Early intervention for the prevention of atopic dermatitis

Based on a lecture given to the European Society for Pediatric Allergy and Clinical Immunology.
Diseases associated with atopy are increasing throughout the world. Individuals appear to have a genetic predisposition to atopy which is then provoked by environmental influences. Ingested or inhaled allergens provoke an antibody response and a state of sensitization. In many but not all sensitized individuals subsequent exposure to allergen will provoke a release of histamine and other mediators from sensitized mast cells and produce clinical signs of an allergic reaction in the target organ or throughout the body. At the present time one approach to the prevention or reduction of such reactions appears to be the identification of the high-risk infant and then preventing or limiting exposure to the potentially allergenic protein materials in the child's diet or immediate environment.
This paper outlines the problems of identifying high-risk infants and comments on the success claimed in the intervention studies that have been undertaken. The possible hazards to mothers and infants of dietary exclusion are emphasized and the provision of appropriate medical and dietetic support are regarded as of paramount importance. Although more studies are needed, the Isle of Wight intervention programme offers hope to families at high-risk of atopy that the problem can be reduced for the next generation.     

Food Allergy in childhood: phenotypes,prevention and treatment

The prevalence of food allergy in childhood increased in the last decades, especially in Westernized countries where this phenomenon has been indicated as a second wave of the allergic epidemic. In parallel, scientific interest also increased with the effort to explain the reasons of this sudden rise and to identify potential protective and risk factors. A great attention has been focused on early exposures to allergenic foods, as well as on other nutritional factors or supplements that may influence the immune system in a positive direction. Both interventions on maternal diet before birth or during breastfeeding and then directly on infant nutrition have been investigated. Furthermore, the natural history of food allergy also seems to be changing over time; IgE‐mediated cow's milk allergy and egg allergy seem to be more frequently a persistent rather than a transient disease in childhood, as described in the last years. Food avoidance and the emergency drugs in case of an adverse event, such as epinephrine self‐injector, are currently the first‐line treatment in patients with food allergies, with a resulting impairment in the quality of life and social behaviour. During the last decade, oral immunotherapy emerged as an optional treatment with remarkable results, offering a novel perspective in the treatment for and management of food allergy.     

Dietary prevention of allergic diseases in infants and small children

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.     

Factors associated with maternal dietary intake,feeding and weaning practices,and the development of food hypersensitivity in the infant

Maternal diet during pregnancy and breastfeeding, as well as infant feeding and weaning practices, may play a role in the development of sensitization to food and food hypersensitivity (FHS) and need further investigation. Pregnant women were recruited at 12 wk pregnancy. Information regarding family history of allergy was obtained by means of a questionnaire. A food frequency questionnaire was completed at 36 wk gestation. Information regarding feeding practices and reported symptoms of atopy was obtained during the infants’ first 3 yr of life. Children were also skin‐prick tested at 1, 2 and 3 yr to a pre‐defined panel of food allergens. Food challenges were conducted where possible. Maternal dietary intake during pregnancy, and breast‐feeding duration did not influence the development of sensitization to food allergens or FHS, but weaning age (≥16 wk) did for sensitization at 1 yr (p = 0.03), FHS by 1 yr (p = 0.02), sensitization at 3 yr (p = 0.01) and FHS by 3 yr (p = 0.02). In contrast, children who were not exposed to a certain food allergen before the age of 3–6 months were less likely to become sensitized or develop FHS. Women with a family history of allergic disease were more likely to breastfeed exclusively at 3 months (p = 0.008) and avoid peanuts from the infant’s diet at 6 months (p = 0.03). Maternal dietary intake during pregnancy, and breast‐feeding duration did not appear to influence the development of sensitization to food allergens or FHS. Weaning age may affect sensitization to foods and development of FHS. A history of allergic disease has very little impact on maternal dietary, feeding, and weaning practices.     

Dietary prevention of allergic diseases in infants and small children.

The role of primary prevention of allergic disease has been a matter of debate for the last 40 years. In order to shed some light into this issue a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. The design of observational and interventional studies was evaluated with relevance to the important factors influencing outcome of studies on allergy development/prevention. in this analysis the statements of evidence as defined by WHO were applied. Best evidence of recommendations are those fulfilling the criteria for statements category 1 and 2 and grade of recommendations A and B as proposed by WHO. This survey include target group for dietary prevention and methods and diagnostic criteria of atopic dermatitis, asthma and food allergy for prevention studies.     

