Karina Gonzaga da Costa¹

Davide Carlos Joaquim²

Letícia Pereira Felipe³

Ana Carolina Matias Dinelly Pinto⁴

Ana Karine Rocha de Melo Leite⁵

Erika Helena Salles de Brito⁶

Ana Caroline Rocha de Melo Leite⁷

¹U= niversidade da Integração Internacional da Lusofonia Afro-Brasileira – (UNILAB). Redenç= ão, Ceará – Brasil. Orcid: https://orcid.org/0000-0002-= 4127-0424

²Universidade Federal do Ceará (UFC). Fortaleza, Ceará – Brasil. Orcid: https://orcid.org/0000-0003-= 0245-3110

³Universidade da Integração Internacion= al da Lusofonia Afro-Brasileira – (UNILAB). Redenção, Ceará – Brasil. Orcid: https://orcid.org/0000-0003-= 2551-9143

⁴Fundação para o Desenvolvimento Cientí= fico e Tecnológico em Saúde – (FIOTEC). Fortaleza, Ceará – Brasil. Orcid: https://orcid.org/0000-0002-= 2411-6708

⁵Centro Universitário Christus- Unichristus. Fortaleza, Ceará – Brasil. Orcid: https://orcid.org/0000-0003-= 4135-4545

⁶Universidade da Integração Internacion= al da Lusofonia Afro-Brasileira – (UNILAB). Redenção, Ceará – Brasil. Orcid: https://or= cid.org/0000-0002-2807-4867

⁷Universidade da Integração Internacion= al da Lusofonia Afro-Brasileira – (UNILAB). Redenção, Ceará – Brasil. Orcid: https://orcid.org/0000-0002-= 9007-7970

Autor correspondente

Ana Caroline Rocha de Melo Leite. Universidade da Integração Internacional da Lusofonia Afro-Brasileira – UNILAB, Campus das Auroras – Rua José Franco de Oliveira,= s/n – CEP – 62.790-970 - Redenção, Ceará – Brasil.
E-mail: acarolmelo@unilab.edu.br. Telefone +55 (85) 99168-0679.

ABSTRACT

Objective: To analyze scientific evidence on the impacts of food restriction on the growth and development of preschool children with a history of food allergy. Method: It is an integrative review of the literature that aimed to answer the following gui= ding question: “What are the impacts of food restriction on the growth and development of children in the preschool phase with a history of food aller= gy?”. = The database search was conducted on the Scopus, PubMed, LILACS and CINAHL platforms in August 2020. Results: Of the 9 articles included, 55.56% were in Scopus, all were in English and 33.33% were case-control. The publications found a higher number of children who manifested immunoglobulin E-mediated allergy,= who used to avoid 1 or more foods, especially cow milk. Reductions in Z scores (≤ -2) of height/age, weight/age and weight/height were observed among children with food allergy and food restriction. Conclusion: The articles= were limited to certain areas and a median level of evidence. However, they were= not restricted to evaluating the growth of children allergic to foods on a restrictive diet, investigating, among other factors, the quality of life of caregivers and serum concentrations of vitamins.

Keywords: Food hypersensitivity. Restriction of Food Intake. Preschool. Development and Growth

RESUMEN

Objetivo: Analizar la evidencia científica sobre los impactos de la restricción alimentaria en el= crecimiento y desarrollo de preescolares con antecedentes de alergia alimentaria. Mé= todo: Se trata de una revisión integrativa de la literatura que tuvo como objetivo responder a la siguiente pregunta orientadora “¿Cuáles son los impactos de = la restricción alimentaria en el crecimiento y desarrollo de niños en edad preescolar con antecedentes de alergia alimentaria?”. La búsqueda en bases = de datos se realizó en las plataformas Scopus, PubMed, LILACS y CINAHL en agos= to de 2020. Resultados: De los 9 artículos incluidos, el 55,56% estaban= en Scopus, todos estaban en inglés y el 33,33% eran sensibles a mayúsculas y minúsculas. Las publicaciones encontraron un mayor número de niños que manifestaban alergia mediada por inmunoglobulina E, que solían evitar 1 o m= ás alimentos, especialmente la leche de vaca. Se observaron reducciones en las puntuacion= es Z (≤ -2) para altura/edad, peso/edad y peso/talla entre niños con alerg= ia alimentaria y restricción alimentaria. Conclusión: Los artículos se limitaron a ciertas áreas y un nivel de evidencia medio. Sin embargo, no se limitaron a evaluar el crecimiento de niños alérgicos a alimentos con dieta restrictiva, investigando, entre otros factores, la calidad de vida de los cuidadores y las concentraciones séricas de vitaminas.

