БИОМЕДИЦИНА ВА АМАЛИЁТ ЖУРНАЛИ
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ЖУРНАЛ БИОМЕДИЦИНЫ И ПРАКТИКИ
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Aziza Yakubjonovna SAIDOVA
Dilfuza Tashpulatovna ASHUROVA
Zilola Ubaydullayevna SHARIPOVA
Department of Propedeutics of Childhood Diseases,
Hematology, Tashkent Pediatric Medical Institute
PRIMARY PREVENTION OF FOOD ALLERGY IN CHILDREN
For citation: A.Y. Saidova, D.T. Ashurova, Z.U. Sharipova PRIMARY PREVENTION OF FOOD
ALLERGY IN CHILDREN Journal of Biomedicine and Practice. 2021, vol. 6, issue 3, pp.52-57
http://dx.doi.org/10.26739/2181-9300-2021-3-7
ANNOTATION
Despite of advances in the treatment of food allergy, the prevalence is continuously rising. Therefore,
it is very important to find the successful preventive measures for suppressing the incidence of food
hypersensitivity starting from younger age. The etiology of food allergy is multifactorial. Number of
risk factors, genetic polymorphisms, atopy, increased hygiene, the microbiome, vitamin D deficiency,
dietary fat (reduced consumption of omega-3-polyunsaturated fatty acids), the time and route of
exposure to groceries have been recognized or suggested to facilitate food allergy or sensitization. In
this review we used online published sources providing relevant data on common risk factors and
prevention of food allergy in children using resources from PubMed Central® (PMC), the Cochrane
library and selected randomized clinical trials in children, systematic reviews and clinical guidelines.
Keywords:
probiotic, food allergy, food hypersensitivity, atopy, allergy, immunoglobulin, IgE,
sensitization and eczema.
Азиза Якубжоновна САИДОВА
Дилфуза Ташпулатовна АШУРОВА
Зилола Убайдуллаевна ШАРИПОВА
Кафедра пропедевтики детских болезней, гематологии,
Ташкентский Педиатрический Медицинский Институт
ПЕРВИЧНАЯ ПРОФИЛАКТИКА ПИЩЕВОЙ АЛЛЕРГИИ У ДЕТЕЙ
АННОТАЦИЯ
Несмотря на успехи в лечении пищевой аллергии, заболеваемость постоянно растет. Поэтому
очень важно найти успешные профилактические меры для подавления случаев пищевой
гиперчувствительности, начиная с более раннего возраста. Этиология пищевой аллергии
мультифакториальная. Количество факторов риска, генетический полиморфизм, атопия,
повышенная гигиена, микробиом, дефицит витамина D, диетические жиры (снижение
потребления омега-3-полиненасыщенных жирных кислот), время и путь контакта с
БИОМЕДИЦИНА ВА АМАЛИЁТ ЖУРНАЛИ
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продуктами питания способствуют пищевой аллергии или сенсибилизации. В этом обзоре мы
использовали опубликованные в интернет источнике, содержащие соответствующие данные
об общих факторах риска и профилактике пищевой аллергии у детей, с использованием
ресурсов
PubMed
Central®
(PMC),
Кокрановской
библиотеки
и
отдельных
рандомизированных клинических исследовааний у детей, систематических обзоров и
клинических рекомендаций.
Ключевые слова:
пробиотик, пищевая аллергия, пищевая гиперчувствительность, атопия,
аллергия, иммуноглобулин, IgE, сенсибилизация и экзема.
