Can Vitamin D Supplementation in the First Year of Life Prevent Food Allergy in Infants? The VITALITY Trial: Parts 1&2

Phase 4Active Not RecruitingNCT02112734

Murdoch Childrens Research Institute2,739 enrolled

Overview

We report that Australia has the highest prevalence of Immunoglobulin(Ig)E-mediated food allergy in the world, with 10% of infants having challenge-proven food allergy in Melbourne. There has been a 5-fold increase in hospital admissions for life-threatening anaphylaxis. These changes are most pronounced in children less than 5 years, suggesting a causal role for early life determinants. We have primary data to inform hypotheses for the rise in food allergy, which appears to result from potentially modifiable factors related to the modern lifestyle, particularly Vitamin D insufficiency (VDI). We propose an intervention study to assess if infant Vitamin D supplementation during the first year of life significantly decreases the risk of early-onset food allergy and other allergic disease at 12 months (part 1) and 6 years of age (part 2). Australia is ideally placed to answer this important question since, unlike the USA, Canada and Europe, there are no population recommendations for routine infant supplementation with Vitamin D and we are one of the few developed countries that do not supplement the food chain supply with Vitamin D.

There is an urgent need to prevent the onset and progression of food allergy in our population. Evidence demonstrates that food allergy and atopic eczema represent the earliest manifestations of the atopic march with 50% of infants with food allergy predicted to develop respiratory allergic diseases later in life. We report that Australia has the highest prevalence of Immunoglobulin(Ig)E-mediated food allergy in the world, with 10% of infants having challenge-proven food allergy in Melbourne. There has been a 5-fold increase in hospital admissions for life-threatening anaphylaxis. These changes are most pronounced in children less than 5 years, suggesting a causal role for early life determinants. We have primary data to inform hypotheses for the rise in food allergy, which appears to result from potentially modifiable factors related to the modern lifestyle, particularly Vitamin D insufficiency (VDI), and have demonstrated an association between VDI and increased risk of challenge-proven food allergy in 12-month old infants, which supports numerous ecological studies showing an increased risk of food allergy the further a child resides from the equator (associated with decreased UV exposure and Vitamin D levels). Despite Australia's sunny climate, population rates of VDI have steadily increased in infants and pregnant women in parallel to the apparent rise in food allergic disease. This association is biologically plausible, as there is evidence Vitamin D is critical to the healthy development of the immune system in early life. We propose an intervention study to assess if infant Vitamin D supplementation during the first year of life significantly decreases the risk of early-onset food allergy and other allergic disease at 12 months (part 1) and 6 years of age (part 2). Australia is ideally placed to answer this important question since, unlike the USA, Canada and Europe, there are no population recommendations for routine infant supplementation with Vitamin D and we are one of the few developed countries that do not supplement the food chain supply with Vitamin D.

Eligibility

Sex: ALLMin age: 6 WeeksMax age: 12 WeeksHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Each participant must meet the following criteria to be included in this study: * Healthy, term (born no earlier than 2 weeks before estimated date of delivery), predominantly breastfeeding infants aged 6 to 12 weeks (inclusive) who are expected to be predominantly breastfed for at least 6-months. This will be determined by answering yes/no to question 'do you intend/wish to breastfeed until your infant is at least 6 months of age.' Up to one bottle (approx. 120mL) of formula per 24 hours at the time of screening is acceptable, as this will contain \<100 IU vitamin D. * Has a parent/legally acceptable representative (LAR) capable of understanding the informed consent document and providing consent on the subject's behalf, * The parent must expect to be able to complete 4 online questionnaires over the infant's first 12 months of life and for the infant to be available for skin prick testing (+/- food challenge) at The Royal Children's Hospital at 12 months of age. Exclusion Criteria: Participants meeting any of the following criteria will be excluded from the study: * Infants who are currently receiving vitamin D supplementation * Infants on medication that interferes with vitamin D metabolism * Poor health due to a current or past significant disease state or congenital abnormality. * Prematurity \<37 weeks/low birth weight \<2500 g/Small for gestational age (SGA) * Unable to provide consent without the aid of an interpreter. * Women at high risk of vitamin D deficiency with infants on vitamin D supplementation.

Outcomes

Primary Outcomes

The prevalence of challenge-proven food allergy at 12 months of age

The prevalence of challenge-proven food allergy at 12 months of age determined by a positive SPT and a positive oral food challenge