Palabras clave: Hipersensibilidad a los Alimentos; Restricción de la Ingesta de Alimentos; Preescolar; Desarr= ollo y Crecimiento.

RESUMO

Objetivo: Analisar evidências científicas sobre os impactos da restrição alimentar no crescime= nto e desenvolvimento de crianças em fase pré-escolar com história de alergia a alimentos. Método: Trata-se de uma revisão integrativa da literatura= que teve como intuito responder a seguinte pergunta norteadora “Quais os impact= os da restrição alimentar no crescimento e desenvolvimento de crianças na fase pré-escolar com história de alergia a alimentos?”. A busca na base de dados= foi conduzida nas plataformas Scopus, PubMed, LILACS e CINAHL, em agosto de 202= 0. Resultados: Dos 9 artigos incluídos, 55,56% constavam na Scopus, todos estavam em inglê= s e 33,33% eram caso-controle. As publicações constataram um maior quantitativo= de crianças que manifestavam alergia imunoglobulina E mediada, que costumavam evitar 1 ou mais alimentos, especialmente o leite de vaca. Foram observadas reduções nos escores Z (X= 04; -2) de altura/idade, peso/idade e peso/altura entre as crianças com alergia alimentar e restrição de alimentos. Conclusão: Os artigos se limitar= am a determinadas áreas e a um nível de evidência mediano. Contudo, eles não se restringiram a avaliar o crescimento de crianças alérgicas a alimentos em d= ieta restritiva, investigando, dentre outros fatores, a qualidade de vida de cui= dadores e as concentrações séricas de vitaminas.

Palavras-chave: Hipersensibilidade Alimentar; Restrição da Ingestã= o de Alimentos; Pré-escolar; Desenvolvimento e Crescimento. <= /span>

<= /o:p>

INTRODUCTION

Food alle= rgy consists of an adverse immune reaction triggered by previous contact with s= ome food and/or its ingestion. Among the immunological mechanisms involved, we highl= ight the immediate hypersensitivity reaction (IgE-mediated allergy), whose proce= ss includes the production of antibody or immunoglobulin E (IgE) and its bindi= ng to receptors present in mast cells and basophils that, since the second con= tact with the allergen, triggers the release of vasoactive mediators and helper = 2 T-cell cytokines (Th2 cell)⁽¹⁾.

Another proposed mechanism corresponds to non-IgE-mediated allergy, in which, altho= ugh there are points to be clarified, there is no participation of IgE, but probable involvement of T cells, inducing a later clinical response. Another possible mechanism that has been proposed is mixed allergy, characterized by the action of IgE, T lymphocytes and pro-inflammatory cytokines^(1).

Regarding epidemiological aspects, between 240 and 550 million individuals suffer from food allergy worldwide, with the highest incidence of severe cases occurrin= g in children, affecting about 5 to 8% of children, while in adults this percent= age is reduced to 1 to 2%⁽²⁾. In Brazil, in a survey conducted with 9,265 children, the prevalence of food allergy among preschoolers reported = by parents was 17.6%⁽³⁾.

Although = the number of children with food allergy has increased in recent years due to changes in eating habits and lifestyle, there is an overestimation in the prevalence of this immune condition. In fact, in the survey by Gonçalves et= al.⁽³⁾, in which 17.6% of the preschoolers had a food allergy reported by their parents, after medical investigation, only 0.4% of them had the diagnosis f= or this type of allergy. In this light, the diagnosis adopted without medical confirmation exposes healthy children to unnecessary treatments, capable of impairing their growth and development⁽³⁾.

Concerning the recommended treatment for food allergy, it consists in the elimination = of the food that triggers the immune reaction⁽⁴⁾. However, this restriction may interfere with the intake of micro and macronutrients and, consequently, impact child growth and development⁽⁵⁾. Thus, it is necessary to establish nutritional counseling as a more effective measure f= or adequate nutritional intake and growth, as well as the establishment of laboratory biomarkers equivalent to those of healthy children⁽⁶⁾= .

Another aspect to consider is the individual’s own immune condition, capable of promoting frequent gastrointestinal symptoms and local or systemic inflamma= tion processes that interfere with nutrient absorption. As a result, there may be impairments in nutritional status, such as the reduction of iron absorption, frequently observed in these groups⁽⁷⁾.

