Emerging evidence reveals that earlier introduction of highly allergenic foods into infants’ diets may actually lead to immune tolerance. Here’s what you should know.
Although many parents report food allergy in their children and the incidence of parental report has increased over time,1,2 the actual incidence of confirmed food allergy is much lower.3,4 However, food allergy still is estimated to impact 2% to 10% of pediatric patients, and its prevention is an important goal in pediatric practice because there is no current cure.5,6
The pediatrician needs to be aware of changing practice recommendations related to the introduction of complementary foods for children. Although pediatricians who have been in practice for some time may have previously asked parents to delay the introduction of highly allergenic foods, emerging evidence now suggests just the opposite. Earlier introduction of highly allergenic foods may actually prevent food allergy.
Food allergy basics
WHAT IS FOOD ALLERGY?
Food allergies refer to reactions that occur as a result of immunologic reactions in response to certain foods. Food allergies are generally classified as either immunoglobulin (Ig)E mediated or non–IgE mediated and have different clinical presentations.7
WHAT ARE THE MOST COMMON FOOD ALLERGENS?
Whereas any food can theoretically lead to an allergic reaction, the most common offenders are:
· Cow’s milk
· Tree nuts
HOW DO FOOD ALLERGIES PRESENT?
Immunologic IgE-mediated reactions may present with the following symptoms:7
· Gastrointestinal anaphylaxis
· Generalized anaphylaxis
· Oral allergy syndrome
Non–IgE-mediated food allergies are more likely to present with subacute, chronic symptoms that are isolated to the gastrointestinal tract or skin.7
History of recommendations
Based on the idea that delaying exposure to solid foods might prevent atopic dermatitis and other allergic disease, the American Academy of Pediatrics (AAP) recommended in 2000 that children at high risk for developing food allergies delay the introduction of certain foods8: delay cow’s milk until age 1 year; eggs until age 2 years; peanuts, tree nuts, and fish until age 3 years. Although not specifically recommended, many pediatricians incorporated these guidelines into their routine recommendations in some form or fashion for other lower-risk children.
In 2008, the AAP updated its policy statement that included recommendations for the prevention of atopic disease. The report concluded that there was insufficient data and evidence to justify delaying the timing of complementary foods beyond the age of 4 to 6 months and that there was no protective effect of any dietary intervention beyond this age impacting the development of atopic disease.9
In a 2019 policy update,10 the AAP summarizes additional research since the 2008 report, concluding that there is no evidence that delaying the introduction of highly allergenic foods such as peanuts, eggs, and fish beyond age 4 to 6 months prevents atopic disease.10 The report goes on to cite evidence that early introduction of peanuts may prevent peanut allergy.
Preventing peanut allergy
The Learning Early About Peanut (LEAP) study was the first randomized controlled trial (RCT) to show that early exposure to peanut could prevent peanut allergy in high-risk infants.11 The authors believe that early exposure to peanut in the environment (ie, skin) leads to sensitization while early dietary exposure may lead to immune tolerance.
In this study, high-risk infants from the United Kingdom (UK), defined as having severe eczema, egg allergy, or both, were randomized into 2 groups of peanut exposure and then stratified based on pinprick testing (children with a response greater than 4 mm were excluded): early (aged between 4 and 11 months), or delayed (avoidance until age 5 years).
Only 1.7% of participants with early peanut exposure developed peanut allergy after age 5 years whereas 13.7% of participants randomized to avoidance as a prevention strategy developed peanut allergy. The 11.8% absolute difference in risk of peanut allergy (95% confidence interval [CI], 3.4-20.3; P<0.001) represents a greater than 85% relative risk (RR) reduction. The LEAP study demonstrated that early peanut exposure decreases peanut allergy in both sensitized infants and nonsensitized infants.
In a follow-up study known as LEAP-On, both the avoidance and consumption groups were asked to avoid peanut for 1 year at the conclusion of LEAP. Peanut allergy continued to be more common in the original avoidance group compared with the early exposure group (18.6% vs 4.8% of children, respectively; P=0.25).12
Early introduction of peanut was also found to prevent peanut allergy in the Enquiring About Tolerance (EAT) RCT.13 In this study, exclusively breastfed infants were randomized to receive early introduction of peanut or 5 other allergenic foods (cooked egg, cow’s milk, sesame, whitefish, or wheat) at age 3 months, or continue exclusive breastfeeding until age 6 months. Infants in the early introduction group were less likely to develop peanut allergy compared with children randomized to UK Department of Health advice to delay food introduction to age 6 months (0% vs 2.5%, respectively; P=0.003). A meta-analysis of the LEAP and EAT studies determined with “moderate certainty” that early introduction of peanut decreased the risk of peanut allergy (RR, 0.29; 95% CI, 0.11-0.74).14
In 2017, the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored expert panel on peanut allergy issued a 3-tiered recommendation for the introduction of peanut into an infant’s diet. The guideline provides the option for assessments that may be performed in a primary care practice or for referral for specialty care (Table).15
Preventing egg allergy
Six RCTs have been published since 2008 looking at the introduction of egg to prevent egg allergy.16-21
One example is the Prevention of Egg Allergy with Tiny Amount Intake (PETIT) study.20 The PETIT study, which was stopped early due to benefit, demonstrated that ingesting heated egg powder daily from age 6 months lowered the rate of egg allergy compared with infants who avoided egg completely until age 1 year (9% vs 38%, respectively; P=0.0012).
