Current Evidence to Guide Practice, Policy, and Research: COVID-19 Vaccination During Pregnancy

Abstract

Pregnant and lactating women continue to have some of the lowest levels of vaccine uptake despite COVID-19 vaccine recommendations. It is important to consider why COVID-19 vaccine uptake has lagged counter to robust evidence on vaccine benefits, including concerns about vaccine safety and effectiveness. In this column, I present a summary of research findings, limitations, future directions, and a compilation of guidelines and recommendations from professional and governmental organizations.

The author provides current evidence on the recent proposal to extend Medicaid coverage in the postpartum period.

Summer Sherburne Hawkins, PhD, MS

I closed my last column by highlighting the increase in maternal mortality during the first year of the COVID-19 pandemic and widening racial and ethnic disparities in maternal deaths (Hoyert, 2022). Provisional data from the U.S. Government Accountability Office (GAO, 2022) illustrated that trends in maternal mortality have continued, and COVID-19 contributed to 25% of these deaths in 2020 and 2021. Women who become infected with COVID-19 during pregnancy are at higher risk for severe illness, complications from previous comorbidities, and preeclampsia, and their infants are more likely to be low birth weight and stillborn (Allotey et al. 2020; Villar et al., 2021; Wei et al., 2021).

COVID-19 is a preventable risk factor for maternal and infant morbidity and mortality, and vaccination is a critical preventive measure. The Centers for Disease Control and Prevention (CDC, 2022), American College of Obstetricians and Gynecologists (ACOG, 2022), and other professional organizations (ACOG, 2021) recommended that persons who are pregnant, trying to get pregnant or may try in the future, or breastfeeding receive the COVID-19 vaccine primary series and bivalent booster. However, currently and throughout the pandemic, vaccine uptake among pregnant women has remained at similar or lower levels than uptake for women of reproductive age who are not pregnant (CDC, 2023), despite the fact that pregnant women are at higher risk for severe disease. As such, it is important to consider why COVID-19 vaccination has lagged counter to a robust body of evidence on vaccine benefits and the clinical and policy implications for increasing vaccine uptake.

Starting in December 2020, pregnant women became eligible to receive any of the three available COVID-19 vaccines through emergency use authorization (U.S. Department of Health and Human Services, 2022). However, in the initial mRNA vaccine trials, pregnant women were excluded. Bianchi et al. (2021) highlighted the missed opportunity to include pregnant and lactating people in the COVID-19 safety and efficacy vaccine trials: “Pregnant people were excluded from participating in clinical trials of COVID-19 vaccines, but they are now being encouraged to receive the vaccine on a clinical basis” (p. 1041). Some of the first evidence on the safety of the mRNA COVID-19 vaccine in pregnant persons was published online in April 2021 based on an evaluation of the v-safe After Vaccination Health Checker for COVID-19 Vaccine surveillance system, v-safe COVID-19 Vaccine Pregnancy Registry, and Vaccine Adverse Event Reporting System (Shimabukuro et al., 2021). Shimabukuro et al. (2021) compared adverse events and pregnancy and infant outcomes between women who were vaccinated versus those who were not and concluded that no safety concerns were associated with the mRNA COVID-19 vaccine.

While research findings specific to pregnant women were slowly being released, COVID-19 vaccine uptake remained low among this group during the first 6 months of the vaccine rollout. Using data from the CDC’s Vaccine Safety Datalink, Razzaghi et al. (2021) found that through May 2021, 16.3% of pregnant women received at least one dose of a COVID-19 vaccine; uptake was lower among younger, Black, and Hispanic women, while uptake was higher among older, White, and Asian women. In addition, the CDC did not issue its first formal statement about the safety of COVID-19 vaccines for pregnant and lactating women until August 11, 2021 (CDC, 2021). This statement was released 8 months after adults first started receiving the vaccine through emergency use authorization and 4 months after the publication of the Shimabukuro et al. (2021) study on COVID-19 vaccine safety. In contrast, ACOG issued its first guidance on vaccination for pregnant and lactating people in December 2020 (ACOG, 2022).