Aziza Yakubzhonovna SAIDOVA
Dilfuza Tashpulatovna ASHUROVA
Zilola Ubaydullaevna SHARIPOVA
Bolalar kasalliklari propedevtikasi, gematologiya
kafedrasi, Toshkent Pediatriya Tibbiyot Instituti
BOLALARDA OZIQ-OVQAT ALLERGIYASINI BIRLAMCHI PROFILAKTIKASI
ANNOTATSIYA
Oziq-ovqat allergiyasini davolashda erishilgan yutuqlarga qaramay, kasallik uchrashi doimiy
ravishda oshib bormoqda. Shu sababli, erta yoshlikdan boshlab oziq-ovqat mahsulotlariga yuqori
sezuvchanlik holatini kamaytirish uchun muvaffaqiyatli profilaktika choralarini topish juda
muhimdir. Oziq-ovqat allergiyasining etiologiyasi ko'p faktorlidir. Bir qancha xavf omillari, genetik
polimorfizmlar, atopiya, gigienik nazariya, mikrobiom, D vitamini etishmovchiligi, parhez yog'i
(omega-3-ko'p to'yinmagan yog'li kislotalarning kam iste'mol qilinishi) oziq-ovqat allergiyasi
rivojlanishiga yoki sezuvchanlikni oshishiga ta'sir qilishi aniqlangan. Ushbu sharhda biz PubMed
Central® (PMC) manbalaridan foydalangan holda bolalardagi umumiy xavf omillari va oziq-ovqat
allergiyasining oldini olish bo'yicha tegishli ma'lumotlarni taqdim etadigan onlayn nashr qilingan
manbalardan foydalanganmiz. Tadqiqotimizda biz, bolalarda o’tkazilgan randomizatsiyalangan
klinik tadqiqotlar, muntazam tekshiruvlar va klinik qo'llanmalarga asoslanganmiz.
Kalit so'zlar:
probiotik, oziq-ovqat allergiyasi, ovqatga yuqori sezuvchanlik, atopiya, allergiya,
immunoglobulin, IgE, sensibilizatsiya va ekzema.
Introduction
Allergic disease in children begins to develop early in life in the form of atopic dermatitis and /or
food allergy. After drug allergy,
food allergy is on the first place among children population causing
anaphylactic reaction.
Clinical reaction to food involves multiple organ
and systems, including the skin, the
respiratory tract, the gastrointestinal tract and the cardiovascular system.
Majority of children with atopic dermatitis (AD) have food allergy and AD is the starting point of
allergic march that manifests to IgE mediated food allergy, allergic rhinitis and/or allergic asthma
later on.
Factors that induce the development of food allergy include atopic family history (eczema,
allergic asthma, allergic rhinitis), genetic polymorphisms, atopic dermatitis and environmental
factors.
Food allergy prevention could be accomplished in 3 different ways, namely, primary,
secondary and tertiary. Primary prevention aims to hinder sensitization (the presence of food-specific
immunoglobulin E (IgE)) in healthy children. Sensitization is characterized with a positivity of a skin
prick test (SPT) and/or increased level of specific IgE (>0.35 kU/L) against any allergen, food
allergens, and/or aeroallergens.
Secondary prevention strategy includes reducing the progression of symptoms and the
development of allergy in sensitized/ill children. Tertiary preventive measures include measures in
diseased children in order to prevent further progression and exacerbations of the ongoing illness.
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Studies observed a correlation between allergic disease and farming exposures in European children.
Children of farm families had lower incidence of atopic dermatitis, asthma and allergic rhinitis than
children from suburban areas [1].
Moreover, when solid food is introduced later than as scheduled, children with high risk of
atopy will have a high chance of weak protection against allergy. However, administration of 6 major
allergenic foods (peanut, cooked egg, cow’s milk, sesame, whitefish, and wheat) into the diet of
infants before 4 months of age was unsuccessful. Therefore, preventing sensitization and food allergy
is crucial. For that reason, we aimed to study and highlight the major important factors in the
development of sensitization and food allergy in children.
It is well recognized, that early exposure to a farming environment has a significant impact
on reduction of risk of sensitization and allergy. It is explained due to variety of bacterial experience
during prenatal farming exposure that is rich of microbial and biological compounds leading to
alterations in the innate immune system of the child.
The role of epicutaneous sensitization
Skin and/or gut epithelial barrier failure has an important contribution in the pathomechanism
of food allergy. Disrupted skin barrier or damaged epithelium integrity by mechanical, chemical or
genetic mutations enables allergens to transfer through the skin [2].
