Paediatrics (RCH) - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 11
-
ItemGenetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy(WILEY, 2017-08)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.
-
ItemThe skin barrier function gene SPINK5 is associated with challenge-proven IgE-mediated food allergy in infants(WILEY, 2017-09)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.
-
ItemFormula and breast feeding in infant food allergy: A population-based study(WILEY, 2016-04)AIM: To determine whether infant-feeding practices, including duration of exclusive breastfeeding and use of partially hydrolysed formula, modify the risk of developing infant food allergy. METHODS: In an observational population-based study, 1 year olds were recruited from community immunisation clinics in Melbourne, Australia. Parent-reported data on infant-feeding practices and potential confounders were collected prior to infant skin prick testing for four food allergens. Sensitised infants attended hospital-based oral food challenges to establish food allergy status. Multiple logistic regression was used to investigate associations between breastfeeding and formula-feeding and infant food allergy adjusting for possible confounding variables. RESULTS: A total of 5276 (74% response) infants participated. Of the 4537 for whom food allergy status was determined, 515 (11.3%) were food allergic (challenge-proven in the context of skin prick testing positive (≥2 mm)). After adjusting for confounding variables, there was no association between duration of exclusive breastfeeding and food allergy. Use of partially hydrolysed formula did not reduce the risk of food allergy compared with cow's milk formula in the general population (adjusted odds ratios 1.03 (confidence interval 0.67-1.50)). CONCLUSION: Duration of exclusive breastfeeding and use of partially hydrolysed formula were not associated with food allergy at 1 year of age in this large population-based study. These findings have implications for population-based infant-feeding guidelines and do not support the use of partially hydrolysed formula for food allergy prevention.
-
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.
-
ItemAssociation between the age of solid food introduction and eczema: A systematic review and a meta-analysis(WILEY, 2018-08)INTRODUCTION: Eczema is a common childhood ailment responsible for a considerable disease burden. Both timing of introduction to solid food and allergenic food are believed to be related to childhood eczema. Despite the growing body of evidence, the relationship between timing of any solid food introduction (allergenic and/or non-allergenic) and development of eczema has not previously been systematically reviewed. METHODS: PubMed and EMBASE databases were searched using food and eczema terms. Two authors selected papers according to the inclusion criteria and extracted information on study characteristics and measures of association. Meta-analyses were performed after grouping studies according to the age and type of exposure. RESULTS: A total of 17 papers met the inclusion criteria, reporting results from 16 study populations. Of these, 11 were cohort studies, 2 case-controls, 1 cross-sectional study and 2 randomized controlled trials. Limited meta-analyses were performed due to heterogeneity between studies. Timing of solid food introduction was not associated with eczema. One randomized controlled trial provided weak evidence of an association between early allergenic (around 4 months) food introduction and reduced risk of eczema. CONCLUSIONS: The available evidence is currently insufficient to determine whether the timing of introduction of any solid food influences the risk of eczema.
-
ItemNo obvious impact of caesarean delivery on childhood allergic outcomes: findings from Australian cohorts(BMJ PUBLISHING GROUP, 2020-07)BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: In two unselected populations using harmonised protocols, the likely association of caesarean delivery with developing childhood allergy was small.
-
ItemAre Young Children With Asthma More Likely to Be Less Physically Active?(AMER ACAD PEDIATRICS, 2021-12)BACKGROUND: Previous research suggests that children who experience asthma may be less physically active; however, results have been inconclusive. This study aimed to investigate whether the presence of asthma or wheeze is associated with lower physical activity levels in children, and whether sex, body mass index or earlier asthma or wheeze status modifies the association. METHODS: This study was conducted in 391 HealthNuts participants in Melbourne, Australia. Asthma and wheeze data were collected via questionnaire at age 4 and 6, and physical activity was measured through accelerometry. Using adjusted linear regression models, the cross-sectional and longitudinal associations were investigated. RESULTS: There was no evidence of a difference in time spent in moderate-to-vigorous physical activity (MVPA) at age 6 years between children with and without asthma at age 4; children with asthma spent 8.3 minutes more time physically active per day (95% CI: -5.6, 22.1, P = .24) than children without asthma. Similar results were seen for children with current wheeze (5.8 minutes per day more, 95% CI: -5.9, 17.5, P = .33) or ever wheeze or asthma (7.7 minutes per day more, 95% CI: -4.8, 20.2, P = .23) at age 4 years. Comparable null results were observed in the cross-sectional analyses. Interaction with BMI could not be assessed; however, previous asthma or wheeze status and sex were not found to modify these associations. CONCLUSION: This analysis found no evidence of asthma hindering physical activity in these young children. These results are encouraging, as they indicate that the Australian asthma and physical activity public health campaigns are being effectively communicated and adopted by the public.
-
ItemThe Impact of Family History of Allergy on Risk of Food Allergy: A Population-Based Study of Infants(MDPI AG, 2013-11)The apparent rapid increase in IgE-mediated food allergy and its implications are now widely recognized, but little is known about the relationship between family history (an indirect measure of genetic risk) and the risk of food allergy. In a population-based study of 5,276 one year old infants (HealthNuts), the prevalence of oral food challenge-confirmed food allergy was measured. Associations between family history of allergic disease and food allergy in infants were examined using multiple logistic regression. Food allergy was diagnosed in 534 infants. Compared to those with no family history of allergic disease, children meeting the current definition of "high risk" for allergic disease (one immediate family member with a history of any allergic disease) showed only a modest increase (OR 1.4, 95% CI 1.1-1.7) in food allergy, while having two or more allergic family members was more strongly predictive of food allergy in the child (OR 1.8, 95% CI 1.5-2.3). There were also differences in the associations between family history and egg and peanut allergy in the child. Re-defining "high risk" as two or more allergic family members may be more useful for identification of groups with a significantly increased risk of food allergy both clinically and within research studies.
-
ItemPopulation Response To Change In Infant Feeding Guidelines For Allergy Prevention(MOSBY-ELSEVIER, 2014-02)
-
ItemThe prevalence and socio-demographic risk factors of clinical eczema in infancy: a population-based observational study(WILEY, 2013-06)BACKGROUND: 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. OBJECTIVES: We aimed to measure the population prevalence of infantile eczema using novel sampling methodology, and identify socio-demographic risk factors for eczema in the first year of life. METHODS: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.