In this context, preschool children with food allergy become more vulnerable to imp= acts on their growth and development, since, in addition to the lack of interest= in eating, appetite fluctuations, low acceptance of certain foods, and repetit= ions of preferred foods typical of this phase⁽⁷⁾, they have impaired intestinal absorption that, associated with dietary restrictions, put at ri= sk the intake of essential macro and micronutrients.

Given the need for nutritional monitoring and its influence on the growth and develop= ment of children with food allergy, nurses emerge as professionals capable of contributing substantially to this process, since they are responsible for conducting childcare consultations, recommended for early childhood. Moreov= er, the continuous bond will enable health promotion, child monitoring, and surveillance of diseases, facilitating the early identification of allergic diseases and their consequences⁽⁸⁾.

In additi= on, through childcare consultations, it is possible to monitor children’s growth and integral development, as well as the assessment of nutritional status a= nd guidance on breastfeeding and feeding of these children, contributing to the prevention and minimization of possible unexpected harms to this phase^=
(9).

Therefore, the present study aimed to identify and evaluate scientific evidence on the impacts of food restriction on the growth and development of preschool chil= dren with a history of food allergy.

&nbs= p;

METHOD

This is an integrative review of the literature, a method that contributes to the synthesis of knowledge from a collection of independent studies that address similar themes, aiming to facilitate its applicability in clinical practice. In addition, the integrative review is conducted t= hrough a rigorous systematic process, especially in the data analysis, a factor th= at favors the reduction of biases and research errors⁽¹⁰⁾.

Regarding= the stages of preparation of an integrative review, it can be conducted as foll= ows: identification of the theme and elaboration of the guiding question; establishing inclusion and exclusion criteria for studies; definition of the questions to be extracted from the selected studies and their categorizatio= n; evaluation of the studies included in the integrative review; interpretatio= n of the results and presentation of the review/synthesis of the subjects^(1=
1).

It is noteworthy that the delimitation stage of the guiding question requires a qualified elaboration, because it defines the information on which we will focus to solve the clinical situation, in addition to optimizing the search= in the database. In general, to organize this question, the PICO strategy is u= sed, an acronym meaning “Patient” (Person/Problem), “Intervention”, “Comparison/= Control” and “Outcome”, fundamental elements in evidence-based research^(12).

In the present study, the application of this strategy defined the “P” as children= who manifest food allergy in the preschool phase, “I” represented the restricti= on of foods that trigger allergic reaction, “C” had no attribution to it, and = “O” referred to the impacts of food restriction on the growth and development of these children. Thus, the study raised the following question: “What are the impacts of food restriction on the growth and development of preschool chil= dren with a history of food allergy?”.

Based on = the guiding question, the descriptors “Child/Preschool”, “Food Hypersensitivity”, “Food Fussiness” and “Growth and Development” were defined, extracted from the He= alth Sciences Descriptors (DeCS) platform, in order to facilitate access to articles. In addition, the combination of the descriptors allowed us to res= trict the search for possible articles that were able to answer the predefined gu= iding question. To this end, we used the Boolean operators “AND”, “OR”, “AND NOT”, resulting in the search: “Child/Preschool AND Food Hypersensitivity OR Food Fussiness AND Growth and Development”.

Following= the pre-established steps, the inclusion criteria of the search were primary articles, available electronically, indexed in the databases Scopus, Nation= al Library of Medicine (PubMed), Latin American and Caribbean Health Sciences = Literature (LILACS) and Cumulative Index to Nursing & Allied Health Literature (CINAHL), published in the last 10 years (2010-2020), in Portuguese, English and Spanish. As exclusion criteria, we established studies that did not cov= er the theme, case studies, studies already included in one or more of the databases analyzed, editorials, reports, theses, dissertations, monographs, books, and reviews (narrative, systematic and integrative).

Regarding= the search for the articles in the databases, it was carried out on August 12th 2020, when the titles and abstracts were read, followed by the selection of publications that answered the guiding question and met the inclusion and exclusion criteria. As they were selected, the studies were organized sequentially and subsequently read in full.

For the synthesis of the articles included in the review, we prepared a table consi= sting of the authors’ names, journal, year of publication, country of publication, database, level of evidence, general objective, and results.