The loss of functional mutations in the filaggrin gene (FLG) is a risk factor for atopic
dermatitis and food allergy. Epidermal protein - Filaggrin helps to build up a strong skin barrier [3].
In filaggrin mutation or in a defect of the skin barrier, there is a decrease or complete absence of
filaggrin (Fig. 1). This could promote allergen penetration to a great extent. Type 2 CD4+ T cells are
elevated in patients with FLG mutations [4] that are crucial in the development and maintenance of
IgE-mediated food allergy [5].
Picture 1. The role of the epidermal barrier in the development of atopy
A.
Unaffected skin: abundance of keratohyalin granules in the granular layer, consisting of
profilaggrin.
B.
Disruption of the skin barrier. Modified from Saidova Aziza, monograph (Zamin-
nashr 2020)
There now is evidence that peanut sensitization in children frequently occurs via the skin. The
LEAP study has also confirmed the role of skin exposure in the development of early sensitization in
children [6]. “Skin is the route for sensitization and early oral exposure is the route for tolerance”
suggested Gideon Lack [7]. Sensitization through the skin is executed due to Th2 type of response,
whereas oral exposure is achieved through Th1 and Treg responses [2].
In 74% of children from BASELINE birth cohort study, food allergy was diagnosed in the absence
of atopic dermatitis and was associated with Transepidermal water loss (TEWL) [8].
Maternal and infant nutrition in prevention of food allergy
E
p
id
er
m
is
Cornified layer
А.
B.
Granular layer
Basal layer
Spinous layer
allergens
keratohyalin granules
langerhans cell
Th2 immune response
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Fetus acquires humoral immunity from a mother through allergen-specific IgG that is
transported through placenta. Connection between food allergy and factors, as the gut microbiome,
the diet of the mother during pregnancy is highly possible.
Studies suggest there is a link between fetal immune development in utero and the
development of allergy. It includes the environmental factors and the maternal microbiome (probiotic
and/or prebiotic supplementation and nutrition) [9].
The result of a systematic review and meta-analysis studying 17 randomized controlled trials
showed that children from families with high risk of allergic diseases will have lower risk of atopy
and allergy to food if their mothers have received probiotics prenatally and postnatally [10].
For the last 20 years, recommendations to complementary feeding has been changed due to
high prevalence of allergy in children. Until recently, exclusive breast-feeding was fixed for infants
till 6 months of age. But now, as early we introduce allergenic foods to infants with higher risk of
allergy, the chance of reducing the risk of allergy is higher. Peanut allergy risk is decreased in children
with severe atopic dermatitis and/or egg allergy after adding peanut into the diet at the age of four
months [6].
The prevalence of allergy to peanut and egg was dramatically reduced in children when peanut
and egg was administered starting from the age of 3 months and also it was dose depended. 2 g of
peanut or egg-white protein ingestion once a week was resulted in a significant reduction compared
to lower doses [11].
Effect of polyunsaturated fatty acids in food allergy
Fish oil supplement to a pregnant woman resulted in a significant increase of polyunsaturated
fatty acids (PUFAs) in neonatal cell membranes. Fish and fish oils are sources of omega-6 (ω-6) and
omega-3 (ω-3) (PUFAs). There is evidence that PUFAs has a positive effect in preventing child from
becoming allergic [12]. However, these findings are controversial, while randomized controlled study
SiPS (Salmon in Pregnancy Study) showed that IgE concentrations, immunologic responses and the
severity of atopic dermatitis, or sensitization rates did not change among 2 groups, infants born from
women eating 2 portions of farmed salmon (150 g/portion) per week and infants from women with
habitual diet (control group) during pregnancy, respectively. IL-10 production against ovalbumin
(OVA) and salmon (Sals1) allergens was lower in the cord blood mononuclear cell (CBMC) of infants
from the SiPS main group. Significant increase of polyunsaturated fatty acids (PUFAs) in neonatal
cell membranes was observed at birth. In the fish oil group, total ω-3 PUFAs in neonatal erythrocyte
membranes was higher and total neonatal ω-6 PUFA composition was significantly lower [13]. Cell
membrane ω-3 PUFA suppresses the production of the eicosanoid mediators, produced from ω-6
PUFA, leukotrienes and prostaglandins that is responsible for promoting allergic inflammation and
IgE induction [13]. Prostaglandin 2 (PGD2) contributes to the generation of DCs that stimulates type
2 cell development and sensitization [14]. A similar study also demonstrated that fish-oil
supplementation in pregnancy resulted in decreased secretion of IL-10 by CBMCs in response to
ovalbumin compared to control group, supplementation with olive oil. However, sensitization to egg
allergen in infants in the fish oil group was 3 times lower compared to infants with placebo at 1 years
of age [15].
