Reducing Food Allergies in Kids: ’Early and Regular’ Better than ’Later and Avoided’

PreventADALL study: Miniscule portions of allergenic foods starting at 3 months can lower allergy risks

06/29/2022
Liz Meszaros, Deputy Managing Editor, BreakingMED™
Kevin Rodowicz, DO, Assistant Professor, St. Luke’s University/Temple University
Take Away
  1. Exposure to allergenic foods from 3 months of age reduced food allergy at 36 months in a general population of infants.

  2. Results from the PreventADALL study support the early introduction of common allergenic foods as a safe and effective way to prevent food allergy.

Exposing infants to allergenic foods such as peanuts, cow’s milk, wheat, and egg at age 3 months may effectively—and safely—reduce food allergies at 3 years of age, according to researchers of the Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) study, who added that small amounts of these foods, given regularly and early in life, was key.

"[O]ur findings indicate that regular exposure to allergenic foods from 3 months of age complementary to regular feeding might be an effective, low-cost, and safe strategy to prevent food allergy in children, even in the absence of screening for risk of allergy. Our study thereby supports the hypothesis that early exposure, rather than avoidance or delayed introduction of allergenic foods, reduces the risk of food allergy," wrote Håvard Ove Skjerven, PhD, of the Oslo Center for Biostatistics and Epidemiology, Oslo University Hospital, Norway, and colleagues in The Lancet.

"Since food allergy represents a significant burden to the child and the family, with a potential to cause acute life-threatening reactions on exposure, it is likely that early food exposure might have an impact on reducing the overall burden of food allergy. However, previous reports of possibly increased rates of aspiration of peanut and other nuts highlights the importance of educating parents about safe introduction of solid foods to the infant diet," they added.

Skjerven and fellow researchers conducted this 2×2 factorial, cluster-randomized trial, randomizing a total of 2,397 newborns to the following groups at birth:

  • No intervention (n=597).
  • Skin intervention, comprised of skin emollients, including bath additives and facial cream from age 2 weeks to less than 9 months, at least four times weekly (n=575).
  • Food intervention, comprised of early feeding of peanut, cow’s milk, wheat, and egg from age 3 months (n=642).
  • Combined intervention of both skin and food interventions (n=583).

"The food intervention was chosen based on foods that are commonly associated with sensitization and food allergy in early childhood," researchers noted.

They limited these to three common foods plus peanut. Foods were introduced between 12-16 weeks of age. Peanut butter was introduced at the 3-month follow-up, and one week later, cow’s milk was introduced. One week after this, infants were fed wheat porridge, followed by scrambled eggs one week later.

Importantly, noted Skjerven and colleagues, these food amounts were miniscule.

"Parents were instructed to let the infant taste each of the foods from the finger of a parent or from a teaspoon at least 4 days per week, complementary to regular feeding, and to continue to include the food in the infant’s diet until at least 6 months of age without any dose restrictions," they explained.

The skin intervention was comprised of 5-10–minute baths with an added emulsified petrolatum-based oil and Ceridal cream applied to the face at least 4 days/week from age 2 weeks to 8 months. Infants were brought for follow-up visits at 3, 6, 12, 24, and 36 months. Parents were also instructed to keep electronic weekly diaries from birth to 26 weeks, as well as fill out electronic questionnaires every 3 months.

The primary outcome of the study was allergy to any interventional food at 36 months.

Food allergies were diagnosed in 44 children, including 2.3% of those in the no intervention group, 3.0% of those in the skin intervention group, 0.9% of those in the food intervention group, and 1.2% of those in the combined intervention group.

Thirty-two children developed a peanut allergy, 12 egg allergy, four milk allergy, and none develop a wheat allergy. Compared with the no intervention group, the prevalence of food allergies was reduced in infants in the food intervention group (risk difference: −1.6; 95% CI: –2.7 to –0.5; OR: 0.4; 95% CI: 0.2-0.8). However, this was not true in comparison with the skin intervention group (risk difference: 0.4%; 95% CI: –0.6 to 1.5%; OR: 1.3; 95% CI: 0.7-2.3; Pinteraction=1.0).

The prevention of food allergy in one child required early exposure to allergenic food in 63, noted Skjerven et al.

In all, 25% of children in the no intervention group developed atopic dermatitis at age 36 months, compared with 24% of those in the skin intervention group, 25% of 641 participants in the food intervention group, and 17% in the combined intervention group. While neither intervention alone reduced the development of atopic dermatitis—with a risk difference of –1.3% (95% CI: –6.2 to 3.7) for the skin intervention, and 0.3% (95% CI: –4.5 to 5.2) for the food intervention—a combination of the two seemed to be most effective, reducing atopic dermatitis by –7.4% (95% CI: –12.1 to –2.7).

No serious adverse events were reported.

"The PreventADALL regimen consisted of normal foods and was inexpensive and safe. Similar to the EAT study, no deleterious impact was observed on breastfeeding at the end of the key early introduction period at 6 months of age. Although the desire for the food and skin interventions to be pragmatic was understandable, since families were not asked to record the actual amount of allergenic food consumed, there is residual uncertainty regarding the dose of food required to induce tolerance," noted Michael R. Perkin, MB, BS, PhD, of the Population Health Research Institute, St. George’s, University of London, U.K., in his accompanying editorial comment.

"The prevalence of food allergy in the general population is low and further studies to attempt to resolve the issues of dose and duration of consumption required to induce tolerance would have to be prohibitively large. Furthermore, arguably such studies are unnecessary, with PreventADALL providing robust evidence to support early allergenic food introduction among all infants, including infants not at high risk of food allergy in whom the majority of food allergies occur," Perkin concluded.

Disclosures

The PreventADALL study was funded by several public and private funding bodies: the Regional Health Board South East, the Norwegian Research Council, Oslo University Hospital, the University of Oslo, Health and Rehabilitation Norway, the Foundation for Healthcare and Allergy Research in Sweden–Vårdalstiftelsen, the Swedish Asthma and Allergy Association’s Research Foundation, the Swedish Research Council–the Initiative for Clinical Therapy Research, the Swedish Heart-Lung Foundation, SFO-V Karolinska Institutet, Østfold Hospital Trust, the European Union (MeDALL project), the Norwegian Association of Asthma and Allergy, the Kloster foundation, Thermo-Fisher Scientific (through supplying allergen reagents), Fürst Medical Laboratory, Oslo, Norway (through performing IgE analyses), Norwegian Society of Dermatology and Venerology, Arne Ingel’s legat, Region Stockholm (ALF-project and individual grants), Forte, Swedish Order of Freemasons Foundation Barnhuset, the Sven Jerring Foundation, the Hesselman foundation, the Magnus Bergwall Foundation, the Konsul Th C Bergh’s Foundation, the Swedish Society of Medicine, the King Gustaf V 80th Birthday Foundation, KI Foundations & Funds, the Cancer and Allergy Foundation, the Pediatric Research Foundation at Astrid Lindgren Children’s Hospital, and the Samaritan Foundation for Pediatric research.

Skjerven reported no disclosures.

Perkin is a co-principal investigator of the EAT study discussed in this Comment, and has received research funding from the National Institute for Health and Care Research for unrelated research.

Sources

Skjerven HO, et al "Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicenter, cluster-randomized trial" Lancet 2022; 399: 2398-2411.

Perkin MR "Early introduction of allergenic food for all infant" Lancet 2022; 399: 2330-2331.