Maternal COVID-19 Vaccination and Lactation Outcomes

美国可用的冠状病毒病(新冠肺炎)疫苗对有症状的新冠肺炎的疗效高达95%。然而，孕妇和哺乳期个体被排除在最初的临床试验之外。新冠肺炎疫苗目前正在怀孕中期或晚期的孕妇身上进行试验，但预计要到2022年或2023年才能结束，而且还没有计划对哺乳结果进行评估。新冠肺炎疫苗是高效的，越来越多的证据表明，接种新冠肺炎疫苗的母亲的母乳喂养的婴儿具有免疫原性保护。到目前为止，还没有发表过关于新冠肺炎疫苗在怀孕或哺乳期间对母乳喂养的婴儿的安全性、乳汁生产和排泄或其他与哺乳相关的后果的研究。缺乏安全数据可能会破坏孕妇和哺乳期妇女的疫苗接种努力。用于许可证后监测的传统数据来源与哺乳结果的相关性有限。自发报告系统由于其自愿性质而存在报告偏差；它们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。疾控中心的V-Safe计划，即基于智能手机的疫苗副作用监测，不能捕获哺乳期状态。正在进行的以医疗保健声明为基础的监测研究也不会常规地捕获哺乳期。招募接种COVID的哺乳期妇女的观察性研究主要依赖于自我报告的结果，推广能力有限。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接种新冠肺炎疫苗以及母婴对中与哺乳相关的结果的新研究，包括超过11,000对母乳喂养对。我们将使用与四大医疗系统的国家免疫数据相关联的电子健康记录数据，研究婴儿生长、婴儿保健利用、母亲乳腺炎以及母亲接种新冠肺炎疫苗后7个月内的母乳喂养状况。此外，我们还将探讨母亲接种新冠肺炎疫苗后的急性婴儿结局和婴儿发育异常筛查。我们处于独特的地位，可以克服缺乏关于哺乳状况的信息、报告和志愿者偏见的问题，使用常规收集的关于母乳喂养的信息，为确定的人口提供良好的儿童访问。我们将应用严格的流行病学方法，包括倾向评分调整，以解决混淆问题。以哺乳期为重点，我们的研究将补充其他关于孕期接种新冠肺炎疫苗的研究，以及从接种新冠肺炎疫苗的志愿者那里收集牛奶样本的研究。它将提供关于围产期接种新冠肺炎疫苗后与哺乳相关的结局的基本证据，目前尚无相关证据。支持安全性的发现可以减少疫苗的犹豫不决，而识别潜在危害的结果将对患者决策提供信息。此外，通过拟议的研究开发的研究哺乳相关结果的新途径和方法可以用于有效地评估目前推荐或正在研究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.