The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study.

OBJECTIVES: A birth cohort was followed-up to age 4 years to record the development of allergic disorders and to study the influence of genetic and environmental factors. METHODS: Information on family history and environmental factors was obtained at birth, and serum cord IgE was measured. At age 4 years, 1218 children were reviewed. RESULTS: By age 4 years, 27% of the children had symptoms of allergic disease. Period prevalence of asthma increased from 8.7% in infancy to 14.9% at 4 years. Family history of atopy was the single most important risk factor for atopy in children. Sibling atopy was a stronger predictor of clinical disease than maternal or paternal atopy, whereas paternal atopy, male sex, and high cord IgE were significant for the development of allergen sensitization. Children of asthmatic mothers were three times more likely to have asthma (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.6-5.8) and rhinitis (OR: 2.9, CI: 1.1-7.4). Formula feeding before 3 months of age predisposed to asthma at age 4 years (OR: 1.8, CI: 1.2-2.6). The effect of maternal smoking on childhood wheeze seen at 1 and 2 years was lost by age 4, except for a subgroup with negative skin test responses (nonatopic asthma). Less than half (46%) of the infantile wheezers were still wheezing at 4 years of age. CONCLUSION: Family history of atopy remains the most important risk factor for atopy in children, but other markers can be identified with a potential for intervention at an early age.

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.

Cohort study of peanut and tree nut sensitisation by age of 4 years.

OBJECTIVE: To determine the prevalence of sensitisation to peanuts and tree nuts in all children born during one year in one geographical area. DESIGN: Birth cohort study with structured review at ages 1, 2, and 4 years. SETTING: All children born on the Isle of Wight between January 1989 and February 1990. SUBJECTS: Of 1456 children originally included, 1218 were reviewed at age 4 years. Of these, 1981 had skin prick tests. MAIN OUTCOME MEASURES: Positive skin test results, clinical atopic disease, and risk factors for the development of atopy. RESULTS: 15 of 1218 (1.2%) children were sensitised to peanuts or tree nuts (13 to peanuts). Six had had allergic reactions to peanuts (0.5% of the population), one to hazelnuts, and one to cashew nuts; three had had anaphylactic reactions. Seven children had positive skin test results or detectable IgE to peanuts without clinical symptoms. Two children who reacted to peanut in infancy had lost their sensitivity by 4 years. Family history of atopy, allergy to egg (odds ratio 9.9, 95% confidence interval 2.1 to 47.9, and eczema (7.3, 2.1 to 26.1) were important predictors for peanut allergy. CONCLUSIONS: IgE mediated allergy to peanuts is common in early childhood. In many the allergy persists but a minority may develop tolerance.

Allergen avoidance in infancy and allergy at 4 years of age.

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.

Allergy prevention--an attainable objective?

Few authorities doubt that here has been a significant rise in IgE mediated diseases in almost all populations in which they have been studied. There is less agreement why this should have occurred and a number of genetic and environmental influences almost certainly play a part. Although the present discussions are concentrating on dietary factors these cannot be expected to play more than a partial role in the pathogenesis and expression allergy. The approach to the prevention of allergy, generally implying IgE mediated disease, has been described as primary, secondary or tertiary. Primary prevention means prevention of sensitisation, secondary prevention means prevention of manifestation of disease in an already sensitised individual, and tertiary means attempting to reduce or abolish expression of allergy in an individual already showing symptoms. Such as classification is convenient although the borders become blurred. It had until recently been assumed that sensitisation rarely if ever took place before birth. Recent studies from Melbourne (Tang et al., 1994), Southampton (Warner JA et al., 1994) and Japan (Kondo et al., 1992) suggest this may no be so. Their studies have given evidence of intrauterine programming. Warner showed a raised peripheral blood mononuclear proliferative response in infants born to atopic families in those who developed atopic eczema with positive skin prick test to foods. The Melbourne group has recently shown a reduced IFN-chi in cord blood mononuclear cells from infants of atopic families. Thus previous attempts at primary prevention may indeed be secondary prevention as immune responses are already developed at birth. Additionally it may be necessary to move attempts at intervention back into early pregnancy or even pre-conception. This would compound the problems of an already difficult area of preventive medicine.

Effect of allergen avoidance in infancy on allergic manifestations at age two years.

BACKGROUND: One hundred twenty children, identified before birth as being at high risk for atopy, were prenatally assigned to prophylactic or control groups. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The effect of genetic and environmental factors on the prevalence of allergic disorders at the age of two years.

