Primary prevention of atopic diseases: The Prevention of Allergy among Children in Trondheim (PACT) study

Abstract

There has been a substantial increase in asthma, atopic dermatitis and allergic rhinoconjunctivitis in countries with a “western lifestyle” since the 1960s. Today the prevalence of these atopic diseases is high. Both a loss of protective factors and the emergence of new risk factors are likely to contribute to the worldwide differences and changes in prevalence of atopic diseases. Controlled intervention studies are necessary to identify factors that are feasible and effective as early interventions for counteracting the increasing incidence of atopic diseases. Two such studies include the Prevention of Allergy among Children in Trondheim (PACT) study and Probiotics in the PACT (Pro- PACT) study. In this thesis, our overall aim has been to study the impact of different specific interventions on atopic disease and sensitization during the first 2 years of life. In the Pro-PACT study, we also investigated the effect of a probiotic regime on the mothers’ and children’s intestinal microbiota to elucidate possible mechanisms of a clinical effect. The aim of Paper I, based on data from the PACT study, was to study the impact of environmental factors such as parental smoking, indoor dampness and increased intake of n-3 polyunsaturated fatty acids (PUFAs) and oily fish on atopic diseases at 2 years of age in a controlled intervention study in primary health care. The participants in both the control cohort and the intervention cohort followed the ordinary scheduled program for pre- and postnatal follow-up in primary health care. The interventions were to be implemented throughout Trondheim, regardless of participation in the PACT study or not. Questionnaires from the control cohort were collected before the intervention started. We found a reduced incidence in parental-reported doctor diagnosed asthma and use of asthma medication at 2 years of age in the intervention cohort. The difference was found in girls, but not in boys. This indicates that the asthma phenotype among girls is more susceptible to environmental tobacco smoke (ETS) and intake of oily fish and n-3 PUFAs, and that the pathophysiology of asthma may be dependent on the sex of the child. The reduced incidence of asthma might be due to the differences between the cohorts in the interventional measures, with less parental smoking, and higher intake of oily fish and n-3 PUFAs. As we did not find any difference between the cohorts regarding indoor dampness, the reduced incidence of asthma probably cannot be ascribed to this interventional measure. However, during the intervention period of the study, smoking bans in public places and anti-tobacco mass media campaigns took place, and there was a decrease of smoking in Norway in general. This has likely resulted in less ETS of the pregnant women and the children in the intervention cohort, and has probably contributed to the lower asthma incidence. The aim of Paper II, using data from the Pro-PACT study, was to study whether a probiotic supplement containing three probiotic bacteria strains given to pregnant women during the last 4 weeks of pregnancy until 3 months after birth would reduce the incidence of atopic disease and atopic sensitization at 2 years of age in a randomized double-blind trial. We did not administer probiotics to the infants. We found a 40% risk reduction of atopic dermatitis in the probiotic group compared to placebo. The probiotics did not postpone the first appearance, indicating a primary preventive effect. Among children with AD, the severity was reduced in the probiotic group. The effect was stronger in children without a family history of atopy compared to those with a positive family history. We found no effect on atopic sensitization, asthma or allergic rhinoconjunctivitis. In Paper III, using samples collected during the Pro-PACT study, we aimed to investigate whether a probiotic supplement altered the colonization and the diversity of the mothers’ and children’s intestinal microbiota. We found that all the three administered probiotics colonized the mothers 3 months after birth. Only the Lactobacillus rhamnosus GG (LGG) bacteria colonized the children at 10 days and 3 months of age. At 1 and 2 years of age, however, the difference between the groups was no longer apparent. This indicates that different probiotic species have different ability to transfer from the mother to the child, and might indicate the preventive effect on AD found in Paper II, to be mediated through early colonization with LGG. However, results from trials with a postnatal supplementation alone have not shown a clinical effect, and the effect may partially occur during pregnancy or postnatally via breast milk. We found no indication that the administered probiotics altered the gut microbial composition, or gut microbial diversity of the children at 3 months and 2 years of age.