Meta-analysis of the evidence for a partially hydrolyzed 100% whey formula for the prevention of allergic diseases

Abstract

Objective:

Infants with a documented hereditary risk of atopy (i.e., an affected parent and/or sibling) who cannot be breastfed exclusively are recommended to receive a formula with confirmed reduced allergenicity, i.e., a partially or extensively hydrolyzed formula (pHF and eHF, respectively), as a means of preventing allergic reactions. The efficacy of each hydrolyzed formula for the prevention of allergic diseases should be established separately, as factors such as the protein source, hydrolysis method and degree of hydrolysis that often depend on the manufacturer contribute to differences among hydrolysates. The aim was to systematically review data on the efficacy of a partially hydrolyzed 100% whey formula (pHF) in reducing the risk of allergy in healthy infants at high risk for allergy.

Methods:

The Cochrane Library, MEDLINE, EMBASE, and CINAHL databases were searched in September 2009 (from inception to September 2009) for randomized and quasi-randomized controlled trials (RCTs); additional references were obtained from reviewed articles. The company that manufactures the pHF used was contacted for unpublished data.

Results:

The search yielded 84 citations. Fifteen RCTs were included, some of which had potential methodological limitations such as unclear or inadequate allocation concealment, no intention-to-treat analysis, and no true blinding. For primary outcomes, i.e., all allergic diseases and atopic eczema/atopic dermatitis, use of the pHF compared with standard formula (SF) was associated with reduced risks (incidence, cumulative incidence, period prevalence) that were statistically significant for most, albeit not all, time points. Comparison of groups who received the pHF versus extensively hydrolyzed (eH) whey formula revealed no significant differences in outcomes except for reductions in the cumulative incidences of all allergic diseases at 0 to 36 months of age. Comparison of groups who received the pHF versus eH casein formula revealed no significant difference in outcomes between groups.

Conclusions:

The use of the pHF compared to SF is effective in allergy prevention in children at high risk for allergy at most time points. These results should be interpreted with caution due to a lack of methodological rigor in many trials. Reassuringly, the strongest evidence comes from a well-designed and conducted, independently funded RCT.

Key words::

• Allergy
• Children
• Infant formula
• Meta-analysis
• Prevention
• Protein hydrolysates

Transparency

Declaration of funding

A grant from Nestlé Nutrition Institute (NNI) supported this review. The Institute was not involved in the review, design, data collection (except for providing a file with published and unpublished papers), data analysis, data interpretation, writing of the review, or in the decision to submit the report for publication. Both authors saw and approved the final version of the manuscript. The corresponding author had full access to all of the data in the study and had final responsibility for the decision to submit for publication.

Declaration of financial/other relationships

H.S. has disclosed receiving research funding; speaking fees, consultancy, and advisory committee payments from NNI. A.H. has disclosed she has no relevant financial relationships.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she has received research funding from excelleRx, Inc; that he/she has acted as an advisor to King Pharmaceuticals; and that he/she is on the speakers bureau of Pricara. Peer Reviewer 2 has disclosed that he/she has no relevant financial relationships.

Acknowledgments

The authors thank freelance medical writer Dr. Laura J. Blakemore for her editorial assistance, which was funded by a grant from Nestlé Nutrition Institute.