Leone Thiele

Vitamin D insufficiency is associated with challenge-proven food allergy in infants

BACKGROUND Epidemiological evidence has shown that pediatric food allergy is more prevalent in regions further from the equator, suggesting that vitamin D insufficiency may play a role in this disease. OBJECTIVE To investigate the role of vitamin D status in infantile food allergy. METHODS A population sample of 5276 one-year-old infants underwent skin prick testing to peanut, egg, sesame, and cows milk or shrimp. All those with a detectable wheal and a random sample of participants with negative skin prick test results attended a hospital-based food challenge clinic. Blood samples were available for 577 infants (344 with challenge-proven food allergy, 74 sensitized but tolerant to food challenge, 159 negative on skin prick test and food challenge). Serum 25-hydroxyvitamin D levels were measured by using liquid chromatography tandem mass spectrometry. Associations between serum 25-hydroxyvitamin D and food allergy were examined by using multiple logistic regression, adjusting for potential risk and confounding factors. RESULTS Infants of Australian-born parents, but not of parents born overseas, with vitamin D insufficiency (≤50 nmol/L) were more likely to be peanut (adjusted odds ratio [aOR], 11.51; 95% CI, 2.01-65.79; P=.006) and/or egg (aOR, 3.79; 95% CI, 1.19-12.08; P=.025) allergic than were those with adequate vitamin D levels independent of eczema status. Among those with Australian-born parents, infants with vitamin D insufficiency were more likely to have multiple food allergies (≥2) rather than a single food allergy (aOR, 10.48; 95% CI, 1.60-68.61 vs aOR, 1.82; 95% CI, 0.38-8.77, respectively). CONCLUSIONS These results provide the first direct evidence that vitamin D sufficiency may be an important protective factor for food allergy in the first year of life.

The Natural History and Clinical Predictors Of Egg Allergy In The First 2 Years Of Life: A Prospective, Population-Based, Cohort Study

BACKGROUND 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. OBJECTIVE We aimed to assess the natural history of egg allergy and identify clinical predictors for persistent egg allergy in a population-based cohort. METHODS 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. RESULTS 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. CONCLUSION 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.

The HealthNuts population-based study of paediatric food allergy: validity, safety and acceptability

Background 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.

Predetermined challenge eligibility and cessation criteria for oral food challenges in the HealthNuts population-based study of infants.

epinephrine being delivered intramuscularly, the concern is that it might. Needle lengths of EAIs have already been cited as potentially inadequate to reliably deliver epinephrine to the muscle bed. Any amount of unexpected recoil that occurs while using a real EAI during an emergency might further reduce the likelihood of successful intramuscular administration. On the basis of this pilot study, it might be prudent for practitioners to inform patients that there are indeed differences with regard to how much force is required to activate different brands of EAIs, as well as differences in recoil generated. This might be of particular importance for those patients or providers who have been using one brand of EAI exclusively and then switch to a different brand of EAI. Encouraging patients to practice with real expired EAIs on tissue simulants, such as an orange, might also be beneficial. Regardless of the brand of EAI used, providers should instruct patients to firmly grasp the device and to continually depress the EAI into the thigh after activation occurs. This compression might also help displace subcutaneous fat and reduce the distance to muscle in some patients, potentially increasing the likelihood of intramuscular administration of epinephrine.

Persistent Food Allergy and Food Allergy Coexistent with Eczema Is Associated with Reduced Growth in the First 4 Years of Life.

BACKGROUND Food allergy has been associated with lower weight and height in cross-sectional studies in children; however, this has not been investigated in longitudinal studies to explore growth over time, and previous studies have not accounted for coexisting eczema. OBJECTIVE The objective of this study was to examine the association of IgE-mediated food allergy and eczema with anthropometric measures at 1 and 4 years of age. METHODS In the HealthNuts population-based cohort, infants recruited at age 1 year underwent a skin prick test to egg, peanut, and sesame; those sensitized had oral food challenges. Food challenges repeated at 4 years determined food allergy persistence or resolution. Eczema was defined as parent report of eczema diagnosis. Parent-reported weight and height and child health record data were used to calculate age- and sex-adjusted percentiles from World Health Organization charts. Multivariable linear regression models were fitted to examine the effect of food allergy and eczema on weight and height controlling for potential confounders. RESULTS Children with both food allergy and eczema at age 1 had lower percentiles for mean weight (51.3 vs 58.3 percentile, P = .001) and height (48.4 vs 53.4, P = .028) at age 1 compared with those with neither condition. There was no difference for children with only food allergy or eczema at age 1. By age 4, children with persistent food allergy and persistent eczema, but not those with resolved food allergy, were still shorter and lighter. CONCLUSIONS Children with both food allergy and eczema were shorter and lighter throughout early childhood, with more pronounced differences in those with persistent food allergy.

Food Challenge and Community-Reported Reaction Profiles in Food-Allergic Children Aged 1 and 4 Years: A Population-Based Study

BACKGROUND Oral food challenge is the main tool for diagnosing food allergy, but there is little data on the reaction profiles of young children undergoing challenges, nor how these reactions compare to reactions on accidental ingestion in the community. OBJECTIVES To compare reaction profiles from food challenges and parent-reported reactions on accidental ingestion, and assess predictors of severe reactions. METHODS HealthNuts is a longitudinal population-based cohort study of 5276 1-year-old infants. Infants underwent skin prick tests and those with identifiable wheals were offered food challenges. Food challenges were repeated at age 4 years in those with previous food allergy or reporting new food allergies. Community-reported reactions were ascertained from parent questionnaires. RESULTS Food challenges were undertaken in 916 children at age 1 year and 357 children at age 4 years (a total of 2047 peanut, egg, or sesame challenges). Urticaria was the most common sign in positive challenges at both ages (age 1 year, 88.7%, and age 4 years, 71.2%) although angioedema was significantly more common at age 4 years (40.1%) than at age 1 year (12.9%). Anaphylaxis was equally uncommon at both ages (2.1% and 2.8% of positive challenges at ages 1 and 4 years, respectively) but more common for peanut than for egg (4.5% and 1.2% of positive challenges at ages 1 and 4 years, respectively). The patterns of presenting signs reported during community reactions were similar to those observed in formal food challenges. Serum food-specific IgE levels of 15 kU/L or more were associated with moderate to severe reactions but skin prick test was not. CONCLUSIONS There was a shift from the most common presenting reaction of urticaria during food challenges toward more angioedema in older children. Serum food-specific IgE levels were associated with reaction severity.