For many years, allergists and pediatricians recommended avoidance of highly allergenic foods, such as cow’s milk, egg, wheat, soy, peanut, tree nuts and seafood, until after infancy in an effort to prevent food allergies. There was little to no evidence to support these recommendations, but it seemed to make sense: avoidance prevents allergy.

However, we now have very strong evidence that early introduction of peanut (LEAP study) can prevent the development of peanut allergy. Does this apply to other allergenic foods? The authors of the newest research study, Enquiring About Tolerance (EAT) sought to answer this question.

Who did the EAT study include?

Similar to the LEAP study, EAT was performed in the United Kingdom. Unlike LEAP, the EAT study enrolled younger infants 3 months of age from the general population who were exclusively breast fed.

LEAP children were 4-11 months of age and all had moderate to severe eczema and/or egg allergy and were considered high risk for developing a peanut allergy. That was a very different group compared with the EAT study.

Infants in EAT were randomly placed into two groups:

• Early-introduction: infants underwent skin prick testing followed by introduction of milk (yogurt), (boiled) egg, peanut, sesame, whitefish and wheat.
• Standard-introduction: infants maintained exclusive breastfeeding until 6 months of age, and then could introduce these foods.

Both groups maintained breastfeeding until at least 5 months of age. They enrolled 1,162 infants. At enrollment, babies had a median age of 3.4 months; 91% completed the final study visit.

What were the EAT researchers looking for?

The most important outcome was to determine if the children developed food allergy. The researchers tested the children, at age 3, with oral food to see if they had a proven allergy to any of these foods.

The authors assessed adherence to the protocol (eating each food at least 3 times per week). They also studied various indicators, such as repeat skin prick testing.

What did the EAT researchers find?

The authors performed different types of analysis on the data collected from the EAT study:

• Intention-to-treat analysis: includes all the participants who had data that could be evaluated.
• Per-protocol analysis: includes all participants who adhered adequately to the assigned regimen.

The EAT study found that there were similar rates of food allergy, with no significant difference, between both groups (7.1% in standard and 5.6% in early introduction) according to initial enrollment and their intention-to-treat analysis.

Egg and peanut allergies had the highest prevalence compared with other foods and did not differ between groups.

However, when the authors evaluated the infants that were able to maintain the study protocol by eating these foods consistently each week, they did find a significant difference in rates of food allergy:

• 2.4% in the early introduction group versus
• 7.3% in the standard group

This represents a relative risk reduction of 67%. This protective effect was strongest in prevention of peanut (0 vs 2.5%) and egg allergy (1.4 vs 5.5%).

Rates of positive skin prick tests were lower in both the intention-to-treat and per-protocol groups.

Continued ability to eat these foods consistently at such an early age was low. Only 31.9% of all infants enrolled in the early-introduction group consumed these foods consistently from 3 months of age. The authors identified four factors associated with 78% of non-adherence:

• persons of color
• parent perception of symptoms due to food introduction
• lower maternal quality of life
• presence of eczema in the child at enrollment

Adherence to egg was lowest (43.1%) and highest for peanut (61.9%) and milk (85.2%). There were no cases of anaphylaxis upon introduction of foods in either group of infants.

Does early introduction of foods help prevent food allergies?

So what does this all mean? On the surface, the EAT study failed to show if the early introduction of allergenic foods works to prevent food allergy. However, this may be related to low adherence to the protocol. Infants who were able to consume allergenic foods consistently from 3 months of age had a 67% relative reduction in food allergy at 3 years compared with those who delayed introduction. This effect was strongest for peanut and egg.

What were the limits to the study?

There are limitations to consider before we start introducing foods early to all children:

• It is quite possible that adherence was low due to development or perception of symptoms from eating these foods.
• We may be able to target specific populations at highest risk, such as infants with eczema, and assess risk by skin testing prior to introduction.
• If infants are unable or unwilling to eat these foods, or more importantly, unable to keep these foods in their diet, then broad recommendations for early feeding may not work.

We also do not know what would happen to high-risk infants who start eating these foods early, but then go long periods without eating them. Is it possible for them to become sensitized but tolerant, then develop allergy after a period of avoidance? Many questions regarding the mechanisms of prevention and tolerance remain unanswered.

While prior recommendations to avoid foods until later in life were based upon opinion and not evidence, we now have emerging evidence supporting early introduction of allergenic foods, especially peanut, to prevent the development of food allergy. The EAT study offers an important initial assessment of how we may begin to address the prevention of food allergies to foods other than peanut.

Reference:

Perkin, Michael R., Ph.D., et al. (2016). “Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants.” The New England Journal of Medicine. Retrieved March 4, 2016. http://www.nejm.org/doi/full/10.1056/NEJMoa1514210

Related article:

The LEAP Trial 12 Months Later: Are We Ready to LEAP-On Peanut Allergy?