Complementary Feeding for Allergy Prevention: Does Timing Matter?

Author(s):
Julia C. de Leon, MD, DPPS, FPSAAI

The recommendations on when to introduce allergenic foods to infants for lowering risks of allergy development has shifted through the years. From delaying and avoidance of allergens as it was believed to result in increased risk of allergic sensitisation, to now earlier exposure to these foods to achieve better tolerance. Through the dull-allergen exposure hypothesis, it was seen that controlled exposure may have more favorable results in terms of lowered risks of allergy development. However, it must be emphasized that the introduction of allergenic foods must consider the readiness of the infant to wean, proper timing of feeding, necessary food safety precautions, and must be done alongside the necessary ascending gradient of risk assessment.

Key messages:

• Previously, it has been the recommendation to delay the introduction of complementary allergenic foods in high-risk infants because increased permeability may result in an increased risk of allergic sensitization.

• Presently, because of evidence from various trials, there is a shift from avoidance to controlled exposure which aids in the achievement of tolerance. The recommendation is to introduce allergenic food between 4-6 months of age.

• An ascending gradient of risk assessment for the development of food allergy is proposed to help families understand their baby’s risk of developing food allergy compared to other infants along with practical suggestions on introduction of allergenic foods in high-risk infants.


It had previously been the recommendation to delay the introduction of complementary allergenic foods in high-risk infants because increased permeability may result in an increased risk of allergic sensitisation.

However, because of evidence from various trials, there has now been a shift from avoidance to controlled exposure, which aids in the achievement of tolerance. The recommendation is to introduce allergenic food between 4-6 months of age.

An ascending gradient of risk assessment for the development of food allergies is proposed to help families understand their baby’s risk of developing an allergy compared to other infants, along with practical suggestions on the introduction of allergenic foods in high-risk infants.

Weaning or the introduction of complementary feeding is a significant milestone for our infants. As their need for energy and nutrients begins to go beyond what mothers provide via breastfeeding, the WHO and the American Academy of Pediatrics have recommended that complementary foods be introduced to the general population at around six months of age.1

When it comes to feeding infants who are at-risk for allergic disease, it isn’t as straightforward. Through the years, we have seen an increase in the prevalence of IgE-mediated food allergies among infants and children.2  There are quite a number of dietary interventions proposed for the primary prevention of allergic disease.

In an article by Fleischer, their consensus group proposed a risk gradient (Figure 1) for the development of food allergy. Simply being at-risk for developing food allergies (having a parent or sibling with a known allergy) does not necessarily mean that the child will develop one. 3 Proper evaluation by an allergist may be needed, possibly including testing before introduction, in those who might be higher up in the risk assessment gradient.

Figure 1: Ascending gradient of risk assessment for the development of food allergy among infants. The bottom of the pyramid represents standard risk and the peak of the highest risk for developing food allergy

Earlier strategies advised delaying introduction of complementary allergenic food, but delaying may increase the risk of food allergy or eczema. Now, the current paradigm is shifting from avoidance to controlled exposure,4 which may be critical in achieving tolerance.5 It is believed that through the “dual-allergen exposure hypothesis”, oral administration of food allergens favors the achievement of tolerance through the expansion of TH1 and Treg populations.5 This has resulted in a change in recommendations. Present guidelines recommend that complementary allergenic food be given between 4-6 months of age.

Landmark clinical trials that support this include the LEAP (Learning Early About Peanut Allergy) study, the EAT (Enquiring About Tolerance) study and the PETIT (Prevention of Egg Allergy with Tiny Amount Intake Trial). Noted in the LEAP study was a 81% risk reduction of peanut allergy in high-risk infants who were given the recommended amount of peanut protein each week hence early introduction of peanut-based products led to the prevention of peanut allergy in high-risk infants. 6 A consensus published by 12 societies in 2015 recommended that peanut be introduced from 4-11 months in high-risk infants.7 

The purpose of the EAT study was to see if early introduction before 6 months of age of some amount of multiple allergenic foods (cow’s milk, peanut, hard-boiled hen’s egg, sesame, cod and wheat) would reduce the risk of developing allergies. Infants were randomly assigned to one group consuming the 6 allergenic foods at 3 months old, and the other group avoiding them for at least 6 months. At 1 and 3 years, the prevalence of any food allergy, peanut and egg allergy specifically, was lower in the earlyintroduction group compared with the standard-introduction group in the per-protocol analysis (2.4 versus 7.3% respectively, for any food allergy). 8 In the PETIT study, infants with eczema were given heated egg in a stepwise manner or avoided egg for 6 months. Results showed gradual intro of egg resulted in a 79% decrease in egg allergies in high-risk infants.9

There is a paucity of articles that discuss how to introduce highly allergenic foods in at-risk infants, but general advice was suggested by Fleischer 10 with additional practical suggestions based on consensus guidelines:

• The infant should be at least 4 months old and should be developmentally prepared for complementary feeding (e.g., good head control).

• Always make sure to introduce foods in an infant-safe form (nut butter instead of raw nuts) in accordance with the family’s cultural preferences

• They should be able to tolerate a few of the common complementary foods (fruits, vegetables, cereals) before giving highly allergenic foods. Single ingredient food is suggested

• If this has been achieved, the infant can be given an initial taste of one of the allergenic foods at home (not at a restaurant) with oral antihistamines available.

• Egg should not be introduced raw but should be given well-cooked

• If there is no reaction, the food may be introduced gradually in increasing amounts

• Introduction should be done at a pace of one new food every 3-5 days if no reactions happen. Make sure to also introduce a variety of food with different textures, as diet diversity during infancy and childhood significantly reduces food allergies in the first 10 years of life11

These recommendations provide guidance for feeding and food allergy prevention, while keeping in mind the family’s values and preferences.


References

1. https://www.who.int/health-topics/ complementary-feeding

2. Gupta, et al. The Public Health Impact of Parent-Reported Childhood Food Allergies in the United States. Pediatrics. 2018.

3. Fleischer DM, et al. Consensus Approach to the Primary Prevention of Food Allergy Through Nutrition. J Allergy Clin Immunol Pract. 2021

4. West C. Introduction of Complementary Foods to Infants. Ann Nutr Metab. 2017

5. Ferrante G, et al. Current Insights on Early Life Nutrition and Prevention of Allergy. Pediatrics. 2020.

6. Du Toit G, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015.

7. Fleischer, D. M., et al. Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants. The World Allergy Organization Journal. 2015.

8. Perkin MR, et al. Enquiring About Tolerance (EAT) study: Feasibility of an early allergenic food introduction regimen. J Allergy Clin Immunol. 2016.

9. Natsume O, 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.

10. Fleischer DM, et al. Primary prevention of allergic disease through nutritional interventions. J Allergy Clin Immunol Pract. 2013.

11. Venter C, et al. Different Measures of Diet Diversity During Infancy and the Association with Childhood Food Allergy in a UK Birth Cohort Study. J Allergy Clin Immunol Pract. 2020.