Optimization of Antibiotics in Mothers and their Breastfed Infants Using Pharmacomicrobiomic and Metabolomic Analyses

Project Summary/Abstract Pregnant people are particularly vulnerable to SARS-CoV-2 and at risk of developing a more serious or complicated disease course, including about a 70% increased risk of death. Infection in pregnancy also appears to be related to increased risk for preterm delivery as well as other adverse pregnancy outcomes, such as stillbirth. For this reason, pregnant people are considered a priority population for vaccination. Limitations in the design of existing clinical trials with pregnant persons and the lack of a comparison group in the V-Safe Registry point to the urgent need for additional vaccine safety and efficacy data by trimester of vaccine exposure and encompassing both short and longer term outcomes for pregnant people and their offspring relative to an unexposed comparison group. With administrative supplement funding to parent award 1P50HD106463-01 and using the established U.S. MotherToBaby pregnancy cohort study at UC San Diego, we propose to complete new enrollment and follow-up of 900 COVID-19 vaccine exposed individuals (all brands, all doses, all trimesters of exposure) and 900 unvaccinated comparators to evaluate pregnancy outcomes including major congenital malformations, spontaneous abortion, stillbirth, preterm delivery, small for gestational age infants, postnatal growth through one year of age. In addition, through one year post-partum we will compare the incidence of SARS-CoV-2 infection post-vaccination in maternal/child pairs who were vaccinated in pregnancy to the incidence of infection in gestational-age matched maternal/child pairs who were not vaccinated in pregnancy. Finally, in a subset of 180 vaccinated individuals (60 per trimester of exposure) representing exposure to one of the two mRNA vaccine products we will obtain blood samples following the last vaccination dose in pregnancy in order to examine immune response in pregnancy. These data will provide essential safety and efficacy information that can support COVID-19 vaccine-related public health recommendations in this special population.