As for the level of evidence, it was categorized, based on Stillwell et al.^{(13),
as follows: - level 1, which comprises systematic review and meta-analysis
studies – randomized controlled trials or clinical guidelines inspired by
systematic reviews of randomized controlled clinical trials; - level 2, whi=
ch
covers well-delineated randomized controlled clinical trials; - level 3, wh=
ich
constitutes well-delineated non-randomized clinical trials; - level 4, which includes cohort and case-control
studies – well-delineated and non-randomized; - level 5, in which studies
originate from systematic reviews of descriptive and qualitative studies; -
level 6, which has evidence of a single descriptive or qualitative study; -
level 7, which aggregates opinion of authorities and/or report of expert
committees.}

&nbs= p;

RESULTS

According= to the methodological continuity of the study, 1,215 articles were identified,= of which, after temporal delimitation, 762 remained. Out of these, after readi= ng titles and abstracts, 744 were excluded for not answering the guiding quest= ion and 8 for duplicity. Of the 10 remaining publications read in full, 1 was excluded because it did not correspond to the target population. Thus, 9 articles remained in the review.

Regarding the databas= e, 55.56% (n =3D 5) of the studies were included in Scopus, 33.33% (n =3D 3) i= n PubMed and 11.11% (n =3D 1) in CINALH. Concerning the language, all the studies included = were in the English language. Regarding the year of publication, 22.22% (n =3D 2) of the articles were published in= 2018, 22.22% (n =3D 2) in 2015 and 11.11% (n =3D 1) in 2010, a percentage also ob= served in 2013, 2014, 2017 and 2019.

Concerning the place of study, 22.22% (n =3D 2) of= the publications were conducted in the United States of America, 22.22% (n =3D = 2) in Finland, 11.11% (n =3D 1) in Thailand, the same percentage obtained among t= hose developed in Korea, France and the United Kingdom, and 11.11% (n =3D 1) were carried out in seven countries, represented by the United Kingdom, United States of America, South Africa, Brazil, Netherlands, Spain, and Thailand. About the field of publication, 33.33% (n =3D 3) of the papers were publish= ed in journals in the area of nutrition and 22.22% (n =3D 2) in the field of pedi= atrics, quantitative equal to that found among the journals of allergology and immunology and pediatric allergology and immunology (Table 1).

Regarding= the research design, 33.33% (n =3D 3) of the articles were case-control studies, 22.22% (n =3D 2) approached a prospective cohort study and 11.11% (n =3D 1) comprised cross-sectional observational studies, a percentage also found am= ong the retrospective and prospective observational studies and retrospective cohort studies included here. Regarding the level of evidence, 66.67% (n = =3D 6) of the publications were classified as level IV and 33.33% (n =3D 3) as lev= el VI.

&nbs= p;

Table 2 – Characterization of the publications included in the review, according to the objectives and results. Redenção, CE, 2020

