Primary Prevention of Food Allergy

  • Matthew J. Greenhawt
  • David M. Fleischer
Food Allergy (T Green, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Food Allergy


Food allergy is estimated to affect approximately 8% of children in the USA. This is a disease without any known treatment or cure and, for some, a disease that can be quite severe, even life-threatening. While recent advances in potential treatment have made remarkable strides, with two food-targeted immunotherapy products now in phase III trials, perhaps the biggest gains in the field have come in the advent of potential preventative strategies to avoid the development of food allergy in high-risk individuals. There have been multiple, randomized, controlled trials (RCTs) performed in the past 5 years that have demonstrated significant risk reduction from early allergen introduction. These include two trials for early peanut introduction and five trials for early egg introduction in the first year of life. The results indicate that primary prevention of food allergy through early allergen introduction may represent a strategy that could potentially avert tens of thousands of children from becoming food allergic. In support of the data for peanut, the National Institute of Allergy and Infectious Diseases recently sponsored an addendum to the 2010 food allergy guidelines, specifically recommending peanut be introduced in both high- and standard-risk infants to reduce the risk of developing peanut allergy. To date, no formal recommendations have been made for egg, however. This review will focus on the latest evidence supporting early introduction as a strategy to prevent food allergy, as well as on practical aspects for its successful implementation.


Food allergy Peanut allergy Allergy treatment Immunotherapy Food allergy guidelines 



Randomized controlled trials


Randomized, placebo-controlled trial


Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood


Relative risk


Oral food challenge


Learning Early About Peanut Study


Relative risk reduction


Absolute risk reduction


Number needed to treat


Enquiring About Tolerance


Solids Timing for Allergy Reduction


Starting Time for Egg Protection


Beating Egg Allergy Study


Hen’s Egg Allergy Prevention


Prevention of Egg Allergy with Tiny Amount Intake


American Academy of Pediatrics


National Institute of Allergy and Infectious Diseases


American Academy of Allergy, Asthma and Immunology


Skin prick test


Compliance with Ethical Standards

Conflict of Interest

Matthew Greenhawt is supported by grant 1K08HS024599-01 from the Agency for Healthcare Quality and Research; was an Expert Panel member of the NIAID-sponsored Guidelines for Peanut Allergy Prevention; represented the American College of Allergy, Asthma and Immunology in the formation of the Consensus Communication on Early Peanut Introduction and the Prevention of Peanut Allergy in High-Risk Infants; has served as a consultant for the Canadian Transportation Agency and Aimmune Therapeutics; is a member of physician/medical advisory boards for Aimmune, Nutricia, Kaleo Pharmaceutical, Nestle, and Monsanto; is a member of the scientific advisory boards for the National Peanut Board; has received honorarium for lectures from Thermo Fisher, ReachMD, and the Kentucky/Pennsylvania/Aspen/New York allergy societies, the ACAAI, the EAACI, and UCLA/Harbor Medical Center; and is a member of the Joint Taskforce on Allergy Practice Parameters.

David Fleischer is a member of the scientific advisory council for the National Peanut Board, represented the American Academy of Allergy, Asthma and Immunology in the formation of the Consensus Communication on Early Peanut Introduction and the Prevention of Peanut Allergy in High-Risk Infants; was a Coordinating Committee and Expert Panel member of the NIAID-sponsored Guidelines for Peanut Allergy Prevention; is a member of physician/medical advisory boards for Aimmune, Kaleo Pharmaceutical, Nestle, and Monsanto; and received grant support from Nestle, Monsanto, DBV Technologies, and Aimmune Therapeutics.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Sources of Support



Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Gupta RS, Springston EE, Warrier MR, Smith B, Kumar R, Pongracic J, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128:e9–17.CrossRefPubMedGoogle Scholar
  2. 2.
    Greenhawt M. Food allergy quality of life and living with food allergy. Curr Opin Allergy Clin Immunol. 2016;16:284–90.CrossRefPubMedGoogle Scholar
  3. 3.
    Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, et al. Food allergy: a practice parameter update—2014. J Allergy Clin Immunol. 2014;134:1016–25. e43CrossRefPubMedGoogle Scholar
  4. 4.
    • Venter C, Maslin K, Patil V, Kurukulaaratchy R, Grundy J, Glasbey G, et al. The prevalence, natural history and time trends of peanut allergy over the first 10 years of life in two cohorts born in the same geographical location 12 years apart. Pediatr Allergy Immunol. 2016;27:804–11. This recent update to the Isle of Wight cohort questions if the prevalence of peanut allergy has really increased.CrossRefPubMedGoogle Scholar
  5. 5.
    •• Ierodiakonou D, Garcia-Larsen V, Logan A, Groome A, Cunha S, Chivinge J, et al. Timing of allergenic food introduction to the infant diet and risk of allergic or autoimmune disease: a systematic review and meta-analysis. JAMA. 2016;316:1181–92. A cutting edge meta-analysis of food allergy prevention trials showing sginficant risk reduction is associated with both early egg and early peanut introduction.CrossRefPubMedGoogle Scholar
  6. 6.
    Muraro A, Halken S, Arshad SH, Beyer K, Dubois AE, Du Toit G, et al. EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy. Allergy. 2014;69:590–601.CrossRefPubMedGoogle Scholar
  7. 7.
    Joseph CL, Ownby DR, Havstad SL, Woodcroft KJ, Wegienka G, MacKechnie H, et al. Early complementary feeding and risk of food sensitization in a birth cohort. J Allergy Clin Immunol. 2011;127:1203–10. e5CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Nwaru BI, Erkkola M, Ahonen S, Kaila M, Haapala AM, Kronberg-Kippila C, et al. Age at the introduction of solid foods during the first year and allergic sensitization at age 5 years. Pediatrics. 2010;125:50–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Schnabel E, Sausenthaler S, Schaaf B, Schafer T, Lehmann I, Behrendt H, et al. Prospective association between food sensitization and food allergy: results of the LISA birth cohort study. Clin Exp Allergy. 2010;40:450–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Alm B, Aberg N, Erdes L, Mollborg P, Pettersson R, Norvenius SG, et al. Early introduction of fish decreases the risk of eczema in infants. Arch Dis Child. 2009;94:11–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Nwaru BI, Takkinen HM, Niemela O, Kaila M, Erkkola M, Ahonen S, et al. Introduction of complementary foods in infancy and atopic sensitization at the age of 5 years: timing and food diversity in a Finnish birth cohort. Allergy. 2013;68:507–16.CrossRefPubMedGoogle Scholar
  12. 12.
    Roduit C, Frei R, Depner M, Schaub B, Loss G, Genuneit J, et al. Increased food diversity in the first year of life is inversely associated with allergic diseases. J Allergy Clin Immunol. 2014;133:1056–64.CrossRefPubMedGoogle Scholar
  13. 13.
    Nwaru BI, Takkinen HM, Kaila M, Erkkola M, Ahonen S, Pekkanen J, et al. Food diversity in infancy and the risk of childhood asthma and allergies. J Allergy Clin Immunol. 2014;133:1084–91.CrossRefPubMedGoogle Scholar
  14. 14.
    • Du Toit G, Katz Y, Sasieni P, Mesher D, Maleki SJ, Fisher HR, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008;122:984–91. The study that prompted the LEAP study.CrossRefPubMedGoogle Scholar
  15. 15.
    Koplin JJ, Osborne NJ, Wake M, Martin PE, Gurrin LC, Robinson MN, et al. Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol. 2010;126:807–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Katz Y, Rajuan N, Goldberg MR, Eisenberg E, Heyman E, Cohen A, et al. Early exposure to cow’s milk protein is protective against IgE-mediated cow’s milk protein allergy. J Allergy Clin Immunol. 2010;126:77–82. e1CrossRefPubMedGoogle Scholar
  17. 17.
    •• Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803–13. The LEAP study, and the basis of the revised NIAID policy to introduce peanut early.CrossRefPubMedGoogle Scholar
  18. 18.
    •• Perkin MR, Logan K, Tseng A, Raji B, Ayis S, Peacock J, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374:1733–43. An innovtive study showing small risk reduction in the development of peanut and egg allergy in standard risk breast fed infants introduced peanut and egg at 3 months vs. 6 months of life, but in the per protocol analysis only.CrossRefPubMedGoogle Scholar
  19. 19.
