Introducing multiple allergenic foods during the first year of life is associated with reduced risk of food allergy development, according to a systematic review and meta-analysis published in the Journal of the American Medical Association Pediatrics.
Early introduction of peanut and egg to the infant diet is likely to reduce the risk of peanut and egg allergies; however, it is unknown whether earlier introduction of such allergenic foods reduces overall food allergy prevalence. Investigators assessed the association between introduction of allergenic foods during infancy and the risk for developing a food allergy. The researchers also evaluated rates at which infants were withdrawn from the intervention due to safety considerations. The primary efficacy endpoint was IgE-mediated allergy to any food assessed by double-blind, placebo-controlled food challenge, medical diagnosis, or open food challenge. The primary safety endpoint was withdrawal from the intervention (including loss to follow-up).
The reviewers search for randomized clinical trials assessing introduction of allergenic food to infants (wheat, peanuts, tree nuts, shellfish, egg, milk, fish, and soya) on the Embase, CENTRAL, and Medline databases from inception through December 2022. Toddlers from 1 to 5 years of age were included in a search for immunoglobulin E (IgE)-mediated food allergy. Trials using breastfeeding or breast milk, amino acid formula, other low-allergen exposures, or standard care as the comparator were included as were studies comparing earlier and later allergenic food introduction and different doses and types of exposure. Nonrandomized trials, trials in specific populations, and trials of solid food introduction that did not use allergenic foods were excluded.
The reviewers identified 23 eligible trials (56 articles; n=13,794 participants; 21/23 studies conducted in high-income countries) for analysis. Data were analyzed using a random-effects model.
In 4 trials (n=3295), the researchers found evidence (with moderate-certainty) that introduction of multiple allergenic foods from 2 to 12 months of age (median age, 3-4 months) was associated with reduced risk of food allergy (risk ratio [RR], 0.49; 95% CI, 0.33-0.74; I2=49%). For a population with 5% incidence of food allergy, absolute risk difference was -26 cases (95% CI, -34 to -13) per 1000 population.
In 3 trials (n=2827), the researchers found evidence (with low-certainty) that early introduction of multiple allergenic foods was associated with risk for any food sensitization (RR, 0.77; 95% CI, 0.54-1.10; I2=73%).
In 5 trials (n=4703), the researchers found evidence that introduction of multiple allergenic foods from 2 to 12 months of age was associated (with moderate-certainty) with increased withdrawal from the intervention (RR, 2.29; 95% CI, 1.45-3.63; I2=89%). For a population with 20% withdrawal from the intervention, absolute risk difference was 258 cases (95% CI, 90-526 cases) per 1000 population. Notably, in the 2 large pragmatic trials in which multiple allergenic foods were introduced early in life, only about 30% of participants were able to fully adhere to the intervention.
Investigators noted that in 4 trials (n=3796), introduction of peanut from 3 to 10 months of age was associated (with high-certainty) with reduced risk of peanut allergy (RR, 0.31; 95% CI, 0.19-0.51; I2=21%). in 9 trials (n=4811), the researchers found evidence that introduction of egg from 3 to 6 months of age was associated (with high-certainty) with reduced risk for egg allergy (RR, 0.60; 95% CI, 0.46-0.77; I2=0%).
There was very low certainty of evidence for timing of introduction of cow’s milk and risk for cow’s milk allergy.
Review and meta-analysis limitations include high levels of heterogeneity, lack of formal individual patient data analysis, and possible lack of generalizability of clinical trial findings.
Overall, “Earlier introduction of multiple allergenic foods was associated with reduced IgE-mediated allergy to any food,” said investigators, who also noted that “multiple food interventions can be difficult to adhere to,” and that initiating feeding interventions prior to 6 months of age, as was done in many of the reviewed studies, is contrary to World Health Organization guidance. “The findings support the concept of using earlier allergenic food introduction to prevent food allergy but highlight the need for more acceptable forms of multiple allergenic foods,” the researchers concluded.
Scarpone R, Kimkool P, Ierodiakonou D, et al. Timing of allergenic food introduction and risk of immunoglobulin E-mediated food allergy: a systematic review and meta-analysis. JAMA Pediatr. Published online March 27, 2023. doi:10.1001/jamapediatrics.2023.0142