The Role of Partially Hydrolyzed Whey Formula for the Prevention of Allergic Disease

Evidence and Gaps

Adrian J Lowe; Shyamali C Dharmage; Katrina J Allen; Mimi LK Tang; David J Hill

Expert Rev Clin Immunol. 2013;9(1):31-41.

Five-year View

Given the long history of controversy concerning the role of pHWF for the prevention of allergic disease, it appears likely that this will remain the case for the next 5 years. Formula studies have major logistical issues, and are open to a range of potential bias including difficulty in blinding the distinct smell of each formula. New developments to improve the quality of formula trials are required to obtain definitive evidence on their role in preventing allergic disease. If this is not possible, alternate new approaches for prevention should be explored such as early introduction of allergen. In the next 5 years, trial-based evidence relating to the effect of allergen exposure in early life (4–6 months of age) will emerge and elucidate the role of early life exposure to intact allergens on the development of allergic disease.

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Financial & competing interests disclosure
AJ Lowe was previously supported by Dairy Australia, CRC for Asthma & Airways and VicHealth. Currently, AJ Lowe and SC Dharmage are supported by the Australian National Health & Medical Research Council. KJ Allen is funded by a Vietel Senior Medical Research Fellowship, and has received speaker fees from Abbott, Nutricia and Pfizer. DJ Hill has received support from Nutricia, SHS International and Nestlé for research and has presented lectures at sponsored meetings. MLK Tang is a member of Medical Advisory Boards for Nestlé Nutrition Institute and Nutricia, has sat on advisory committees for Pfizer, and has received payment for speaking engagements with Danone. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

Table 1. Selected recommendations and statements concerning the role of hydrolyzed formulae for the prevention of allergic disease.
Organization	Recommendation/statement	Ref.
US FDA^† (May 2011)	"For healthy infants who are not exclusively breastfed and who have a family history of allergy, feeding a 100% whey protein partially hydrolyzed infant formula from birth up to 4 months of age instead of a formula containing intact cow's milk proteins may reduce the risk of developing atopic dermatitis throughout the first year of life and up to 3 years of age. FDA has concluded that the relationship between 100% whey protein partially hydrolyzed infant formulas and the reduced risk of atopic dermatitis is uncertain, because there is very little scientific evidence for the relationship."	[102]
AAP (January 2008)	"In studies of infants at high risk of atopy and who are not exclusively breastfed for 4–6 months, there is modest evidence that the onset of atopic disease may be delayed or prevented by the use of hydrolyzed formulas compared with formula made with intact cow milk protein, particularly for atopic dermatitis."	[11]
ASCIA (2010)	"If infant formula is required in the first months of life before solid foods are introduced, there is some evidence that hydrolyzed formulas may reduce the risk of allergic disease in high-risk infants, with a history of allergy in their parents or siblings …. In Australia and New Zealand only partially hydrolyzed formulas (usually labeled 'HA' or Hypoallergenic) are recommended for allergy prevention."	[101]
ESPACI and ESPGHAN	"In bottle fed infants with a documented hereditary atopy risk (affected parent or sibling), the exclusive feeding of a formula with a confirmed reduced allergenicity is recommended because it can reduce the incidence of adverse reactions to food, especially to cows' milk protein. There is no conclusive evidence to support the use of formulas with reduced allergenicity for preventive purposes in healthy infants without a family history of allergic disease."	[77]
Section on Pediatrics, EAACI	"A dietary regimen is effective for prevention of allergy to the avoided food, in high-risk infants, particularly in early infancy regarding food allergy (cow's milk allergy) and eczema (atopic or nonatopic). Evidence that such avoidance affects the later allergic manifestations such as asthma and rhinitis is lacking. The most effective dietary regimen is exclusively breastfeeding for at least 4–6 months or, in case of lack of breast milk, formulas with documented reduced allergenicity for at least 4 months, combined with avoidance of solid food and cow's milk for the same period may be considered."	[12]

†This statement is an extract from a letter of reply by the US FDA in response to a petition to allow a health claim concerning partially hydrolyzed whey formula, submitted on behalf of Nestlé Nutrition. The FDA approved four wordings of a health claim concerning the use of pHWF [102]. This is the third of these approved provisional health claims. AAP: American Academy of Pediatrics; ASCIA: Australasian Society of Clinical Immunology and Allergy; EAACI: European Academy of Allergology and Clinical Immunology; ESPACI: European Society for Paediatric Allergology and Clinical Immunology; ESPGHAN: European Society for Paediatric Gastroenterology, Hepatology and Nutrition.