Although there are differences in these studies related to the types of patients enrolled, mechanisms used to prevent allergy, and in the assessed outcomes/results that can make drawing conclusions difficult,6 Ierodiakonou and colleagues performed a meta-analysis of 5 studies that included nearly 2000 infants and found “moderate certainty” that introduction of egg between age 4 to 6 months reduced the risk of egg allergy (RR, 0.56; 95% CI, 0.36-0.87).14
The pediatrician needs to be aware of changing recommendations and the changing environment for the prevention of food allergy. With significant changes in recommendations over the last 20 years and more likely to come over the next several years, the pediatrician must examine his or her current recommendations for the introduction of highly allergenic foods into a child’s diet based on that child’s risk and determine how he or she will communicate these changes to parents going forward.
1. Peters RL, Koplin JJ, Gurrin LC, et al; HealthNuts Study. The prevalence of food allergy and other allergic diseases in early childhood in a population-based study: HealthNuts age 4-year follow-up. J Allergy Clin Immunol. 2017;140(1):145.e8-153.e8.
2. Verrill L, Bruns R, Luccioli S. Prevalence of self-reported food allergy in U.S. adults: 2001, 2006, and 2010. Allergy Asthma Proc. 2015;36(6):458-467.
3. Venter C, Pereira B, Grundy J, et al. Incidence of parentally reported and clinically diagnosed food hypersensitivity in the first year of life. J Allergy Clin Immunol. 2006;117(5):1118-1124.
4. EggesbÃ¸ M, Botten G, Halvorsen R, Magnus P. The prevalence of CMA/CMPI in young children: the validity of parentally perceived reactions in a population-based study. Allergy. 2001;56(5):393-402.
5. Chafen JJ, Newberry SJ, Riedl MA, et al. Diagnosing and managing common food allergies: a systematic review. JAMA. 2010;303(18):1848-1856.
6. Du Toit G, Sampson HA, Plaut M, Burks AW, Akdis CA, Lack G. Food allergy: update on prevention and tolerance. J Allergy Clin Immunol. 2018;141(1):30-40.
7. Burks AW, Tang M, Sicherer S, et al. ICON: food allergy. J Allergy Clin Immunol. 2012;129(4):906-920.
8. Committee on Nutrition; American Academy of Pediatrics. Hypoallergenic infant formulas. Pediatrics. 2000;106(2 pt 1):346-349.
9. Greer FR, Sicherer SH, Burks AW, American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Allergy and Immunology. 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(1):183-191.
10. Greer FR, Sicherer SH, Burks AW; Committee on Nutrition, Section on Allergy and Immunology. The effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, hydrolyzed formulas, and timing of introduction of allergenic complementary foods. Pediatrics. 2019;143(4):e20190281.
11. Du Toit G, Roberts G, Sayre PH, et al; LEAP Study Team. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803-813. Erratum in: Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2016)
12. Du Toit G, Sayre PH, Roberts G, et al; Immune Tolerance Network LEAP-On Study Team. Effect of avoidance on peanut allergy after early peanut consumption. N Engl J Med. 2016;374(15):1435-1443.
13. Perkin MR, Logan K, Tseng A, et al; EAT Study Team. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374(18):1733-1743.
14. Ierodiakonou D, Garcia-Larsen V, Logan A, 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(11):1181-1192.
15. Togias A, Cooper SF, Acebal ML, et al. Addendum guidelines for the prevention of peanut allergy in the United States: summary of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. Pediatr Dermatol. 2017;34(1):5-12.
16. Palmer DJ, Metcalfe J, Makrides M, et al. Early regular egg exposure in infants with eczema: a randomized controlled trial. J Allergy Clin Immunol. 2013;132(2):387.e1-392.e1.
17. Bellach J, Schwarz V, Ahrens B, et al. Randomized placebo-controlled trial of hen’s egg consumption for primary prevention in infants. J Allergy Clin Immunol. 2017;139(5):1591.e2-1599.e2.
18. 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. 2017;139(5):1600.e2-1607.e2.
19. Wei-Liang Tan J, Valerio C, Barnes EH, et al; Beating Egg Allergy Trial (BEAT) Study Group. A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy. J Allergy Clin Immunol. 2017;139(5):1621. e8-1628.e8.
20. Natsume O, Kabashima S, Nakazato J, et al; PETIT Study Team. 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(10066):276-286.
21. Perkin MR, Bahnson HT, Logan K, et al. Association of early introduction of solids with infant sleep: a secondary analysis of a randomized clinical trial. JAMA Pediatr. 2018;172(8):e180739.
22. Fleischer DM, Spergel JM, Assa’ad AH, Pongracic JA. Primary prevention of allergic disease through nutritional interventions. J Allergy Clin Immunol Pract. 2013;1(1):29-36.
23. Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 2012;129(3):e827-e841.