Impact of vitamin D in sensitization and food allergy
Vitamin D deficiency is a major public health issue worldwide, especially in Asia, with continuous
rise. Apart from rickets, caused due to lack of vitamin D, level of vitamin D also has an impact in
the development of allergic sensitization and food allergy [16].
Vitamin D has an impact in the management of innate and adaptive immune system by regulating the
action of T cells, B cells, monocytes and dendritic cells [17].
Cross-sectional study carried out in Korea among children aged 3-24 months with atopic dermatitis
or suspected food allergy demonstrated that prevalence of food allergen sensitization was higher in
children with low vitamin D level, especially to milk and wheat [18].
However, the connection of vitamin D and the development of food allergy remains controversial.
A randomized, double blind controlled trial evaluated the effect of vitamin D supplementation
dose on allergic sensitization and allergic diseases of infants born from allergic parents. Daily
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administration of vitamin D to infants in doses of 10 μg (400 IU) or 30 μg (1200 IU) from 2 weeks
and 2 years of age raised the risk of milk allergy. Higher dose of vitamin D supplementation (30 μg)
had a higher chance to develop sensitization. However, other allergic diseases and incidence of
wheezing did not differ between the groups. Moreover, allergic sensitization was most likely in
infants with high cord blood 25-Hydroxy-vitamin-D (25(OH)D
)
concentration [19]. Similar result
was seen also by German LINA cohort study (Lifestyle and environmental factors and their Influence
on Newborns Allergy risk). Higher maternal 25(OH)D
3
resulted in a higher risk for sensitization in
children at the age of two, 22.3% against food allergens, 87.5% had increased total IgE, and 6.0%
against inhalant allergens and atopic dermatitis in 18.8%. Furthermore, there was a negative
correlation between the level of 25(OH)D3 in the cord blood and the regulatory T cell numbers which
may have had a key role in the development of sensitization [20].
Treg is responsible for tolerance, which possibly acts to support the mechanistic link between
vitamin D and food hypersensitivity [21]. Furthermore, the role of Vitamin D in allergy is
accomplished through enhanced IgE production by skewing Th1/Th2 responses or by preventing B-
cell proliferation/differentiation and suppressing IgE secretion eventually [22]. There is also evidence
that vitamin D deficiency could be associated with gene–vitamin D interaction. Infant cohort with
certain genes were considered to be in high risk of food sensitization [23].
Conclusion
Primary prevention of food allergy has to cover 3 main periods, pregnancy, breastfeeding and
infants directly. A number of recent studies interpreted the above-mentioned main factors.
Association between vitamin D and food allergy is challenging and requires further clinical studies.
Skin care and improvement of the epidermal barrier is crucial in infants with atopic dermatitis or with
high risk of allergy is very important, since exposure via the skin is also common for food allergens.
Introduction of allergenic foods should not be delayed for children with high risk of food allergy. and
mothers of infants with high-risk, in absence of allergy should not follow specific hypoallergenic
diets. Special diet is not necessary for pregnant or lactating mother of high-risk child, in the absence
of allergy.
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