Paediatrics (RCH) - Research Publications
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ItemNut allergy prevalence and differences between Asian-born children and Australian-born children of Asian descent: a state-wide survey of children at primary school entry in Victoria, Australia(WILEY, 2016-04)BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
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ItemTiming of routine infant vaccinations and risk of food allergy and eczema at one year of age(WILEY, 2016-04)BACKGROUND: Epidemiological evidence suggests that routine vaccinations can have nontargeted effects on susceptibility to infections and allergic disease. Such effects may depend on age at vaccination, and a delay in pertussis vaccination has been linked to reduced risk of allergic disease. We aimed to test the hypothesis that delay in vaccines containing diphtheria-tetanus-acellular pertussis (DTaP) is associated with reduced risk of food allergy and other allergic diseases. METHODS: HealthNuts is a population-based cohort in Melbourne, Australia. Twelve-month-old infants were skin prick-tested to common food allergens, and sensitized infants were offered oral food challenges to determine food allergy status. In this data linkage study, vaccination data for children in the HealthNuts cohort were obtained from the Australian Childhood Immunisation Register. Associations were examined between age at the first dose of DTaP and allergic disease. RESULTS: Of 4433 children, 109 (2.5%) received the first dose of DTaP one month late (delayed DTaP). Overall, delayed DTaP was not associated with primary outcomes of food allergy (adjusted odds ratio (aOR) 0.77; 95% CI: 0.36-1.62, P = 0.49) or atopic sensitization (aOR: 0.66; 95% CI: 0.35-1.24, P = 0.19). Amongst secondary outcomes, delayed DTaP was associated with reduced eczema (aOR: 0.57; 95% CI: 0.34-0.97, P = 0.04) and reduced use of eczema medication (aOR: 0.45; 95% CI: 0.24-0.83, P = 0.01). CONCLUSIONS: There was no overall association between delayed DTaP and food allergy; however, children with delayed DTaP had less eczema and less use of eczema medication. Timing of routine infant immunizations may affect susceptibility to allergic disease.
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ItemNo Preview AvailableNatural history of HFE simple heterozygosity for C282Y and H63D: A prospective 12-year study(WILEY, 2015-04)BACKGROUND AND AIM: The risk of hemochromatosis-related morbidity for HFE simple heterozygosity for either the C282Y or H63D substitutions in the HFE protein was assessed using a prospective community-based cohort study. METHODS: HFE genotypes were measured for 31,192 persons of northern European descent, aged between 40 and 69 years when recruited to the Melbourne Collaborative Cohort Study, and subjects were followed for an average of 12 years. For a random sample of 1438 participants stratified according to HFE genotype, two sets of biochemical iron indices performed 12 years apart and, at follow-up only, the presence/absence of six disease features associated with hereditary hemochromatosis were obtained. Summary data for 257 (139 female) C282Y simple heterozygotes and 123 (74 female) H63D simple heterozygotes were compared with 330 (181 female) controls with neither HFE mutation. RESULTS: At baseline, mean transferrin saturation (TS) (95% confidence interval) and prevalence of TS > 55% were 35.14% (33.25, 37.04) and 3/112 (3%), 33.03% (29.9, 36.15) and 0/39 (0%), and 29.67% (27.93, 31.4) and 3/135 (2%) for C282Y, H63D and wild-type male participants, respectively. At follow-up, mean TS levels remained similar to baseline levels for both men and women irrespective of simple heterozygosity for either mutation. No HFE C282Y or H63D simple heterozygotes had documented iron overload (based on hepatic iron measures or serum ferritin greater than 1000 mg/L at baseline with documented therapeutic venesection). CONCLUSION: No documented iron overload was observed for HFE simple heterozygotes for either C282Y or H63D, and morbidity for both HFE simple heterozygote groups was similar to that of HFE wild-type participants.
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ItemDo Variants in GSTs Modify the Association between Traffic Air Pollution and Asthma in Adolescence?(MDPI AG, 2016-04)Polymorphisms in genes involved in the oxidative stress response may partially explain the documented heterogeneous associations between traffic-related air pollution (TRAP) exposure and asthma and allergies in children. We investigated whether the GSTT1, GSTM1 and GSTP1 gene polymorphisms modified the associations between TRAP exposure during the first year of life and asthma, wheeze and hay fever in adolescence. We used a birth cohort of 620 high risk infants from the Melbourne Atopy Cohort Study. TRAP exposure during the first year of life was defined as the cumulative length of major roads within 150 m of each participant's residence during the first year of life. Wheeze, asthma and hay fever were measured at ages 12 (n = 370) and 18 (n = 434) years. The associations and interactions with glutathione S-transferases (GST s) were investigated using regression models. Overall, there was no relationship between TRAP exposure during the first year of life and current asthma, wheeze and hay fever at ages 12 or 18 years. However, in GSTT1 null carriers, every 100 m increase in cumulative lengths of major road exposure during the first year of life was associated with a 2.31-fold increased risk of wheeze and a 2.15-fold increased risk of asthma at 12 years. TRAP is associated with some respiratory outcomes in carriers of genetic polymorphisms in oxidative stress metabolism genes.
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ItemShould HFE p.C282Y homozygotes with moderately elevated serum ferritin be treated? A randomised controlled trial comparing iron reduction with sham treatment (Mi-iron)(BMJ PUBLISHING GROUP, 2015)INTRODUCTION: HFE p.C282Y homozygosity is the most common cause of hereditary haemochromatosis. There is currently insufficient evidence to assess whether non-specific symptoms or hepatic injury in homozygotes with moderately elevated iron defined as a serum ferritin (SF) of 300-1000 µg/L are related to iron overload. As such the evidence for intervention in this group is lacking. We present here methods for a study that aims to evaluate whether non-specific symptoms and hepatic fibrosis markers improve with short-term normalisation of SF in p.C282Y homozygotes with moderate elevation of SF. METHODS AND ANALYSIS: Mi-iron is a prospective, multicentre, randomised patient-blinded trial conducted in three centres in Victoria and Queensland, Australia. Participants who are HFE p.C282Y homozygotes with SF levels between 300 and 1000 μg/L are recruited and randomised to either the treatment group or to the sham treatment group. Those in the treatment group have normalisation of SF by 3-weekly erythrocytapheresis while those in the sham treatment group have 3-weekly plasmapheresis and thus do not have normalisation of SF. Patients are blinded to all procedures. All outcome measures are administered prior to and following the course of treatment/sham treatment. Patient reported outcome measures are the Modified Fatigue Impact Scale (MFIS-primary outcome), Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study 36-item short form V.2 (SF36v2) and Arthritis Impact Measurement Scale 2 short form (AIMS2-SF). Liver injury and hepatic fibrosis are assessed with transient elastography (TE), Fibrometer and Hepascore, while oxidative stress is assessed by measurement of urine and serum F2-isoprostanes. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Ethics Committees of Austin Health, Royal Melbourne Hospital and Royal Brisbane and Women's Hospital. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: Trial identifier: NCT01631708; Registry: ClinicalTrials.gov.