N.	Objective	Results
1	Make a worldwide assessment of the impact of food allergies on child growth	Of the 430 children included, 45% had IgE-mediat= ed allergy, 30% non-IgE-mediated and 25% mixed. The most avoided allergen was cow milk. Regarding growth, 6% had low weight, 9% atrophy, 5% malnutrition and 8% overweight. Regarding the impacts on growth, the restriction of cow milk led to lower Z scores in all parameters and wheat exclusion reduced height/age Z scores. Children who were accompanied by a nutritionist had higher growth parameters in weight/age, height/age, and BMI. Children diagnosed early had a lower BMI average than those diagnosed late.
2	Assess the quality of life (QoL) of caregivers a= nd the growth of children with food allergy reported by parents	200 children with allergy reported by their pare= nts were included, of whom 69% were allergic to one food, 21% to two allergen= s. The most allergenic food was cow milk. The mean duration of avoidance was= 10 months. Weight and height, according to age, showed no differences when compared to the general population. There was no statistical difference between children allergic or not to cow milk in relation to weight and he= ight for age.
3	Compare the growth and nutrient intake patterns = of children with elimination of milk and/or wheat and barley or rye to their corresponding controls	Of the 295 children with diet restriction and 265 controls, those with milk restriction grew less, tending to have this reduction after 1 year of restriction, and without recovery until the age= of 5 years. On the other hand, 2.9%, 1.7%, 1.6% and 0.7% were 2 standard deviations above the height expected for their age at 1, 2, 3, 4 and 5 ye= ars, respectively, in the entire study population. The obesity rate at 5 years= was 4.7% for children who restricted milk, and 5.7% for controls. The elimina= tion of wheat and milk, barley or rye had an impact on growth similar to milk restriction alone. In relation to avoided foods, there was no association between the amount of these foods and growth. In the nutritional aspects, protein and calcium intake was lower in children in the milk elimination group than in the control group. However, children on a milk elimina= tion diet consumed less saturated fats and sugar and more vitamin C and iron t= han children in the control group.
4	Identify factors related to the severity of atop= ic dermatitis and nutritional status in pediatric patients with atopic dermatitis and food allergy.	77 children were included. Before the nutritional intervention, 2 children had a <-2 Z score of weight/age and 5 of them= had a Z < -2 weight/height score. Of the participants, 48.1% had experienc= ed dietary restriction, but only 27.8% had nutritional follow-up. Children w= ho were in food restriction had a higher rate of atopic dermatitis. The aver= age energy intake, as well as the consumption of n-6 and n-3 fatty acids, calcium, folic acid, and vitamin D, was lower than the recommended intake= for Koreans. After individualized nutritional intervention, weight/height increased, and height/age decreased. As for the index of atopic dermatiti= s, it decreased significantly.
5	Compare growth, nutritional status and nutrient intake in children with food allergy, avoiding cow milk or cow milk and w= heat	Of the 46 children under 3.5 years included, 18 eliminated only cow milk from the diet (group M) and 28 avoided milk and wheat (MW group). Both groups had weight and height for age in common, but below healthy children. Two children in group M and five in group MW had = a Z score <-1 of height/age and one child in group MW had a Z score <-2= of height. Two children from group M and six from group MW had a relative weight <= ;10% and none had this weight <20%. Group MW consumed more total calories, proteins, and fats than group M. The intake of iron, calcium and vitamin D was comparable between groups. Growth, nutritional status and nutrient in= take were similar between groups.
6	Compare anthropometric measurements and food int= ake of children with cow milk allergy with the corresponding controls. Evaluate serum concentrations of vitamin A and 25 (OH) D in children with cow milk allergy	Twenty-seven children allergic to cow milk (CMA)= and 30 controls were included. More than 70% of allergic participants did not receive regular vitamin and mineral supplementation. The CMA group showed lower height in relation to the control group and lower calcium and lipid intake. Low serum concentrations of retinol, β-carotene, lycope= ne and 25 (OH) D were found in 25.9%, 59.3%, 48.1% and 70.3% of the CMA grou= p, respectively.
7	Examine the effects of food deprivation on the growth of children with food allergy	Of the 9,938 children, 439 (4.4%) avoided one or more foods. Those with food allergy and commercial health insurance were significantly shorter and weighed less than children without food allergy. In contrast, children with food allergy and state insurance were not smaller than healthy children, in height or weight. Children allergic to milk weighed less compared to the other children. Among child= ren seen as white, food allergies impacted height and weight. These findings = were not observed among Hispanic/Latin, Black or Asian children.
8	Evaluate food intake and nutritional status of children with food allergy on an elimination diet	Of the 96 children with food allergy (FA) includ= ed, 88% were advised by nutritionists and the others by pediatricians. The we= ight and height score by age was lower in the group of allergic children when compared to the control. The weight/height ratio had no significant difference between the groups. Nine children with FA had a <-2 Z score= of weight/age and no control had this weight score. Seven allergic participa= nts and two controls had a <-2 height/age Z score. Children allergic to th= ree or more foods were smaller than those allergic to up to two foods. Energy, protein and calcium intake was similar between the two groups.
9	Establish growth status in children allergic to = food receiving dietary information in the United Kingdom	Of the 97 children, 45 had IgE-mediated allergy,= 29 had an allergy not mediated by IgE and 23 had mixed allergy. Of the total number of participants, 66 excluded two or more foods from the diet and 30 excluded three or more. The exclusion of three or more foods had an impac= t on weight/age elevation. Of the children, 8.5% had Z score ≤ -2 (underweight) and 8.5% had Z score ≥ +2 (overweight). Of the participants, 11.5% were short for their age and 5.5% were tall for their= age. Of the total number of children, 3.7% had moderate malnutrition, with Z s= core ≤-2 of weight/height, and 7.5% were obese, Z score ≥ +2 weight/height. Of the participants, 91.5% are unlikely to be underweight = and 89% will not have atrophy, although they may still have food allergies.

