Paediatrics (RCH) - Research Publications
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ItemPrevalence and determinants of antibiotic exposure in infants: A population-derived Australian birth cohort study(WILEY, 2017-10-01)AIM: 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. METHODS: The Barwon Infant Study is a birth cohort study (n = 1074) with an unselected antenatal sampling 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. RESULTS: 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. CONCLUSION: 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.
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ItemAdvice about infant feeding for allergy prevention: A confusing picture for Australian consumers?(WILEY, 2017-09-01)AIM: Early feeding plays an important role in programming the immune system, particularly the risk of food allergy. There are many infant feeding guides published for consumers available in Australia, with most based on the National Health and Medical Research Council (NHMRC) 2012 Infant Feeding Guidelines for Health Workers and the Australasian Society of Clinical Immunology and Allergy (ASCIA) Infant Feeding Advice for allergy prevention. We sought to compare allergy-specific content of infant feeding educational material written for parents with these two documents. METHODS: Australian websites of children's hospitals, early child health organisations and consumer groups providing information about diet during pregnancy, breastfeeding and early infancy were compared with NHMRC and ASCIA guidelines. RESULTS: Twenty-five sets of infant feeding information were identified. Food allergy was discussed in 18 resources. Recommended length of exclusive breastfeeding and timing of commencing solid foods was consistently around 6 months, with some variation in wording. Advice regarding to include and not delay introduction of common allergens into babies' diets was generally consistent with NHMRC and ASCIA recommendations, however the audit identified some resources that still recommended delayed introduction of common allergens. CONCLUSION: As consumers have access to a plethora of health information it is imperative that information about infant feeding from health-care authorities is simple, evidence-based and consistent to avoid confusion. Use of consensus wording related to infant feeding guidelines to prevent allergies will provide clear messages related to the timing of introduction to solid foods and inclusion of allergens in the early diet.
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ItemGenetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy(WILEY, 2017-08-01)BACKGROUND: 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. OBJECTIVE: Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy. METHOD: 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 sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. RESULTS: IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (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. CONCLUSIONS AND CLINICAL RELAVANCE: 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.
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ItemAge at onset and persistence of eczema are related to subsequent risk of asthma and hay fever from birth to 18 years of age(WILEY, 2017-06-01)BACKGROUND: Few studies have simultaneously addressed the importance of age of onset and persistence of eczema for the subsequent development of asthma and hay fever, particularly into early adulthood. METHODS: A high-risk birth cohort was recruited comprising 620 infants, who were then followed up frequently until 2 years of age, annually from age 3 to 7, then at 12 and 18 years, to document any episodes of eczema, current asthma, and hay fever. The generalized estimation equation technique was used to examine asthma and hay fever outcomes at 6 (n = 325), 12 (n = 248) and 18 (n = 240) years, when there was consistency of associations across the follow-ups. RESULTS: Very early-onset persistent (onset <6 months, still present from 2 to 5 years) eczema was related to current asthma (adjusted OR = 3.2 [95% CI = 1.7-6.1]), as was very early-onset remitting eczema (onset <6 months but not present from 2-5 years, OR = 2.7, 95% CI = 1.0-7.2) and early-onset persistent eczema (onset from 6-24 months, OR = 2.3, 95% CI = 1.2-4.7). Late-onset eczema (commenced from 2-5 years) was associated with increased risk of asthma at 12 years (OR = 3.0, 95% CI=1.1-8.2) but not at age 6 years. Only very early-onset persistent eczema was associated with increased risk of hay fever (aOR = 2.4, 95% CI = 1.4-4.1). CONCLUSION AND CLINICAL RELEVANCE: Eczema which commences in early infancy and persists into toddler years is strongly associated with asthma, and to a lesser extent hay fever, in high-risk children. If these associations are causal, prevention of early-life eczema might reduce the risk of respiratory allergy.
