease diagnosis were independently associated with a higher anxiety score male sex, higher disability, being unemployed, less physical activity, and antidepressant and/or anxiolytic-sedative medication use were independently associated with a higher depression score. Higher disability, immunomodulatory medication use, other disease diagnosis and anxiolytic-sedative medication use were independently associated with having fatigue, while female sex, higher BMI, having had a concussion, being unemployed and higher disability were associated with a higher fatigue score. These results support previous findings of the commonality of anxiety, depression and fatigue in established MS and extend this to post-FCD and early MS cases. The clustering of the three symptoms indicates that they may share common antecedents.
Publisher: BMJ
Date: 24-07-2017
Abstract: Due to the lack of prospective studies with longitudinal data on relapse, past genetic studies have not attempted to identify genetic factors that predict relapse risk (the primary endpoint of many pivotal clinical trials testing the efficacy of multiple sclerosis (MS) disease-modifying drugs) at a genome-wide scale. We conducted a genome-wide association analysis (GWAS) to identify genetic variants that predict MS relapse risk, using a three-stage approach. First, GWAS was conducted using the southern Tasmania MS Longitudinal Study with 141 cases followed prospectively for a mean of 2.3 years. Second, GWAS was conducted using the Ausimmune Longitudinal Study with 127 cases having a classic first demyelinating event followed for 5 years from onset. Third, the top hits with p<5.0×10 In the pooled results, using these three unique longitudinal MS cohorts, we discovered one novel locus ( The finding of a genetic locus that has extensive effects on neuronal development and repair is of interest as a potential modulator of MS disease course.
Publisher: Elsevier BV
Date: 12-2005
Publisher: Oxford University Press (OUP)
Date: 04-07-2022
DOI: 10.1093/BRAINCOMMS/FCAC181
Abstract: Understanding the predictors of progression from a first to a second demyelinating event (and formerly, a diagnosis of clinically definite multiple sclerosis) is important clinically. Previous studies have focused on predictors within a single domain, e.g. radiological, lacking prospective data across multiple domains. We tested a comprehensive set of personal, environmental, neurological, MRI and genetic characteristics, considered together, as predictors of progression from a first demyelinating event to clinically definite multiple sclerosis. Participants were aged 18–59 years and had a first demyelinating event during the study recruitment period (1 November 2003–31 December 2006) for the Ausimmune Study (n = 216) and had follow-up data to 2–3 years post-initial interview. Detailed baseline data were available on a broad range of demographic and environmental factors, MRI, and genetic and viral studies. Follow-up data included confirmation of clinically definite multiple sclerosis (or not) and changes in environmental exposures during the follow-up period. We used multivariable logistic regression and Cox proportional hazards regression modelling to test predictors of, and time to, conversion to clinically definite multiple sclerosis. On review, one participant had an undiagnosed event prior to study recruitment and was excluded (n = 215). Data on progression to clinically definite multiple sclerosis were available for 91.2% (n = 196) 77% were diagnosed as clinically definite multiple sclerosis at follow-up. Mean (standard deviation) duration of follow-up was 2.7 (0.7) years. The set of predictors retained in the best predictive model for progression from a first demyelinating event to clinically definite multiple sclerosis were as follows: younger age at first demyelinating event [adjusted odds ratio (aOR) = 0.92, 95% confidence interval (CI) = 0.87–0.97, per additional year of age) being a smoker at baseline (versus not) (aOR = 2.55, 95% CI 0.85–7.69) lower sun exposure at age 6–18 years (aOR = 0.86, 95% CI 0.74–1.00, per 100 kJ/m2 increment in ultraviolet radiation dose), presence (versus absence) of infratentorial lesions on baseline magnetic resonance imaging (aOR = 7.41, 95% CI 2.08–26.41) and single nucleotide polymorphisms in human leukocyte antigen (HLA)-B (rs2523393, aOR = 0.25, 95% CI 0.09–0.68, for any G versus A:A), TNFRSF1A (rs1800693, aOR = 5.82, 95% CI 2.10–16.12, for any C versus T:T), and a vitamin D-binding protein gene (rs7041, aOR = 3.76, 95% CI 1.41–9.99, for any A versus C:C). The final model explained 36% of the variance. Predictors of more rapid progression to clinically definite multiple sclerosis (Cox proportional hazards regression) were similar. Genetic and magnetic resonance imaging characteristics as well as demographic and environmental factors predicted progression, and more rapid progression, from a first demyelinating event to a second event and clinically definite multiple sclerosis.
