To the Editor:
A nationwide questionnaire-based survey conducted throughout nursery
schools in Japan revealed that 7.6% children have accidental ingestion
within one year.1 Younger age, male sex, and wheat
allergy are risk factors for accidental ingestion.2However, the frequency of accidental ingestion of each allergen and risk
factors for treatment-required moderate-to-severe accidental ingestion
remain unknown in nursery schools. This study examined the prevalence
of accidental ingestion of four
common allergens and risk factors for treatment-required accidental
ingestion in nursery schools in Japan.2
Data were analyzed using a large dataset from a previous nationwide
questionnaire survey, entitled “Survey on allergic disease status of
children admitted to nursery schools and allergy measures at nursery
schools.” Web-based survey forms containing instructions were
dispatched to all childcare facilities in Japan through post (Table
S1),1 covering two-thirds of preschool children who
attended nursery schools in Japan (Supplementary Information). The
survey had questions about the presence of accidental ingestion between
April 2015 and February 2016 and details about the accidental ingestion.
We enrolled children with egg, milk, wheat, or peanut allergy (four
common allergens) and excluded children with allergy to multiple foods
or to foods other than egg, milk, wheat, or peanut. We also excluded
patients with missing data.
This study was approved by the ethics committee of Jikei University.
Informed consent from the guardians of the participating children was
not required because no personal data that identified the participants
were obtained. Detailed methods of the survey administered to nursery
schools and the regulations in Japan are listed in Supplementary
Information.
Food allergy was defined as doctor-diagnosed IgE-mediated food
allergy3 with written evidence submitted to the
nursery school. If children experienced multiple episodes of allergic
symptoms due to accidental ingestion, the most severe episode was
investigated. Accidental ingestion was defined as unintended accidental
allergen intake leading to allergic symptoms. Treatment-required
accidental ingestion was defined as accidental ingestion that required
treatment at the clinic or hospital.
Data are expressed as n (%) or arithmetic mean (standard deviations).
Fisher’s exact tests, with
Bonferroni correction and Mann-Whitney U tests, were used, andp <0.05 was considered statistically significant.
Logistic regression was used to perform multivariate analysis. SPSS
Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY, USA), was
used for statistical analyses.
In
total, 1,390,481 children were enrolled in the survey (Figure S1). Among
56,121 children with food allergy, 10,315 were excluded owing to missing
data. We further excluded 17,794 children with allergy to multiple foods
and 5,251 children with allergy to foods other than egg, milk, peanut,
or wheat. Finally, 22,761 children
with egg, milk, wheat, or peanut allergy met the inclusion criteria.
Mean age of the children was 2.0 ± 1.5 years (median: 2.0 years) (Table
1). Egg allergy was most common, followed by allergy to milk, peanuts,
and wheat (Table S1). Overall, 1383 (6.1%) children experienced
accidental ingestion and presented with symptoms during the last 1 year,
78 (5.6%) of whom required treatment at the clinic or hospital and 12
(0.9%) were hospitalized. Only 1 child (0.01%) used an adrenaline
auto-injector in their nursery school. There were no fatal cases
requiring treatment in the intensive care unit or resuscitation.
Misdistribution of meals was the most common reason for accidental
ingestion (31.3%) and eating other children’s meal was the second
common reason (11.9%).
Accidental ingestion correlated with male sex, younger age, and history
of anaphylaxis to causative food (Table 1). The incidence of accidental
ingestion was highest (10.6%) in wheat allergic children and
significantly higher than that in egg (5.9%) (p =0.001) and
peanut (5.3%) allergy (p =0.011), even after Bonferroni
correction (Figure 1). Significant differences were not seen in milk
(6.8%) allergy after Bonferroni correction (p =0.07). Similarly,
among children with accidental ingestion, the incidence of
treatment-required accidental ingestion was most common in wheat allergy
(31.4%), followed by peanut (18.8%) (p =0.49), milk (10.7%)
(p =0.019), and egg (8.6%) (p <0.001) allergy
(Figure 1).
