Q&A: Consistent, timely exposures ‘key’ to infant food allergen introduction

PHOENIX — Allergens should not be avoided but rather introduced early and often into an infant’s diet to reduce risk for food allergy, according to a presentation at American Academy of Allergy, Asthma & Immunology Annual Meeting.

Healio spoke with Amanda Cox, MD, FAAAAI, assistant professor of pediatrics in the division of pediatric allergy at Icahn School of Medicine at Mount Sinai, to learn more about the guidance and research behind early introduction of allergens, and best feeding practices to ensure infants have a diverse diet.

Healio: What is the latest guidance on the early introduction of food allergens to infants?

Cox: Several medical societies have guidance on this issue.

Amanda Cox

The National Institute of Allergy and Infectious Diseases (NIAID) issued guidelines in 2017 recommending that infants with severe eczema and/or egg allergy introduce peanut as early as 4 to 6 months, whereas those with mild to moderate eczema introduce peanut around 6 months. Infants without eczema or food allergy should be introduced peanut-containing foods at an age-appropriate time and in accordance with the family’s diet and cultural practices.

The most recent American Academy of Pediatrics (AAP) guidelines, from 2019, state that for infant feeding:

• There is no evidence that avoiding allergenic foods during pregnancy and lactation prevents atopic disease.
• There is no evidence that delaying introduction of allergenic foods beyond 4 to 6 months of age prevents atopic disease; there is evidence that early introduction of infant-safe forms of peanut reduces the risk for peanut allergies.
• The data are less clear for timing of introduction of egg.

The AAP guidance also states that there is evidence that breastfeeding for the first 3 to 4 months decreases eczema in the first 2 years of life, any duration of breastfeeding beyond 3 to 4 months is protective against wheezing in the first 2 years of life (irrespective of exclusivity), with some evidence that longer duration of breastfeeding protects against asthma, and that no conclusion can be made about the role of breastfeeding in preventing or delaying the onset of specific food allergies. AAP also recognized a lack of evidence that hydrolyzed infant formula prevents atopic disease even in infants and children at high risk for allergic disease.

Lastly, AAAAI/American College of Allergy, Asthma and Immunology/Canadian Society for Allergy and Clinical Immunology consensus guidelines from 2020 state:

• There is strong evidence that early introduction of peanut and egg within the first year of life can prevent the development of food allergy to these foods (around 6 months but not before 4 months; using only cooked forms of egg).
• Screening infants for evidence of sensitization to peanut and/or egg before initial introduction is not required, although this may be a preference-sensitive care choice.
• If screening is performed, clinician should consider offering all sensitized infants a supervised oral food challenge to determine allergy or tolerance.
• With respect to other potentially allergenic foods (milk, soy, wheat, tree nuts, sesame, fish, shellfish) there are no data suggesting that early introduction at or around 6 months of life is harmful; there are observational data suggesting harm from intentional delayed introduction.

Healio: What is the evidence and published data backing this guidance?

Cox: We only have evidence from large studies showing that early introduction of peanut starting between 4 to 6 months of age (for those with severe eczema and/or egg allergy) or around 6 months of age (for those with mild to moderate eczema) prevents peanut allergy for infants at high risk. The data are suggestive of a similar preventive effect of early egg introduction, but the U.S. does not provide detailed guidelines regarding egg; the guidelines do, however, differ in other areas of the world.

There is emerging evidence based on the SPADE study from Sakihara and colleagues that early and frequent cow’s milk exposure, even at low volumes, may prevent cow’s milk allergy. We do not have strong evidence for other foods, but the general consensus is not to delay any allergenic food introduction for infants.

Given the limitations to the allergen introduction guidelines that are currently published, shared decision-making between physicians and parents is essential.

Healio: Are there any common misconceptions about the early introduction of food allergens that are still prevalent despite these data?

Cox: I have noticed that most parents are getting the correct information and guidance from their pediatricians regarding when to start solid foods and when to introduce allergenic foods, including peanut.

Overall, there has been hesitancy in terms of these guidelines being widely adopted. Pediatricians and allergists have not been as eager to promote early introduction as we would have expected, and parents remain tentative. There is overall still fear of an infant having an allergic reaction, in particular to peanut, so introduction is often still delayed despite published evidence and updated guidelines encouraging early introduction.

