Please push the peanuts!

"An ounce of prevention is worth a pound of cure." Ben Franklin's advice to Philadelphians threatened by fire in the 1700s applies well today to peanut allergy, a lifelong disease that despite the investment of millions of dollars, remains without a cure. With the publication of the Learning Early About Peanut (LEAP) trial, many of us were optimistic that the prevalence of peanut allergy would drop dramatically with the simple advice to introduce infant-safe forms of peanut into the diet early. Numerous international guidelines have been published to disseminate this practical and seemingly implementable advice across cultures (Table I).1Sampath V. Abrams E.M. Adlou B. Akdis C. Akdis M. Brough H.A. et al.Food allergy across the globe.J Allergy Clin Immunol. 2021; 148: 1347-1364Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Unfortunately, our "simple" advice may have caused confusion, especially regarding practical implementation in the primary care setting. Parents, pediatricians, and allergists have been scratching their heads over what "high-risk" means, which kids "need peanut," and how a pediatrician addresses fears of inducing an allergic reaction with first introduction in a brief well child checkup filled with discussions that are already monopolized by vaccine hesitancy and developmental milestones.2Togias A. Cooper S.F. Acebal M.L. Assa'ad A. Baker Jr., J.R. Beck L.A. 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: 29-44Abstract Full Text Full Text PDF PubMed Scopus (296) Google Scholar, 3Gupta R.S. Bilaver L.A. Johnson J.L. Hu J.W. Jiang J. Bozen A. et al.Assessment of pediatrician awareness and implementation of the addendum guidelines for the prevention of peanut allergy in the United States.JAMA Netw Open. 2020; 3e2010511Crossref Scopus (24) Google Scholar, 4Fleischer D.M. Chan E.S. Venter C. Spergel J.M. Abrams E.M. Stukus D. et al.A consensus approach to the primary prevention of food allergy through nutrition: guidance from the American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; and the Canadian Society for Allergy and Clinical Immunology.J Allergy Clin Immunol Pract. 2021; 9 (e4): 22-43Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 5Lai M. Sicherer S.H. Pediatricians underestimate parent receptiveness to early peanut introduction.Ann Allergy Asthma Immunol. 2019; 122: 647-649Abstract Full Text Full Text PDF PubMed Scopus (15) Google ScholarTable ISummary of international food allergy recommendations1Sampath V. Abrams E.M. Adlou B. Akdis C. Akdis M. Brough H.A. et al.Food allergy across the globe.J Allergy Clin Immunol. 2021; 148: 1347-1364Abstract Full Text Full Text PDF PubMed Scopus (62) Google ScholarOrganization and dateRecommended introductory food(s)Definition of high-riskAllergen introduction adviceASCIA, 2017All foodsInfants with severe eczema and/or egg allergyAll infants, including HR infants, should be given allergenic solid foods, including PN, cooked HE, cow's milk, and wheat in their first yearHR infants: good evidence that regular PN intake at age <12 mo can reduce PN allergy and moderate evidence that cooked HE at age <8 mo (with family history of allergy) may reduce the likelihood of development of HE allergyNIAID, 2017PNInfants with AD and/or HE FADifferent PN introduction schedules depending on risk: at age 4-6 mo in infants with severe AD and/or HE allergy and at around age 6 mo in infants with mild-to-moderate AD; family and cultural feeding practices should be followed in infants with no AD or FAUK Committee on Toxicity, 2018PNInfants with a history of early-onset AD or suspected FAInfants at general risk: PN and HE need NOT be differentiated from other complementary foods. Exclusion of PN and HE beyond age 6-12 mo may increase risk of FA to these foodsParents of HR infants may wish to seek medical advice before introducing PN and HEAPAPARI, 2018All foodsInfants with severe eczemaAt-risk infants with nonsevere eczema or a family history of allergy: introduction of allergenic foods should not be delayedHR infants with severe eczema: SPT and/or OFC to PN and egg may be required; introduction of allergenic foods should not be delayedBSACI, 2018All foodsInfants with a history of early-onset AD or suspected FAInfants at general risk: introduce PN and HE as part of the family dietHR infants: introduce HE and PN when ready, from age 4 mo onward; HE should be introduced before PNEAACI, 2020All foodsPopulations with high prevalence of PNallergy independent of risk factorsAll infants: introduce PN and well-cooked HE as part of complementary food introduction from age 4 to 6 moJPGFA, 2020All foodsInfants with eczemaAll infants/HR infants: delayed introduction of food allergens not recommendedAAAAI, ACAAI, and CSACI consensus statement, 2021All foods- Highest risk: infants with severe AD- Potentially at some increased risk: mild-to-moderate AD, family history of atopy in either or both parents, and/or infants with 1 known FAIntroduce PN and cooked HE to all infants irrespective of risk starting around age 6 mo but not before age 4 moDo not delay introduction of other potentially allergenic complementary foods (cow's milk, soy, wheat, tree nuts, sesame, fish, shellfish) at around 6 age mo but not before age 4 moACAAI, American College of Asthma, Allergy and Immunology; AD, atopic dermatitis; APAPARI, Asia