*BMI – Body = Mass Index.

Source: The authors

DISCUSSION

This revi= ew showed that food restriction, for the most part, impaired the growth and nu= trient intake by children with food allergy during the preschool phase. However, regular dietary monitoring, as well as vitamin and mineral supplementation, proved to be effective against anthropometric and nutritional deficit of th= ese children. Therefore, this survey alerts health professionals about the risks that allergic children are exposed to in the growth phase, in addition to providing a scientific basis for the appropriate therapeutic monitoring of = this clinical condition.

Regarding= the database that provided more articles aimed at the guiding question, the fact that the Scopus platform stood out can be understood if it is assumed that = this database has the largest collection of peer-reviewed abstracts and scientif= ic citations, ensuring better credibility in its publications⁽¹⁴⁾. = For the language, the predominance of English may be linked to the fact that it= is the official language of the United States of America, a country that assum= es the 1^st place in the world ranking of scientific publications(15). Another justification for this finding is that English is a universal langu= age⁽¹⁶⁾, which can expand the reach of studies published in this language.

As for the year of publication, the increase in the number of articles in 2015 and 201= 8, although associated with a fall in 2017 and 2019, demonstrates the interest= of the scientific community in researching the theme addressed here. Notedly, = the reduction of studies published in 2019 can be justified by the redirection = that occurred among scientific productions to cope with Coronavirus Disease 19 (COVID-19), decreasing publications in other lines of study in that year(17).

Concernin= g the country where the study was conducted, the predominance of the US is consis= tent with the high stimulus to scientific production experienced by this nation.= In relation to Finland, its greater involvement with studies portraying the th= eme of this review can be understood observing the increased prevalence of food allergy among children of up to 5 years of age⁽¹⁸⁾, in addition = to the increase in cases of hospitalization for allergic reactions among child= ren aged 0 to 19 years recorded in recent decades in this country^(19).

As for the fact that the highest percentage of articles included in the review are pub= lished in journals in the field of nutrition, this result can be justified based on the fact that one of the focuses of the study involved the impact of dietary restriction. In particular, this piece of data highlights the importance th= at the nutrition professional exerts in the dietary management of children allergic to food, through evaluation, diagnosis, prescription and dietary intervention⁽²⁰⁾, helping in the growth and development of child= ren.

Regarding= the study design, the focus that the studies presented here had on the methodologies of case-control research shows the interest of evaluating the contribution of the risk/exposure factor in the outcome of the event(s) (occurrence of the disease) in predefined groups, represented by cases (in which an outcome is expected) and controls (in which it is not expected)(21). This information is relevant if it is assumed that the case-control study is considered as the first stage of the etiological study of a disease^(22=
).

For the predominance of the level of evidence IV among the publications discussed, = this result arises from the predominance of case-control studies among these articles, classified by Stillwell et al.⁽¹³⁾ with this level of evidence. Although a high degree of relevance is not attributed to this lev= el, this knowledge can support the clinical performance of health professionals, integrating clinical experience with scientific evidence and enabling ethic= al respect and safety in interventions⁽²³⁾.

Regarding= the objectives mentioned in the articles, the central focus in assessing the gr= owth and nutritional status of children with food allergies who were on a restrictive diet is based on the fact that the treatment of this type of allergy consists of restrictive diets, which, for the most part, require the removal of multiple foods, sources of micro and macronutrients essential for child growth and development⁽⁵⁾.

Among the other objectives, the study assessing the quality of life of caregivers of = children with food allergy may be associated with the condition that, due to the ris= ks of fatal manifestations to which allergic children are susceptible, the qua= lity of life of their caregivers is impaired by vulnerability to stress, depress= ion and social isolation, especially due to constant fear of exposure to the allergen⁽²⁴⁾.

Another objective contemplated in the articles was the evaluation of the severity of atopic dermatitis in children allergic to food (article n. 4). This objecti= ve is consistent with the evidence that around one third of individuals with moderate to severe atopic dermatitis are diagnosed with food allergy^(2=
5). According to the authors, the loss of immune tolerance is a consequence of restrictive diets made by children with more severe manifestations of dermatitis. In this context, for Kim et al.⁽²⁶⁾ (article n. 4), adequate dietary guidance reduces the manifestations of atopic dermatitis.<= o:p>