Early introduction of allergenic foods for the prevention of food allergy from an Asian perspective—An Asia Pacific Association of Pediatric Allergy,Respirology & Immunology (APAPARI) consensus statement

Emerging evidence for the early introduction of allergenic foods for the prevention of food allergies, such as peanut allergy in Western populations, has led to the recent publication of guidelines in the USA and Europe recommending early peanut introduction for high‐risk infants with severe eczema or egg allergy. Peanut allergy is, however, much less prevalent in Asia compared to the West. Varying patterns of food allergy are seen even within Asian countries—such as a predominance of wheat allergy in Japan and Thailand and shellfish allergy in Singapore and the Philippines. Customs and traditions, such as diet and infant feeding practices, also differ between Asian populations. Hence, there are unique challenges in adapting guidelines on early allergenic food introduction to the Asian setting. In this paper, we review the evidence and discuss the possible approaches to guide the timely introduction of allergenic food in high‐risk infants in Asia.     

Dietary prevention of allergic diseases in infants and small children.

Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.     

Tree nut introduction in a peanut-allergic child: To eat,to screen,or to avoid?

There is no defined standard of care around tree nut introduction in a peanut-allergic child, and the role of screening prior to tree nut introduction is controversial. There is some evidence that peanut-allergic children are at increased risk of tree nut allergy, with approximately 23–68% of children with co-existent peanut/tree nut allergy. In some studies, it has been shown that tree nut allergy in children has the potential to be a severe allergy. However, this appears to be age-specific as infant anaphylaxis in general tends to be milder, and there has been no fatality reported on the first ingestion of an allergen in infancy. Familial hesitancy has been identified as a possible condition for undertaking screening tests prior to allergen introduction. Indeed, there has been limited evidence that caregiver hesitancy may exist in peanut-allergic families with tree nut introduction. However, pre-emptive screening has the potential to overdiagnose tree nut allergy and delay introduction (which could paradoxically increase risk). As a result, the decision is best made in the context of shared decision-making and patient preference-sensitive care.     

Relative validity of a dietary interview for assessing infant diet and compliance in a dietary intervention trial

The objective of this study was to assess the relative validity of a dietary interview method for use in an infant population. A dietary interview covering a 1-month period was completed during a study visit at 3 or 6 months of age. It included structured questions and a short food frequency questionnaire (FFQ). The information was compared with data from two 48-h recall interviews conducted during the month previous to the study visit. The agreement between the FFQ and 48-h recalls was analysed as proportion of subjects classified into the same categories of consumption frequency and by the kappa analysis. A total of 100 subjects, at the age of 2-3 months (n = 50) and 5-6 months (n = 50), were included. The kappa values for breastmilk and study formula ranged from 0.82 to 0.95, indicating very good agreement. The agreement for other foods and vitamin D supplementation ranged from fair to very good. We also found a strong correlation for the reported amount of study formula consumed per feeding at 3 months (r(s) = 0.87, n = 24) and 6 months of age (r(s) = 0.73, n = 35) between the questionnaire and 48-h recall data. However, the average amount of study formula per feeding was significantly higher when estimated for a 1-month period, compared with a mean calculated from the two 48-h recalls. As a conclusion, the interview was found to be a useful tool for assessing diet and compliance in a dietary intervention for infants.     

Prevention and management of food allergy

The phenotypic expression and natural history of food allergy vary widely according to the patient's age, disease presentation and type of offending food. Prevention of food allergy might be achieved by altering the dietary factors responsible for the sensitization and phenotypic expression of the disease. Owing to the peculiarity of the atopic status, a minute amount of allergens can trigger both sensitization and symptoms in atopic individuals. The oral dose of β-lactoglobulin causing sensitization can be estimated to be between 1 ng and several milligrams. In food allergy, sensitization and treatment are allergen specific; therefore, for primary prevention (avoiding sensitization) and secondary prevention of food allergy (avoiding symptoms in an already sensitized subject), a product without immunogenic and allergenic epitopes should be given in each case. Babies of atopic parents are particularly prone to develop food allergy and for this reason they are called high-risk babies. Cow's milk is the most commonly offending food in both gastrointestinal and cutaneous manifestations. Cow's milk proteins are potent allergens and around 2.5% of infants experience cow's milk allergy in the first years of life. The major risk factors for cow's milk allergy are positive family history of atopy and early exposure to cow's milk proteins. Hydrolysate formulae have been developed for the purpose of reducing the allergenicity of cow's milk proteins. More recently, partially and extensively hydrolysed formulae have also been used for feeding babies with a high risk of atopy for the prevention of cow's milk allergy. However, according to the results of a recent randomized controlled study, only an extensively hydrolysated formula, and not a partially hydrolysated formula, significantly decreased the prevalence of cow's milk allergy.     

