THE EFFECT OF HYDROLYZED COW’S MILK FORMULA FOR ALLERGY PREVENTION IN THE FIRST YEAR OF LIFE: THE GERMAN INFANT NUTRITIONAL INTERVENTION STUDY, A RANDOMIZED, DOUBLE-BLIND TRIAL
von Berg A, Koletzko S, Grubl A, et al. J Allergy Clin Immunol. 2003;111:533–540
Purpose of the Study.
Feeding extensively or partially hydrolyzed formulas to infants might reduce their risk of developing allergic disorders, but the scope of benefit remains unclear. The authors sought to assess the preventive effect of different hydrolyzed formulas versus cow’s milk in a prospective study among high-risk infants.
The subjects were 2252 infants with hereditary risk of atopy, defined as at least 1 biological parent or sibling with an allergic disease.
Infants were randomly assigned at birth, in a blinded manner, to 1 of 4 formulas, ie, cow’s milk formula (CMF), partially hydrolyzed whey formula, extensively hydrolyzed whey formula, or extensively hydrolyzed casein formula (eHF-C). However, all mothers were encouraged to breastfeed exclusively for the first 4 to 6 months. Study formula was provided for the first 6 months. Avoidance of solid foods for the first 4 months was advised, with subsequent avoidance of cow’s milk, eggs, soy, fish, peanuts, nuts, tomatoes, and citrus fruits during the first 1 year. Mothers maintained diaries of milk sources for the first 6 months. Children were examined at 1, 4, 8, and 12 months of age. The primary end point at 1 year of age was the presence of allergic manifestation, which was defined as atopic dermatitis (AD), gastrointestinal manifestations of food allergy, allergic urticaria, or a combination of these. Both immunoglobulin E-mediated and non—immunoglobulin E-mediated reactions were considered for gastrointestinal manifestations of food allergy, and symptoms needed to disappear with elimination of the suspected formula and to recur with challenge for diagnosis. Asthma and allergic rhinitis were excluded from consideration as allergic manifestations, because diagnoses are usually difficult to establish in the first 1 year of life.
Of the 2252 infants enrolled, 889 were exclusively breastfed for the first 4 months, of whom 865 were monitored for the entire study period. Of the 1249 infants assigned to a study formula, 418 left before completion of enrollment data, left thereafter, or were excluded because of noncompliance. A total of 945 infants who adhered to the study formula protocol for the entire 12 months remained. Among the hydrolyzed formulas, only eHF-C was associated with a significant decrease in allergic manifestations, compared with CMF. However, when the outcome of AD was analyzed specifically, both eHF-C and partially hydrolyzed whey formula were associated with more favorable outcomes, compared with CMF. A family history of AD was associated with lesser benefit, with only eHF-C approaching statistical significance, compared with CMF (P = .077). The results for exclusively breastfed infants were not included in the analysis, because it was not possible to randomize to breastfeeding for ethical reasons and mothers who chose to nurse differed from the mothers of formula-fed infants with respect to important variables, including greater family prevalence of AD, less smoking, and fewer pets.
The expression of allergic diseases in the first 1 year of life is favorably modified by the use of less allergenic milk sources, especially in the absence of a family history of AD. Individual hydrolysate formulas must be studied more extensively in this role.
The findings of this study are consistent with various observations on the role of hypoallergenic formulas in ameliorating allergic disease early in life. Of course, this study was not designed to look beyond the first 1 year of life, and most evidence to date suggests that the protective benefits of such early food allergen avoidance are limited to AD and immunologic reactions to food proteins, without significant effects on lifetime risks for asthma and allergic rhinitis.