The development and prediction of atopy in high-risk children: follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance. Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study. Early life environmental control: effect on symptoms, sensitization, and lung function at age 3 years. House dust mite allergen reduction and allergy at 4 yr: follow up of the PIAMA-study. The Canadian Childhood Asthma Primary Prevention Study: outcomes at 7 years of age. The Canadian asthma primary prevention study: outcomes at 2 years of age. Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study. Prevention of asthma during the first 5 years of life: a randomized controlled trial. Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study. Effect of allergen avoidance in infancy on allergic manifestations at age two years. Allergen avoidance in infancy and allergy at 4 years of age.
The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders. This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort, previously reported from birth to age 4 years.
                In this prospective, randomized, controlled study of food allergen avoidance in infancy, the prophylactic-treated group consisted of infants whose mothers avoided cow's milk, egg, and peanut during the last trimester of pregnancy and lactation and who, themselves, avoided cow's milk until age 1 year (casein hydrolysate supplementation before age 1), egg until age 2 years, and peanut and fish until age 3 years. The control group consisted of maternal/infant pairs who followed standard feeding practices.
                Despite a significant reduction in food allergy and milk sensitization before age 2 years, none of the following differed between the groups at age 7 years: food allergy, atopic dermatitis, allergic rhinitis, asthma, any atopic disease, lung function, food or aeroallergen sensitization, serum IgE level, or presence of nasal eosinophils or nasal basophilic cells. Children with food allergy by 4 years evidenced higher 7-year (current) prevalences of allergic rhinitis and asthma (p < 0.01). Atopic diseases/parameters at age 7 years were shown, by multivariate analysis (p < 0.05), to be associated with several genetic and environmental risk factors (male gender, maternal nonwhite ethnicity and asthma, and household smoking), as well as predictive atopic markers during infancy (elevated serum IgE level; egg, cow's milk, and peanut sensitization; and nasal eosinophils and nasal basophilic cells).
                These findings help to: (1) elucidate the natural history of atopic disease in high-risk children; (2) document the progression of allergy from atopic dermatitis, food allergy, and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy; (3) identify allergy predictive markers; and (4) expand our appreciation of the interactions of genetic and environmental factors in the development of atopy. Two factors thought to influence the risk of asthma are the promoting effect of sensitization to house dust mites and the preventive effect of increased omega-3 fatty acids. Although house dust mite allergen avoidance has been used as a preventive strategy in several trials, the effect of omega-3 fatty acid supplementation in the primary prevention of asthma and allergic disease is not known.
                To measure the effects of dietary supplementation with omega-3 fatty acids and house dust mite allergen avoidance in children with a family history of asthma.
                A total of 616 children at high risk of asthma were enrolled antenatally in a randomized controlled trial, and 526 children remained in the trial at age 3 years. The outcomes were symptoms of allergic disease and allergen sensitization.
                There was a significant 10.0% (95% CI, 3.7-16.4) reduction in the prevalence of cough in atopic children in the active diet group ( P=.003; number needed to treat, 10) but a negligible 1.1% (95% CI, -7.1 to 9.5) reduction cough among nonatopic children. There was a 7.2% (95% CI, 10.11-14.3) reduction in sensitization to house dust mite in the active allergen avoidance group ( P=.05; number needed to treat, 14). No significant differences in wheeze were found with either intervention.
