In a Nutshell: What is the LEAP Study?

Peanut allergy is one of the most common food allergies among children in Western countries. In majority, the allergy persists until adulthood.¹ A US database study found an increase in peanut allergy prevalence from 1.7% in 2001 to 5.2% in 2017.¹  In Asia, the incidence of peanut allergy seems to be lower, with an estimated prevalence of 0.47%-0.64% in Singaporean school children.² However, peanuts are fast becoming triggers in anaphylactic reactions in the region due to changes in dietary habits.^2,3

To prevent allergic reactions in high-risk infants, guidelines from 1998 to 2000 recommended avoidance of allergenic foods in infant and maternal diets. Still, this strategy failed to prevent the development of IgE-mediated food allergies.⁴

Published in 2015, the study called Learning Early About Peanut (LEAP) has helped improve feeding methods for children who are at high-risk for food allergies. LEAP takes inspiration from another study done on Jewish children in the UK and Israel. The original study found that the prevalence of peanut allergy was 10 times higher in children from the UK who were introduced to peanuts after 1 year of age, compared to children in Israel who were fed peanuts much earlier (around 7 months old).⁵ While this result did not indicate causality, it became the motivation for conducting LEAP.⁴

The LEAP study was a randomized, open-label, and controlled trial conducted in the UK and aimed to ascertain if early infant feeding of peanuts can prevent peanut allergy. A total of 640 infants (4-11 months old) with severe eczema, egg allergy, or both  were randomly assigned to either eat or avoid peanuts until they were 60 months old.The infants were then divided into two groups based on pre-existing peanut sensitivity, as determined by a skin prick test (SPT). The main endpoint was to determine the proportion of infants who developed peanut allergy by 60 months of age.⁴

At least thrice a week, the infants assigned to peanut consumption were given either a snack food made of peanut butter and puffed maize or smooth peanut butter. Moreover, all participants were regularly assessed from baseline and at 12, 30, and 60 months, and these assessments included determination of peanut-specific immunoglobulins. Regular phone consultations and additional visits were also conducted. Those who had adverse reactions were asked to minimize peanut consumption and were included in the intention-to-treat analysis.⁴

At 60 months of age, peanut allergy was more prevalent in SPT-negative infants who avoided peanuts (13.7%) compared to those who consumed peanuts (1.9%). The absolute difference in the risk of 11.8% represents a high relative reduction (86.1%) in the prevalence of peanut allergy. Among the SPT-positive infants, peanut allergy was more prevalent among those who refrained from peanuts (35.3%) versus those who consumed peanuts (10.6%) (Figure 1).^4,6

Figure 1. Primary outcomes (intention-to-treat analysis) in the LEAP study⁶

When the LEAP results came out in 2015, existing early complementary feeding guidelines already suggested that highly allergenic foods need not be delayed beyond 4–6 months of age. However, these guidelines did not actively advocate for peanut introduction at 4–6 months of age in high-risk infants. Data from the LEAP study shows that early peanut introduction is safe and effective in a specific high-risk population.⁷ Following the results of the LEAP study, the National Institutes of Allergy & Infectious Diseases (NIAID) released the Addendum Guidelines for preventing peanut allergy in the United States. for the prevention of peanut allergy in the United States. These guidelines address specific infant risk categories for introducing peanut-containing foods (Table 1).⁸ 

Table 1. Summary of Addendum Guidelines⁸

The LEAP study highlighted primary and secondary prevention, as it showed a reduction in peanut allergy at 5 years old in those who consumed peanuts and peanut-containing foods earlier, regardless of their baseline sensitization status.⁹ The findings of this landmark trial provided the first direct evidence that delayed peanut introduction significantly increases the risk of peanut allergy and that early introduction can be successfully done in high-risk infants.⁷

References:

1. Lieberman JA, et al. The global burden of illness of peanut allergy: A comprehensive literature review. Allergy. 2021;76:1367–1384.
2. Liew WK, et al. Paediatric anaphylaxis in a Singaporean children cohort: changing food allergy triggers over time. Asia Pac Allergy. 2013;3(1):29-34.
3. Goh DL, et al. Pattern of food-induced anaphylaxis in children of an Asian community. Allergy. 1999;54(1):84-86.
4. Du Toit G, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015 Feb 26;372(9):803-13.
5. Du Toit G, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008 Nov; 122(5):984-91.
6. Fleischer DM. Life after LEAP: How to implement advice on introducing peanuts in early infancy. J Paediatr Child Health. 2017 Mar;53(S1):3-9.
7. Fleischer DM, et.al. Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants. J Allergy Clin Immunol. 2015 Aug;136(2):258-61.
8. Togias 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: 29–44.
9. Du Toit G, et al. Food allergy: Update on prevention and tolerance. J Allergy Clin Immunol. 2018 Jan;141(1):30-40.