This is the first large-scale, multicenter, prospective study evaluating the frequency and circumstances of reactions due to multiple foods in children with a certain or likely diagnosis, having received avoidance advice. Our cohort comprised infants and preschool-aged children enrolled with likely milk or egg allergy, at risk for peanut allergy, a common clinical presentation of food allergy for this age group.17,18
We describe a large number of reactions (1171), their circumstances, and treatment response. Key findings and their implications are highlighted in .
Key Study Findings and Management Implications for Infants/Young Children With Proven or Likely Egg or Milk Allergy
The few previous studies about rates of reactions typically focus on older children and evaluate single foods.5,20,22
In a 1-year retrospective study of 3 year olds with milk allergy (n
= 88) in Spain, 40% had 53 reactions,22
compared with 42.2% over the period of our study. In a retrospective study of 252 Canadian children (mean age 8.1 years) with peanut allergy, an annual rate of 14.3% was observed,20
compared with 6% in our group. However, direct comparisons are limited by the different age groups and study design. Advantages of our study include a large cohort, a prospective design, capturing reactions to multiple foods, and a prolonged observation period. Caregivers in the current investigation were not only aware of their child’s food allergies, they also received standardized milk, egg, and peanut avoidance advice. Despite instruction, 72% of participants experienced a reaction. It should be noted that reactions to all foods were collected in the study, but we chose to primarily focus on milk, egg, and peanut because these were the foods to which we had confirmed allergy in the former 2 with testing and advised families on avoidance of all 3 allergens unless tolerance was confirmed. The majority of reactions being to milk/egg might be expected because these are ubiquitous foods and the infants/children had these common allergies.
The authors of previous studies have identified specific pitfalls in management but have methodological differences from our study.5–7
Literature regarding food-allergic reactions and response to symptoms primarily include retrospective chart reviews,10,11
or oral food challenge data.15,16
Errors have been identified including misreading labels, poor communication in restaurants, cross-contact of allergens, and lack of vigilance.5–7
In our comprehensive prospective study, we identified a number of pitfalls, including novel ones (purposeful exposure, high frequency of reactions from food not provided by parents), and their relative frequency, that warrant attention for anticipatory guidance and have implications for education ().
Nonaccidental (purposeful) ingestion of known food allergens has so far only been addressed and reported for teenagers with risk-taking behaviors.8,9
An unexpected, worrisome finding in this study is that 11% of milk, egg, or peanut reactions resulted from these exposures. In some cases, reactions occurred to a food that was given in a larger amount than before, which is a nuance worth considering when taking a medical history of young children with possible food allergies. Reasons for these exposures need further exploration but may reflect parental testing for resolution of allergy. A preemptive discussion of the risks of purposeful exposure is advisable.
As reported previously,20,23
there is a hesitancy to administer epinephrine for anaphylaxis. We found 65 reactions where the caretaker failed to administer epinephrine even though they felt it was indicated. Education about treatment and reassuring caretakers about the safety of administering epinephrine24
is indicated because some caretakers reported being afraid to use it.
We identified a number of baseline factors that were associated with having reactions (). An association with higher food-specific IgE supports observations that more sensitive children are at risk25
but should not be construed to warrant different care instructions based upon IgE levels. We found a higher rate of reactions among the children with a greater number of food allergies, a finding that might be expected based upon probability. These and other associations (eg, income, paternal education) must be interpreted with caution as they may reflect factors unique to the study population but provide results of interest for future studies on risk factors.
There is often concern that casual exposure, such as skin contact or inhalation (eg, via boiling milk), might trigger severe reactions.7,26,27
However, we found that the vast majority of severe reactions were caused by isolated ingestion, which emphasizes the increased risks associated with ingestion compared with inhalation or skin contact. Although severe reactions were more likely to be caused by peanut, our results indicate that severe reactions can involve many other foods.
A common public perception is that reaction severity increases with repeated allergen exposure, a notion that remains controversial.20,28–30
We found no statistical evidence that reactions worsen with second exposure to the same foods. For milk, there was some suggestion that additional exposures had worsening severity; there were too few repeated reactions to egg and peanut to address severity escalation. Our data support the notion that subsequent reaction severity is not easily predicted, but more research is needed.
Limitations of the study include the possibility that not all reactions were captured, that parental reports included inaccuracies about details, recall bias since not all reactions were reported immediately, and parents might have been reluctant to report reactions to purposeful exposures. The generalizability of the results is affected by the enrollment criteria (a convenience sample with likely egg/milk allergy without known peanut allergy), and demographic factors (mostly a middle class, white population). Nonetheless, the study focused upon the most common allergies in this age group, following standard avoidance instructions. We suspect that children with fewer visits for food allergy may have higher rates of reactions than we observed. Our relatively lower rate of peanut reactions could be attributed to the enrollment criteria excluding known peanut allergy, but given that most participants were sensitized and many likely allergic, the lower rate could also reflect more vigilance; however, further studies would be needed to determine this possibility.