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

项目总结/摘要 怀孕的人特别容易感染SARS-CoV-2，并有可能发展成更严重或 复杂的疾病过程，包括约70%的死亡风险增加。妊娠期感染也会出现 与早产风险增加以及其他不良妊娠结局有关，如 死胎因此，孕妇被视为接种疫苗的优先人群。局限性 现有妊娠患者临床试验的设计以及V-Safe登记研究中缺乏对照组 指出迫切需要按疫苗暴露的三个月提供额外的疫苗安全性和有效性数据， 包括孕妇及其后代的短期和长期结果， 未暴露对照组。与行政补充资金，以家长奖1 P50 HD 106463 -01和 使用在加州大学圣地亚哥分校建立的美国MotherToBaby妊娠队列研究，我们建议完成 新入组并随访900名COVID-19疫苗暴露者（所有品牌、所有剂量、所有妊娠期 暴露）和900例未接种疫苗的对照动物，以评价妊娠结局，包括重大先天性 畸形、自然流产、死产、早产、小于胎龄儿、产后 一岁的成长。此外，通过产后一年，我们将比较 在怀孕期间接种疫苗的母亲/儿童对接种疫苗后的SARS-CoV-2感染 妊娠期未接种疫苗的胎龄匹配母婴对的感染发生率。 最后，在180名接种疫苗的个体（每三个月暴露60名）的亚组中， 对于这两种mRNA疫苗产品，我们将在妊娠期末次接种疫苗后采集血样 以检测怀孕期间的免疫反应。这些数据将提供基本的安全性和有效性 这些信息可以支持针对这一特殊人群的COVID-19疫苗相关公共卫生建议。

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.