Publisher: Wiley
Date: 10-2014
DOI: 10.1002/OBY.20871
Abstract: Cardiorespiratory fitness and adiposity may influence cardiovascular risk through their effects on inflammation. The long-term effects of these modifiable factors on adult inflammation remain uncertain. The associations of childhood and adulthood cardiorespiratory fitness and adiposity with adult inflammation [C-reactive protein (CRP), fibrinogen] were examined. 1,976 children examined in 1985 and re-examined as young adults in 2004-2006 were included. Cardiorespiratory fitness and adiposity were assessed at both waves. CRP and fibrinogen were measured at follow-up. Higher childhood fitness was associated with lower adult inflammation in both sexes. After adjusting for childhood adiposity, the association with CRP attenuated in males, but remained in females (average reduction of CRP 18.1% (95% CI 11.3-24.4%) per 1-SD increase in childhood fitness). Higher adult fitness, adjusting for childhood fitness (an increase in fitness from childhood to adulthood), was associated with lower adult CRP in females and lower fibrinogen in males. Higher childhood and adulthood adiposity (an increase in adiposity from childhood to adulthood) were associated with higher adult inflammation in both sexes. Prevention programs to increase fitness and reduce adiposity in childhood, and maintain a favorable fitness and weight into adulthood, may lead to reduction in adult systemic inflammation.
Publisher: Wiley
Date: 07-1995
DOI: 10.1111/J.1365-3016.1995.TB00141.X
Abstract: A population-based retrospective case-control study has been conducted in Tasmania since October 1988. Study measurements pertained to the scene of death of last sleep, as well as a verbal questionnaire on relevant exposures. From 1 October 1988 to 1 October 1991, 62 cases of sudden infant death syndrome (SIDS) occurred. Case response rate for retrospective interviews was 94% (58/62). The initial control response rate was 84% (101/121). After stratification for maternal age and birthweight, there was no increase in risk associated with the usual side position (odds ratio [OR] 1.05 [0.27, 5.02]), compared with the supine position (OR 1.00, reference). The prone position was associated with increased risk [OR 5.70 (1.67, 25.58)], relative to the supine position. In the final multivariable model, predictors of SIDS in this study were usual prone position (P < 0.001), maternal smoking (P = 0.008), a family history of asthma (P = 0.045) and bedroom heating during last sleep (P = 0.039). Protective factors were maternal age over 25 years (P = 0.013) and more than one child health clinic attendance (P = 0.003). The results provide further support for current health education activities which aim to inform parents of modifiable risk factors for SIDS, including the prone sleeping position, thermal stress and infant exposure to tobacco smoke.
Publisher: Wiley
Date: 08-09-2010
DOI: 10.1111/J.1365-2222.2010.03562.X
Abstract: The incidence of hospital admissions for food allergy-related anaphylaxis in Australia has increased, in line with world-wide trends. However, a valid measure of food allergy prevalence and risk factor data from a population-based study is still lacking. To describe the study design and methods used to recruit infants from a population for skin prick testing and oral food challenges, and the use of preliminary data to investigate the extent to which the study s le is representative of the target population. The study s ling frame design comprises 12-month-old infants presenting for routine scheduled vaccination at immunization clinics in Melbourne, Australia. We compared demographic features of participating families to population summary statistics from the Victorian Perinatal census database, and administered a survey to those non-responders who chose not to participate in the study. Study design proved acceptable to the community with good uptake (response rate 73.4%), with 2171 participants recruited. Demographic information on the study population mirrored the Victorian population with most the population parameters measured falling within our confidence intervals (CI). Use of a non-responder questionnaire revealed that a higher proportion of infants who declined to participate (non-responders) were already eating and tolerating peanuts, than those agreeing to participate (54.4% 95% CI 50.8, 58.0 vs. 27.4% 95% CI 25.5, 29.3 among participants). A high proportion of in iduals approached in a community setting participated in a food allergy study. The study population differed from the eligible s le in relation to family history of allergy and prior consumption and peanut tolerance, providing some insights into the internal validity of the s le. The study exhibited external validity on general demographics to all births in Victoria.
