Maternal COVID-19 Vaccination and Lactation Outcomes

美国现有的冠状病毒病（COVID-19）疫苗对有症状的COVID-19的有效性高达95%。然而，妊娠和哺乳期个体被排除在初始临床试验之外。COVID-19疫苗试验目前正在妊娠中期或晚期的孕妇中进行，但预计要到2022年或2023年才能结束，目前还没有计划对哺乳结果进行评估。COVID-19疫苗非常有效，越来越多的证据表明，接种COVID-19疫苗的母亲母乳喂养的婴儿具有免疫原性保护。迄今为止，尚未发表关于哺乳期婴儿在妊娠或哺乳期间接种COVID-19疫苗的安全性、乳汁产生和排泄或其他哺乳相关结局的研究。缺乏安全数据可能会破坏孕妇和哺乳期妇女的疫苗接种工作。用于许可后监测的传统数据来源与哺乳结局的相关性有限。自发报告系统因其自愿性质而存在报告偏倚;由于缺乏接种疫苗的哺乳期妇女的分母，因此无法进行风险估计。CDC的V-Safe计划，基于智能手机的疫苗副作用监测，不捕获哺乳状态。正在进行的基于医疗保健索赔的监测研究也没有常规地捕获哺乳。招募COVID疫苗接种的哺乳期妇女的观察性研究主要依赖于自我报告的结果，并且具有有限的普遍性。为了满足对全面安全数据的需求，我们提出了一项关于产前和产后COVID-19疫苗接种以及母婴对（包括超过11，000对母乳喂养的婴儿）哺乳相关结果的新研究。我们将使用电子健康记录数据与四个大型卫生系统的国家免疫数据相关联，以研究婴儿生长，婴儿保健利用，母亲乳腺炎以及母亲接种COVID-19疫苗后分娩后长达7个月的母乳喂养状况。此外，我们还将探讨母亲接种COVID-19疫苗后的急性婴儿结局和异常婴儿发育筛查。我们处于独特的地位，以克服缺乏信息的哺乳状态和报告和志愿者的偏见，使用常规收集的信息母乳喂养在良好的儿童访问的一个定义的人口。我们将采用严格的流行病学方法，包括倾向评分调整，以解决混杂问题。以哺乳为重点，我们的研究将补充妊娠期COVID-19疫苗接种的其他研究，以及从接种COVID-19疫苗的志愿者中收集乳汁样本的研究。它将提供关于围产期COVID-19疫苗接种后哺乳相关结果的重要和目前不可用的证据。支持安全性的发现可以减少疫苗犹豫，而识别潜在危害的结果对于告知患者决策非常重要。此外，通过拟议研究开发的研究哺乳期相关结局的新方法和方法可用于有效评估目前推荐或正在研究的用于孕妇或产后妇女的药物和疫苗的安全性。

The efficacy of coronavirus disease (COVID-19) vaccines available in the US is up to 95% against symptomatic COVID-19. However, pregnant and lactating individuals were excluded from initial clinical trials. COVID-19 vaccine trials are now underway in pregnant women in their second or third trimester but are not expected to conclude until 2022 or 2023, and evaluation of lactation outcomes is not planned. COVID-19 vaccines are highly effective, and mounting evidence suggests immunogenic protection for breastfed infants of mothers receiving COVID-19 vaccines. To date, there are no published studies on COVID-19 vaccine safety during pregnancy or lactation for breastfed infants, milk production and excretion, or other lactation-related outcomes. This lack of safety data threatens to undermine vaccination efforts in pregnant and lactating women. Traditional data sources used for post-licensure surveillance have limited relevance for lactation outcomes . Spontaneous reporting systems suffer from reporting bias due to their voluntary nature; their lack of a denominator of vaccinated lactating women precludes risk estimates. The CDC's V-Safe program, smart phone-based monitoring for vaccine side effects, does not capture lactation status. Ongoing health care claims-based surveillance studies also do not routinely capture lactation. Observational studies enrolling COVID-vaccinated lactating women rely primarily on self-reported outcomes and have limited generalizability. To address the need for comprehensive safety data, we propose a novel study of antenatal and postpartum COVID-19 vaccination and lactation-related outcomes in mother-infant pairs, including more than 11,000 breastfeeding dyads. We will use electronic health record data linked with state immunization data across four large health systems to study infant growth, infant heath care utilization, maternal mastitis, and breastfeeding status up to 7 months after delivery following maternal COVID-19 vaccination. Also, we will explore acute infant outcomes and abnormal infant developmental screens following maternal COVID-19 vaccination. We are uniquely positioned to overcome lack of information on lactation status and reporting and volunteer bias using routinely collected information on breastfeeding at well-child visits for a defined population. We will apply rigorous epidemiologic methods, including propensity score adjustment, to address confounding. With a focus on lactation, our study will complement other studies of COVID-19 vaccination in pregnancy and studies collecting milk samples from COVID-19-vaccinated volunteers. It will provide essential and currently unavailable evidence regarding lactation-related outcomes following perinatal COVID-19 vaccination. Findings supporting safety can reduce vaccine hesitancy, whereas results identifying a potential harm will be important for informing patient decision making. Furthermore, the novel approach and methods for studying lactation­ related outcomes developed through the proposed study can be adapted to efficiently evaluate the safety of drugs and vaccines currently recommended or being investigated for use in pregnant or postpartum women.