Early introduction of egg or peanut is associated with a lower risk of developing allergy to those foods, a new meta-analysis suggests.

The findings support recommendations not to delay the introduction of allergenic foods, although "most guidelines do not yet advise early feeding of such foods," lead author Despro Ierodiakonou, MD, PhD, and colleagues write in an article published in the September 20 issue of JAMA.

In fact, given the imperfect nature of systematic reviews, the authors caution that these data "should not automatically lead to new recommendations to feed egg and peanut to all infants."

"The rigorous, comprehensive meta-analysis by Ierodiakonou and colleagues is an important addition to the evidence regarding food allergy prevention," writes Matthew Greenhawt, MD, in an accompanying editorial. "Delay of introduction of these foods may be associated with some degree of potential harm, and early introduction of selected foods appears to have a well-defined benefit."

The advantage of a meta-analysis is that "in combining similar studies to reach a conclusion, it can account for enrollment issues that may prevent a study from finding a significant conclusion if one truly exists," Dr Greenhawt, assistant professor of pediatrics, Allergy Section, Children's Hospital of Colorado, University of Colorado, Denver, School of Medicine, told Medscape Medical News.

For example, in the case of the egg studies, "the end result of pooling multiple studies that came very close to showing a significant effect, in combination with a smaller trial that did show a very significant effect, was a significant protective effect. [In their analysis,] the authors removed the one significant study and still noted the pooled protective effect was significant, which is reassuring, but I do think that the authors would be less guarded in their conclusions if [the results of the other studies had been stronger]."

Dr Greenhawt notes there has been a significant increase in the prevalence of food allergies between 1999 and 2009. This coincided with advice published in 2000 that parents actively delay the introduction of high-risk foods in an effort to prevent allergies, "something that more recent data ironically suggests may be associated with an increased risk of developing allergy," Dr Greenhawt told Medscape Medical News.

Clinicians should "be proactive about emphasizing the message that since 2008, the guidelines have not recommended delay in introducing foods past 4 to 6 months, as there has never been any evidence that this actually reduced the risk of developing food allergy," Dr Greenhawt said.

Current data are "as strong as the field has ever had" showing that early, rather than delayed, introduction of these foods may be protective. "I would recommend to any parent that the diet be as diverse as possible, even with early introduction of high-risk allergens," he said.

Dr Ierodiakonou, from the Section of Paediatrics, Imperial College of London, United Kingdom, and coauthors searched six major databases for interventional and observational studies evaluating the introduction of milk, egg, fish, shellfish, tree nuts, wheat, peanuts, or soya during the first year of life and allergic or autoimmune disease at any age. Other systematic reviews also were included if they covered studies not captured in the original search.

The authors considered both allergic and autoimmune outcomes, including wheeze, eczema, allergic rhinitis, food allergy, allergic sensitization (defined as "presence of specific [immunoglobulin E] to an allergen"), type 1 diabetes mellitus, celiac disease, inflammatory bowel disease, and juvenile rheumatoid arthritis. The search, which covered the period from January 1, 1946, to March 8, 2016, yielded a total of 146 studies, including 24 intervention and 69 observational studies that evaluated allergy in 155,401 participants, and five intervention and 48 observational studies that evaluated the development of autoimmune disease in 69,199 participants.

Nine trials studied the effect of egg introduction at 4 to 6 months of age. Of those, five studies with 1915 participants showed moderate-certainty evidence of a lower risk for egg allergy compared with later egg introduction (risk ratio [RR], 0.56; 95% confidence interval [CI], 0.36 - 0.87; P = .009; moderate heterogeneity [I 2 = 36%]). For a population with a 5.4% incidence of egg allergy, the absolute risk reduction was 24 cases (95% CI, 7 - 35 cases per 1000 population).

However, when the investigators looked at the outcome of egg sensitization, defined as "presence of specific [immunoglobulin E] to an allergen", a meta-analysis of four trials, with 1786 participants, showed no relationship between the age at which egg was introduced and risk for sensitization.

Two trials, with 1550 participants, showed moderate-certainty evidence of a lower risk for peanut allergy associated with introduction of peanut between 4 and 11 months of age (RR, 0.29; 95% CI, 0.11 - 0.74; P = .009; high heterogeneity [I 2 = 66%]). For a population with a 2.5% incidence of peanut allergy, this translated into an absolute risk reduction of 18 cases per 1000 population (95% CI, 6 -22 cases). In a third trial, a significant reduction in the risk for peanut allergy associated with early peanut introduction was reported, but no numerical data were provided, and a fourth trial demonstrated no significant association between the timing of peanut introduction and risk for sensitization.

Meta-analysis of four cohort studies, with a total of 12,781 participants, showed low-certainty evidence that introducing fish before 6 to 12 months of age was associated with a lower risk for allergic rhinitis at 4 years of age or younger (odds ratio, 0.59; 95% CI, 0.40-0.87; high heterogeneity [I 2 = 59%]).

No other significant associations were seen between age at food introduction and sensitization to that food, the authors write. Nor did the meta-analysis yield any other significant or consistent association between timing of food introduction and the appearance of specific conditions such as eczema or celiac disease.

Several limitations must be accounted for in this meta-analysis, the authors write. "Key findings were affected by the study of select populations with either active allergic disease, absence of allergic sensitization to the intervention food, or both." Significant variation also was observed in the populations studied in each trial and in the nature of the intervention. The quality of the evidence "was therefore reduced in several analyses because of indirectness of the population or intervention."

The authors note that when they performed trial sequential analyses to test the statistical reliability of the findings, the data were uncertain. "It cannot be confidently concluded that early egg introduction reduces egg allergy by at least 30%; further trials are required to quantify the treatment effect," they write.

Similarly, they found that more data were needed to confidently assess the effect of timing of gluten introduction on risk for celiac disease. Moreover, there was an insufficient number of trials to perform a sequential trial analysis on the timing of peanut introduction.

The authors conclude, "[E]arly introduction of egg or peanut to the infant diet was associated with lower risk of developing egg or peanut allergy. These findings must be considered in the context of limitations in the primary studies."

The study authors disclosed no relevant financial conflicts of interest. Dr Greenhawt is a member of the scientific advisory council for the National Peanut Board.

JAMA. 2016;316:1181-1192; 1157-1159. Article abstract, Editorial extract

For more news, join us on Facebook and Twitter