Should partially hydrolyzed infant formula be given to the general infant population for the primary prevention of allergic disease?

Abstract

Peptides must be in the range of 10-70 kD to act as an allergen. Whole cow milk-based formulas contain proteins in the range of 14-67 kD. Partially hydrolyzed infant formula (PHF) was developed to reduce protein allergenicity through heat treatment and chemical and enzymatic hydrolysis, resulting in a reduced molecular weight and peptide size. PHF contains shortened oligopeptides that have a molecular weight <5 kD (range, 3-10 kD), and extensively hydrolyzed infant formula contains peptides with a molecular weight <3 kD. 1) Primary prevention involves blocking immunologic sensitization to an allergen. For the primary prevention of allergic disease, studies have focused on high-risk infants with a family history of allergic disease. For all infants, exclusive breastfeeding is recommended for at least the first 4-6 months of life. A Cochrane review published in 2018 presented no evidence that the use of hydrolyzed formula over breastfeeding prevents allergic disease. 2) According to current infant feeding guidelines, if breastfeeding is impossible, the use of extensively hydrolyzed infant formula (EHF) is recommended for patients of cow milk allergy, and the use of EHF or PHF can be considered in cases of high-risk infants as a strategy for preventing allergic disease. 3,4) However, questionable and negative outcomes with the use of PHF for the prevention of allergic disease have been reported very recently. According to the results of a 15-year followup of the German Infant Nutritional Intervention (GINI) study, a prospective randomized double-blind trial of full-term neonates with atopic heredity in a German birth cohort, PHF failed to show a significant influence on immunoglobulin E sensitization but showed a preventative effect on eczema until adolescence without a rebound phenomenon. 5) A systematic review and meta-analysis of studies published between 1946 and 2015 found no consistent evidence to support the current recommendations; rather, it reported evidence of publication bias, methodological bias, and conflicts of interest in those studies reporting allergic outcomes, including the GINI study. 6) The authors suggested that the current recommendation of using hydrolyzed formula in place of standard cows' milk formula to prevent allergies in high-risk infants be revised. 6) A Cochrane review published in 2018 also found no evidence to support prolonged feeding of a hydrolyzed compared with standard formula for preventing allergic disease in infants who cannot be exclusively breastfed. 2) Another recent meta-analysis showed positive prevention outcomes with PHF from one company, but the majority of included studies were industry-supported. 7) A pharmacoeconomic analysis demonstrated that PHF compared with standard formula was cost-effective for high-risk infants for preventing atopic dermatitis and cost-saving compared with extensively hydrolyzed infant formula when used in prevention, but this study was also industry-supported. 8) In the current issue of Korean Journal of Pediatrics, Vandenplas et al. 1) r...