Evidence has continued to build on the safety and effectiveness of COVID-19 vaccines for pregnant women (Fu et al., 2021; Rawal et al., 2022). Blakeway et al. (2022) compared pregnancy and infant outcomes in a cohort of pregnant women from the United Kingdom who received at least one dose of the COVID-19 vaccine before birth versus those who had not. Although there was low vaccine uptake at 28.5%, the adverse pregnancy and infant outcomes were similar between groups, which supported earlier findings on vaccine safety (Shimabukuro et al., 2021). Receiving at least two doses of COVID-19 vaccines has been shown to reduce severe disease and mortality during pregnancy. Through a data linkage study, Paixao et al. (2022) examined the effectiveness of the CoronaVac COVID-19 vaccine in pregnant women in Brazil by comparing severe, hospitalized, or fatal COVID-19 between women who had versus those who had not been vaccinated. The authors found that one dose of the CoronaVac vaccine was 67.7% effective, two doses were 85.4% effective against severe COVID-19, and there were no deaths among partially or fully vaccinated women. Using a case-control study, Schrag et al. (2022) examined the effectiveness of zero, two, and three doses of the mRNA vaccine on medically-attended COVID-19 visits in the United States, which they defined as COVID-19-related emergency department or urgent care encounters or hospitalization. The authors found that two or three mRNA doses were at least 75% effective against medically-attended COVID-19 visits during the Delta variant period, but protection waned during Omicron. Schrag et al. (2022) concluded that these findings provide evidence to support boosters for pregnant women, which is consistent with current recommendations.

Researchers also found that the benefits of COVID-19 vaccination among pregnant women extended to their infants (Fu et al., 2021; Rawal et al., 2022). Gray et al. (2021) found that mRNA vaccine-induced antibody titers were similar among pregnant, lactating, and nonpregnant women and were overall higher than those induced by COVID-19 infection. Furthermore, vaccine-generated antibodies were evident in all umbilical cord blood and breast milk samples, which suggests that immunity for infants is conferred via the placenta and breast milk. Similarly, Shook et al. (2022) found that vaccinated women had higher titers at birth than those who were infected by COVID-19, and umbilical cord titers were higher after vaccination than natural infection. The authors followed the infants to 6 months and found that 57% of those born to COVID-19 vaccinated mothers had detectable antibodies compared with 8% of those born to mothers naturally infected. Halasa et al. (2022) found that completion of the two-dose mRNA primary vaccine series during pregnancy was associated with a 61% reduction in COVID-19-related hospitalizations among infants aged less than 6 months and an 80% reduction if the series was completed later in pregnancy. Taken together, these findings are promising and suggest that immunity conferred through maternal COVID-19 vaccination protects against severe illness and lasts until infants are eligible to receive the COVID-19 vaccine at age 6 months (CDC, 2022).

Despite expanded vaccine rollout and Food and Drug Administration authorization of the COVID-19 vaccine in August 2021 (U.S. Department of Health and Human Services, 2022), as of mid-December 2022, 71.5% of pregnant people have completed the COVID-19 vaccine primary series and racial and ethnic disparities in vaccine uptake are consistent with those from mid-2021 (CDC, 2023): 58.2% of Black women, 68.1% of White women, 70.9% of Hispanic women, and 89.4% of Asian women have completed the primary series. Even with recent recommendations for the bivalent booster (ACOG, 2022; CDC, 2022; USDHHS, 2022), only 17.1% of pregnant people have received the booster; the lowest uptake is among Black (9.0%) and Hispanic (9.3%) women, and the highest uptake is among Asian (23.7%) and White (23.9%) women (CDC, 2023).