Risk factors for treatment-required accidental ingestion were assessed
among children with accidental ingestion during the last 1 year (Table
2). Multivariate analysis revealed the factors significantly associated
with treatment-required accidental ingestion for adjusted odds ratio
(aOR) adjusted for parameters listed in Table 1. History of anaphylaxis
to causative foods was a significant risk factor in egg (aOR: 3.069),
milk (aOR: 5.325), peanut (aOR: 30.286), and wheat (aOR: 11.721)
allergy. Younger age was a significant risk factor in egg (per one-year
increase; aOR: 0.758) and milk (per one-year increase; aOR: 0.668)
allergy.
Among wheat allergic children with a history of anaphylaxis to wheat (n
= 69), 16 (23.2%) experienced accidental ingestion (Figure S2). Nine
(36.3%) of the 16 patients had treatment-required symptoms.
Our study is the first to confirm
the potential risk of accidental ingestion of wheat in the general
setting of nursery schools based on a nationwide survey.
Although our previous results indicated that wheat allergy was a major
risk factor for accidental ingestion among nursery school children in
Japan2, the study design could not clarify the
incidence of accidental ingestion among different food allergens in
participants with multiple food allergy. In this study, we compared the
frequency and severity of symptoms due to accidental ingestion of each
allergen. Wheat allergic children had accidental ingestion more
frequently than children allergic to foods other than wheat. Wheat is
one of the most lethal food allergens in the Japanese population, often
inducing anaphylaxis4. Reactions that require
treatment are more common in oral food challenges (OFCs) to wheat than
in OFCs to other foods.5,6. Our results are similar to
the results of previous studies. The prevalence of wheat allergy differs
between countries,7 and wheat allergy is more common
in Asian countries than in European countries and the United
States.8,9 Wheat is the third most common allergen and
the primary cause of anaphylaxis in Japan.3 Therefore,
we should consider common allergens that cause anaphylaxis in preschool
children according to the country.
A history of anaphylaxis to causative food was a risk factor for
treatment-required accidental ingestion. A history of anaphylaxis is a
risk factor for severe reaction during OFC among school-aged high-risk
patients.4 In a study of anaphylaxis recurrence,
one-fifth of children with a history of food anaphylaxis experienced at
least one anaphylaxis recurrence at a mean interval of 12
months.10 We confirmed similar results in younger and
generalized populations. Indeed, one-fourth of the children with a
history of anaphylaxis had accidental ingestion within 1 year, and
one-third of them were treated in the hospital or clinic for accidental
ingestion (Figure S2). Therefore, we should consider the causative food
type and a history of anaphylaxis when children enter nursery school to
prevent accidental ingestion.
Our study had several limitations. The study is a questionnaire-based
survey and therefore has the potential for bias. We excluded many
patients with multiple food allergens known as risk factors for
recurrent anaphylaxis,10 which may indicate selection
bias. This survey did not consider complications including bronchial
asthma and allergic rhinitis, which may affect the severity of
accidental ingestion.
In conclusion, we should recognize
and understand the difference in the incidence of accidental ingestion
induced by each food allergen and risk factors for treatment-required
accidental ingestion, including a history of anaphylaxis in nursery
school children. To generalize these results, further prospective
studies on accidental ingestion in other populations will be needed.
Keywords : Accidental exposure, Anaphylaxis, Food allergy,
Ingestion, Nursery schools, Pediatric, Risk factors
Noriyuki Yanagida,
MDa,b, Motohiro Ebisawa, MD, PhDb,
Toshio Katsunuma, MD, PhDc, Jyoji Yoshizawa, MD,
PhDd
aDepartment of Pediatrics, National Hospital
Organization, Sagamihara National Hospital, Kanagawa, Japan
bJapan Clinical Research Center for Allergy and
Rheumatology, National Hospital Organization, Sagamihara National
Hospital, Kanagawa, Japan
cDepartment of Pediatrics, The Jikei University Daisan
Hospital, Tokyo, Japan
dDivision of Pediatric Surgery, Department of Surgery,
The Jikei University
School of Medicine, Tokyo, Japan
Acknowledgements : We are particularly grateful to the staff
members who participated in the survey and data collection. Assistance
in English language editing was provided by Editage, Cactus
Communications.