Background: Respiratory and gastrointestinal infections are common during childhood, especially in young infants < 2 years of age. Although these common infections are rarely fatal inhigh-income countries as Denmark, they are a source of significant morbidity burden to thechildren and their families, and lead to a substantial economic burden on society. Childrenattending daycare have an increased risk of infections, mainly due to an increased exposure topathogens through social interaction between children, and due to a not yet fully developedimmune system. Strategies to prevent infections in daycare settings are of great importance in acountry like Denmark, where 90 % of children are cared for outside the home in daycare facilitiesby the age of 2 years. Probiotics, defined as live microorganisms that when administered inadequate amounts, confer a health benefit on the host have been suggested in prevention ofrespiratory and gastrointestinal infections in children. Objective: The main objective of this PhD thesis was to examine the effect of probiotics inreducing absence from daycare due to respiratory and gastrointestinal infections in Danish infantsduring their first months in a daycare setting, and to explore potential factors modifying the riskof infections. Further, the current evidence on the use of probiotics in prevention of respiratoryinfections in children attending daycare was systematically reviewed. Methods: Paper I reports on a randomized, placebo-controlled trial investigating the effect ofprobiotics on absence from daycare due to respiratory and gastrointestinal infections in Danishinfants (The ProbiComp study). A total of 290 infants were randomly allocated to receive placeboor a combination of Bifidobacterium animalis subsp. lactis BB-12 and Lactobacillus rhamnosusGG in a dose of 109 colony-forming units per day of each for a 6-month intervention period. Absence from daycare, symptoms of illness, and doctors visits were registered by the parentsusing daily and weekly web-based questionnaires. Information on household characteristics, i. e. household size, number and age of siblings, family history of allergy, pets, and parental educationwas obtained in background interviews with the parents. Paper II consists of a systematic review and meta-analysis, which were performed according tothe guidelines in the Cochrane Handbook for Systematic Reviews of Interventions. The reviewincluded randomized placebo-controlled studies examining the effect of probiotics on respiratoryVIIIinfections in children attending daycare, and meta-analyses were performed on subgroups forseparate probiotic strains or combination of strains used in the studies. In Paper III, longitudinal data from the ProbiComp study was used to explore potential risk factorsof respiratory infections, diarrhea and absence from daycare during the first months afterenrolment to daycare, including factors related to the household, child characteristics, and the typeof daycare. Results: In Paper I, we found no difference in number of days absent from daycare between theprobiotic and placebo group. Moreover, there were no group differences in any of the secondaryoutcomes including number of children with doctor diagnosed upper or lower respiratoryinfections, number of doctors visits, number of antibiotic treatments, occurrence and duration ofdiarrhea, days with symptoms of common cold, days with fever, days with vomiting, and parentalabsence from work due infant illness. In Paper II, 15 randomized controlled trials were included, with a total of 5,121 children aged 3months to 7 years. However, due to a very high diversity in reported outcomes and in probioticstrains used in the studies, the number of studies available for strain-specific analysis was limited. Based on data from three studies, children receiving Lactobacillus rhamnosus GG showed asignificant reduction in duration of respiratory symptoms, whereas no significant differences wereobserved for other analyzed outcomes. Based on data from two studies, Bifidobacterium animalissubsp. lactis BB-12 had no beneficial effect on duration of respiratory symptoms and daycareabsence. Meta-analysis on other strains or combination of strains was not possible due to limiteddata and differences in ways of reporting the outcome. Paper III included 269 infants, observed for a mean of 5.6 months following enrolment to daycare. The risk of acquiring at least one URTI was higher in infants with previous respiratory infections, and was inversely associated with birthweight, infant age at enrolment to daycare. Moreover, therisk was lower in infants in family daycare compared to infants in age-integrated facilities and ininfants from households with pets. No significant risk factors of lower respiratory infections anddiarrhea were identified. Discussion and conclusion: The findings from the ProbiComp study do not support the use of acombination of Bifidobacterium animalis subsp. lactis BB-12 and Lactobacillus rhamnosus GGfor prevention of absence from daycare due to respiratory and gastrointestinal infections in Danishinfants during the first months in daycare. The systematic review and meta-analysis suggested thatIXLactobacillus rhamnosus GG may be beneficial in reducing duration of respiratory symptoms inchildren attending daycare, whereas the potential effects of other probiotic strains were notpossible to assess due to limited available data. A number of previously published studies havesuggested that probiotics may play a role in prevention of respiratory and gastrointestinalinfections in children. However, the findings from this PhD thesis underline that the evidence isstill not clear on which particular strains to recommend, the optimal dose, and the timing. Thereis, therefore, still a need for more studies in this area. In order to plan and target preventivestrategies to those at highest risk, it is important to identify potential factors modifying the risk ofinfections, and results from the ProbiComp study suggested that infection risk in infants startingdaycare is modified by both environmental factors and factors.