Publisher: Wiley
Date: 23-11-2018
DOI: 10.1111/PHP.13045
Abstract: Cutaneous sun exposure is an important determinant of circulating vitamin D. Both sun exposure and vitamin D have been inversely associated with risk of autoimmune disease. In juvenile idiopathic arthritis (JIA), low circulating vitamin D appears common, but disease-related behavioral changes may have influenced sun exposure. We therefore aimed to determine whether predisease sun exposure is associated with JIA. Using validated questionnaires, we retrospectively measured sun exposure for 202 Caucasian JIA case-control pairs born in Victoria Australia, matched for birth year and time of recruitment. Measures included maternal sun exposure at 12 weeks of pregnancy and child sun exposure across the life-course prediagnosis. We converted exposure to UVR dose and looked for case-control differences using logistic regression, adjusting for potential confounders. Higher cumulative prediagnosis UVR exposure was associated with reduced risk of JIA, with a clear dose-response relationship (trend P = 0.04). UVR exposure at 12 weeks of pregnancy was similarly inversely associated with JIA (trend P = 0.011). Associations were robust to sensitivity analyses for prediagnosis behavioral changes, disease duration and knowledge of the hypothesis. Our data indicate that lower UVR exposure may increase JIA risk. This may be through decreased circulating vitamin D, but prospective studies are required to confirm this.
Publisher: Wiley
Date: 06-04-2005
DOI: 10.1111/J.1398-9995.2005.00757.X
Abstract: We examined the role of fish intake in the development of atopic disease with particular reference to the possibility of differential effects on allergen-specific subgroups of sensitization. The exposure of interest was parental report of fish intake by children aged 8 years at the 1997 Childhood Allergy and Respiratory Health Study (n = 499). The outcomes of interest were subgroups of atopy: house dust mite (HDM)-pure sensitization [a positive skin-prick test (SPT) > or = 2 mm to Der p or Der f only], ryegrass-pure sensitization (a positive SPT > or = 2 mm to ryegrass only) asthma and hay fever by allergen-specific sensitization. A significant association between fish intake and ryegrass-pure [adjusted odds ratio (AOR) 0.37 (0.15-0.90)] but not HDM-pure sensitization [AOR 0.87 (0.36-2.13)] was found. Fish consumption significantly decreased the risk for ryegrass-pure sensitization in comparison with HDM-pure sensitization [AOR 0.20 (0.05-0.79)]. We have demonstrated a differential effect of fish intake for sensitization to different aeroallergens. This may be due to the different timing of allergen exposure during early life. Further investigation of the causes of atopic disease should take into account allergen-specific subgroups.
Publisher: Springer Science and Business Media LLC
Date: 26-01-2019
Publisher: Wiley
Date: 12-2012
Abstract: Multiple sclerosis (MS) is a debilitating disease that causes significant morbidity within a young demographic. Diagnostic guidelines for MS have evolved, and imaging has played an increasingly important role in diagnosis over the last two decades. For imaging to contribute to diagnosis in a meaningful way, it must be reproducible. Consensus guidelines for MRI in MS exist to define correct sequence type and imaging technique, but it is not clear to what extent they are followed. This study reviewed MRI studies performed on Australian in iduals presenting with a first clinical diagnosis of central nervous system demyelination (FCD) for adherence to published guidelines and discussed practical implementation of MS guidelines in light of recent updates. The Ausimmune study was a prospective case control study of Australian participants presenting with FCD from 2003 to 2006. Baseline cranial and spinal cord MRI studies of 226 case participants from four separate Australian regions were reviewed. MRI sequences were classified according to anatomical location, slice plane, tissue weighting and use of gadolinium-containing contrast media. Results were compared with the 2003 Consortium of Multiple Sclerosis Centres MRI protocol for the diagnosis of MS. The composition of core cranial MRI sequences performed varied across the 226 scans. Of the studies, 91% included sagittal fluid attenuated inversion recovery (FLAIR) sequences. Cranial axial T2-weighted, axial FLAIR and axial proton density-weighted sequences were performed in 88%, 60% and 16% (respectively) of scans. Only 25% of the studies included a T1-weighted contrast-enhanced sequence. Concordance with the guidelines in all sequences was very low (2). Only a small number of MRI investigations performed included all of the sequences stipulated by consensus guidelines. This is likely due to poor awareness in the imaging community of the guidelines and the rationale behind certain sequences. Radiologists with a sub-speciality interest in neuroradiology should take ownership of this issue and ensure that recommended imaging guidelines are followed.
