Timing of Allergenic Food Introduction and the Risk of Immunoglobulin E–Mediated Food Allergy
abstract
This abstract is available on the publisher's site.
Access this abstract nowIMPORTANCE
Earlier egg and peanut introduction probably reduces risk of egg and peanut allergy, respectively, but it is uncertain whether food allergy as a whole can be prevented using earlier allergenic food introduction.
OBJECTIVE
To investigate associations between timing of allergenic food introduction to the infant diet and risk of food allergy.
DATA SOURCES
In this systematic review and meta-analysis, Medline, Embase, and CENTRAL databases were searched for articles from database inception to December 29, 2022. Search terms included infant, randomized controlled trial, and terms for common allergenic foods and allergic outcomes.
STUDY SELECTION
Randomized clinical trials evaluating age at allergenic food introduction (milk, egg, fish, shellfish, tree nuts, wheat, peanuts, and soya) during infancy and immunoglobulin E (IgE)-mediated food allergy from 1 to 5 years of age were included. Screening was conducted independently by multiple authors.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Data were extracted in duplicate and synthesized using a random-effects model. The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess certainty of evidence.
MAIN OUTCOMES AND MEASURES
Primary outcomes were risk of IgE-mediated allergy to any food from 1 to 5 years of age and withdrawal from the intervention. Secondary outcomes included allergy to specific foods.
RESULTS
Of 9283 titles screened, data were extracted from 23 eligible trials (56 articles, 13 794 randomized participants). There was moderate-certainty evidence from 4 trials (3295 participants) 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%). Absolute risk difference for a population with 5% incidence of food allergy was -26 cases (95% CI, -34 to -13 cases) per 1000 population. There was moderate-certainty evidence from 5 trials (4703 participants) that introduction of multiple allergenic foods from 2 to 12 months of age was associated with increased withdrawal from the intervention (RR, 2.29; 95% CI, 1.45-3.63; I2 = 89%). Absolute risk difference for a population with 20% withdrawal from the intervention was 258 cases (95% CI, 90-526 cases) per 1000 population. There was high-certainty evidence from 9 trials (4811 participants) that introduction of egg from 3 to 6 months of age was associated with reduced risk of egg allergy (RR, 0.60; 95% CI, 0.46-0.77; I2 = 0%) and high-certainty evidence from 4 trials (3796 participants) that introduction of peanut from 3 to 10 months of age was associated with reduced risk of peanut allergy (RR, 0.31; 95% CI, 0.19-0.51; I2 = 21%). Evidence for timing of introduction of cow's milk and risk of cow's milk allergy was very low certainty.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, earlier introduction of multiple allergenic foods in the first year of life was associated with lower risk of developing food allergy but a high rate of withdrawal from the intervention. Further work is needed to develop allergenic food interventions that are safe and acceptable for infants and their families.
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Additional Info
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Timing of Allergenic Food Introduction and Risk of Immunoglobulin E-Mediated Food Allergy: A Systematic Review and Meta-analysis
JAMA Pediatr 2023 Mar 27;[EPub Ahead of Print], R Scarpone, P Kimkool, D Ierodiakonou, J Leonardi-Bee, V Garcia-Larsen, MR Perkin, RJ BoyleFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
There is great data on how early introduction of peanut or egg into a child’s diet seems to reduce the risk of allergy to those items — yes, that peanut about-face from advice over 10 years ago was pretty dramatic; however, the data coming from the delayed introduction of peanut showed it was worsening allergy, not improving it. In contrast, early introduction seems to have a protective effect, which is good to know, given the impact food allergies can have on people’s lives.
How useful is early introduction with regards to other types of foods, however? Could earlier food introduction reduce the risk of allergy for other common types of allergens? This systematic review and meta-analysis of 23 trials with almost 14,000 participants looked at this question for milk, egg, fish, shellfish, tree nuts, wheat, peanuts, and soy.
What did the authors find? Introducing these foods between 2 and 12 months of age did indeed reduce the risk of developing allergy, and the benefit of early introduction was confirmed with high certainty in the peanut and egg groups. However, there was also an increased risk of withdrawal from the intervention in these groups. Those risks were lower in certain trials, where they were using food protein powders rather than “normal” foods. There is an excellent contemplation of this in the Discussion section of the paper that I will refer interested readers to, which also includes some musings on effects on breastfeeding (none seen) and other such factors.
Therefore, can we start suggesting earlier food introductions for the purposes of reducing allergy risk? I would probably not rush to that quite yet, and await development of better guidelines and policy statements. I am bothered by the study numbers in this — the authors' initial search yielded about 9200 non-duplicate studies, but then they screened the titles and abstracts and removed over 9100 studies. Of the remaining 148, they removed even more, yielding a mere 23 studies. Although I appreciate the need to only study the appropriate papers, it felt like their search terms were perhaps overly broad, and I wonder about what might have been left out that might affect the final results. Hence…I would like to see more evidence and the development of strategies of precisely how to do food introductions appropriately before we rush headlong into this developing world.