Researchers have also confirmed racial and ethnic disparities in vaccine uptake in systematic reviews (Galanis et al., 2022; Rawal et al., 2022; Sarantaki et al., 2022) and identified additional predictors of COVID-19 vaccine refusal among pregnant women, including younger age, less education, mistrust in the government, and fear about the safety and side effects of the vaccine (Galanis et al., 2022; Rawal et al., 2022). In contrast, COVID-19 vaccine uptake is higher among women who are older, have higher socioeconomic circumstances, have more comorbidities, know more about COVID-19, are confident that the vaccine is safe and effective, and have had communication with a medical professional about the vaccine (Rawal et al., 2022; Sarantaki et al., 2022).

While it is necessary to consider how limited study designs (e.g., non-randomized controlled trials) and delayed guidance from the CDC may have contributed to low COVID-19 vaccine uptake during pregnancy (CDC, 2023; Razzaghi et al., 2021), the social context in the United States cannot be ignored. Misinformation about the COVID-19 vaccine has been rampant throughout the pandemic, and pregnant women have not been spared. Regan et al. (2022) conducted a national online survey of 2,213 pregnant persons in the United States between December 2020 and July 2021 and found that 55.4% planned to or received a COVID-19 vaccine before or during pregnancy, 27.0% planned to get vaccinated after pregnancy, and 17.5% were unsure or had no plans to get vaccinated. Pregnant women who believed that COVID-19 vaccines were safe and whose health care providers recommended vaccination were more likely to plan to or receive vaccines than those who did not believe vaccines were safe or have a provider who recommended vaccination. While the most commonly cited reason for being vaccinated was to protect themselves (34.2%) or their infants (32.7%), the primary reason for refusing vaccination was concern about side effects (42.6%; Regan et al., 2022).

As we head into the third year of the pandemic, misinformation and beliefs continue to be barriers to vaccine uptake. In May 2022, the Kaiser Family Foundation conducted a nationally representative survey of 1,537 women who were pregnant or trying to get pregnant and found that 24% believed pregnant women should not get a COVID-19 vaccine, 17% believed it was unsafe for lactating women to get vaccinated, and 16% believed the vaccine caused infertility. However, an additional 40% of women reported that they had heard misinformation about each of these beliefs and were unsure if they were true. Based on these findings, nearly three-fourths of respondents who were pregnant or trying to get pregnant believed or had heard misinformation against getting the COVID-19 vaccine (Kaiser Family Foundation, 2022).

While hindsight is 20-20, learning from the current pandemic will ensure a more thoughtful response to the next. Bianchi et al. (2021) called for the implementation of the recommendations of the Task Force on Research Specific to Pregnant Women and Lactating Women, particularly the inclusion of pregnant and lactating women in clinical research (Eunice Kennedy Shriver National Institute of Child Health and Human Development, 2018). To date, researchers have had to use innovative study designs and data linkage to investigate the safety and effectiveness of COVID-19 vaccines among pregnant women and infants. As the pandemic continues, it is essential for researchers to conduct longitudinal studies to more fully understand the long-term immunological and health effects of the vaccine. In addition, researchers who design studies to examine predictors of vaccine uptake and acceptance need to use consistent measures to compare findings across populations and time to inform interventions.

Timely, clear, and consistent communication from the CDC and professional organizations is essential for patients to make informed decisions and providers to encourage and support COVID-19 vaccine uptake. It is necessary for recommendations to explicitly include pregnant and lactating women. Research on developing effective communication and combating misinformation through interdisciplinary collaborations between communication experts, public health leadership, and clinicians will help move this agenda forward. Furthermore, researchers need to ensure representativeness and include sufficient sample sizes to examine vaccine uptake, safety and effectiveness, misinformation, and barriers to vaccination overall and across marginalized groups. Increasing vaccination among women of color needs to be a priority. Focused efforts are required to engage with women of color and partner with their communities to pursue research and develop interventions that address and ultimately eliminate racial and ethnic disparities in vaccine uptake (Marcell et al., 2022; Obasanya et al., 2022).

Biography

Summer Sherburne Hawkins, PhD, MS, is an associate professor, School of Social Work, Boston College, Chestnut Hill, MA.