    Palmer DJ, Metcalfe J, Makrides M, Gold MS, Quinn P, West CE, et al. Early regular egg exposure in infants with eczema: a randomized controlled trial. J Allergy Clin Immunol. 2013;132:387–92. e1CrossRefPubMedGoogle Scholar
  20. 20.
    Palmer DJ, Sullivan TR, Gold MS, Prescott SL, Makrides M. Randomized controlled trial of early regular egg intake to prevent egg allergy. J Allergy Clin Immunol. 2016; doi: 10.1016/j.jaci.2016.06.052.Google Scholar
  21. 21.
    •• Bellach J, Schwarz V, Ahrens B, Trendelenburg V, Aksunger O, Kalb B, et al. Randomized placebo-controlled trial of hen’s egg consumption for primary prevention in infants. J Allergy Clin Immunol. 2016; doi: 10.1016/j.jaci.2016.06.045. An early egg introduction study suggesting possible increased risk of allergy and the potential that egg-senstized individuals are at risk of severe reaction upon early egg introduction.PubMedGoogle Scholar
  22. 22.
    •• Natsume O, Kabashima S, Nakazato J, Yamamoto-Hanada K, Narita M, Kondo M, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;389:276–86. A highly successful trial of early cooked egg introduction in eczematous children where their eczema was conrolled before introduction. The trial was halted early as it showed clear benefit.CrossRefPubMedGoogle Scholar
  23. 23.
    Wei-Liang Tan J, Valerio C, Barnes EH, Turner PJ, Van Asperen PA, Kakakios AM, et al. A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy. J Allergy Clin Immunol. 2016; doi: 10.1016/j.jaci.2016.08.035.PubMedGoogle Scholar
  24. 24.
    American Academy of Pediatrics, Committee on Nutrition. Hypoallergenic infant formulas. Pediatrics. 2000;106:346–9.CrossRefGoogle Scholar
  25. 25.
    Greer FR, Sicherer SH, Burks AW. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics. 2008;121:183–91.CrossRefPubMedGoogle Scholar
  26. 26.
    Fleischer DM, Spergel JM, Assa’ad AH, Pongracic JA. Primary prevention of allergic disease through nutritional interventions. J Allergy Clin Immunol Pract. 2013;1:29–36.CrossRefPubMedGoogle Scholar
  27. 27.
    •• Togias A, Cooper SF, Acebal ML, Assa’ad A, Baker Jr JR, Beck LA, et al. Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases—sponsored expert panel. J Allergy Clin Immunol. 2017;139:29–44. The most up-to-date US infant feeding policy, recmmending early peanut introduction.CrossRefPubMedGoogle Scholar
  28. 28.
    Du Toit G, Roberts G, Sayre PH, Plaut M, Bahnson HT, Mitchell H, et al. Identifying infants at high risk of peanut allergy: the Learning Early About Peanut Allergy (LEAP) screening study. J Allergy Clin Immunol. 2013;131:135–43 e1-12.CrossRefPubMedGoogle Scholar
  29. 29.
    Greenhawt M, Chan ES, Fleischer DM. Peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:2164–5.PubMedGoogle Scholar
  30. 30.
    Wood RA, Burks AW. LEAPing forward with the new guidelines. J Allergy Clin Immunol. 2017;139:52–3.CrossRefPubMedGoogle Scholar
  31. 31.
    Greenhawt M. Early allergen introduction for preventing development of food allergy. JAMA. 2016;316:1157–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Koplin JJ, Peters RL, Dharmage SC, Gurrin L, Tang ML, Ponsonby AL, et al. Understanding the feasibility and implications of implementing early peanut introduction for prevention of peanut allergy. J Allergy Clin Immunol. 2016;138:1131–41. e2CrossRefPubMedGoogle Scholar
  33. 33.
    O'Connor C, Kelleher M, Horrihane J. Calculating the effect of population-level implementation of the Learning Early About Peanut Allergy (LEAP) protocol to prevent peanut allergy. J Allergy Clin Immunol. 2016;137:1263–4 e1-2.Google Scholar
  34. 34.
    Greenhawt M, Fleischer D, Chan ES, Venter C, Stukus D, Gupta R, et al. LEAPing through the looking glass: secondary analysis of the effect of skin test size and age of introduction on peanut tolerance after early peanut introduction. Allergy 2016.Google Scholar
  35. 35.
    Australioasian Society of Clinical Immunology and Allergy infant feeding guidelines. At Accessed December 4, 2016.
  36. 36.
    Greenhawt M. The National Institutes of Allergy and Infectious Diseases sponsored guidelines on preventing peanut allergy: a new paradigm in food allergy prevention. Allergy Asthma Proc. 2017;38:92–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Pongracic JA, Bock SA, Sicherer SH. Oral food challenge practices among allergists in the United States. J Allergy Clin Immunol. 2012;129:564–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Tey D, Allen KJ, Peters RL, Koplin JJ, Tang ML, Gurrin LC, et al. Population response to change in infant feeding guidelines for allergy prevention. J Allergy Clin Immunol. 2014;133:476–84.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Pediatrics, Allergy/Immunology Section, Children’s Hospital ColoradoUniversity of Colorado Denver School of MedicineAuroraUSA

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