The effect of genetic and environmental factors on the prevalence of allergic disorders in early childhood was determined in a prospective follow-up study. Information was available on 1174 children at the age of 2 years. Two-hundred and seventy-five were considered to have an allergic disorder. The prevalence varied from 3.2% for rhinitis to 10.9% for asthma. At 2 years 60 children reacted positively on skin-prick test (SPT). Multivariate logistic regression analysis was used to obtain adjusted odds ratios (95% confidence interval) for each factor. For asthma, positive family history, male sex, low birth-weight, maternal smoking and season of birth were significant risk factors. For eczema, positive family history was the only significant risk factor. For rhinitis, lower socio-economic group and autumn birth were significant. Male sex and low birth-weight were significant for skin test positivity. Positive family history and low birth-weight were significant risk factors for any allergy. Low birth-weight was also a significant risk for skin test reactivity to house dust mite. Genetic and environmental factors have a profound effect on the development of allergic disorders in the first two years of life.

Acarosan and the Acarex test in the control of house dust mite allergens in the home.

House dust mites are believed to be major triggers for allergic disease in atopic individuals. As part of a programme controlling dietary and aero-allergen exposure in high-risk infants, an acaricidal foam and powder (Acarosan) was applied to bedroom and main living room carpets, as well as upholstered furniture, on four occasions in the first year of life. Dust was assayed for mite antigen (Der p1) and these results compared with the semi-quantitative assay of guanine content (Acarex Test). After nine months mean Der p1 levels had decreased by 70% in the treatment group. Proportionally, the greatest fall occurred in those items that had the highest initial mite antigen content. The Acarex score does show a correlation with Der p1 levels, but cannot replace antigen assay when accurate data is required. A chemical acaricide may help reduce house dust mite antigen levels, but is not by itself sufficient to reduce levels below that considered critical for sensitisation.

Effect of environmental factors on the development of allergic disorders in infancy.

A total of 1167 infants were followed for 1 year in a population-based prospective study to assess the effect of environmental factors on the development of allergic disorders. Some of these environmental factors are interdependent. Mothers who formula fed their infants smoked more often (p less than 0.001) and tended to belong to lower social classes (p less than 0.01). Logistic regression analysis was performed to adjust for these confounding variables. Maternal smoking adversely affected the prevalence of asthma (p = 0.003) defined as three or more separate episodes of wheezing and total allergy (p = 0.02). Infants in lower socioeconomic groups developed asthma significantly more often (p = 0.03) than infants born in higher socioeconomic groups. There was a nonsignificant trend for infants born in summer to develop asthma more than infants born in winter (p = 0.08). No effect of these factors was observed on eczema, food intolerance, or on the subgroup of infants with definite allergy (clinical disorder with positive skin prick test [SPT]). Exposure to animal dander did not influence the prevalence of clinical disorder, but positive SPT reaction to cat dander was more prevalent in infants who were exposed to cats and/or dogs (p = 0.04). Positive SPT to house dust mite occurred significantly more often in infants who were formula fed (p = 0.05). The environmental factors had a profound effect on the prevalence of asthma but not on other allergic disorders.

Effect of allergen avoidance on development of allergic disorders in infancy.

There is much evidence that the development of allergic disorders may be related to early exposure of allergens, including those in breastmilk. We have tried to find out whether avoidance of food and inhaled allergens in infancy protects against the development of allergic disorders in high-risk infants. In a prenatally randomised, controlled study 120 infants with family history of atopy and high (greater than 0.5 kU/l) cord-blood concentrations of total IgE were allocated randomly to prophylactic and control groups. In the prophylactic group (n = 58), lactating mothers avoided allergenic foods (milk, egg, fish, and nuts) and avoided feeding their infants these foods and soya, wheat, and orange up to the age of 12 months; the infants' bedrooms and living rooms were treated with an acaricidal powder and foam every 3 months, and concentrations of Dermatophagoides pteronyssinus antigen(Der p l) in dust samples were measured by enzyme-linked immunosorbent assay. In the control group (n = 62), the diet of mothers and infants was unrestricted; no acaricidal treatment was done and Der p l concentrations were measured at birth and at 9 months. A paediatric allergy specialist unaware of group assignment examined the infants for allergic disorders at 10-12 months. Odds ratios were calculated by logistic regression analysis for various factors with control for other confounding variables. At 12 months, allergic disorders had developed in 25 (40%) control infants and in 8 (13%) of the prophylactic group (odds ratio 6.34, 95% confidence intervals 2.0-20.1). The prevalences at 12 months of asthma (4.13, 1.1-15.5) and eczema (3.6, 1.0-12.5) were also significantly greater in the control group. Parental smoking was a significant risk factor for total allergy at 12 months whether only one parent smoked (3.97, 1.2-13.6) or both parents smoked (4.72, 1.2-18.2).