ABSTRACT

The incidence of atopy and allergic diseases has increased during the last decades. Recent research has shifted attention from allergens to factors that may programme the initial susceptibility to allergic diseases. In the present dissertation, three hypotheses were addressed; the classical hygiene hypothesis, the gut microflora hypothesis, and the in utero programming hypothesis.

Number of siblings is inversely associated with risk of allergic diseases. According to the hygiene hypothesis, siblings are a surrogate measure of early life infections, which mature the immune system and protect against allergic diseases. However, we found the risk to increase with each additional infectious disease. A protective effect of an increasing number of older siblings, early day care, furry pet ownership and farm residence remained after controlling for number of clinically apparent infectious diseases, suggesting that their effect is mediated early in life and independently of these infectious diseases. A weak effect of breastfeeding seemed to depend on genetic predisposition, but was not mediated by an effect on infectious diseases.

According to the gut microflora hypothesis, the maturation of the immune system takes place by stimulation from the microbes in the gut flora. During delivery, the foetus acquires micro-organisms from the mother's vaginal flora. Accordingly, a disturbed maternal microflora has been suggested as a possible explanation for a disturbed gut flora of the infants. We found maternal vaginal colonization with Ureaplasma urealyticum in pregnancy to be associated with infant wheezing, but not asthma. The study added maternal colonization with Staphylococci and use of antibiotics in pregnancy to the possible risk factors for asthma.

Newborns with a large head circumference are more prone to have elevated total IgE levels. It has been hypothesised that a large head circumference is associated with a small thymus, and a small thymus is associated with increased IgE levels. We found a large head circumference to be associated with a small thymus size. Furthermore, a small thymus size was not correlated with allergic disease during the first five years of life. However, we did find evidence that birth weight, gestational age and head circumference are associated with later allergic diseases.

In conclusion, our results challenge the classical interpretation of the hygiene hypothesis and lend some support to the gut microflora hypothesis. However, the latter cannot account for all the existing data. Three broad influences, from genetic disposition, in utero programming, and early microbial stimulation of the immature immune system, along with their complex interactions, may be the general framework for the ontogeny of allergic diseases.