HOUSTON -- Young children at high risk for peanut allergy were much less likely to develop the allergy if they were regularly exposed to peanuts early in life, researchers reported here.
Among children who had a negative result on a skin-prick test at ages 4 to 11 months, 13.7% of those who avoided peanuts had become allergic by 5 years of age compared with 1.9% of those who regularly ate peanuts, an absolute difference of 11.8 percentage points (95% CI 3.4-20.3, P<0.001) and an 86.1% relative reduction in prevalence of the allergy, according to , of King's College London and St. Thomas' National Health Service Foundation Trust in London, and colleagues.
Action Points
- In young children at high risk for peanut allergy, early oral exposure to peanuts is associated with markedly lower likelihood of actually developing peanut allergy.
- Levels of peanut-specific IgG4 and IgG were higher in those consuming than in those avoiding peanuts, an effect that mimics successful allergen immunotherapy.
Moreover, for those who had a positive skin-prick test, 35.3% of those who avoided peanuts were allergic by age 5 compared with 10.6% of those who consumed peanuts, for a difference of 24.7 percentage points (95% CI 4.9-43.3, P=0.004) and a 70% relative reduction in prevalence, the researchers reported in a special session at the
"We now have an intervention that has been statistically significant to be highly efficacious and to have an 80% preventive effect," lead author George Du Toit, MBBCh, told ѻý.
"This was an very strong effect, and the findings are based on an extremely rigorous design," said Du Toit, who is a pediatric allergy consultant, also at King's College and St. Thomas' in London.
"The question of whether early exposure or avoidance is the better strategy to prevent food allergies remains open," wrote the authors of the study, which was also published online in the
Strict avoidance is the standard of care today, but elimination diets have been consistently
Lack and colleagues previously observed that Jewish children living in the U.K., who rarely were given peanut products early in life, had 10 times the rate of peanut allergy than their Israeli counterparts, who begin eating peanuts at about 7 months of age. They hypothesized that early exposure minimized the likelihood of the allergy developing, and conducted the Learning Early about Peanut Allergy (LEAP) study to test the hypothesis.
So during the years 2006 to 2009, they enrolled 640 infants who were considered to be at high risk for developing peanut allergy because they already had severe eczema or egg allergy.
All participants underwent a skin-prick test. A total of 530 had negative tests, and 98 who developed a wheal 1 to 4 mm in diameter were considered to have a low-positive test. Children with a wheal larger than 4 mm were excluded because of safety concerns.
At several study visits, serum levels of peanut IgE, IgG, and IgG4 antibodies were measured, and the IgG4:IgE ratio calculated, to assess immune responses and antigen exposure. Peanut allergy at age 5 years was determined by an oral food challenge.
Children in the consumption group were given 6 g or more of peanut protein each week, most often in a snack food known as Bamba.
Adherence to consumption or avoidance was reported at 92%.
Adverse events that occurred more often in the consumption group included upper respiratory tract infections, gastroenteritis, skin infections, urticaria, and conjunctivitis, but most were mild or moderate.
Levels of peanut IgG and IgG4 were higher in the consumption group and the increases occurred earlier. "This effect mirrors the immunologic changes seen in successful allergen immunotherapy," the investigators noted.
An editorial accompanying the study noted that the prevalence of peanut allergy has quadrupled during the past 13 years, rising from 0.4% in 1997 to more than 2% by 2010, according to , of the University of Texas Southwestern Medical Center in Dallas, and , of the Jaffe Food Allergy Institute at the Icahn School of Medicine at Mount Sinai in New York City.
The results of LEAP are "striking," Gruchalla and Sampson wrote, and "because the results of this trial are so compelling, and the problem of the increasing prevalence of peanut allergy so alarming," new guidelines addressing the problem should be developed.
Du Toit agreed. "We would strongly encourage modification of current weaning recommendations," he said in an interview. "Soon after weaning peanuts should be added to the diet," he said.
"However, for high-risk infants, such as those who have severe eczema, skin-prick testing is needed. If the child is low-positive, with a wheal of 1 to 4 mm, peanuts can be introduced, but in experienced hands. If the child is high-positive, with a wheal of 5 mm or more, a discussion can be had about it," he said.
A problem now is the children who are already allergic, noted , who moderated the press briefing.
"We've already created a cohort of children who are highly allergic. My grandchildren can't bring peanut butter to preschool," said Drazen, who is the editor-in-chief of the New England Journal of Medicine and Parker B. Francis Professor of Medicine, Harvard Medical School.
"We've figured out how to prevent and lower the incidence of peanut allergy, but we already have a bunch of kids who are allergic to peanuts. How are we going to help kids get their peanuts early while not contaminating those children with peanut allergy. It's going to be a tough problem for the PTA," Drazen said.
Disclosures
The study authors received support from NIAID, the U.K. Department of Health, the U.K. Food Standards Agency, MRC and Asthma U.K. Center, The National Peanut Board, Osem, Food Allergy and Research Education, Action Medical Research, Stallergenes, Thermo Scientific, Meridien Foods, and DBV Technologies.
Editorialist Sampson disclosed relationships with Allertein Therapeutics, Regeneron, Sanofi, Danone Research Institute, Genentech, and Medimmune.
Primary Source
New England Journal of Medicine
De Toit G, et al "Randomized trial of peanut consumption in infants at risk for peanut allergy" N Engl J Med 2015; DOI: 10.1056/NEJMoa1414850.
Secondary Source
New England Journal of Medicine
Gruchalla R, Sampson H "Preventing peanut allergy through early consumption: Ready for prime time?" N Engl J Med 2015; DOI: 10.1056/NEJMe1500186.