Dietary exposures and allergy prevention in high-risk infants: A joint statement with the Canadian Society of Allergy and Clinical Immunology

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk for developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps to prevent allergy, the protective effect of early introduction of potentially allergenic foods (at four to six months of age) remains under investigation. Recent research appears to suggest that regularly ingesting a new, potentially allergenic food may be as important as when that food is first introduced.     

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.     

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 into this issue, a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. In this paper, the immunology of the fetus and newborn is reviewed as well as the post-natal development of the immune system. The influence of post-natal environment and breastfeeding on tolerance induction and sensitization are examined. Allergic diseases result from a strong relationship between genetic and environmental factors. Sensitization to food allergens occurs in the first year of life and cow's milk allergy is the first food allergy to appear in the susceptible infants. Hypoallergenicity of food formulas to be used is a critical issue both for treatment of cow's milk-allergic children and for prevention. Methods to document hypoallergenicity are discussed and evaluated in the preclinical and clinical steps.     

Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas

This clinical report reviews the nutritional options during pregnancy, lactation, and the first year of life that may affect the development of atopic disease (atopic dermatitis, asthma, food allergy) in early life. It replaces an earlier policy statement from the American Academy of Pediatrics that addressed the use of hypoallergenic infant formulas and included provisional recommendations for dietary management for the prevention of atopic disease. The documented benefits of nutritional intervention that may prevent or delay the onset of atopic disease are largely limited to infants at high risk of developing allergy (ie, infants with at least 1 first-degree relative [parent or sibling] with allergic disease). Current evidence does not support a major role for maternal dietary restrictions during pregnancy or lactation. There is evidence that breastfeeding for at least 4 months, compared with feeding formula made with intact cow milk protein, prevents or delays the occurrence of atopic dermatitis, cow milk allergy, and wheezing in early childhood. In studies of infants at high risk of atopy and who are not exclusively breastfed for 4 to 6 months, there is modest evidence that the onset of atopic disease may be delayed or prevented by the use of hydrolyzed formulas compared with formula made with intact cow milk protein, particularly for atopic dermatitis. Comparative studies of the various hydrolyzed formulas also indicate that not all formulas have the same protective benefit. There is also little evidence that delaying the timing of the introduction of complementary foods beyond 4 to 6 months of age prevents the occurrence of atopic disease. At present, there are insufficient data to document a protective effect of any dietary intervention beyond 4 to 6 months of age for the development of atopic disease.     

A systematic review of the role of hydrolyzed infant formulas in allergy prevention

OBJECTIVE: To critically examine the published literature to determine whether feeding hydrolyzed infant formulas from birth has a role in allergy prevention. DATA SOURCES: We identified data through a MEDLINE search using allergy prevention and infant formulas as indexing terms. The search was restricted to 1985 through the present, English-language articles, and human subjects. STUDY SELECTION: Criteria for inclusion in the review were prospective controlled trials published in peer-reviewed journals. DATA EXTRACTION: Symptoms of allergy were defined and observed by health care providers (physicians and nurses). DATA SYNTHESIS: Nine published trials evaluated the use of extensively hydrolyzed formulas, 12 evaluated the use of partially hydrolyzed formulas in high-risk infants, and 1 evaluated the use of partially hydrolyzed formulas in an unselected infant population. The reports compared hydrolyzed formulas with breastfeeding, cow's milk formulas, soy formulas, and combinations thereof. The cohort of studies consistently showed reductions in the cumulative incidence of atopic disease from 12 to 60 months of age among high-risk infants fed extensively hydrolyzed casein formulas or partially hydrolyzed whey formulas vs cow's milk formulas. No studies showed an increase in allergy risk with any hydrolyzed formulas. CONCLUSIONS: Extensively hydrolyzed casein formulas and partially hydrolyzed whey formulas are appropriate alternatives to breast milk for allergy prevention in infants at risk. Because atopic disease in children cannot be predicted, the use of these formulas in the general population should be considered, and one must weigh cost, compliance, and long-term benefits.     

Breastfeeding in primary prevention of atopic diseases - is it really protective?

The role of human milk in the development of allergic sensitization remains controversial, especially in view of the difficulty to perform randomized clinical trials as well as methodological differences in the existing data. The incapability of human milk to prevent from allergic phenotype may be ascribed to genetic predisposition, environmental factors and also to differences in the immune contents of human milk, resulting in a lack of oral tolerance development. This article presents controversial results of recently published studies and current recommendations regarding the role of breastfeeding in allergy prevention.     

