10.1586/ECI.12.80 31 ISSN 1744-666X © 2013 Expert Reviews Ltd www.expert-reviews.com Perspective Allergic conditions cause a substantial burden of illness worldwide both in children and adults [1,2] . These conditions impact on the individual, their family and the healthcare system. The common manifestations of allergic disease shift with increasing age of the child; in early infancy, eczema and food allergy are the most common symptoms, while asthma and allergic rhinitis become more important as the child ages. There was a rapid rise in the prevalence of allergic con- ditions in the later part of the 20th century [3–5] . While prevalence of childhood asthma appears to have reached a plateau, or declined in some countries [1] , it remains a major cause of hospital- ization and healthcare expenditure. The rates of allergic rhinitis and eczema in children continue to increase in many parts of the world [1] , and there is also evidence that the rate of other sys- temic allergic conditions, including anaphylaxis and food allergy, are increasing [6–8] . Despite active research, the reasons for these shifts in prevalence of disease remain unclear. Research in this area aims at identifying interventions that can prevent children from developing these conditions in the first place. If early forms of disease can be prevented, there is a potential for sustained long-term benefits and reduced risk of other forms of allergic disease in later life [9] . Despite substantial research efforts, there are currently no interventions that have been clearly demonstrated to prevent children developing these conditions, although it is known that early life exposures (during pregnancy and early infancy) may be critical [10] . The infant diet, including breast or formula feeding and the introduction of solid foods, has attracted par- ticular attention as early life exposures that may influence allergic disease risk and importantly, have the potential to be easily modified. Currently, international expert guidelines from the USA (American Academy of Pediatrics) [11] , Europe (European Academy of Allergy and Clinical Immunology/European Society for Paediatric Gastroenterology, Hepatology and Nutrition) [12] and Australia (Australasian Society of Clinical Immunology and Allergy) [101] recommend a limited number of inter- ventions for prevention of allergic disease. All Adrian J Lowe* 1,2 , Shyamali C Dharmage 1,2 , Katrina J Allen 1,3,4 , Mimi LK Tang 1,3,4 and David J Hill 1 1 Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Australia 2 Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia 3 Department of Paediatrics, University of Melbourne, Melbourne, Australia 4 Department of Allergy and Immunology, Royal Children’s Hospital *Author for correspondence: Tel.: +61 3 8344 0878 Fax: +61 3 9349 5815 lowe.adrian@gmail.com Hydrolyzed formulae are created by using enzymatic processes to break native proteins into smaller fragments. They may prevent development of allergic diseases by reducing exposure to intact allergens. Partially hydrolyzed whey formula (pHWF) is particularly promising for allergy prevention, as it is cheap to manufacture and palatable. Scientific organizations have recommended the use of hydrolyzed formula in the first 4–6 months of life for the prevention of allergic disease based on a limited number of trials. Three recent developments challenge these recommendations: our growing understanding of the importance of allergen exposure for induction of immune tolerance, recently published evidence that failed to identify a protective effect of pHWF, which the authors and other experts believe will necessitate updating of systematic reviews, and methodological limitations of available trials and systematic reviews on which these recommendations are based. Until more definitive evidence is obtained, the authors recommend continuing to advocate that ‘breast is best’, and caution against overstating the potential for pHWF to prevent allergic disease. The role of partially hydrolyzed whey formula for the prevention of allergic disease: evidence and gaps Expert Rev. Clin. Immunol. 9(1), 31–41 (2013) KEYWORDS:฀allergic฀rhinitis฀•฀allergy฀prevention฀•฀asthma฀•฀conventional฀cows’฀milk฀formulae฀•฀eczema฀ •฀infant฀formulae฀•฀partially฀hydrolyzed฀whey฀formula For reprint orders, please contact reprints@expert-reviews.com