Dear Editor,
The SARS-CoV-2 virus remains a major cause of illness and death worldwide, and an ongoing public health concern with inevitable physical and mental health challenges worldwide. According to global reports, by February 2024, more than 703 million people have been infected and 6.9 million people have died worldwide. There are treatments to help reduce severity of COVID-19 approved by the FDA, and the EMA (European Medicine Agency), e.g., Paxlovid, Molnupiravir, and Remdesivir. Therefore, vaccination is now a critical strategy against COVID-19 to control its spread in communities.
Pregnant women are considered as a vulnerable group that are prone to experience a severe form of SARS-CoV-2 infection.1 In this regard, SARS-CoV-2 infection has become a serious concern for the health of mother and fetus. However, there are several challenges regarding the vaccination of pregnant women with COVID-19 vaccines, for example, there is disagreement about the exact timing of SARS-CoV-2 vaccination during pregnancy.2 Additionally, pregnant women have been excluded from COVID-19 vaccine trials due to safety concerns. The low acceptability of pregnant women to receive a COVID-19 vaccine in the early stages of the SARS-CoV-2 epidemic, in turn, contributes to limiting knowledge about the safety and efficacy of vaccination during pregnancy. Herein, we discuss about the effectiveness and safety of COVID-19 vaccination of pregnant women and their infants using evidence reported through previously published relevant meta-analyses.
Previous meta-analyses concluded that SARS-CoV-2 infections significantly increase risks such as the need for intensive care, invasive ventilation, premature birth, pre-eclampsia, stillbirth, and also maternal mortality.1 Thus, although SARS-CoV-2 infection is associated with poor pregnancy outcomes in pre-immune pregnant women, there is controversial evidence regarding the safety and efficacy of COVID-19 vaccination among these individuals. Hameed et al. evaluated the effectiveness of vaccines during pregnancy using data from 10 observational studies. They suggested that COVID-19 vaccination can prevent infection, as well as reduce COVID-19-related hospitalization and is protective against neonatal NICU admission. However, the authors noted that COVID-19 vaccines do not change adverse outcomes in pregnancy.3 Shafiee et al. elucidated that there is no significant difference in adverse neonatal outcomes, as well as poor pregnancy outcomes (e.g., small for gestational age, cesarean delivery, post-partum hemorrhage, and stillbirth) in COVID-19 vaccinated pregnant mothers compared with no-vaccinated ones.4 Although there are no more relevant meta-analyses to discuss about the clinical efficacy of SARS-CoV-2 vaccines on pregnancy outcomes, we hypothesize that COVID-19 vaccination does not reduce the risk of poor pregnancy outcomes compared to pregnant women who have not received vaccination against COVID-19. According to the literature review, COVID-19 vaccination meaningfully reduces the risk of SARS-CoV-2 infection during pregnancy, and its related challenges particularly ICU admission.2–4 However, the exact time of vaccination during pregnancy remains unclear.
Unavoidable side effects are also challenges in vaccines, which are important in immunocompromised individuals, especially in pregnant women. Hagrass et al. conducted a meta-analysis using data from 13 included studies to demonstrate the clinical safety of COVID-19 vaccines on the health of mothers and their neonates. They noted that there was no significant effect of SAR-CoV-2 vaccination in the risk of miscarriage, length of hospitalization, puerperal fever, post-partum hemorrhage, birth weight, as well as Apgar score.2 Ding et al. also pooled data from 43 observational studies on the safety of SARS-CoV-2 vaccines during pregnancy. They reported that COVID-19 vaccination during pregnancy was not associated with complications such as congenital anomalies, pre-term birth, NICU admission, Apgar score at 5 min, low birth weight, miscarriage, cesarean delivery, and post-partum hemorrhage.5 According to these studies, Ciapponi et al. revealed the clinical safety of COVID-19 vaccination during pregnancy through 71 included studies; the authors concluded that there was no safety concern regarding SARS-CoV-2 vaccination in pregnancy.6 According to the literature, COVID-19 vaccines are safe for pregnant women regardless of the vaccine type or the trimester of vaccination.
In conclusion, currently, COVID-19 vaccination is the only option available to interrupt transmission chains in communities. However, limited knowledge regarding the clinical benefits and safety of COVID-19 vaccines for mothers and neonates is the main reason for the low acceptability of COVID-19 vaccination among pregnant women. Overall, our literature review concluded that COVID-19 vaccination is not proven to be associated with adverse pregnancy outcomes' reduction. Nevertheless, vaccination during pregnancy is safe without side effects and also significantly reduces the risk of SARS-CoV-2 infection. In the end, because most of the studies included in the mentioned meta-analyses were observational, more large-scale randomized trials are needed to measure the precise benefits of the COVID-19 vaccination during pregnancy.