Protocol design for the ACTIVATE clinical trial: Exposure to vaginal microbiome in cesarean-delivered infants at high risk for allergies.

Background: Food allergy is increasingly common in the United States. Studies suggest that rising cesarean delivery rates are associated with many immune disorders, including allergic diseases. A preceding proof-of-concept study showed that the microbiota of infants born by cesarean delivery could be partially restored via vaginal microbiome exposure at birth via "vaginal seeding". Objectives: Described here is the design of a clinical trial to evaluate the effects of vaginal seeding in infants born by cesarean delivery on food allergen sensitization (egg, milk, and peanut) at 12 months of age. Methods: This study is supported by the Immune Tolerance Network in collaboration with the National Institute of Allergy and Infectious Diseases. ACTIVATE is a single-center, randomized, double-blind, placebo-controlled trial enrolling pregnant women and their newborns who have a first-degree relative with atopic disease (NCT03567707). Forty infants born vaginally and 80 infants born by cesarean delivery, randomized 1:1 to receive vaginal or placebo seeding, will be enrolled. Families are followed for 1 year, with an option to extend the follow-up for a total of 3 years. Results: The study is currently underway with an enrollment goal of 120 mother-infant pairs. Surveys and samples are collected from mothers and infants during the follow-up period including blood, stool, skin swabs, oral swabs, nasal swabs, maternal vaginal swabs, and breast milk. Conclusions: This pilot study will provide important data on the effects of vaginal seeding on allergen sensitization, the microbiome, and the development of immune responses in the first 3 years of life.