Genetic and environmental factors affecting the development of atopy through age 4 in children of atopic parents: a prospective randomized study of food allergen avoidance

The effect of food allergen avoidance, as well as other environmental and genetic factors, on the development of atopy were determined in this follow-up report of a prospective randomized controlled study of 288 infants of atopic parents, in which 78% were available for evaluation at age 4 years. The prophylactictreated group consisted of mothers who avoided cow milk. egg. and peanut during the last trimester of pregnancy and lactation and of infants who avoided cow milk until 1 year (casein hydrolysate supplementation prior to 1 year) and egg, peanut, and fish until after 2 years. The control group consisted of maternal/infant pairs who followed standard feeding practices. The cumulative prevalence of food allergy and food sensitization remained lower in the prophylactic treated group from 1 to 4 years of age. However, the period (current) prevalence of food allergy in both study groups was similar (about 5%) at 3 and 4 years. Such findings suggest that period prevalence may represent the more appropriate measure to assess the impact of intervention measures on the development of atopic disease at older ages. Prophylactic-treated children evidenced lower levels of IgG beta lacloglobulin (BLG) at 4 months and I and 2 years (p < 0.0001) and lower IgG ovalbumen/ovomucoid (OVA) levels only at 2 years (p < 0.001). Both groups evidenced similar prevalences of asthma, allergic rhinitis, and positive inhalant skin tests from birth to 4 years. Children with food allergy evidenced higher 4 year cumulative prevalences of allergic rhinitis and asthma (p < 0.05). Risk factors for atopic disease by age 4 years were shown by multivariate analysis (p < 0.05) to include (1) unrestricted diet and elevated cord blood IgE with food allergy, (2) male gender and lower paternal level of education with asthma, and (3) non-caucasian ethnicity and spring/summer birth with atopic dermatitis and allergic rhinitis. Serum IgE levels were not significantly different between groups at 3 and 4 years, despite their being a trend towards lower serum IgE levels in the prophylactic-treated group at 4 months (p < 0.07). In the control group, formula feeding prior to 4 months was associated with higher 4 month serum IgE levels (p < 0.05). Stepwise linear regression revealed that serum IgE variability from birth to 4 years was influenced by male gender, non-caucasian ethnicity, maternal and paternal serum IgE levels, 4 month IgG BLG levels, positive food and inhalant skin tests, and the development of atopic dermatitis, food allergy, asthma, and allergic rhinitis. These findings demonstrate the strength of genetic factors and their modulation by dietary and envi-ronmental influences in the development of atopy and reveal that the reduction in food allergy in infancy by maternal/infant food allergen avoidance fails to affect respiratory allergy development from birth to 4 years.