Publisher: Elsevier BV
Date: 10-2017
Publisher: SAGE Publications
Date: 23-04-2018
Abstract: In the general population, variation in the serotonin-transporter-linked polymorphic region ( 5-HTTLPR) has been shown to modify the association between stressful events and depression/anxiety. This has not been examined in people with multiple sclerosis (MS). We examined the interaction between significant life events (SLE), 5-HTTLPR and depression/anxiety. A population-based longitudinal cohort of 198 people with MS was followed biannually for 2.5 years. Depression and anxiety symptoms were measured at each review using the Hospital Anxiety and Depression Scale (HADS). SLEs were assessed using a questionnaire based on the Social Readjustment Rating Scale. We found an interaction between SLE load in the previous 12 months and functional variation in the 5-HTTLPR allele type in predicting depression, with the association between SLE load and depression being stronger for those with S/S allele type (β = 0.21 (95% confidence interval (CI): 0.09–0.33) per 10-unit increase) and S/L (β = 0.14 (95% CI: 0.05–0.24)) compared to L/L allele type (β = 0.04 (95% CI: −0.05 to 0.24) p interaction 0.001). No convincing evidence of an interaction was found with anxiety. We found that the association between SLE load and MS depression severity was stronger among those with one or two copies of the short allele of the 5-HTTLPR. The identification of a gene–environment interaction between SLEs and depression in a population where depression is partly disease-driven is novel.
Publisher: Informa UK Limited
Date: 2008
Publisher: Wiley
Date: 07-03-2007
DOI: 10.1111/J.1399-3038.2006.00509.X
Abstract: Studies on the role of non-milk fluids in the development of child atopic disease are scarce. We had a unique opportunity to investigate prospective association between the introduction of fruit syrup, orange juice, sterilized water, vitamins and honey at 1 month and the development of child atopic disease. The exposure of interest was measured by parental report of non-milk fluids introduction to infants aged 1 month at the Tasmanian Infant Health Survey, 1988-89, Tasmania. Data on the outcomes of interest (atopic sensitization, asthma, eczema and hay fever) were collected during the 1997 Childhood Allergy and Respiratory Health Study when children were 8 yr old. Relative risks were derived from generalized linear model with a log link function and binomial error structure. None of the non-milk fluids appeared to be a significant predictor of atopic sensitization. Only sterilized water was a significant risk factor for asthma (adjusted relative risk = 1.59 95% confidence intervals: 1.14-2.22), which may be partly because of associated overall better hygienic conditions and decreased exposure to early infections in the household. In summary, we were unable to find evidence for an association between introduction of non-milk fluids in infancy and childhood atopic disease.
Publisher: BMJ
Date: 21-07-2001
Publisher: Springer Science and Business Media LLC
Date: 27-09-2002
Abstract: Syndrome X (clustering of insulin resistance, dyslipidaemia and hypertension) in adults with central obesity has been suggested to be a consequence of poor foetal development. We investigated clustering of syndrome X factors in a s le of 8-y-old Australian children, and whether the clusters were associated with size at birth and childhood obesity. Longitudinal, 1997 follow-up of children enrolled as singleton-born neonates in 1989. A total of 298 healthy Australian children (208 boys, 90 girls, age range 7.4-8.9 y). Anthropometry at birth and at 4 weeks. In 1997, at 8 y of age: fasting insulin and glucose, total and HDL-cholesterol, triglycerides and blood pressure. Adverse levels of insulin and glucose, cholesterol and triglycerides co-existed more often than expected by chance (P<0.01). Three factors were identified in factor analysis: one loading on systolic and diastolic blood pressure ('blood pressure') a second loading on insulin and glucose ('insulin resistance') and a third loading negatively on HDL-cholesterol and positively on triglycerides ('dyslipidaemia'). The blood pressure factor was correlated with fatness at age 8 y (eg fat mass estimated from skin folds, r=0.11) and, after adjustment for current size, with birth weight (r=-0.15). Fat mass was also correlated with both 'insulin resistance' (r=0.24) and 'dyslipidaemia' (r=0.19). The increase in 'insulin resistance' (P=0.03) and 'dyslipidaemia' (P<0.01) per category of fat mass was greatest for subjects with higher-than-median subscapular-to-triceps ratio of skin folds. Neither 'insulin resistance' nor 'dyslipidaemia' was associated with anthropometry at birth. The Syndrome X risk variables clustered among children who had a tendency to deposit fat on the trunk. There was no evidence in this s le that infant size predicts development of the insulin resistance or dyslipidaemic components of the syndrome by age 8.
Publisher: BMJ
Date: 11-08-2011
Abstract: This review of the considerable evidence linking Epstein-Barr virus (EBV) infection to risk and disease progression in multiple sclerosis (MS) builds on the background to the virus and its interactions with the human host available in the online supplement (see supplement, available online only). The evidence for a similarity in the geographic patterns of occurrence of MS and EBV infection (with infectious mononucleosis or EBV specific serology used as surrogate markers), when reviewed critically, is very limited. There is strong evidence however that people with MS are more likely to report a past history of infectious mononucleosis (thought to represent initial EBV infection at an older age), and higher titres of EBV specific antibodies are associated with an increased risk of developing MS. Elevated levels of the latter are apparent many years before MS onset (compared with non-MS controls) and there is a dose-response relationship between MS risk and antibody titre, with antibodies to the EBV nuclear antigen-1 particularly important. The evidence in relation to EBV DNA load in blood or CSF is conflicting, as is that in relation to T cell responses to EBV. Several hypotheses that have been proposed to explain the links between EBV and MS risk are reviewed and gaps requiring further research are identified.