In additi= on to the objectives reported above, the study by Boaventura et al.^{(27)
(article n. 6) sought to evaluate the serum concentrations of vitamin A and=
25
(OH) D in children with cow milk protein allergy (CMPA), confirming a decre=
ase
in these levels in 70.4% and 59.3% of the sample, respectively. According to
Cavichini and Martins⁽²⁸⁾, the deficit of 25 (OH) D, circulating
form of vitamin D in the blood after hepatic hydroxylation, is considered a
risk factor for the development of CMPA.}

In this sense, the literature points out, as one of the possible mechanisms involve= d in this relationship, the fact that vitamin D provides a greater differentiati= on of naive T cells into regulatory T cells (Tregs), which inhibit responses f= rom T helper 2 cells (Th2) and, consequently, the production of IgE. On the oth= er hand, CMPA seems to favor vitamin D deficiency by interfering in the absorp= tion of this vitamin and inducing a systemic inflammatory response, which may be associated with a deficiency of fat-soluble vitamins, such as vitamin D. It= can also be proposed that mothers of children with CMPA and exclusive breastfee= ding may restrict the consumption of cow milk and dairy, without vitamin D supplementation, which may compromise the child’s access to this vitamin(29).

Regarding= the relationship between vitamin A and CMPA, the biomarker β-carotene, a type of carotenoid present in colorful fruits and vegetables and source of vitamin A⁽³⁰⁾, represents a protective agent against food allergy, since it can inhibit the production = of specific IgE and the degranulation and chemotaxis of mast cells and basophi= ls⁽³¹⁾.

Regarding= the immunogenic profile, the manifestation of IgE-mediated allergy among the children evaluated (articles n. 1 and 9) stood out, result which resembled Chong et al.⁽³²⁾. In this context, it is worth mentioning that f= ood allergy can be classified, according to the immunological mechanism, in IgE-mediated, non-IgE-mediated and mixed. The first, admittedly the most frequent in childhood⁽³³⁾, involves the production of IgE, its fixation to mast cell and basophil receptors and degranulation of these cell types, triggering acute signs and symptoms. The second does not involve the production of IgE, but the participation of other cell types (supposedly T cells), inducing late symptoms. On the mixed dietary allergic reaction, it comprises the participation of IgE and T cells^(1,34).

In refere= nce to the number of foods that caused an immune reaction and were avoided, the included publications indicated a predominance of one (articles n. 2 and n.= 7) to two (articles n. 5 and n. 9) foods avoided by the participants, which corroborated Mendonça et al.⁽³⁵⁾. However, in the study by Meyer= et al.⁽⁵⁾, they observed a higher number of participants that avoid= ed four or more foods.

On the fa= ct that cow milk was the most avoided food among the works of this review (articles n. 1, 2, 5 and 6), this was an expected result, since it is among= the 8 most allergenic foods (“big eight”), along with egg, peanut, crustacean, = soybean, tree nuts, sources of gluten, and fish⁽³⁶⁾. In fact, there is a = high incidence of reaction to this type of food, with almost all children in the studies by Meyer et al.⁽⁵⁾ and Mendonça et al.⁽³⁵⁾ be= ing affected by it.

Regarding= the growth of preschoolers with food allergy, in general, weight/age was in unspecified deficit (articles n. 7 and n. 8) or in Z score ≤ -2 (arti= cles n. 1, 4 and 9) and height/age was low and undetermined (articles n. 4, 6 an= d 7) or in Z score ≤-2 (articles n. 1, 3, 8 and 9) between publications, w= hile weight/height ranged between Z score ≤ -1 (articles n. 5 and n. 7) an= d Z score ≥ +2 (articles n. 1, 3 and 9). These findings of growth retarda= tion coincide with Pavic and Kolacek⁽³⁷⁾ and Chong⁽³²⁾, wh= ich showed that food allergy hinders the growth process, making allergic childr= en lighter and smaller.

For the result of obesity in the BMI of these children, we suppose that the attempt= to compensate for foods restricted by adding others, without adequate guidance, results in the consumption of more caloric foods. These data raise the need= for the multidisciplinary team to be alert for weight deviations when accompany= ing patients with food hypersensitivity⁽³⁷⁾.

Concerning the aggravating factors of inadequate growth in children with food allergy mentioned in the publications presented in this review, they were similar to those mentioned by Venter, Laitinen and Vlieg-Boerstra⁽³⁸⁾, represented by having “multiple food allergies”, “elimination of various fo= ods from the diet”, “elimination of basic foods (such as milk and cereals)” and= “extreme self-restriction of food”. However, as Chong et al.⁽³²⁾ state, t= he risk factor for inadequate growth in food allergy is a multifactorial issue, requiring further studies to establish the relationship between these facto= rs and this type of hypersensitivity.

