A child’s colonization with a CagA-negative-strain was associated with an increased risk of asthma (Odds ratio 2.11; 95% CI 1.23-3.60, but this differed for European (3.64; 1.97-6.73) and non-European (0.52; 0.14-1.89) children. multivariate logistic regression analyses among 3,797 subjects. Results In children, the positivity rate was 8.7%, and 29.2% of these were CagA-positive. A child’s colonization with a CagA-negative-strain was associated with an increased risk of asthma (Odds ratio 2.11; 95% CI 1.23-3.60, but this differed for European (3.64; 1.97-6.73) and non-European (0.52; 0.14-1.89) children. When taking into account maternal status, only positive children with an negative mother had increased risk of asthma (2.42; 1.11-5.27), accounting for 3.4% of the asthma risk. Conclusions Colonization of a European child with a CagA-negative-strain at age 6 was associated with an increased prevalence of asthma, but there was no association for non-European children. The underlying mechanisms for the observed risk differences require further research. has been used as a proxy for this modern phenomenon (2). Studies in mice have demonstrated that experimental infection with prevents allergic asthma through the induction of regulatory T cells (Tregs) (3). Direct contact between and dendritic cells (DCs) was found to be essential for the induction of tolerogenic DCs. These DCs produce IL-18, important for the conversion of na?ve T-cells into Tregs (3). Eventually, these Tregs may suppress asthmatic immune responses in the airways (4). This interaction between and the immune system may be affected by its genotype: expression of the colonization has dropped dramatically in Western countries (6). Currently, fewer than 10% of children born in Western countries are positive (7) (8). Several epidemiologic studies examined the relation between colonization and asthma and asthma-related conditions in childhood (9-14). However, results from these studies appear contradictory. This may have been due to differences in study design (9, 10, 14), low number of participants (9, 10, 13), differing methods and timing of status identification (11, 14), and insufficient accounting for potential confounders (12, 14). It also is unclear whether maternal colonization during pregnancy affects the child’s risk for asthma and related conditions. Maternal colonization during pregnancy may be a risk factor for foetal growth retardation (15, 16), which subsequently might lead to increased risk for asthma (17). Children of an colonization in children, and secondly we focused on the effect of paired maternal and child’s status on these outcomes. These analyses were facilitated by a large multi-ethnic population-based prospective Rabbit Polyclonal to HSL (phospho-Ser855/554) cohort study in Rotterdam, The Netherlands. Methods Design and setting This study was embedded in the Generation R Study, a population-based prospective cohort study of pregnant women and their children in Rotterdam, The Netherlands (18). All children were born between April 2002 and January 2006. The Medical Ethics Committee of the Erasmus University Medical Centre approved the study protocol and parents gave written informed consent for themselves and their children. For the current study, data from 3,797 children with information on colonization and any asthma or related conditions were available (Figure 1). Open in a separate window Figure 1 Study design and number of participants colonization in children and their mothers colonization of children was defined by measuring IgG antibody levels in serum using an enzyme-linked immunosorbent assay (ELISA) (19). Sera samples were obtained at age 6 PI4KIIIbeta-IN-10 years. A separate ELISA was performed to determine serum IgG antibodies against a specific recombinant truncated cytotoxin-associated gene PI4KIIIbeta-IN-10 A (CagA) protein (20). Both ELISAs were validated locally, by adapting the ELISA properties based on positive and negative controls. and CagA colonization in mothers was measured from serum samples obtained during mid-pregnancy (gestational age 18-25 weeks) (21). Similar ELISAs were used for mothers and children, with specific properties known from use in previous birth cohorts PI4KIIIbeta-IN-10 (19, 22). Asthma and related conditions at school age Wheezing in the prior 12 months (no, yes), physician-diagnosed asthma ever (no, yes) and physician-diagnosed eczema in the last 12 months (no, yes) were assessed using questions adapted from the International Study on Asthma and Allergy in Childhood (ISAAC) core questionnaires at age 6 years (23). Inhalant allergy was assessed by questionnaire at age 6 years; a positive history was defined as inhalant allergy to pollens, mites, or pets in the prior 12 months (no, yes), diagnosed by a physician. Covariates Information on birth weight, gestational age, and sex of the children were obtained from midwife and hospital registries at birth. Postnatal questionnaires at ages of 6 and 12 months supplied information on breastfeeding, and at age of 6.