Publisher: Trans Tech Publications Ltd.
Date: 15-01-2006
Publisher: Wiley
Date: 09-10-2016
DOI: 10.1111/IJPO.12187
Abstract: 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. The aim of this study was to investigate the association between maternal pre-pregnancy BMI and newborn adiposity and inflammation. Paired maternal (28-week gestation) and infant (umbilical cord) blood s les 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. Maternal pre-pregnancy BMI was positively associated with increased birth weight (mean difference 17.8 g per kg m Higher maternal pre-pregnancy BMI is associated with increased newborn adiposity and inflammation. These associations may be partially mediated by maternal inflammation during pregnancy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
DOI: 10.1161/HYPERTENSIONAHA.108.125914
Abstract: Recent studies reported an association between smaller birth size and narrower retinal vascular caliber, but it remains unclear whether this association is attributed to confounding by shared environment or genetic factors. At a mean age of 9.3 years, 266 twins (49 monozygotic and 84 dizygotic pairs) in the Twins Eye Study in Tasmania underwent an ophthalmic examination including retinal photography. Retinal vascular caliber was measured using a validated protocol. The majority of these twins were also in the Tasmanian Infant Health Study, which prospectively collected data on birth parameters and antenatal maternal factors. We conducted the main analysis using linear mixed models, accounting for birth set clustering. Both the within-pair (−9.73 95% CI: −14.68 to −4.77 μm per 5-cm decrease in birth length) and between-pair associations (−7.15 95% CI: −11.54 to −3.01) with retinal arteriolar caliber were significant and of similar magnitude (difference in effect, P =0.61), after adjusting for age, sex, maternal smoking, mean arterial blood pressure, and other confounders. These associations remained within dizygotic and monozygotic pairs. Analyses of head circumference and retinal arteriolar caliber were similar to those of birth length (within-pair regression coefficient: −2.41 95% CI: −5.09 to 0.28 between-pair regression coefficient: −2.60 95% CI: −5.00 to −0.19). For birth weight, only a between-pair association was evident (−7.28 95% CI: −13.07 to −1.48). This study demonstrates a consistent association between smaller birth size and narrower retinal arterioles in twins. The independent effect of shorter birth length on retinal arteriolar caliber supports a role for twin-specific supply line factors affecting fetal growth on vascular structure.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JAIP.2018.07.042
Abstract: We previously reported that infants with Asian-born parents are 3 times more likely to have IgE-mediated food allergy than those with Australian-born parents. It is unknown whether this translates to the increased risk of other allergic diseases later in childhood and whether ancestry interacts with other risk factors for allergic disease development. To compare prevalence and risk factors for allergic rhinitis, asthma, and aeroallergen sensitization at age 6 between children with East Asian-born and Caucasian-born parents. A total of 5276 1-year-old infants were recruited into a population-based longitudinal study of allergy. A total of 4455 children participated in age 6 follow-up (84.4%), including 3015 with Caucasian-born parents and 415 with East Asian-born parents. Children underwent skin prick tests to aeroallergens and questionnaires captured data on asthma, eczema, and allergic rhinitis. Compared with children with Caucasian-born parents, children of East Asian-born parents had more allergic rhinitis (19.9% [95% confidence interval (CI) 14.9-26] vs 9.3% [95% CI 8-10.8], P < .001) and aeroallergen sensitization (64.3% [95% CI 57.5-70.5] vs 34.4% [95% CI 32.2-36.7], P < .001) at age 6. Asthma was similar in both groups (9.1% [95% CI 6.2-13.2] vs 11.7% [95% CI 10.4-13.1]), P = .21. Children with IgE-mediated food allergy and eczema in infancy were 3 times more likely to have asthma and 2 times more likely to have allergic rhinitis at age 6, irrespective of ancestry. Children of East Asian ancestry born in Australia have a higher burden of most allergic diseases in the first 6 years of life, whereas asthma may follow a different pattern. IgE-mediated food allergy and eczema at age 1 increase the risk of asthma and allergic rhinitis irrespective of ancestry.