Several posters in today’s AAAAI morning poster session have highlighted this issue.

As I am a pediatric allergist, those who see me have been appropriately referred for evaluation, so my personal perspective is somewhat skewed.

Some other important points to remember are that:

• A positive allergy test (skin prick test or specific IgE level) to a food does not necessarily mean a child is allergic to the food. These are tests of sensitization. The risk for or presence of clinical allergy requires additional diagnostic evaluation.
• All infants do not require screening for food allergies.
• Eczema is generally not caused by food allergy, but it is a risk factor for the development of food allergy and is an associated atopic condition in many infants and children who also have food allergies. In particular, uncontrolled/untreated and significantly flared eczema predispose an infant to the development of both food and environmental allergen sensitization. Still, we do not recommend large panel food allergy testing or dietary restrictions (in either a nursing mom or feeding infant) as means to diagnose or treat eczema in infants or children.

Healio: What are some key clinical characteristics of infants at high risk for food allergies?

Cox: From the LEAP trial and prior studies, we know that:

• Infants with severe eczema are at the highest risk for food allergies, especially egg and peanut. Those with moderately severe eczema are also at increased risk for egg and peanut allergy.
• Infants with an existing food allergy are at risk for additional food allergies.
• Infants with these conditions should be evaluated and screened for food allergies. Guidance does not specify which specific food allergies should be screened for; this is at the discretion of the physician and patient.

Infants with a strong family history of food allergies (in particular, siblings with food allergy) or other allergic conditions may be at some increased risk for food allergies, however screening before introduction of allergenic foods is not routinely recommended.

As with most therapeutic considerations, however, the decision whether to perform allergy tests for an infant should involve a discussion between the physician and parent.

Healio: Introducing allergens is an anxiety-provoking experience for parents. How can clinicians reassure parents of children at high risk that early introduction is the right thing to do?

Cox: Clinicians can provide documents and instructions that guide parents on introduction of allergenic foods. I like to print out pages from the NIAID addendum guidelines.

Also, clinicians should discuss that delaying allergenic foods increases the risk for developing food allergies, in particular if delayed beyond a year of age.

For those who have a previously diagnosed food allergy, we always ensure that the family has an active prescription for an epinephrine auto-injector, has been trained in its use, and has reviewed with us a food allergy action plan, such that they are familiar with the signs and symptoms of an allergic reaction and know the indications for using epinephrine.

Clinicians also should ensure that the infant is developmentally ready for the introduction of solid foods, including allergenic foods, and they should recommend a highly diverse infant diet, not just with respect to allergenic foods. Whole grains, fruits, vegetables, legumes and meats should also be incorporated in age-appropriate forms and maintained.

If an infant tolerates a food three or more times, the family should feel reassured that this is not an allergy for the baby and should feel comfortable maintaining it in the diet without concern about the baby developing an allergy to that food (as long as there are no long stretches where it is avoided).

Healio: What is known about the co-occurrence of food allergens?

Cox: The presence of one food allergen does increase the risk for developing an allergy to another food, in particular if it has not yet been introduced or if introduction has been delayed. Allergenic foods that are already in the diet and tolerated should be maintained in the diet on a regular basis, and not removed or avoided for any prolonged period.

We do know that the presence of egg allergy is associated with an increased risk for peanut allergy, and similarly the presence of peanut allergy increases the likelihood of the presence or development of tree nut allergies.

Some foods are cross-reactive and allergy to one is highly likely to predict allergy to another. For instance, tree nuts are predictive for allergy to other tree nuts; cashew and pistachio are highly cross-reactive, as are walnut and pecan; and finned fish predict risk for other finned fish allergies, as do shellfish for other shellfish.

Healio: What are the best practices clinicians can tell their patients about introducing food allergens?

Cox: Based on the LEAP study, peanut should be introduced between 4 to 6 months or at 6 months of age and maintained as 6 g per week (2 g given three times per week or the equivalent of 2 tsp peanut butter per serving). Peanut can be given in any infant-safe form — for example, pureed or watered-down smooth peanut butter, peanut flour mixed into another soft food, Bamba (peanut puff) curls dissolved in liquid or soft food, etc. I do not recommend giving an infant any peanut/nut butter directly (it is too thick) or whole nuts (choking hazard).

