To the Editor
We read with great interest the European Academy of Allergy and Clinical
Immunology (EAACI) guideline on prevention of food allergy (FA) (1). In
particular, recommendation 3.1.2 states: “The EAACI Task Force suggests
introducing well-cooked hen’s egg, but not raw egg or uncooked
pasteurized egg, into the infant diet as part of complementary feeding
to prevent egg allergy in infants.” The authors declare in advance that
only Intention-To-Treat (ITT) analyses were considered and they cite, in
support of the aforementioned recommendation, four studies (2-5).
However, according to the ITT analysis, the first two studies (2, 3)
find no evidence that consumption of hen’s egg prevents hen’s egg
allergy. The third study (4) reports an efficacy in this regard, but the
authors: a) enrolled children with eczema, therefore a category at
increased risk of developing FA; b) have associated aggressive eczema
treatment, and it is not possible to establish the weight of one and the
other treatment on the final outcome; c) excluded from the final
analysis of the data about 18% of randomized patients, and it is
difficult for statistical significance to be maintained if the
worst-case scenario analysis were applied. Moreover, we consider
technically difficult for a parent to be able to weigh 50 mg of cooked
egg powder to be given to their child, as Natsume et al (4) suggest. At
the end, the authors (4) evaluated the effectiveness of their preventive
strategy with an oral food challenge with 7 g of heated whole-egg
powder, and therefore the study in question cannot tell us anything
about the possible effectiveness in the prevention of allergy to raw or
undercooked egg. The fourth study (5) cited by the EAACI Task Force (1),
is based on a subgroup analysis that did not benefit from a specific
randomization. The previously unplanned subgroup analysis, in the
absence of specific randomization, is well used for formulating
hypotheses to be tested with a specifically planned study, but is less
adequate to support a recommendation contained in a guideline.
In short, it seems to us that recommendation 3.1.2 (1) cannot be issued.
Moreover, no times and doses are indicated to start the possible
administration of well-cooked egg, and even this definition seems a bit
vague (“well cooked” means baked? Or hard boiled?). Contrary to our
objection, other position papers of very authoritative scientific
societies (6-10) substantially agree with recommendation 3.1.2 of the
EAACI Task Force (1). However, even in these documents, the supporting
evidence does not seem sufficient. In particular, table IV by Fleischer
et al (7), which effectively summarizes the evidence available until
2021 on this topic, is very clear in this regard. Examining it, in fact,
it is clear that we do not have the availability of methodologically
valid studies that allow us to argue that the introduction of cooked egg
during the complementary feeding, as the only intervention, reduces the
likelihood of hen’s egg allergy, neither in infants at increased risk of
developing FA nor in those at normal risk.
Stefano Miceli Sopo a Prof
Dario Sinatti a MD
Francesco Mastellone b MD
Giulia Bersani a MD
Mariannita Gelsomino b MD.
a Pediatric Allergy Unit, Pediatrics Section,
Department of Life Sciences and Public Health, Policlinico Gemelli
Universitary Foundation IRCCS, Catholic University of Sacre Hearth, Rome
00168, Italy.
b Post-Graduate School of Pediatrics, Department of
Life Sciences and Public Health, Policlinico Gemelli Universitary
Foundation IRCCS, Catholic University of Sacre Hearth, Rome 00168,
Italy.