Regarding= the nutritional intake of preschoolers, it was reduced in both essential micron= utrients and macronutrients, an aspect that diverged from the literature, which demonstrated a greater impairment in the consumption of essential micronutrients in relation to macronutrients⁽³⁹⁾. In this contex= t, in spite of the low intake of nutrients helping to investigate risks of nutritional deficiency, a deeper analysis of blood markers is necessary bef= ore the confirmation of the deficiency⁽⁴⁰⁾.

Although dietary restriction has shown low nutrient intake by allergic children, oth= er studies show that, with regular nutritional monitoring, growth was equivale= nt to that of healthy children, in addition to adequate food intake^(41).

As for the emphasis of iron consumption in the face of food restriction, it may be rel= ated to the role that this mineral plays in the synthesis of the hemoglobin’s he= me group and, consequently, in the transport of oxygen and other hemeproteins, responsible for energy production⁽⁴²⁾, in addition to the import= ant contribution to tissue growth in children aged 6 to 12 months^{(43).
For vitamin C, its intake by children in the face of food limitation may be
related to the fact that this vitamin is not produced in the body, in addit=
ion
to participating in several biochemical and physiological processes, includ=
ing
the accumulation of iron in the bone marrow, collaborating in the immunolog=
ical
response against microorganisms⁽⁴⁴⁾.}

Regarding= the limitations of the study, there was a lack of research portraying the impac= t of food allergy on child development, which may include psychosocial and behavioral repercussions in childhood, with increased anxiety, school absen= ces and bullying⁽²⁴⁾. Another limitation occurred due to the reduced engagement of Nursing in the monitoring this clinical condition, especially because of the role played by the multidisciplinary team, which includes nu= rses, in addition to nutritionists, physicians, psychologists and allergists, in ensuring the growth and development of children allergic to foods^{(45)<=
/sup>.}

CONCLUSION

We conclu= de that, although the articles included in this review were published mainly i= n a reference database, in an accessible language, in recent years and a countr= y noted for its research, they were limited to certain areas and a median level of evidence. However, they were not restricted to evaluating the growth of children allergic to foods on a restrictive diet, investigating, among other factors, the quality of life of caregivers and serum concentrations of vitamins.

The accur= ate survey of these predictors can revolutionize multiprofessional care in food allergy, since it directs the intervention to modifiable risks and contribu= tes to the development of strategies to prevent inadequate growth and developme= nt. However, further studies are needed to evaluate these multiple factors and their correlation with the growth of allergic children.

The results of this integrative review w= ill enable the debate of a theme necessary for care practice, in addition to providing= a scientific basis to be applied in clinical practice, considering that allergology is n= ot explored deeply in the curriculum of health courses.

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N.	Authors	Journal/Year	Country	Type of Study	LE*	Database
1	MEYER, R. et al.	Journal of Human Nutrition and Dietetics/2018	UK, USA, SA, Brazil, Netherlands, Spain, and Thailand	Prospective cohort study	IV	Scopus
2	KAJORNRATTANA, T. et al.	Asian Pacific Journal of Allergy and Immunology/ 2018	Thailand	Cross-sectional observational study	VI	Scopus
3	TUOKKOLA, J. et al.=	Acta Paediatrica/2017	Finland	Case-control study	IV	Scopus
4	KIM, S. H.; LEE, J. H.; LY, S.Y.	Asia Pac J Clin Nutr/2015	Korea	Retrospective cohort study	IV	Scopus
5	BERRY, M. J. et al.	Pediatric Allergy and Immunology/2015=	Finland	Prospective cohort study	IV	Scopus
6	BOAVENTURA, R.M. et al.	Allergologia et Immunopathologia/2019	United States of America	Cross-sectional case-control study	IV	Pubmed
7	MEHTA, H. et al.	The Journal of pediatrics/2014=	United States of America	Retrospective observational study	VI	Pubmed
8	FLAMMARION, S. et al.	Pediatric Allergy and Immunology/2010=	France	Cross-sectional case-control study	IV	Pubmed
9	MEYER, R. et al.	Journal of Human Nutrition and Dietetics/2013	United Kingdom	Prospective observational multicenter study=	VI	CINAHL