Early Exposure to Cow's Milk Protein Is Associated with a Reduced Risk of Cow's Milk Allergic Outcomes

doi:10.1016/j.jaip.2018.08.038

The Journal of Allergy and Clinical Immunology: In Practice

Volume 7, Issue 2, February 2019, Pages 462-470.e1

https://doi.org/10.1016/j.jaip.2018.08.038 Get rights and content

Background

Overall early exposure to allergenic foods in the infant's diet is a new strategy for preventing food allergy to that allergen, but the optimal timing of exposure for different allergens is not known.

Objectives

We aimed to examine the relationship between exposure to cow's milk protein in the first 3 months of life and risk of cow's milk allergy at age 12 months.

Methods

HealthNuts is a longitudinal population-based food allergy study that recruited 5,276 twelve-month-old infants. Skin prick testing to cow's milk was conducted on the second half of the cohort (n = 2,715) and sensitization defined as a wheal ≥2 mm. Cow's milk allergy was defined as a parent-reported reaction to cow's milk consistent with IgE-mediated allergy together with evidence of sensitization. Early exposure to cow's milk protein was captured through parental questionnaire administered at 1 year of age and defined as consumption of cow's milk-based infant formula during the first 3 months of life.

Results

Forty-two percent of infants were exposed to cow's milk in the first 3 months of life (n= 1,977/4,712) and 87% of these infants were also breastfed. Early exposure to cow's milk protein was associated with a reduced risk of cow's milk sensitization (adjusted odds ratio [aOR] 0.44, 95% confidence interval [CI] 0.23-0.83), parent-reported reactions to cow's milk (aOR 0.44, 95% CI 0.29-0.67), and cow's milk allergy (aOR 0.31, 95% CI 0.10-0.91) at age 12 months. Age at exposure to cow's milk protein was not associated with the risk of other food allergies.

Conclusions

Exposure to cow's milk protein in the first 3 months of life was associated with a reduced risk of cow's milk allergy. These findings are from an observational study and clinical trials are warranted to further assess this association before any recommendations to infant feeding guidelines can be made.

Section snippets

Methods

The HealthNuts study methods have been described in detail previously.¹⁹ Between 2007 and 2011, 5,276 infants were recruited from council-run immunization sessions and offered skin prick testing (SPT) to 4 common food allergens. All infants underwent SPT to egg white, peanut, and sesame; the first half of the cohort received an additional SPT to shrimp, whereas the second half received SPT to cow's milk. Initially, cow's milk SPT was not conducted because of failure to gain ethics committee

Participation and cow's milk allergy outcomes

A total of 5,276 twelve-month-old infants participated in the HealthNuts study (74% participation). Participation in cow's milk SPT including determination of cow's milk allergy status and proportion of the sample with data on early exposure to cow's milk protein is presented in Figure 1, A. Cow's milk SPT was only conducted on the second half of the cohort and 2.2% (95% CI 1.7-2.8%, n = 60/2,715) were sensitized at the population level. Responses to parent-reported reactions to cow's milk were

Discussion

In this population-based cohort, early exposure to cow's milk protein in the first 3 months of life was associated with a reduced risk of all cow's milk atopic outcomes considered, including sensitization, parent-reported reactions, and presumed allergy at age 1 year, even after adjusting for confounding variables including family history of allergy.

The strengths of this study are the large sample size, high participation fraction, and good internal and external validity.¹⁹ Sensitization to

Acknowledgments

The HealthNuts study thanks the children and parents who participated in the HealthNuts study as well as the staff of Melbourne's Local Government Areas for providing access to community immunization clinics. We thank ALK-Abello SA, Madrid, Spain, for supplying the skin prick testing reagents; and the HealthNuts safety committee comprising Associate Professor Noel Cranswick (Australian Paediatric Pharmacology Research Unit, Murdoch Childrens Research Institute, Parkville, Victoria, Australia),

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: The HealthNuts study was supported by funding from the National Health and Medical Research Council (NHMRC) of Australia, Ilhan Food Allergy Foundation, AnaphylaxiStop, the Charles and Sylvia Viertel Medical Research Foundation, the Victorian Government’s Operational Infrastructure Support Program, and the NHMRC Centre for Food and Allergy Research. S. C. Dharmage, A. J. Lowe, and K. J. Allen hold NHMRC awards.

: Conflict of interest: K. J. Allen personally received consultancy fees from ThermoFisher, and is on the Before Brands Scientific Advisory Board. V. L. McWilliam reports personal fees from Speaker Honorarium for Aspen Global, Abbott Australasia, and Nestle Health Sciences and personal fees from Advisory Panel Consultancy for Nutricia, outside the submitted work. M. L. K. Tang is on the Nestle Medical Advisory Board Oceania and the Danone Nutricia Global Scientific Advisory Board; received consultancy fees from Deerfield Consulting, GLG consulting, and Bayer; is employed by and has stock/employee stock options from ProTA Therapeutics; received payment for lectures from Danone Nutricia, Abbott Australia, and Nestle Health Sciences; receives royalties from Wilkinson Publishing; and has a patent through Murdoch Children's Research Institute. Her institution received grants from the National Health and Medical Research Council Australia and patents from ProTA Therapeutics for other works. A. J. Lowe reports grants from the National Health and Medical Research Council during the conduct of the study. The rest of the authors declare that they have no relevant conflicts of interest.

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Original ArticleEarly Exposure to Cow's Milk Protein Is Associated with a Reduced Risk of Cow's Milk Allergic Outcomes

Background

Objectives

Methods

Results

Conclusions

Section snippets

Methods

Participation and cow's milk allergy outcomes

Discussion

Acknowledgments

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol Pract

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Randomized trial of peanut consumption in infants at risk for peanut allergy

N Engl J Med

Timing of allergenic food introduction to the infant diet and risk of allergic or autoimmune disease: a systematic review and meta-analysis

JAMA

The natural history of milk allergy in an observational cohort

J Allergy Clin Immunol

Original Article
Early Exposure to Cow's Milk Protein Is Associated with a Reduced Risk of Cow's Milk Allergic Outcomes