Hypoallergene Säuglingsnahrung zur Allergieprävention

The fact that more than 30% of children today suffer from at least one atopic manifestation represents a significant challenge for the pediatrician. Apart from certain environmental factors, genetic disposition and early allergen exposure play a major role in the development of allergic diseases. To reduce the allergen burden for the infant at risk during early infancy, hypoallergenic infant formulas are appropriate supplementations to breastfeeding for primary allergy prevention. The overview of studies using hydrolyzed infant formulas has shown a preventive effect of both extensively hydrolyzed formulas and partially hydrolyzed formulas, mainly on the incidence of atopic dermatitis and food allergy. This preventive potential seems not only dependent on the degree of hydrolyzation or the protein source but also on factors such as the processing itself. It is therefore recommended to use only hydrolysates that have been shown effective for primary prevention in prospective controlled trials.     

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.     

Adherence to allergy prevention recommendations in children with a family history of asthma

Allergen avoidance has been a major component of most programs for primary prevention of asthma and allergic diseases in childhood. As a part of the Childhood Asthma Prevention Study, families were provided with written and oral information on measures considered to be helpful in the primary prevention of allergic disease in high-risk infants. Dietary measures included advice to breastfeed for 6 months or longer, to delay the introduction of solid foods until after the infant turned 6 months of age, and to delay giving allergenic foods (egg and peanut butter) until after 12 months of age. In the active group of the randomized controlled trial aimed at reducing house dust mite (HDM) allergen levels, parents were advised to use an HDM-impermeable study mattress cover and an acaricide, to avoid sheep skins, and not to use a pillow before 12 months of age. Families received regular visits from the research nurses at 1, 3, 6, 9 and 12 months and phone calls every 6 wk. Only 43.4% of mothers were breastfeeding by 6 months and less than 20% by 12 months. The introduction of solid foods before 6 months was common, 26% by 3 months and 96% by 6 months. Adherence to infant-feeding recommendations was significantly greater in women over 30 yr of age, women who did not smoke during pregnancy, and women who had a tertiary education. Adherence to HDM reduction measures was greater than to those for infant feeding. The presence of symptoms in the form of an itchy rash by 4 wk did not significantly increase adherence. Complete adherence to infant-feeding recommendations in this intervention study of high-risk infants was low despite the provision of written information and reinforcement at home visits. In considering allergy prevention advice offered during clinical care, the likelihood of adherence is a factor which needs to be evaluated in assessing any potential benefits of allergy prevention regimens.     

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.     

Asthma prevention: Breast is best?

Whilst breastfeeding has been considered to exert a preventative effect on the development of allergic disease, several recent publications have challenged this view, particularly with respect to the long-term outcomes for asthma. There are many other beneficial effects of breastfeeding apart from the possibility of allergy prevention. The suggestion that breastfeeding may increase the development of allergic disease raises concerns about the appropriate steps to take for primary prevention of allergy. It is concluded that breastfeeding can still be recommended for the beneficial effects in reducing atopic disease in childhood in addition to the other demonstrated benefits, and that there are unresolved questions concerning the few studies that suggest the possibility of increased allergic disease in later life.     

水解蛋白配方与婴幼儿牛奶过敏的预防和治疗

食物过敏是婴幼儿最早出现的过敏问题,牛奶是婴幼儿最常见的过敏食物。牛奶过敏的临床表现多种多样,可涉及皮肤、呼吸道、消化道等多器官多系统。母乳喂养是过敏高风险婴儿的首选喂养方式,但对不能进行母乳喂养的婴儿应选择适当的低敏配方奶,水解蛋白是获得低敏配方的最好方法。根据水解的程度,水解蛋白配方分为适度水解蛋白配方和完全水解蛋白配方。完全水解配方被推荐用于牛乳蛋白过敏婴儿的治疗,适度水解配方通常推荐用于特应质高风险婴儿的初级干预。     

Feeding during the first months of life and prevention of allergy]