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ItemThe practice and perception of precautionary allergen labelling by the Australasian food manufacturing industry(WILEY, 2017-07-01)BACKGROUND: The precautionary allergen labelling (PAL) and Voluntary Incidental Trace Allergen Labelling (VITAL® ) tools were designed by industry to assist consumers with selecting safe foods for consumption. However, a sizeable proportion of food products bear no label, and it is unclear whether these products are free from allergens and therefore safe to consume or have simply not undergone a risk assessment and therefore remain unlabelled for that reason. OBJECTIVE: To assess the prevalence of unlabelled products that have undergone a risk assessment process and to examine the factors influencing industry's uptake of the VITAL® process. METHODS: A web-based questionnaire was distributed to Australasian food and grocery manufacturers. RESULTS: One hundred and thirty-seven Australasian manufacturers were contacted, and 59 questionnaires were returned (response rate: 43%). The respondents represented 454 different manufacturing sites. Manufacturers reported that 23% (95% CI 19-28) of products (n=102/434) that had been through the VITAL® risk assessment process had no PAL statement on the label. 34% (95% CI 30-38), (n=204/600) of products that had undergone another (non-VITAL® ) risk assessment process had no PAL statement. In examining the factors that influenced industry's uptake of the VITAL® process, 25 manufacturers reported on factors that influenced the uptake of the VITAL® process, 76% (CI 95% 55-91) reported that VITAL® was an effective tool because it was based on science; 52% (CI 95% 31-72) reported that it was too time-consuming and 36% (CI 95% 18-57) identified a concern with it not being endorsed by the government. CONCLUSION AND CLINICAL RELEVANCE: Currently, we estimate that at least 30% of products may have been through a risk assessment process and yet bear no PAL statement on the label. Permissive labelling could be incorporated onto these products if they have been assessed to be safe for consumption.
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ItemThe skin barrier function gene SPINK5 is associated with challenge-proven IgE-mediated food allergy in infants(WILEY, 2017-09-01)BACKGROUND: 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. OBJECTIVE: To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy. METHOD: 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 sample) 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 individuals. 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 sample 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. RESULTS: SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery sample (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. CONCLUSIONS: We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.
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ItemHFE p.C282Y homozygosity predisposes to rapid serum ferritin rise after menopause: A genotype-stratified cohort study of hemochromatosis in Australian women(WILEY, 2017-04-01)BACKGROUND AND AIM: Women who are homozygous for the p.C282Y mutation in the HFE gene are at much lower risk of iron overload-related disease than p.C282Y homozygous men, presumably because of the iron-depleting effects of menstruation and pregnancy. We used data from a population cohort study to model the impact of menstruation cessation at menopause on serum ferritin (SF) levels in female p.C282Y homozygotes, with p.C282Y/p.H63D simple or compound heterozygotes and those with neither p.C282Y nor p.H63D mutations (HFE wild types) as comparison groups. METHODS: A sample of the Melbourne Collaborative Cohort Study was selected for the "HealthIron" study (n = 1438) including all HFE p.C282Y homozygotes plus a random sample stratified by HFE-genotype (p.C282Y and p.H63D). The relationship between the natural logarithm of SF and time since menopause was examined using linear mixed models incorporating spline smoothing. RESULTS: For p.C282Y homozygotes, SF increased by a factor of 3.6 (95% CI (1.8, 7.0), P < 0.001) during the first 10 years postmenopause, after which SF continued to increase but at less than half the previous rate. In contrast, SF profiles for other HFE genotype groups increase more gradually and did not show a distinction between premenopausal and postmenopausal SF levels. Only p.C282Y homozygotes had predicted SF exceeding 200 μg/L postmenopause, but the projected SF did not increase the risk of iron overload-related disease. CONCLUSIONS: These data provide the first documented evidence that physiological blood loss is a major factor in determining the marked gender difference in expression of p.C282Y homozygosity.
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ItemChanges to infant feeding guidelines: Relevance to dermatologists(WILEY, 2017-11-01)The newly revised Australian Infant Feeding Guidelines recommends that all infants, including those at high risk of allergy, be introduced foods traditionally considered allergenic (such as peanut butter, dairy, wheat and egg) within the first year of life. High-risk infants are those with early onset eczema (<3-months old) or with moderate to severe eczema not responding to treatment (<6-months old). Eczema can also represent a symptom of allergy presentation and the recommended introduction of some foods in this group may lead to allergic reactions at home. Although there have been no reported deaths from gradual food introduction to infants at home and cohort studies have only reported mild to moderate reactions, there is anecdotal evidence that more severe reactions can occur rarely. Allergic reactions, even if they are not life-threatening, can be a terrifying experience for parents. Dermatologists play an important role when dealing with high-risk infants in promoting the message of early allergenic food introduction yet also instigating appropriate allergy testing when necessary. This short review aims to provide an update to Australasian dermatologists on the newly revised Australian Infant Feeding Guidelines and provide a food allergy screening pathway for high-risk infants prior to commencement of allergenic foods.