When to Introduce Allergenic Food to Infants: a Tough Nut to Crack

EBM Focus - Volume 18, Issue 14

Reference: JAMA Pediatr. 2023 Mar 27 early online

Practice Point: Early introduction of eggs, peanuts, and maybe even multiple allergenic foods seems likely to reduce food allergies in some children, but early exposure may not make sense for all infants.

EBM Pearl: In a forest plot, look for the strange trees. Heterogeneity in meta-analyses (reflected in high I2 scores) reduces confidence in the outcomes.

Raise your hand if your mother gave you a little whiskey to get you to sleep when you were a baby. (That explains a lot.) Back in the 1890’s, most American parents waited until 11 months to start solid foods (and whiskey), whereas by the 1950’s, some experts recommended cereal on the first day of life, meat at 4 weeks, and black coffee at 6 weeks! Expert advice about exposing infants to potentially allergenic foods has similarly ranged from complete avoidance to a no holds barred approach to early exposure. This is largely a first-world problem, as most of the world’s babies are born in low- to middle-income regions where food allergies are uncommon and access to allergenic foods is limited. In the US, however, food allergies are more prevalent than ever and understandably on the minds of many (especially new) parents. Clinicians and parents alike seem to want more guidance about when to introduce allergenic foods, preferably based on evidence rather than anecdote or commercial influence. Oh, did we mention that the drastic 1950’s shift towards much earlier introduction of solids happened around the same time that commercial baby food was first marketed?

Well, here we go. A recent systematic review and meta-analysis of randomized trials (primarily in high income countries) asked this question: does early introduction of allergenic foods (at a median of 3-4 months) influence an infant’s risk of developing food allergies after age 1? A forest plot of the primary outcome clearly showed a reduced risk of any food allergy with earlier introduction of multiple allergenic foods, with an NNT of 38 and a marginally acceptable I2 of 49%. (I2 is a measure of how much the heterogeneity between individual trial outcomes affects our confidence in the pooled outcome of the meta analysis. In general an I2 ≥ 25% starts to be concerning, and ≥ 50% is an indication of high heterogeneity and thus low certainty.) That same analysis showed an NNH of 4 for withdrawal from the intervention for reasons potentially related to the intervention, meaning that only 4 babies would need to be fed allergenic foods for one additional family to decide to stop because of some real or perceived downside, including an allergy or intolerance. However, the forest plot for withdrawal was all over the place, with an I2 of 89%. As expected, rates of withdrawal from the intervention were higher when actual foods were used rather than powdered supplements that had allergens in them. Analyses of individual exposures showed significant reductions in allergy risk with higher certainty than the primary outcome for egg (NNT = 63) and peanut (NNT = 59) exposures. However, the direction and extent of the relationship between early exposure to cow’s milk and allergy risk is anyone’s guess, with huge heterogeneity among individual trial outcomes and very low certainty in the nonsignificant pooled results.

While the analyses of individual exposures support existing recommendations about the practice of early introduction of egg and peanuts, we can’t be as certain that introduction of multiple allergenic foods reduces overall risk of food allergies due to potential confounding from differential withdrawal from the intervention in the included trials. And the jury is definitely still out about cow’s milk. The reality is that there is a lot of nuance when it comes to whether early allergenic food exposure is a good thing or not, depending on factors like where an infant lives, access to potentially allergenic foods, and even achievement of developmental milestones that indicate that swallowing thickened liquids or solids is safe. There is also reasonable concern that earlier introduction of solids or even powdered supplements might reduce intake of breastmilk, which especially in lower-resourced countries may offer better overall nutrition. As such, we should be careful what we wish for. It seems that a one-size-fits-all recommendation for when to introduce allergenic foods might be the most dicey exposure of all.

For more information, see the topic Immunoglobulin E (IgE)-mediated Food Allergy in DynaMed.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by Katharine DeGeorge, MD, MS, Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, Deputy Editor at DynaMed; Nicole Jensen, MD, Family Physician at WholeHealth Medical; Vincent Lemaitre, PhD, Senior Medical Writer at DynaMed; Elham Razmpoosh, PhD, Postdoctoral fellow at McMaster University; and Sarah Hill, MSc, Associate Editor at DynaMed.