Allergy consists in the different manifestations resulting from immune reactions triggered by food or respiratory allergens. Both its frequency and severity are increasing. The easiest intervention process for allergy prevention is the reduction of the allergenic load which, for a major allergen such as peanuts, has to begin in utero. The primary prevention strategy relies first on the detection of at risk newborns, i.e. with allergic first degree relatives. In this targeted population, as well as for the general population, exclusive breastfeeding is recommended until the age of 6 months. The elimination from the mother's diet of major food allergens potentially transmitted via breast milk may be indicated on an individual basis, except for peanut, which is systematically retrieved. In the absence of breastfeeding, prevention consists in feeding at-risk newborns until the age of 6 months with a hypoallergenic formula, provided that its efficiency has been demonstrated by well-designed clinical trials. Soy based formulae are not recommended for allergy prevention. Complementary feeding should not be started before the age of 6 months. Introduction of egg and fish into the diet can be made after 6 months but the introduction of potent food allergens (kiwi, celery, crustaceans, seafood, nuts, especially tree nuts and peanuts) should be delayed after 1 year. This preventive policy seems partially efficacious on early manifestations of allergy but does not restrain the allergic march, especially in its respiratory manifestations. Probiotics, prebiotics as well as n-3 fatty polyunsaturated acids have not yet demonstrated any definitive protective effect.     

Profilaktyka alergii pokarmowej już od narodzin

Children of allergic parents or siblings are special risk group for allergy development. The most important method of primary prevention of allergic diseases is mode of feeding. Exclusive breastfeeding in the period of first 4–6 months of life is recommended in allergy prevention. If it is impossible, feeding with partially hydrolyzed formula allows to avoid allergy development in many cases. Many formulas contain additional components with biological activity. Some of them, for example probiotics and prebiotics, long-chain polyunsaturated fatty acids and nucleotides can be effective in prevention of allergic diseases. It is postulated to introduce of new products into infant diet gradually and singly, not before 4^th month and not later then the end of 6^th month of life.     

OPINION: Primary prevention of allergy – Will it soon become a reality?

It is generally accepted that allergic diseases are not curable and not preventable, but mainly controllable using pharmacotherapy (i.e. symptomatic medication). Recent research, however, demonstrated that a number of specific interventions can lead to (partial) primary prevention of allergy, especially of atopic dermatitis (AD) and food allergy (FA). Three types of primary prevention strategies have been successfully studied: early administration of bacterial products (most studies are on probiotics), early moisturizing in infants at risk for AD and early exposure to allergenic foods (peanut and egg). Results of these studies indicate that the stage might have been set. Surely, much more research needs to be carried out before advice can be given in clinical practice. This opinion article discusses the three types of beneficial interventions and gives ideas for future research, which might show the way for better strategies in primary prevention of allergic diseases.     

Clinical practice

The increase in allergic disease prevalence has led to heightened interest in the factors determining allergy risk, fuelled by the hope that by influencing these factors one could reduce the prevalence of allergic conditions. The most important modifiable risk factors for allergy are maternal smoking behaviour and the type of feeding. A smoke-free environment for the child (to be), exclusive breastfeeding for 4–6 months and the postponement of supplementary feeding (solids) until 4 months of age are the main measures considered effective. There is no place for restricted diets during pregnancy or lactation. Although meta-analyses suggest that hypoallergenic formula after weaning from breastfeeding grants protection against the development of allergic disease, the evidence is limited and weak. Moreover, all current feeding measures aiming at allergy prevention fail to show effects on allergic manifestations later in life, such as asthma. In conclusion, the allergy preventive effect of dietary interventions in infancy is limited. Counselling of future parents on allergy prevention should pay attention to these limitations.     

婴儿肠道菌群的形成及其与食物过敏的关系

目的　观察健康婴儿肠道菌群的定植过程及其在食物过敏症患儿的变化 ,分析肠道菌群形成与婴幼儿食物过敏的相互关系。方法　采用荧光定量PCR技术测定细菌 16SrRNA ,经与标准曲线对照计算细菌数量 ,对 71例健康无过敏症母乳喂养婴儿和 10 0例食物过敏婴儿粪便乳酸杆菌、双歧杆菌和大肠杆菌行定量检测。结果　婴儿肠道菌群处于动态定植过程 ,随生长发育 ,双歧杆菌和乳酸杆菌在肠道定植增加 ,大肠杆菌数量减少。食物过敏婴幼儿肠道乳酸杆菌、双歧杆菌数量较健康婴幼儿低 ,而大肠杆菌数量较健康婴幼儿高。结论　婴儿期肠道菌群仍处于动态演替过程。食物过敏婴儿肠道菌群与健康婴儿不同     