                These results suggest that our interventions, designed to be used in simple public health campaigns, may have a role in preventing the development of allergic sensitization and airways disease in early childhood. This offers the prospect of reducing allergic disease in later life. We investigated whether environmental control during pregnancy and early life affects sensitization and lung function at the age of 3 years. High-risk children (n = 251) were prenatally randomized to stringent environmental control (active) or no intervention (control). Questionnaires, skin testing, IgE, and specific airway resistance (sRaw) measurement were completed at the age of 3 years. Children in the active group were significantly more frequently sensitized compared with control subjects (at least one allergen by skin tests: risk ratio, 1.61; 95% confidence interval [CI], 1.02-2.55; p = 0.04; mite by IgE: risk ratio, 2.85; 95% CI, 1.02-7.97; p = 0.05). However, sRaw was significantly better in the active group (kiloPascal/second, geometric mean [95% CI]: 1.05 [1.01-1.10] vs. 1.19 [1.13-1.25], p < 0.0001, active vs. control). Maximal flow at functional residual capacity was measured using rapid thoracic compression at the age of 4 weeks in a subgroup. Prospective lung function data (at infancy and 3 years) were obtained in 32 children (14 active and 18 control). There was no difference in infant lung function between the groups, but at 3 years, sRaw was significantly lower in the active compared with control children (p = 0.003). Stringent environmental control was associated with increased risk of mite sensitization but better results for some measurements of lung function in high-risk children at the age of 3 years. Exposure to high allergen levels in early life is a risk factor for the development of allergy. We previously reported limited effects of mite allergen impermeable mattress covers in the prevention and incidence of asthma and mite allergy (PIAMA) cohort at the age of 1 and 2 yr. We now present the results of follow-up at 4 yr objectives. To examine the effects of early reduction of house dust mite (HDM) allergen exposure by means of mattress covers on the incidence of allergy and asthma symptoms in the PIAMA birth cohort at the age of 4 yr. High-risk children (allergic mother) were prenatally recruited and randomly allocated to three groups; receiving mite allergen impermeable mattress covers (n = 416), placebo covers (n = 394) or no intervention (n = 472). At 4 yr of age, atopy was assessed by questionnaire; specific Immunoglobulin E (IgE) to inhalant and food allergens was measured in serum. Dust samples collected from the children's mattresses were analysed for mite allergens. Dermatophagoides farinae1 allergen (Der f 1) levels in dust were reduced in the active group. However, Dermatophagoides pteronissinus 1 (Der p 1) levels, sensitization and atopic symptoms were similar in all groups. We found no effect of mite allergen impermeable mattress covers on sensitization and atopy at 4 yr. Moreover, the allergen reducing effects of the covers had disappeared for one of the two mite allergens that were measured. Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development.
                The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age.
                Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacholine inhalation tests, and allergy skin tests.
                At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV 1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71).
                The multifaceted intervention program was effective in reducing the prevalence of asthma in high-risk children at 7 years of age. Avoidance of individual risk factors have not been successful in preventing the development of asthma.
                We sought to determine the effectiveness of a multifaceted intervention program in primary prevention of asthma in high-risk infants.
                We identified 545 high-risk infants on the basis of an immediate family history of asthma. Families were randomized into intervention or control groups. Intervention measures included avoidance of house dust mite, pet allergen, and environmental tobacco smoke. Breast-feeding was encouraged with formula supplementation if necessary, and introduction of solid foods was delayed.
                At 2 years of age, 19.5% of the children had asthma, and 14.7% had atopy (positive skin test response to one or more common allergens). Significantly fewer children had asthma in the intervention group compared with in the control group (16.3% vs 23.0%), with 60% less persistent asthma at 2 years. There was a 90% reduction for recurrent wheeze in the intervention group compared with that seen in the control group. Exposure to maternal environmental tobacco smoke during pregnancy or the first year was a risk factor for asthma at 2 years of age. A positive skin test response, particularly to food, at 12 months predicted asthma at 2 years. There was no significant difference for atopy between the intervention and control groups, but daycare reduced atopy at 2 years.
                This multifaceted intervention program during a window of opportunity in the first year of life was effective in preventing asthma in high-risk children at 2 years of age. Future studies with this cohort at school age are important. This prospective, long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy. Infants were randomly assigned to receive either the hydrolysate formula (n = 92) or an adapted cow milk formula (n = 85) alone or with breast-feeding for 4 months. The groups did not differ in family allergy history scores or cord blood IgE levels. After 4 months, total IgE levels and allergic reactions did not differ significantly between groups, although the hydrolysate group had a lower prevalence of eczema. At 12 months of age, neither IgE levels nor allergic reactions were significantly different. At 2 years of age, however, 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group; the differences were significant for eczema (p < 0.001) but not for asthma. At 4 years of age, allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group; the difference was significant only for eczema (p < 0.01). These results suggest that early feeding of a protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma. Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy.
                A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges).
                In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)).
                Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma. Early life exposures may be important in the development of asthma and allergic disease.
                To test house dust mite (HDM) avoidance and dietary fatty acid modification, implemented throughout the first 5 years of life, as interventions to prevent asthma and allergic disease.
                We recruited newborns with a family history of asthma antenatally and randomized them, separately, to HDM avoidance or control and to dietary modification or control. At age 5 years, they were assessed for asthma and eczema and had skin prick tests for atopy.
