Fact: Amino acid-based feed with docosahexaenoic acid (DHA) and arachidonic acid (ARA) support growth in infants and are hypoallergenic and safe.
This "Journal Watch" discusses a comparative study (Extensively hydrolyzed feed vs. Amino-acid based feed) validating that infants with the most severe cow’s milk allergy(CMA)may react to the most extensively hydrolyzed formulas despite being hypoallergenic.
The hypoallergenic feed can provide adequate nutrition to children with cow’s milk allergy and support their growth. However, infants with the most severe CMA react to extensively hydrolyzed infant feed (EHF) that is considered to be a “hypoallergenic” alternative. This warrants the need for amino acid-based feed (AAF).1This Journal Watch brings to light the fact that EHFs may not be suitable for all infants with CMA and provides clinical evidence for AAFs to be truly “hypoallergenic” worldwide.
Breastmilk is the gold standard for infant and is highly recommended, yet, several infants are compelled to consume alternative feed as the only source of nutrition or in addition to breastmilk.1 The American Academy of Pediatrics (AAP) recommends cows’ milk-based feed for such infants. Around 2.5% of infants develop allergies or intolerance to cow’s milk, and hence, require an alternative feed. The search for an appropriate nutrient source further aggravates because infants with CMA frequently develop allergies to other foods as well. Poor management of food allergies can potentially hamper growth at such a tender age.2
Soy-based formula (SF): Although SF has been used as an alternative, its use depends on the type of CMA. Around 14% of infants with IgE-mediated and up to 60% of infants with non-IgE-mediated CMA show allergy to SF.2The European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) and the AAP do not recommend SF in the first six months of life.3
EHF: EHFs are modified cow’s milk-based feeds with proteins that are extensively broken down, thereby reducing their allergenicity.1 EHF has been recommended by the AAP as the first choice for managing nutrition in infants with CMA. However, the small peptide fragments in EHF are capable of eliciting allergic reactions.2 Few of them exhibited allergic reactions towards multiple foods and may display poor growth.2Thus, despite being successful in most of the infants, the conditions for a small fraction of infants don’t seem to improve with EHF.2
AAF: AAF contains only free amino acids; this may have a different implication on protein metabolism. AAF is used in cases in which EHF is not tolerated or well responded to, characterized by severe allergic reactions and multiple food allergies.4
Some commercially available EHFs are deemed to be “hypoallergenic”; however, the AAP recognizes a formula to be hypoallergenic only after being tested in subjects hypersensitive to cow’s milk or cow’s milk-based feed via the elimination-challenge tests. It is required for the tests to ensure 95% confidence that nine out of ten subjects with CMA will not develop reactions to the formula under a double-blind placebo-controlled food challenge (DBPCFC). The feed must then be tested to document allergic reactions over a seven-day period in an open challenge using an objective scoring system.1.
Infants and children with the most severe CMA have been observed to react to the EHFs and require AAFs that contain synthetic amino acids that are completely free of cow’s milk proteins.1 The evidence has been compiled in the next section in Table 1.
Table 1: Clinical evidence on the hypoallergenicity of AAF for infants1,2
|Study 11||Study 21||Study 32|
|Study design|| || || |
|Inclusion criteria||Healthy infants 14±2 days of age with established CMA||Infants and children ≤10 years with established CMA at three clinical sites||Infants between 2 months and 12 years with established CMA who were otherwise healthy from six sites|
|No. of participants||110||29||33|
|Study groups and tests conducted|| || || |
|Remarks|| || || |
|Parameters to be evaluated||Growth, Tolerance, Adverse events||Hypoallergenicity||Hypoallergenicity|
|Results|| Growth: || || DBPCFC: |
|Adverse events:|| || || Open challenge: |
| || || |
*Essential amino acids: isoleucine, leucine, lysine, phenylalanine, tyrosine, threonine, and tryptophan
AAF: Amino acid-based feed, AAP: American Academy of Pediatrics, ARA: Arachidonic acid, CMA: Cow’s milk allergy, DHA: Docosahexaenoic acid, DPBCFC: Double-blind placebo-controlled food challenge, EHF: extensively hydrolyzed feed