食物过敏动物模型研究进展

食物过敏是一种常见的变态反应性疾病.近年来,食物过敏反应的发病率及严重程度有所升高,对儿童的健康成长造成了严重的影响.由于人类对于食物过敏的临床研究受到伦理学限制,因此采用动物模型对食物过敏发病机制和防治方法进行研究是最常用的方法.过敏原种类繁多,过敏机制复杂,目前国际上尚未建立标准统一的食物过敏模型.由于牛奶、鸡蛋、花生是婴幼儿的重要食物,因此在幼年动物过敏模型中常采用这三种食物作为过敏原进行食物过敏的发病机制及防治策略研究.该文即对这三种食物致敏的动物模型研究进展作一综述,为研究者根据不同的研究目的选择动物模型提供参考.     

伴或不伴食物过敏湿疹患儿治疗前后的 生活质量比较

目的探讨湿疹患儿及其家庭治疗前后的生活质量。方法将湿疹患儿分为食物过敏组(FA组,46例)及非食物过敏组(N-FA组,47例)。应用湿疹面积及严重度指数(EASI)对患儿进行评估;对两组湿疹患儿进行规范化干预治疗2个月后,采用食物过敏生活质量问卷-父母版(FAQLQ-PF)和婴儿皮肤病生活质量指数量表(IDQOL)评估治疗前后的生活质量。结果两组患儿在年龄、性别、过敏家族史及喂养方式的差异无统计学意义(P均0.05);FA组中鸡蛋过敏34例(73.91%),牛奶过敏20例(43.48%),胡萝卜过敏2例(4.35%)。两组患儿的EASI、FAQLQ、IDQOL评分在治疗后均有显著下降,与治疗前比较,差异有统计学意义(P均0.05)。治疗前,FA组FAQLQ-PF各模块及总分与N-FA组的差异无统计学意义(P均0.05);治疗两个月后,FA组FAQLQ总分(1.33±1.08)较N-FA组(0.79±0.80)高,差异有统计学意义(Z=2.83,P=0.005);FA组在情绪影响、食物的焦虑、社交/饮食限制模块与N-FA组比较差异亦有统计学意义(Z=2.13~2.89,P均0.05)。结论食物过敏患儿的家长更易担心患儿的情绪变化及社交、饮食受到限制。FAQLQ-PF对于食物过敏生活质量的评估更具特异性。     

Adherence to recommendations for primary prevention of atopic disease in neonatology clinical practice

Passariello A, Terrin G, Baldassarre ME, Bisceglia M, Ruotolo S, Berni Canani R. Adherence to recommendations for primary prevention of atopic disease in neonatology clinical practice.
Pediatr Allergy Immunol 2010: 21: 889–891.
© 2010 John Wiley & Sons A/S The prevalence and severity of atopic manifestations in children are increasing in western countries in the last decades. Specific nutritional intervention may prevent or delay the onset of atopic diseases in infants at high risk of developing allergy. These nutritional interventions should be applied early in the perinatal period to have a chance of success. Thus, we assessed adherence to the dietary management recommendations of the Committee on Nutrition and Section on Allergy and Immunology of the American Academy of Pediatrics (AAP) for the prevention of atopic diseases in neonatal age through an audit study. Questionnaire was administered to the chiefs of 30 maternity units (MU) with more than 1500 live births/yr to report the policy applied in their MU. Twenty‐two MU returned the questionnaire. Identification of high‐risk newborns was routinely performed only in 7/22 MU (31.8%). High‐risk newborns were identified by the presence of at least two or one first‐degree relative (parent or sibling) with documented allergic disease by 18.2% and 45.5% of MU, respectively. Specific maternal dietary restrictions during lactation were adopted in 7/22 MU (31.8%). Extensively or partially hydrolyzed formula was prescribed for bottle‐fed high‐risk infants in 22.7% of MU. Only 2/22 MU have a policy in complete agreement with the nutritional intervention proposed by the AAP. Our study suggest a poor adherence to dietary recommendations for primary prevention of atopic disease in neonatology clinical practice. Further efforts should be planned to improve the knowledge and the application of these preventive strategies.