Effects of dietary counselling on food habits and dietary intake of Finnish pregnant women at increased risk for gestational diabetes – a secondary analysis of a cluster‐randomized controlled trial

The incidence of gestational diabetes mellitus (GDM) is increasing and GDM might be prevented by improving diet. Few interventions have assessed the effects of dietary counselling on dietary intake of pregnant women. This study examined the effects of dietary counselling on food habits and dietary intake of Finnish pregnant women as secondary outcomes of a trial primarily aiming at preventing GDM. A cluster‐randomized controlled trial was conducted in 14 municipalities in Finland, including 399 pregnant women at increased risk for developing GDM. The intervention consisted of dietary counselling focusing on dietary fat, fibre and saccharose intake at four routine maternity clinic visits. Usual counselling practices were continued in the usual care municipalities. A validated 181‐item food frequency questionnaire was used to assess changes in diet from baseline to 26–28 and 36–37 weeks gestation. The data were analysed using multilevel mixed‐effects linear regression models. By 36–37 weeks gestation, the intervention had beneficial effects on total intake of vegetables, fruits and berries (coefficient for between‐group difference in change 61.6 g day^?1, 95% confidence interval 25.7–97.6), the proportions of high‐fibre bread of all bread (7.2% units, 2.5–11.9), low‐fat cheeses of all cheeses (10.7% units, 2.6–18.9) and vegetable fats of all dietary fats (6.1% ‐units, 2.0–10.3), and the intake of saturated fatty acids (?0.67 energy‐%‐units, ?1.16 to ?0.19), polyunsaturated fatty acids (0.38 energy‐%‐units, 0.18–0.58), linoleic acid (764 mg day^?1, 173–1354) and fibre (2.07 g day^?1, 0.39–3.75). The intervention improved diet towards the recommendations in pregnant women at increased risk for GDM suggesting the counselling methods could be implemented in maternity care.     

Food allergy and atopic dermatitis: Prediction,progression, and prevention

The rising burden of allergic diseases in childhood requires a compelling need to identify individuals at risk for atopy very early in life or even predict the onset of food allergy and atopic dermatitis since pregnancy. The development and clinical phenotypes of atopic diseases in childhood depend on a complex interaction between genetic and environmental factors, such as allergen exposure, air pollution, and infections. Preventive strategies may include avoidance measures, diet supplements, and early complementary food introduction. Overall, the management of allergic diseases has been improving to date toward a patient's tailored approach. This review will cover the current understanding of risk factors, prediction, and management of food allergy and atopic dermatitis in childhood and discuss how these may contribute to the modification of the natural history of food allergy and atopic dermatitis.     

Practical approach to nutrition and dietary intervention in pediatric food allergy

Although the need for nutritional and dietary intervention is a common thread in food allergy management, the type of food allergic disorder and the identified food allergen will influence the approach to dietary intervention. A comprehensive nutrition assessment with appropriate intervention is warranted in all children with food allergies to meet nutrient needs and optimize growth. However, dietary elimination in food allergy may also have undesirable consequences. Frequently, an elimination diet is absolutely necessary to prevent potentially life‐threatening food allergic reactions. Allergen elimination can also ease chronic symptoms, such as atopic dermatitis, when a food is proven to trigger symptoms. However, removing a food with proven sensitivity to treat chronic symptoms may increase the risk of an acute reaction upon reintroduction or accidental ingestion after long‐term avoidance, so it is not without risk. Additionally, it is not recommended to avoid foods in an attempt to control chronic symptoms such as AD and EoE when allergy to the specific food has not been demonstrated. Ultimately, allergen elimination goals are to prevent acute and chronic food allergic reactions in the least restrictive, but also the safest environment to supply a balanced diet that promotes health and growth and development in children.