Prevention of allergic disease in childhood: clinical and epidemiological aspects of primary and secondary allergy prevention

Susanne Halken
Pediatric Allergy and Immunology 2004, 15 Suppl 16: 4-5, 9-32
The development and phenotypic expression of atopic diseases depends on a complex interaction between genetic factors, environmental exposure to allergens,and non-specific adjuvant factors, such as tobacco smoke, air pollution and infections. Preventive measures may include both exposure to allergens and adjuvant risk/protective factors and pharmacological treatment. These measures may address the general population, children at risk for development of atopic disease (high-risk infants), children with early symptoms of allergic disease or children with chronic disease. The objective for this review was to evaluate possible preventive measures as regards prevention of development of allergic disease in childhood--primary prevention--and also some aspects of the effect of specific allergy treatment as regards secondary prevention in children with allergic asthma and allergic rhinoconjunctivitis. In one prospective observational study of a birth cohort of unselected infants we evaluated possible predictive/risk factors. In two prospective intervention studies including 1 yr birth cohorts of high-risk(HR) infants we investigated the effect of feeding HR infants exclusively breast milk (BM) and/or hydrolyzed cow's milk-based formula the first 4-6 months as regards: (i) the allergy preventive effect of BM/extensively hydrolysed formula (eHF) compared with ordinary cow's milk-based formula, (ii) the effect of two different eHFs, a whey (Profylac) and a casein-based (Nutramigen) formula, as regards development of cow's milk protein allergy (CMA), and (iii) a comparison of the preventive effect of eHF (Profylac/Nutramigen) with a partially hydrolyzed cow's milk-based formula (pHF) (NanHA) as regards development of CMA. None of the mothers had a restricted diet during pregnancy or lactation period. In two prospective randomized intervention studies we evaluated the preventive effect of specific allergen avoidance and specific immunotherapy (SIT) in children with allergic asthma and allergic rhinoconjunctivitis, respectively. The combination of atopic heredity and elevated cord blood IgE resulted in the best predictive discrimination as regards development of allergic disease. The optimal high-risk group was defined by either double parental atopic predisposition or single atopic predisposition, the latter combined with a cord blood IgE > or = 0.3 kU/1. 66% of unselected infants were daily exposed to tobacco smoke, which was a significant risk factor for recurrent wheezing until the age of 1.5 yr. HR infants were breastfed for a longer period and less exposed to tobacco smoke than unselected infants. Exclusively BM/eHF for at least 4 months was associated with a significantly reduced cumulative prevalence of CMA [3.6% (5/141) vs. 20%(15/75) in the control group] up to 5 yr. The effect of the two different eHFs was similar. Exclusively breastfed infants were significantly less exposed to tobacco smoke and pets, had solid foods introduced later and belonged to higher social classes. pHF was significantly (p = 0.05) less effective than eHF as regards prevention of development of CMA. A diet period of 4 months seems to be as efficient as 6 months or more as regards development of CMA. A few ongoing prospective, randomized intervention studies have produced the first indication that avoidance of indoor allergens such as house dust mite (HDM) in HR infants may reduce the incidence of severe wheeze and sensitization during the first 1-4 yr of age. Long-term follow-up is awaited. In a prospective, double-blind placebo-controlled study in children with doctors diagnosed asthma and documented HDM allergy, we found that semipermeable polyurethane mattress and pillow encasings (Allergy Control) when compared with placebo encasings resulted in a significant perennial reduction of HDM exposure and a significant reduction in the needed dose of inhaled steroids by approximately 50% (mean dose: 408 microg--227 microg/day) after 1-yr follow-up. In another randomized prospective study we investigated the possible preventive effect of SIT in children with allergic rhinoconjunctivitis and grass/birch pollen allergy as regards development of asthma. Among those without asthma significantly fewer in the SIT group developed asthma when compared with the control group (19/79 = 24% vs.32/72 = 44%) after the first 3 yr; and methacholinebronchial provocation test results improved significant in the SIT group. The results of our studies support the evidence that the risk for development of early allergic manifestations e.g. CMA and atopic dermatitis can be reduced significantly by simple dietary measures for the first4 months of life. In all infants breastfeeding should beencouraged for at least 4-6 months, and exposure to tobacco smoke should be avoided during pregnancy and early childhood. In HR infants a documented hypoallergenic formula (at present eHF) is recommended if exclusive breastfeeding is not possible for the first 4 months. In homes of HR-infants, current evidence supports measures to reduce the levels of indoor allergens. e.g. HDM and pets. In symptomatic children allergen-specific treatment may influence both the symptoms and the prognosis. Allergen avoidance can reduce the need for pharmacological treatment, SIT may have the potential for preventing the development of asthma in children with allergic rhinoconjunctivitis. and it may be possible to interfere with the natural course of allergic diseases.

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