Pacific Association of Pediatric Allergy, Respirology & Immunology; ASCIA, Australasian Society for Clinical Immunology and Allergy; BSACI, British Society of Allergy and Clinical Immunology; CSACI, Canadian Society of Allergy and Clinical Immunology; FA, food allergy; HE, hen's egg; HR, high risk; JPGFA, Japanese Pediatric Guideline for Food Allergy; NIAID, National Institute of Allergy and Infectious Diseases; OFC, oral food challenge; PN, peanut; SPT, skin prick testing. Open table in a new tab ACAAI, American College of Asthma, Allergy and Immunology; AD, atopic dermatitis; APAPARI, Asia Pacific Association of Pediatric Allergy, Respirology & Immunology; ASCIA, Australasian Society for Clinical Immunology and Allergy; BSACI, British Society of Allergy and Clinical Immunology; CSACI, Canadian Society of Allergy and Clinical Immunology; FA, food allergy; HE, hen's egg; HR, high risk; JPGFA, Japanese Pediatric Guideline for Food Allergy; NIAID, National Institute of Allergy and Infectious Diseases; OFC, oral food challenge; PN, peanut; SPT, skin prick testing. Disappointingly, even in a population successfully implementing widespread uptake of the recommendations to introduce peanut in the first year of life, the prevalence of peanut allergy remained essentially the same. Soriano et al recently reported that despite near total adherence to early introduction recommendations in Australia, there was no significant effect on the prevalence of peanut allergy.6Soriano V.X. Peters R.L. Moreno-Betancur M. Ponsonby A.L. Gell G. Odoi A. et al.Association between earlier introduction of peanut and prevalence of peanut allergy in infants in Australia.JAMA. 2022; 328: 48-56Crossref PubMed Scopus (22) Google Scholar Remarkably, in 2018-2019, 85.6% of Australian parents introduced peanut before their child was 12 months of age compared with only 21.6% of participants in a comparative sample from the period 2007-2011, and yet, the prevalence of peanut allergy in the population did not change significantly (3.1% adjusted to 2.6% in 2018-2019 vs 3.1% in 2007-2011). Soriano et al6Soriano V.X. Peters R.L. Moreno-Betancur M. Ponsonby A.L. Gell G. Odoi A. et al.Association between earlier introduction of peanut and prevalence of peanut allergy in infants in Australia.JAMA. 2022; 328: 48-56Crossref PubMed Scopus (22) Google Scholar point to an increase in infants of East Asian ancestry (who are characterized by dietary introduction patterns different from those of Australian ancestry) represented in the more recent sample and timing of introduction as contributory factors to the persistent peanut allergy prevalence seen in their population. In this issue of the Journal of Allergy and Clinical Immunology, Roberts et al reexamine the LEAP cohort (ie, childen at high risk of developing peanut allergy) and combine data from the Enquiring About Tolerance (EAT) study (ie, a study of the general population) as well as participants from the Peanut Allergy Sensitization (PAS) study, who were infants screened in the LEAP trial but not included either because they were not considered high risk or because they already had peanut allergy.7Roberts G. Bahnson H.T. Du Toit G. O'Rourke C. Sever M.L. Brittain E. et al.Defining the window of opportunity and the target populations to prevent peanut allergy.J Allergy Clin Immunol. 2023; 151: 1329-1336Abstract Full Text Full Text PDF Scopus (4) Google Scholar Combined data from these 3 groups were used to model the intervention in a general population covering the breadth of risk factors for peanut allergy seen across a normal population. The overall objective was to determine the optimal target population and timing of dietary peanut introduction to prevent peanut allergy in the general population. The findings of Roberts et al7Roberts G. Bahnson H.T. Du Toit G. O'Rourke C. Sever M.L. Brittain E. et al.Defining the window of opportunity and the target populations to prevent peanut allergy.J Allergy Clin Immunol. 2023; 151: 1329-1336Abstract Full Text Full Text PDF Scopus (4) Google Scholar emphasize that targeting the highest-risk infants with severe eczema decreases the population disease burden by only 4.6%, whereas inclusion of the larger number of children with mild eczema or no eczema leads to a 77% reduction in peanut allergy if peanut is introduced into the diets of children with eczema at the age of 4 months and into the diets of those without eczema at the age of 6 months. They also report that the estimated reduction in peanut allergy diminishes with every month of delayed introduction. The identified key risk factors for peanut allergy development are non-White ethnicity, eczema severity, duration of eczema, and age at which peanut is introduced. Limitations to the report by Roberts et al7Roberts G. Bahnson H.T. Du Toit G. O'Rourke C. Sever M.L. Brittain E. et al.Defining the window of opportunity and the target populations to prevent peanut allergy.J Allergy Clin Immunol. 2023; 151: 1329-1336Abstract Full Text Full Text PDF Scopus (4) Google Scholar include the application of the assumptions used to create the prevention models, leading to potential undercalculation or overcalculation of the effect size. Their Table E1 succinctly highlights and justifies potential confounders in the model.7Roberts G. Bahnson H.T. Du Toit G. O'Rourke C. Sever M.L. Brittain E. et al.Defining the window of opportunity and the target populations to prevent peanut allergy.J Allergy Clin Immunol. 