Publisher: Wiley
Date: 11-2022
DOI: 10.1111/PAI.13883
Abstract: Australia has one of the highest prevalence of childhood food allergy in the world, but there are no data on its economic burden in Australia. We used data from the HealthNuts study, a population‐based longitudinal study undertaken in Melbourne, Australia. Infants were recruited at age 12 months between Sept 2007 and Aug 2011 with food allergy diagnosed using oral food challenges. Health care costs of out‐of‐hospital services were collected through data linkage to Australia's universal health insurance scheme Medicare. Two‐part model was used to compare costs after controlling for potential confounders. 2919 children were included, and 390 (13.4%) had challenge‐confirmed food allergy at age 1 year. Compared with children without food allergy, children with food allergy had significantly higher costs for GP visits, specialist visits, tests, and prescriptions in the first four years of life. The total Medicare cost associated with food allergy from age 1 to 4 years was estimated to be AUD$889.7 (95% CI $566.1–$1188.3) or €411.0 (95% CI €261.5–€549.0) per child. This was projected into an annual Medicare cost of AUD$26.1 million (95% CI $20.1–$32.3 million) or €12.1 (95% CI €9.3–€14.9 million) based on population size in 2020. Childhood food allergy causes considerable Medicare costs for out‐of‐hospital services in the first four years after birth in Australia. These findings can help anticipate the financial impact on the health care system associated with childhood food allergy, act as a useful costing resource for future evaluations, and inform management of childhood food allergy internationally.
Publisher: American Association for Cancer Research (AACR)
Date: 07-2017
DOI: 10.1158/1055-9965.EPI-16-0846
Abstract: Background: Conjunctival ultraviolet autofluorescence (CUVAF) area detected from UVAF photographs is a recently developed potential marker for past sun exposure, but its relationship with sun-related factors has not been fully investigated. Methods: The study included 339 healthy children ages 5 to 15 years in Melbourne, Australia. Data were collected by questionnaire and examination at school. CUVAF area was measured using a computer program and analyzed as a continuous and dichotomous outcome (any/none). Results: Fifty-three children (15.6%) had detectable CUVAF, and the youngest age at which a child showed sun damage was 8 years. Compared with silicone skin cast score, there was good inter-grader agreement on CUVAF grading, with Cohen kappa 0.85 [95% confidence interval (CI), 0.65–1.00] for total CUVAF area using both eye photographs. Perfect intra-grader agreement was achieved. Fairer pigmentation, including medium/fair skin color [adjusted odds ratio (AOR), 3.42 95% CI, 1.02–11.48 vs. dark/olive] and blue/gray eye color (AOR, 4.07 95% CI, 1.73–9.55 vs. brown) was associated with increased odds of CUVAF. Increasing lifetime sunburn number (e.g., AOR, 2.89 95% CI, 1.14–7.35 and 4.29 1.04–17.76 for sunburns 2 to 4 and ≥ 5 times, respectively, vs. no sunburns, trend P = 0.004) and freckling by the end of last summer were associated with increased odds of CUVAF. Conclusions: CUVAF area can be an a priori objective measure of past sun exposure in pediatric populations for future research. Impact: To our knowledge, this is the first pediatric study that evaluated associations of sun-related risk factors with CUVAF. Cancer Epidemiol Biomarkers Prev 26(7) 1146–53. ©2017 AACR.
Publisher: Springer Science and Business Media LLC
Date: 07-2014
Publisher: Springer Science and Business Media LLC
Date: 17-01-2020
DOI: 10.1038/S41390-020-0762-4
Abstract: Nuclear magnetic resonance (NMR) metabolic profiling quantifies a large number of metabolites. From adolescence, specific metabolites are influenced by age, sex and body mass index data on early-life metabolic profiles are limited. We investigated associations between sex, birth weight, weight and adiposity with NMR metabolic profile at age 12 months. The plasma NMR metabolic profile was quantified in infants (n = 485) from the Barwon Infant Study. Associations between 74 metabolites and sex, birth weight z-score and 12-month measures (weight z-score, skinfold thickness, weight-for-length z-score) were examined using linear regression models. Several cholesterol and fatty acid measures were higher (0.2-0.3 SD) in girls than in boys we observed modest sex-specific associations of birth weight z-scores and 12-month sum of skinfold thicknesses with metabolites. The pattern of associations between weight z-score and weight-for-length z-score with metabolites at 12 months was more pronounced in girls, particularly for fatty acid ratios. We identified sex differences in the infant metabolic profile. Sex-specific patterns observed differ from those reported in older children and adults. We also identified modest cross-sectional associations between anthropometric and adiposity measures and metabolites, some of which were sex specific.
