The natural history of cow's milk protein allergy/intolerance.

In prospective studies th incidence of cow's milk protein allergy and intolerance (CMPA/CMPI) in infancy in western industrialized countries has been estimated to be about 2-3% based on strict diagnostic criteria. A significant association between early neonatal exposure to cow's milk formula feeding and subsequent development of CMPA/CMPI has been documented. The small amounts of 'foreign' protein in human milk may rather induce tolerance than allergic sensitization. The findings of specific IgE to individual cow's milk proteins in cord blood of the majority of infants who later develop CMPA/CMPI suggests a prenatal sensitization may play a role in the pathogenesis of CMPA/CMPI. Perhaps a weak intrauterine education of low IgE-response may need to 'boosted' neonatally in order to cause clinical disease. The prognosis of CMPA/CMPI is good with a recovery of about 45-56% at one year, 60-77% at two years and 71-87% at three years. Associated adverse reactions to other foods, especially egg, soy, peanut and citrus develop in about 41-54%. Allergy to potential environmental inhalant allergens has been reported in up to 28% by three years and up to 80% before the age of puberty. Especially, infants with an early increased IgE response to cow's milk protein have an increased risk of persisting CMPA, development of persistent adverse reactions to other foods and development of allergy against environmental inhalant allergens. Cow's milk protein/intolerance (CMPA/CMPI), meaning reproducible adverse reactions to cow's milk protein(s) may be due to the interaction between one or more milk proteins and one or more immune mechanisms, possible any of the four basic types of hypersensitivity reactions. Immunologically mediated reactions are defined as CMPA. Mostly, CMPA is caused by IgE-mediated (type I) reactions, but evidence for type III (immune complex) reactions and type IV (cell mediated reactions) have been demonstrated as reviewed by Høst (1994) and Ortolani & Vighi (1995). Non immunologically reactions against cow's milk protein(s) are defined as CMPI. However, it should be stressed that many studies on 'cow's milk allergy' have not investigated the immunological basis of the clinical reactions. In most instances of cow's milk protein hypersensitivity only diagnostic investigations such as skin prick test and RAST indicative of IgE-mediated reactions are performed. In fact, CMPA cannot be ruled out unless extensive diagnostic tests for type II-III-IV reactions have proved negative. Thus, the classification of adverse reactions to cow's milk proteins depends on the extent and the quality of performed diagnostic tests for immune mediated reactions. At present, no single laboratory test is diagnostic of CMPA/CMPI, and differentiation between CMPA and CMPI cannot be based solely on clinical symptoms. Therefore the diagnosis has to be based on strict well-defined elimination and milk challenge procedure (Hill & Hosking, 1991), (Høst, 1994). Preferably, double-blind placebo-controlled challenges (DBPCFC) should be carried out in children older than 1-2 years of age. In infants open controlled challenges have been shown to be reliable when performed under professional observation in a hospital setting (Høst & Halken, 1990).

The effect of hypo-allergenic formulas in infants at risk of allergic disease.

Development of atopic disease seems to depend on both genetic factors and exposure to several environmental factors. At present ther is evidence that the mode of early infant feeding influences the development of food allergy, whereas daily exposure to inhalant allergens and daily exposure to tobacco smoke is found to be associated with an increased risk of recurrent wheezing/asthma and inhalant allergy. In infants with atopic predisposition (first-degree relatives), exclusively breastfeeding > or = four months is found associated with a significant reduction of the cumulative prevalence of cow's milk allergy/intolerance (CMA/CMI) during the first 1-2 years of age. When breastmilk is insufficient or lacking a substitute formula is needed. Several recent prospective studies show a preventative effect of extensively hydrolysed formula (eHF) in combination with avoidance of cow's milk proteins and solid foods during > or = 4 months in high-risk infants on the cumulative prevalence of food allergy and atopic dermatitis during the first 2-4 years of life. Partially hydrolysed formulas (pHF) may be effective in allergy prevention, but due to drawbacks of study design and lack of documentation pHF cannot be recommended at present. The results of studies comparing the preventive effect of eHF and pHF are awaited. The protective effect on the development of cow's milk allergy is a real prevention and not only a postponement of the onset of symptoms. No studies have demonstrated a preventive effect of dietary measures as regards asthma/inhalant allergy, at present until the age of four years. As no studies concerning the preventive effect of avoidance of milk and other foods after the age of 4-6 months of life have been performed, recommendation of preventive elimination diets beyond this age is empirically based. In order to reduce the costs, to minimize the risk of stigmatisation and the risk of malnutrition it is important to avoid unnecessary restrictive and prolonged diets. A diet period of 4-6 months seems sufficient in most infants. At present eHF are recommended for avoidance of cow's milk. Some high risk infants may benefit from maternal diet during lactation, but there is no documented beneficial effect of maternal diet during pregnancy.