Linköping University Medical Dissertations
No. 552

Cows' milk hydrolysates
Prevention and treatment of cows' milk allergy

Göran Oldæus

Akademisk avhandling som för avläggande av doktorsexamen i medicinsk vetenskap offentligt försvaras i Berzeliussalen, vid Hälsouniversitetet bibliotek, onsdagen den 29 april 1998, klockan 9.00. Fakultetsopponent är Dr. Med. Arne Høst, Odense, Danmark.


Cows' milk allergy (CMA) develops early in infancy and the incidence is 2-5% in developed countries. The onset of symptoms is in most cases related to the introduction of a cows' milk based formula. The treatment of choice is total avoidance of cows' milk proteins and, at least in infancy, replacement with a whole protein soy or a hydrolysed cows' milk based formula (HF). The hypoallergenicity of HFs has been questioned, and studies evaluating remaining antigenicity and allergenicity as well as the allergy preventive effect of early feeding with HFs have been prompted.

In vivo allergenicity of HFs was studied by skin prick tests and double-blind placebo controlled oral challenges in cows' milk allergic children, and in vitro allergenicity was analysed by RAST, RAST inhibition, immunoblotting and dot immunobinding. The protein content of the HFs was analysed by chromatography, electrophoresis, and determination of b-lactoglobulin by ELISA (I,II). The allergy preventive effect of feeding a partially (pHF) and an extensively HF (eHF) compared with a regular cows' milk formula from the start of weaning up to 9 months of age, was evaluated in a randomised, blinded study including infants from families with a history of allergy. The children were followed from birth up to 18 months of age (III). The antibody response to cows' milk antigens was analysed at 9 months of age with a chemiluminometric assay (IgE) and a sensitive ELISA (IgG) in a subgroup of these infants, who were fed a randomised formula for at least 3 months (IV). The presence of cord blood IgE, IgG, IgG1 and IgG4 antibodies to cows' milk antigens in relation to subsequent cows' milk sensitisation or allergic disease was evaluated (V).

All tested HFs retained some allergenicity, but it was higher for pHFs than for eHFs, both in vivo and in vitro. The content of b-lactoglobulin was more than 2000 times higher in a pHF than in the eHFs. An allergy preventive effect was seen for the eHF but not the pHF on the development of cumulative atopic symptoms and atopic dermatitis. The IgG response to b-lactoglobulin was more pronounced in the pHF than in the eHF fed group, but markedly reduced in both groups compared with the regular formula group. Cows' milk specific IgE antibodies were detected in 14% of cord blood sera, but the predictive capacity of these antibodies to detect subsequent cows' milk sensitisation and atopic disease up to 18 months of age was poor.

In conclusion, all HFs may retain antigens capable of eliciting allergic reactions, but eHFs are far less allergenic than pHFs. Only eHFs should be recommended for treatment and prevention of cows' milk allergy.

Department of Health and Environment, Division of Paediatrics, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden

ISBN 91-7219-067-1 ISSN 0345-0082