Publisher: Oxford University Press (OUP)
Date: 14-09-2021
DOI: 10.1093/IJE/DYAB199
Abstract: Previous epidemiological studies have found positive associations between maternal infections and childhood leukaemia however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data. Data were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL) secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models. Among 312 879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10–2.58)] and subtypes ALL [1.49 (0.87–2.56)] and AML [2.70 ([0.93–7.86)], but not with any cancer [1.13 (0.85–1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06–2.34)], ALL [1.43 (0.94–2.19)], AML [2.37 (1.10–5.12)] and any cancer [1.33 (1.09–1.63)] influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes. Urinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.
Publisher: Oxford University Press (OUP)
Date: 18-04-2013
DOI: 10.1111/CEI.12077
Abstract: The increasing prevalence of immune-related diseases, including multiple sclerosis, may be partly explained by reduced microbial burden during childhood. Within a multi-centre case–control study population, we examined: (i) the co-morbid immune diseases profile of adults with a first clinical diagnosis of central nervous system demyelination (FCD) and (ii) sibship structure in relation to an autoimmune (FCD) and an allergic (asthma) disease. FCD cases (n = 282) were aged 18–59 years controls (n = 558) were matched on age, sex and region. Measures include: history of doctor-diagnosed asthma sibling profile (number dates of birth) and regular childcare attendance. FCD cases did not differ from controls with regard to personal or family history of allergy, but had a greater likelihood of chronic fatigue syndrome [odds ratio (OR) = 3·11 95% confidence interval (CI) 1·11, 8·71]. Having any younger siblings showed reduced odds of FCD (OR = 0·68 95% CI: 0·49, 0·95) but not asthma (OR = 1·47 95% CI: 0·91, 2·38). In contrast, an increasing number of older siblings was associated with reduced risk of asthma (P trend = 0·04) but not FCD (P trend = 0·66). Allergies were not over-represented among people presenting with FCD. Sibship characteristics influence both FCD and asthma risk but the underlying mechanisms differ, possibly due to the timing of the putative ‘sibling effect’.
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000334693
Abstract: b i Objectives: /i /b To identify Epstein-Barr virus (EBV) genotypes and strains in s les from in iduals with and without a first diagnosis of central nervous system (CNS) demyelinating disease (a possible precursor to multiple sclerosis) and patients with EBV-associated diseases in Australia. b i Methods: /i /b S les from 55 EBV DNA and serology positive subjects including in iduals with (n = 17) and without (n = 21) a first clinical diagnosis of CNS demyelination and patients with EBV-related diseases (n = 17) were examined. EBV genotype and strain were identified by sequence mutations within the Epstein-Barr nuclear antigen-2 region (EBNA-2) using DNA sequence analysis. b i Results: /i /b Both EBV genotypes, A and B, were detected (genotype A, 54/55, 98.2% genotype B, 1/55, 1.8%). Within genotype A, GD1 was the most commonly detected strain (42/54, 77.7%), followed by B95-8 (9/54, 16.7%) and M-ABA (3/54, 5.6%). Genotype B, strain AG876, was found in one in idual with CNS demyelinating disease. b i Conclusions: /i /b EBV genotype A and the GD1 strain were the common EBV genotypes isolated from in iduals with and without CNS demyelinating disease, and in subjects with various EBV-related diseases. Although disease-specific genotypes or strains were not identified, this study provides useful insights into the molecular epidemiology of EBV infection in Australia.
Publisher: BMJ
Date: 03-2021
DOI: 10.1136/BMJOPEN-2020-041984
Abstract: Larger sibships are associated with poorer cognitive and language outcomes but have different impacts on child emotional development. Previous studies have not taken into account sibling age, nor have impacts across multiple neurodevelopmental domains been considered in the same participant group. This study investigated the influence of family size indicators on early childhood cognitive, language and emotional-behavioural development. The effect of sibling age was considered by evaluating these relationships separately for different sibling age categories. Prospective birth cohort study. Participants in the Barwon Infant Study were recruited from two major hospitals in the Barwon region of Victoria, Australia, between 2010 and 2013 (n=1074 children). The 755 children with any neurodevelopmental data at age 2–3 years excluding twins and those with an acquired neurodisability. Cognitive and language development was assessed using the Bayley Scales of Infant and Toddler Development, Third Edition, and emotional-behavioural development was measured with the Child Behaviour Checklist for Ages 1½−5. Greater household size was associated with a reduced cognitive development score (adjusted mean difference (AMD) −0.66 per extra household member 95% CI −0.96 to –0.37 p .001) without age-specific differences. However, poorer expressive language was only observed for exposure to siblings between 2–6 and 6–10 years older. Having siblings 2–6 years older was associated with less internalising behaviour (AMD −2.1 per sibling 95% CI −3.1 to –1.0 p .001). These associations persisted after multiple comparison adjustment. The influence of siblings on early childhood development varies substantially by sibling age and the neurodevelopmental outcome under study. Although family size alone appears important for cognitive development, age-specific findings emphasise the importance of sibling interaction in early childhood expressive language development and emotional behaviour.