2023; 151: 1329-1336Abstract Full Text Full Text PDF Scopus (4) Google Scholar Despite the limitations, the strength of the data presented by Roberts et al7Roberts G. Bahnson H.T. Du Toit G. O'Rourke C. Sever M.L. Brittain E. et al.Defining the window of opportunity and the target populations to prevent peanut allergy.J Allergy Clin Immunol. 2023; 151: 1329-1336Abstract Full Text Full Text PDF Scopus (4) Google Scholar is sufficient to support a reexamination of international guidelines and the guidance that allergists are providing to our patients and primary care providers in our communities. At a population level, delayed introduction of peanut has no benefit. The data presented by Roberts et al7Roberts G. Bahnson H.T. Du Toit G. O'Rourke C. Sever M.L. Brittain E. et al.Defining the window of opportunity and the target populations to prevent peanut allergy.J Allergy Clin Immunol. 2023; 151: 1329-1336Abstract Full Text Full Text PDF Scopus (4) Google Scholar are consistent with observations previously published by Keet et al, who demonstrated that the odds of peanut allergy development were significantly higher for each increase in month of age at introduction, increasing severity of eczema, and Black or Asian race versus White race.8Keet C. Pistiner M. Plesa M. Szelag D. Shreffler W. Wood R. et al.Age and eczema severity, but not family history, are major risk factors for peanut allergy in infancy.J Allergy Clin Immunol. 2021; 147 (e5): 984-991Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Similar benefit was seen in the PreventADALL study, a multicenter, cluster-randomized, factorial trial conducted in Norway and Sweden. In this cohort of infants recruited from the general population, participants were divided into the following groups: (1) a group with skin emollients applied from age 2 weeks to less than 9 months, (2) a food intervention group given peanut, cow's milk, wheat, and egg from 3 months of age, (3) a combined intervention group whose members received both skin emollients and early allergen complementary feeding, and (4) a control group whose members received no intervention.9Skjerven H.O. Lie A. Vettukattil R. Rehbinder E.M. LeBlanc M. Asarnoj A. et al.Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicentre, cluster-randomised trial.Lancet. 2022; 399: 2398-2411Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar Skjerven et al9Skjerven H.O. Lie A. Vettukattil R. Rehbinder E.M. LeBlanc M. Asarnoj A. et al.Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicentre, cluster-randomised trial.Lancet. 2022; 399: 2398-2411Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar prospectively demonstrated that introduction of allergenic solids into the infant diet at 3 months of age effectively reduced the risk of all food allergies, including peanut allergy. With additional evidence from these studies in mind, what is the take-home message for our frontline colleagues who will see the infants before they make it to an allergist? The evidence points toward a clarifying message to introduce peanut into the diet of all infants, particularly those of non-White ancestry and including those without eczema who are aged 4 to 6 months in populations in which peanut allergy is a public health concern. Encouraging early introduction for specific infants based on risk factors seems to have caused confusion and minimized the potential impact across all segments of the population. Certainly, we need to make sure that children with severe eczema have peanut introduced closer to 4 months of age than 6 months of age; however, in the end, splitting hairs over the definition of eczema severity does not advance the message that we need to be communicating to our primary care colleagues, which should be "Please push the peanuts!" (in an age-appropriate form and making sure to keep it in the diet, once introduced!). Additional studies will need to clarify the minimum amount of peanut protein necessary, the regularity of ingestion, and the length of time for which this approach is applied to create long-lasting tolerance. We should also be mindful to improve representation of differing ethnic groups in our food allergy studies. Estimates regarding the prevalence of food allergy have been made on the basis of a relatively small proportion of individuals from differing ethnic backgrounds. As researchers, we absolutely must emphasize diverse representation in clinical trials and interventional studies in order to validate where differences do exist and to understand the potentially complex environmental and dietary cultural factors in children of differing ethnic backgrounds that may be contributing to peanut allergy development even earlier than what has been reported in the predominantly White populations examined in the existing studies. In the meantime, our best chance at achieving a cure is to prevent peanut allergy from occurring in the first place. Defining the window of opportunity and target populations to prevent peanut allergyJournal of Allergy and Clinical ImmunologyVol. 151Issue 5PreviewPeanut allergy affects 1% to 2% of European children. Early introduction of peanut into the diet reduces allergy in high-risk infants. Full-Text PDF Open Access