T07044: Peri-natal egg and milk allergen exposure in relation to tolerance or allergic sensitisation to food in infancy

Study Duration: April 2004 to September 2006

Contractor: University of Southampton

There has been a five-fold increase in the general prevalence of IgE-mediated allergic diseases in developed countries such as the UK over the last 30 years and numerous hypotheses have been proposed to explain this. Food allergies are frequently the first manifestation of atopic disease and affect 6-8% of infants in the first three years of life. Much evidence points to early life as a critical time during which exposure to allergens and programming of immunologic development and function occurs, followed only months or even years later by the onset of disease.

The risk factors associated with the development of an allergic response to food allergens in infancy have not been identified and the mechanisms underlying resolution of allergy are not understood. Why some infants have transient disease while others suffer persistent food allergy and even go onto develop aeroallergen sensitive hayfever/asthma remains unknown.

The impact of allergen dose and route of exposure during fetal life and early infancy on the development of allergy is unresolved. Data from a previous FSA-funded study, T07005, indicate that either high or low levels of exposure to ovalbumin ante-natally (determined by maternal specific IgG levels) are associated with a non-atopic phenotype of the infant.

‘This project proposed to build upon the results obtained from previous FSA-funded projects, to investigate the role of exposure (dose and route) of offspring at genetic risk of atopy to food allergens (egg and milk) during fetal development and/or breastfeeding, in the development of food allergy.

Furthermore, by using a combination of exposure data and measurement of immunological responsiveness at birth, this project hoped to determine if it is possible to predict (i) children who will not develop food allergy, (ii) children who will develop transient food allergy and, (ii) children who will develop persistent allergy. As such, it may be possible to design future therapeutic (including dietary) intervention in order to modify the allergy outcome.

The original proposal was to recruit a cohort of 400 pregnant mothers in to the study in order to have a final cohort size at 2 years of age of 320. Unfortunately, recruitment proved to be much more difficult than the study team anticipated and despite their best efforts it proved impossible to recruit sufficient numbers of subjects in order to make the continuation of the study into the follow-up period viable. At the close of the study, an initial analysis of the small number of infants that had reached the 6 month assessment point provided a suggestion that high dose antenatal exposure to egg (but not milk) might be associated with a lower risk of eczema, but this finding is not definitive since it is based on an incomplete sample. Interestingly, the study also found that there was no correlation between the levels of antibodies to milk or egg in mothers plasma and her dietary intake, which suggests that allergen specific IgG may not be a reliable quantitative marker of dietary exposure.