Publisher: Wiley
Date: 04-09-2013
DOI: 10.1111/ALL.12215
Abstract: Sensitization to food allergens indicates the production of food-specific IgE however, sensitization is not a definite indicator of allergic reaction upon ingestion (N Engl J Med, 344, 2001, 30: J Allergy Clin Immunol, 120, 2007, 491). Currently, food challenge is the best approach to identify the presence or absence of allergy. While 95% positive predictive values (PPVs) thresholds for sIgE can assist with identifying increased likelihood of allergy among those who are sensitized, there are no specific biological markers that differentiate between allergic and sensitized in iduals. To determine whether plasma serum cytokine profiles predict (i) sensitization to peanut and egg and (ii) food allergy among sensitized infants. Peanut-sensitized (PT) and egg-sensitized 14-month-old infants and nonsensitized controls enrolled in HealthNuts, a population-based study of food allergy, underwent an oral food challenge (OFC). Blood was collected within 1 h after OFC. Serum levels of Th1, Th2 and regulatory cytokines were determined in allergic (n = 79), sensitized (n = 40) and nonsensitized, nonallergic (n = 37) infants by multiplex assay. Food-sensitized infants had significantly higher plasma IL-4, IL-13, IL-12p70 and lower IL-10 levels compared to nonsensitized infants. IL-10 and IL-6 levels were significantly higher in sensitized compared with allergic infants. Egg-allergic infants had significantly higher IL-13 and IL-12p70 levels compared to peanut-allergic (PA) infants. Levels of Th2-related cytokines in plasma are higher in food-sensitized infants, irrespective of clinical food allergy status. In contrast, IL-10 levels appear to predict food allergy among sensitized infants. Differences in IL-13 and IL-12p70 between egg- and peanut-allergic infants could help explain the different resolution rates of the allergies.
Publisher: Environmental Health Perspectives
Date: 08-2007
DOI: 10.1289/EHP.9937
Publisher: Wiley
Date: 20-08-2009
DOI: 10.1111/J.1399-3038.2008.00817.X
Abstract: Studies on early life viral respiratory infection and subsequent atopic disease in childhood have conflicting findings. Animal models show that viral respiratory infection in conjunction with allergen presentation can enhance sensitization. This prospective study assesses the influence of an upper respiratory tract infection (URI) in the first month of life and the season of birth on the development of hay fever and ryegrass allergen sensitization in childhood. From a Tasmanian cohort born during 1988 and 1989, a group of 498 children were followed up at 8 yr and another different group of 415 children were followed up at 16 yr. The ryegrass pollen season in Tasmania occurs in November and December. Forty-four (9.6%) children in Follow-up s le 1 and 47 (12.5%) children in Follow-up s le 2 were born in the pollen season. The parental report of an early upper respiratory tract infection (EURI) was documented prospectively by a home interview at 1 month of age (median age 5.1 wk). Sensitization to ryegrass and house dust mite (HDM) was determined at 8 yr of age by skin prick testing and at 16 yr by ImmunoCap. Ryegrass sensitized hay fever was defined as a positive response to a question on hay fever plus the presence of ryegrass allergy. For children tested at age 8 and born in the pollen season, a EURI by postnatal interview was associated with an increased risk of ryegrass sensitization (OR 5.80 95% CI 1.07, 31.31) but not for children with a EURI born outside the pollen season (OR 0.62 95% CI 0.35, 1.08). Similarly, EURI was significantly associated with early onset (< or = 8 yr) ryegrass sensitized hay fever for children born in the pollen season (AOR 4.78 95% CI 1.17, 19.47) but was not associated with early onset ryegrass sensitized hay fever for children born outside the pollen season (AOR 0.76 95% CI 0.43, 1.33). These findings suggest that early life viral URI interacts with ryegrass allergen exposure in the development of ryegrass allergen sensitization and ryegrass sensitized hay fever symptoms.
Location: Australia
No related grants have been discovered for Anne-Louise Ponsonby.