Infants' immunisations, their timing and the risk of allergic diseases (INITIAL): an observational prospective cohort study protocol.

INTRODUCTION: Vaccinations are considered to have a large impact on disease control, hence a multitude of vaccines in infancy is recommended. Retrospective studies suggest a possible relation between timing, kind or number of vaccines given in the first year of life and the subsequent incidence of allergic diseases. It must be clarified whether a causal relationship exists to ensure safety and reduce vaccine hesitancy.

METHODS AND ANALYSIS: Due to the high recommendation rate of vaccines, a long-term randomised controlled trial is not considered as ethically acceptable. Therefore, this study aims to observe prospectively the allergic incidence at the age of 5 years after various vaccine interventions in the early months of life.Parents of infants up to the age of 4-6 weeks will be recruited before the first recommended vaccination. Relevant prognostic factors for allergies, status of immunisation and general health will be evaluated up to the age of 5.Allergic symptoms will be assessed by the International Study of Asthma and Allergies in Childhood-questionnaire and a medical confirmation of the allergy is mandatory.The main objective is to compare the incidence of asthma, atopic dermatitis, rhinoconjunctivitis, food allergy or any of these atopies at the age of 5 between infants who were not vaccinated or were vaccinated according to recommendations in the first year of life.The sample size calculation with about 4000 participants can prove a 5% difference to the basic prevalence with about 80% power and global 5% alpha error for the five primary endpoints adjusting according to Bonferroni-Holm and assuming a rate of 10% not early vaccinated infants.

ETHICS AND DISSEMINATION: The study was registered (DRKS00029677) and has received approval by the ethics committee of Universität Witten/Herdecke (no. 113/2022). The results will be published.