key: cord-0762132-bub7y6su authors: Yang, Chengliang; Zhao, Hedi; Tebbutt, Scott J. title: Balancing the Risks and Benefits of COVID-19 Vaccination for Pregnant Women and Their Children date: 2021-12-16 journal: Front Immunol DOI: 10.3389/fimmu.2021.748456 sha: bf09dad53ecc4d6b29b63dfd5c0c621d403e758e doc_id: 762132 cord_uid: bub7y6su nan confer protection to their offspring via the placenta or human milk. As reported by The Council for International Organizations of Medical Sciences (CIOMS), the inclusion of pregnant women and breastfeeding women in COVID-19 vaccine trials are urgently needed to identify the potential risks and benefits in this population, as well as to the fetus or nursing infant. Some Australian clinicians have recommended that women undergoing in vitro fertilization (IVF) treatment should avoid vaccinating in the days leading up to their embryo transfer or egg collection 1 . Indeed, the stride towards vaccination should be met with prudence, as safety data is limited and health agency guidelines are vague and, in some cases, controversial (15) . Importantly, the COVID-19 vaccines have not been specifically evaluated for pregnant individuals utilizing IVF. A pivotal addition to ongoing studies would be to incorporate an analysis of the pregnancy and infant outcomes in individuals utilizing IVF and how these contrast to the established cumulative live-birth rate of 51% following six cycles of IVF (16) . Lastly, the short-term and long-term effects of COVID-19 vaccination in pregnant and lactating women, the fetus, and infants remain unanswered. Since the immune response to COVID-19 vaccination in pregnant and breastfeeding women cannot be inferred from that of non-pregnant and nonbreastfeeding women, we must highlight the importance of enrolling these individuals in clinical trials. The long-term safety data that speak most clearly to the question of whether the COVID-19 vaccines benefit pregnant women and newborns should be obtained from robust clinical trials. Emerging evidence suggests that global maternal and fetal outcomes have worsened during the pandemic, with a significant increase in maternal and fetal mortality (particularly in low-income and middle-income countries), ruptured ectopic pregnancies, and maternal symptoms of depression (17) . Such factors can often create barriers to vaccination and are further compounded by language barriers, misinformation, misconceptions, reduced literacy, limited access to technology, lack of trust, homelessness, and migrant or refugee statuses. One solution to this problem is comprehensive clinical trials with robust, clear evidence on the potential benefits and risks of exposure to COVID-19 vaccines, giving pregnant women the privilege to make informed decisions regarding their health and the health of their newborns. Here, we suggest that the COVID-19 vaccine should be tested as a critical prevention strategy for pregnant women and their children in ongoing and future clinical trials. We acknowledged that in the absence of a standard vaccine to serve as the control, the use of placebo may be considered; however, the ethics of administering a potentially ineffective therapy to combat a morbid viral infection is unquestionably harmful. This argument is compounded by the risk posed to both the mother and the fetus. Ultimately, these trials may have lower enrollment given the potential risk of contracting COVID-19 when given the placebo. Nevertheless, we hope these trials will elucidate the efficacy, safety, and long-term outcomes of COVID-19 vaccination in pregnant mothers and the developing fetus. And we strongly suggest monitoring the incidence of maternal fever, acetaminophen use, rate of pregnancy loss, developmental outcomes in the newborn, and ADHD in offspring of pregnant women who have received COVID-19 vaccination. By monitoring the outcomes for pregnant and lactating women and their babies, these investigations will further promote informed decision-making for COVID-19 vaccination during pregnancy and lactation, and may lead to a reduction in vaccine-hesitancy. As the COVID-19 pandemic continues, a public health obligation exists to evaluate pregnant women and their children (in all populations and ethnic groups) in welldesigned and well-funded COVID-19 vaccine trials to identify and implement appropriate prevention and care based on strong evidence. 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