Earlier introduction of common allergenic foods in the first year of life was linked to a lower risk of immunoglobulin E (IgE)-mediated food allergy from 1 to 5 years of age, according to a systematic review and meta-analysis of 23 randomized trials.

Moderate-certainty evidence from four trials (n=3,295) showed that the introduction of multiple allergenic foods — including cow’s milk, eggs, and peanuts, among others — at ages 2 to 12 months was associated with reduced risk of food allergy at 1 to 3 years (risk ratio [RR] 0.49, 95% CI 0.33-0.74, I²=49%), reported Robert J. Boyle, MD, PhD, of the National Heart and Lung Institute in London, and co-authors.

The absolute risk difference for a population with 5% incidence of food allergy was -26 cases (95% CI -34 to -13 cases) per 1,000 population, they noted in JAMA Pediatrics.

Of note, there was also moderate-certainty evidence from five trials (n=4,703) that showed that introduction of multiple allergenic foods at ages 2 to 12 months was associated with increased withdrawal from the intervention (RR 2.29, 95% CI 1.45-3.63, I²=89%).

Among a population with 20% withdrawal rates from the intervention, the absolute risk difference was 258 cases (95% CI 90-526) per 1,000 population.

“Safety data from earlier allergenic food introduction trials were generally reassuring, although systemic allergic reactions can occur in infants at higher risk or those who already have a food allergy,” Boyle and team wrote. “However, we found in this systematic review and meta-analysis that earlier allergenic food introduction was associated with high rates of withdrawal from the intervention in the 2 large, pragmatic multiple allergenic food introduction trials. Only 29% and 34% of participants in the earlier introduction groups of these trials were able to fully adhere to the intervention.”

The researchers stressed that one key aspect of the meta-analysis was the focus on reducing multiple food allergies, rather than just one allergy.

“It is unknown whether earlier introduction of allergenic foods will reduce overall food allergy prevalence in populations. Prevention of 1 or 2 specific food allergies without preventing food allergy as a whole may have limited public health impact,” they wrote. “One trial evaluating the effect of earlier multiple allergenic food introduction on risk of any food allergy reported inconclusive findings and a high rate of withdrawal from the intervention. A more recent trial reported reduced food allergy following earlier introduction of multiple allergenic foods, largely attributable to a reduction in peanut allergy.”

Nine of the analyzed trials (n=4,811) showed high-certainty evidence that the introduction of eggs at 3 to 6 months of age was associated with a reduced risk for egg allergy (RR 0.60, 95% CI 0.46-0.77, I²=0%). In a population with a 4% incidence of egg allergy, the absolute risk difference was -16 cases (95% CI -22 to -9) per 1,000 population.

High-certainty evidence from four trials (n=3,796) showed that the introduction of peanut at ages 3 to 10 months was associated with a reduced risk of peanut allergy (RR 0.31, 95% CI 0.19-0.51, I²=21%). The absolute risk difference among a population with a 2.5% incidence of peanut allergy was -17 cases (95% CI -20 to -12) per 1,000 population.

The evidence for timing of introduction of cow’s milk and risk of cow’s milk allergy was very low certainty, Boyle and team noted.

For this systematic review and meta-analysis, the researchers searched Medline, Embase, and CENTRAL databases for articles from database inception to Dec. 29, 2022. They included 23 randomized trials, including 13,794 participants.

Of the 23 studies, nine focused on eggs, eight focused on cow’s milk, one studied peanuts, four focused on multiple allergenic foods, and one compared all interventions. Introductions that were the result of breastfeeding were included. Over 90% of studies took place in high-income countries.

Boyle and colleagues noted that their study did not include formal individual patient data analysis, and further analysis of this kind “may be helpful for better understanding adverse effect data and subgroup analyses.”

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