For egg, the ideal form for introduction is not yet known. Our dietician suggests (for 6 to 12 months of age) hard-boiled, well-scrambled eggs blended into pureed foods or chopped for finger foods. There is no evidence-based guidance for suggesting introducing the yolk separately from the white.

We do not have evidence-based recommendations for timing of introduction, serving size or frequency of feeding for other allergenic foods.

However, for grains, we suggest a whole wheat or fortified infant cereal or whole grain pasta fed to infant in a form and consistency that fits their developmental stage. For dairy, yogurt and cheese are appropriate. Smooth diluted tree nut butters or powders mixed into pureed foods, or unsweetened nut milks, can be mixed into infant cereal or puree as well. Tahini can be mixed in a similar fashion to introduce sesame. For introducing fish, flakes of fish can be blended and mixed into pureed food or soft food.

My best advice is to not avoid anything, and to ensure that the infant has a diverse diet with respect to all foods. I would like for all of my patients to incorporate milk, egg, soy, wheat, peanut, a variety of tree nuts, sesame, fish and shellfish — barring any other dietary restrictions for nonallergic reasons — into the diet along with other solid foods, and I would not delay introduction of anything beyond 12 months of age. The key is to make sure that the exposures are consistent and that none of these foods is avoided or restricted once introduced.

Healio: Is there any merit to available marketed products that can be used to introduce allergens slowly in powder form mixed into foods?

Cox: There are a number of commercial products on the market now but these have not been fully studied in randomized controlled trials; there are ongoing studies, however, so we hope to learn more in the future. The amount of protein of the individual allergenic foods is typically quite small for these commercial products, especially where multiple foods are included, and we do not know whether these quantities provide a protective/preventative or therapeutic effect. The ideal form and serving size, as well as frequency of feeding for introduction of allergenic foods into an infant diet, are not yet known, and clinical trials will be needed before we can say what is ideal.

It is also possible to react to the allergenic foods in these products. Families who have an infant at high risk for food allergy should speak with their pediatrician or an allergist about using these products. For those at low risk for food allergies, these products are probably safe, but there is no evidence at this point that they will prevent the development of food allergies.

Healio: Are there any differences in the introductions of allergens that clinicians should be aware of for families practicing baby-led weaning vs. using traditional purees?

Cox: Baby-led weaning introduces multiple ingredients to an infant at once, so it is not the best way to start feeding an infant new allergenic foods, particularly an infant at high risk for food allergies. If an infant does have an allergic reaction to a food that contains multiple ingredients, it may be difficult to determine which ingredient is the culprit. For initial exposures to allergens, I recommend mixing it into a simple puree, liquid or soft food that the infant has eaten before. Once a food is tolerated it can certainly be combined with other foods. For my patients, for example, I like to recommend a mixed nut butter once they have introduced all of the individual tree nuts. This provides an easy way to feed and maintain multiple tree nuts in the diet.

Healio: Is there anything else you would like to mention?

Cox: This is a growing area of interest and research and much more will be published and known over the next few years.

There are also other areas that are being looked at as food allergy “prevention” measures, including mode of birth/delivery, breastfeeding and duration of breastfeeding, maternal diet, formula selection, probiotic supplementation, microbiome, eczema and skin care.

References:

• Du Toit G, et al. J Allergy Clin Immunol. 2013;doi:10.1016/j.jaci.2012.09.015.
• Fleischer DM, et al. J Allergy Clin Immunol Pract. 2021;doi:10.1016/j.jaip.2020.11.002.
• Greer FR, et al. Pediatrics. 2019;doi:10.1542/peds.2019-0281.
• NIAID. 2017 Addendum Guidelines for the Prevention of Peanut Allergy in the United States. Available at: https://www.niaid.nih.gov/diseases-conditions/guidelines-clinicians-and-patients-food-allergy. Published January 2017. Accessed Feb. 22, 2022.
• Sakihara T, et al. J Allergy Clin Immunol. 2021;doi:10.1016/j.jaci.2020.08.021.