development of bottle-fed infants, specific infant formulas have also been designed for specific needs, by modifying their protein component. As an example, three different types of infant formulas have been designed for the management of allergy to cow’s milk protein.
Allergy is an immune reaction mounted against normally harmless environmental proteins called allergens. It is a consequence of an unbalanced immune system that normally sustains active protection against harmful antigens (e.g. pathogens and toxic compounds) and does not react against ingested food, like proteins. In the gastrointestinal tract, lack of oral tolerance [22] can lead to immune-mediated gastrointestinal diseases such as food allergy, an increasingly prevalent disorder that causes significant medical and psychosocial stress for both patients and families. At present, allergy cannot be cured and the management of food allergy is based on avoidance of the offending food(s) and prompt recognition and treatment of allergic reactions resulting from an accidental exposure.
Food allergy is very common in infancy, and cow’s milk allergy is the most frequent food allergy at early age, affecting about 2.5% of infants during their first years of life [23] with skin, respiratory and/or gastrointestinal symptoms ranging from relatively mild to severe or, although rarely, life-threatening events [24]. Most children naturally outgrow their milk allergy by the age of 3 years, but in some of them milk allergy can persist until adulthood. Importantly, cow’s milk allergy has been associated with an increased risk of developing other forms of allergy, such as asthma, atopic dermatitis, rhinoconjunctivitis or egg allergy, later in life [25], hence the importance of preventing cow’s milk allergy.
Fig. 2. Infant formula designed for allergy management (modification of protein conformation and structure).
The major milk allergens are caseins, α-lactalbumin and β-lactoglobulin, and, in most instances, patients develop an allergic response towards different cow’s milk proteins.
One way to decrease allergenicity of proteins is to disrupt the sequence or to modify the conformation of the allergenic epitopes by enzymatic hydrolysis. According to the process and degree of hydrolysis, different types of formulas can be obtained: partially (pHF) or extensively hydrolyzed formula (eHF) or amino-acid-based infant formulas (fig. 2). The differentiation between eHF and pHF is mostly established by the molecular weight profile and clinical demonstration of reduced allergenicity. Both eHF and pHF comprise a wide range of peptide sizes. In pHFs, the vast majority of the peptides are <5 kDa (with a size distribution of 3-10 kDa) while in eHFs almost all peptides have a molecular weight <3 kDa. Of note, commercially available pHFs may contain a significant percentage of peptides >6 kDa. Considering that peptides ≥3 kDa are able to elicit an allergic reaction [26], it is clear that pHFs are not intended for infants allergic to cow’s milk protein. Thus, present guidelines recommend the use of eHFs in case of cow’s milk protein allergy [27]. This most often allows infants to thrive while progressively outgrowing their cow’s milk protein allergy. However, in cases of very severe allergic reactions to cow’s milk proteins, only amino acid-based infant formulas are able to relieve symptoms since they are totally devoid of allergens.
As mentioned before, pHFs are not intended for cow’s milk protein-allergic infants. They have been developed for infants at high risk of allergy (based on a family history of atopy) to prevent onset of the disease. This is most probably relying on the induction of oral tolerance to cow’s milk protein mediated through the interaction of specific peptides with the immune system [28, 29]. Specific pHFs have been clinically proven to prevent atopic dermatitis when used during the first 4 months in infants with a family history of allergy [30-32]. In the absence of breastfeeding, different pediatric international organizations recommend to use the clinically documented pHFs when breastfeeding is not possible. Moreover, the FDA has granted a health claim on the reduced risk of atopic dermatitis to be used for pHF.
Conclusion
Proteins provided via breast milk or infant formula are essential components of an infant’s diet not just because of their crucial importance for the first stages of growth and development in infancy but also for their effects on health in later life. Therefore, the quality, quantity and conformation of the proteins which are provided in early infancy are essential. Infant formulas should, therefore, mimic as much as possible the characteristics of breast milk proteins.
Disclosure Statement
S. Nutten is an employee of Nestec Ltd.
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