                Of 616 children randomized, 516 (84%) were evaluated at age 5 years. The HDM avoidance intervention resulted in a 61% reduction in HDM allergen concentrations (microg/g dust) in the child's bed but no difference in the prevalence of asthma, wheeze, or atopy (P > .1). The prevalence of eczema was higher in the active HDM avoidance group (26% vs 19%; P = .06). The ratio of omega-6 to omega-3 fatty acids in plasma was lower in the active diet group (5.8 vs 7.4; P < .0001). However, the prevalence of asthma, wheezing, eczema, or atopy did not differ between the diet groups (P > .1).
                Further research is required to establish whether other interventions can be recommended for the prevention of asthma and allergic disease.
                House dust mite avoidance measures and dietary fatty acid modification, as implemented in this trial during infancy and early childhood, did not prevent the onset of asthma, eczema, or atopy in high-risk children. The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cow's milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cow's milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group (p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life. One hundred twenty children, identified before birth as being at high risk for atopy, were prenatally assigned to prophylactic or control groups.
                The infants in the prophylactic group either received breast milk from mothers on an exclusion diet or an extensively hydrolyzed formula. Their bedrooms and living rooms were treated repeatedly with an acaricide, and they used polyvinyl-covered mattresses with vented head areas. The infants in the control group were fed conventionally, and no environmental control was recommended.
                A significant advantage, first demonstrated at 1 year of age, persists for children in the prophylactic group. They have less of any allergy or eczema, but the reduced prevalence of asthma is no longer significant. Only three children in the prophylactic group had positive skin prick test results compared with 16 in the control group, suggesting a significant reduction in sensitization.
                A dual approach to allergen avoidance, focusing on foods and aeroallergens, appears to be beneficial in selected high-risk infants. Avoidance of potent allergens in early life increases the threshold for sensitization in these high-risk infants. Whether sensitization has been avoided or merely deferred has yet to be proved. In an attempt to prevent or reduce the manifestations of atopic disease, a group of infants considered to be genetically at high risk of atopy was entered in a prenatally randomized, controlled study. A prophylactic group (n = 58) was either breast-fed with their mothers excluding foods regarded as highly antigenic from their diets, or given an extensively hydrolysed formula. In addition, strenuous efforts were made to reduce exposure to the house-dust mite by application of acaricide to the bedroom and living room carpets and upholstered furniture. A control group (n = 62) was fed conventionally by breast or on formula, and no specific environmental measures were taken. The results (previously reported) after 1 year showed significantly less total allergy, asthma, and eczema in the prophylactic group. Similar results were obtained at 2 years although the reduction in asthma no longer achieved statistical significance. However, there was significantly less sensitization, as shown by a battery of skin prick tests (SPTs), to both dietary allergens and aeroallergens in the prophylactic group. All the children have now been reviewed at the age of 4 years, and SPTs to a wide range of dietary allergens and aeroallergens have been performed. The control group continues to show more total allergy (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.21-6.13, P < 0.02), definite allergy (allergic symptoms plus positive SPT) (OR 5.6, CI 1.8-17.9, P < 0.005), and eczema (OR 3.4, CI 1.2-10.1, P < 0.05). More control children have positive SPTs (OR 3.7, CI 1.3-10.0, P < 0.02). A dual approach to the prevention of allergic disease, avoiding as far as possible sensitization to food and aeroallergens, significantly reduces the risk of atopic disease. This should be reserved for infants considered at very high risk of atopy, and close medical and dietetic supervision must be available.
The available evidence suggests that the reduction of exposure to multiple allergens compared to usual care reduces the likelihood of a current diagnosis of asthma in children (at ages < 5 years and 5 years and older). Mono-intervention studies have not produced effects which are statistically significant compared with control. In children who are at risk of developing childhood asthma, multifaceted interventions, characterised by dietary allergen reduction and environmental remediation, reduce the odds of a physician diagnosis of asthma later in childhood by half. This translates to a number needed to treat (NNT) of 17. The effect of multi-faceted interventions on parent reported wheeze was inconsistent and had no significant impact on nocturnal coughing or dyspnoea. Data from monofaceted intervention exposed children studies were not significantly different from those of control groups for all outcomes. There remains uncertainty as to whether multiple interventions are more effective than mono-component interventions. The comparisons made were indirect, making the conclusions drawn uncertain. To our knowledge there are no ongoing studies in which both intervention strategies are randomly compared. The findings, however, warrant further direct comparison between multiple- and monofaceted interventions aimed at reducing the prevalence of asthma in children.