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further reduces the allergenicity of many food proteins, most likely by altering the conformation structure of heat-labile proteins and consequently destroying their allergenic epitopes [10]. Microwave treatment (at 200 W for 3 min) increases hydrolysis of β-Lg and bovine whey proteins in comparison with conventional heating and the same proteolytic treatment [11]. High pressure also induces structural changes in (whey) milk proteins, such as denaturation, and enhances accessibility of potentially immunogenic hydrophobic regions to the enzymes and formation of aggregates, which may affect and reduce the allergenic potential of CMPs [12].

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      Partially and Extensively Hydrolyzed Formulas

      pHFs are developed with the aim of minimizing the number of sensitizing epitopes within milk proteins, while at the same time retaining peptides with sufficient size and immunogenicity to possibly stimulate the induction of oral tolerance. Because pHF contains large CM peptides that can cause severe reactions in CMA patients, pHF is not recommended for the treatment of CMA [1-3]. eHFs are extensively hydrolyzed in order to destroy allergenic epitopes, maintaining the nitrogen in the form of free amino-acid formulas (AAFs) or very small peptides which are indicated in treatment but can as well be used in prevention. Which type induces the best oral tolerance in infants, pHF or eHF, is still debated. The MW profile of proteins only enables to differentiate protein characteristics of formulas, but does not clearly determine the allergenic properties and clinical response [18].

      Commercial HFs vary in protein source (e.g. Cas, whey, soy or rice), method and percentage of hydrolysis, content of β-Lg or other proteins, content of nonprotein components (such as lactose, DHA, nucleotides or probiotics) and osmolarity implying that the immune and clinical ‘results’ of one formula cannot be transferred to another.

      Prevention of Allergy

      For infants >4-6 months of age, there are insufficient data to support a protective effect of any dietary intervention regarding the development of atopic disease [2, 17]. A recent study showed that the early introduction of peanuts modulated immune-specific responses and significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy [4].

      Target Population: Who Is the High-Risk Infant?

      The risk of atopy is increased to about 1:3 if the parent or sibling is atopic, and 70% if both parents are atopic [26]. Hence, the presence of a positive family history of atopic disease represents the condition to define the newborn baby as at-risk infant. In the literature, this definition varied from infants/children having two allergic parents or relatives [25] to (a more recent one) at least one parent and/or sibling [17] with a documented (history of) allergic disease sometimes also supplemented with an increased cord blood IgE [2]. However, familiar allergy should be doctor diagnosed and not based on self-reported symptoms, as the perceived prevalence of food allergy is far greater than the real occurrence, determining

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