peanut allergy and food introduction in kids

New Engl J of Med just published the LEAP (Learning about Peanut Allergy) study, which looked at early feeding of peanuts to infants at high risk of having peanut allergy, showing a dramatic decrease in subsequent allergy (see peanut allergy early food intoduction NEJM 2015 in dropbox, or DOI: 10.1056/NEJMoa1414850). see prior blog for other recent data on early food consumption, the effect on the gut microbiome, and subsequent development of allergy, including suggestions from a couple of years ago that introduction of peanuts made sense (http://gmodestmedblogs.blogspot.com/2019/04/food-diversity-in-young-kids-and.html ).  the background, in brief, is that the prevalence of peanut allergy in kids has exploded (doubling in past 10 years, to reach prevalence of 3%), this is the leading cause of anaphylaxis/death from food allergies, peanut allergy in kids has huge psychosocial ramifications for the kids and parents, and there are remarkable differences in different countries: eg, in Israel there is much much less peanut allergy and they introduce peanuts early in life (and a study showed that Jewish kids in the UK have 10x the risk of peanut allergy as Israeli kids of similar ancestry). details of LEAP study:

--640 infants (age 4-11 months old, median age 7.8 months) with severe eczema, egg allergy, or both (known risk factors for developing peanut allergy) were initially tested for peanut allergy by skin-prick testing

--530 with initially negative skin-prick tests were randomized to early peanut introduction (in the form of peanut butter, NOT whole peanuts!!, with 2 grams of peanut protein 3 times/week) vs peanut avoidance and followed to age 5. 

results:

--in the 530 kids with initially negative skin-prick tests: prevalence of peanut allergy, as determined by oral food challenge at age 5, was 13.7% in the peanut avoidance group and 1.9% in the peanut consumption group (86.1% relative risk reduction!!!)  and no difference in serious adverse events. also, the skin-prick wheal size was smaller in those in the peanut consumption group

--98 kids with initially positive skin-prick tests: prevalence of peanut allergy was 35.3% in the peanut avoidance group and 10.6% in the peanut consumption group  (70.0% relative risk reduction!!!)  and no difference in serious adverse events. of note, 7 of these kids who had been assigned to the peanut consumption group had positive results to peanut food challenge and were instructed to avoid peanuts, and 9 terminated peanut consumption because of allergic symptoms

--levels of peanut-specific IgG4 antibody were increased mostly in the peanut consumption group

--levels of peanut-specific IgE levels, on the other hand, were marginally higher in the peanut avoidance group;​ the wheal sizes in subsequent skin-prick tests were higher and strongly correlated with being in the peanut avoidance group. all kids in the peanut-avoidance group who had peanut-specific IgE levels >10.0 kU/liter were allergic to peanuts.
--the IgG4/IgE ratio was calculated (which presumably reflects immune modulation) and statistically higher in the peanut consumption group 

very impressive study, and is concordant with other allergy studies, including those suggesting early exposure to environmental allergens decreases the risk of asthma (see the above-mentioned blog for more details). we should keep in mind that the LEAP study was open-labeled, not blinded -- parents knew which diet the kids were on. of particular importance to generalizing this study, low-risk infants were not included (and they also did not include high risk kids with very large wheal reactions of >4mm) on skin-prick testing. so, my sense is that the prior nutritional guidelines suggesting avoiding peanut protein in infants stemmed from a flawed model, just as the flawed nutritional guidelines in the 1970s led to lower fat consumption and more obesity. and this brings up the issue of always testing and retesting our conceptual models to assess their real-world accuracy and not just following what seems to make sense at the time.  in terms of what to do with peanuts, these are really impressive results. it will be interesting to see how the various guidelines will evolve as a result of this study. at this point, probably the most cautious approach in high-risk infants would be to have skin-prick testing done prior to introducing peanut protein, and if positive, to have peanuts introduced under the guidance of an allergy clinic.