Countering COVID-19 vaccine hesitancy in pregnancy: the “4 Cs”

Abstract

Despite evidence to support the safety and efficacy of COVID-19 vaccination in pregnancy, and clear recommendations from professional organizations and the CDC for pregnant people to get vaccinated, COVID-19 vaccine hesitancy in pregnancy remains a significant public health problem. The emergence of the highly transmissible B.1.617.2 (Delta) variant among primarily unvaccinated people has exposed the cost of vaccine hesitancy. In this commentary, we explore factors contributing to COVID-19 vaccine hesitancy in pregnancy and potential solutions to overcome them.

Introduction

As obstetricians caring for pregnant patients throughout the COVID-19 pandemic, we felt tremendous relief in December of 2020 when the Pfizer-BioNTech COVID-19 vaccine received Emergency Use Authorization (EUA) from the FDA. We could foresee a time in the not-so-distant future when we would be able to better protect ourselves, our families, and our patients; severe COVID-19 disease would gradually be eradicated. The continued roll-out of COVID-19 vaccines to the larger public, eventually reaching all adults age 18 and over, and then all children age 12 and older, was encouraging and still in line with this optimistic vision of our shared future. For a few weeks in April 2021, the United States was among the fastest vaccine distributors in the world, with up to 4 million people a day receiving COVID-19 vaccines.¹ Concerns turned to the low availability of effective COVID-19 vaccines in other countries across the world, and reports proliferated describing how vaccine production could be ramped up to meet demand.² However, by early summer, it became clear that a different picture was emerging.³ Daily vaccine rates halved rapidly in May, then halved again, and again. Ultimately, the number of unused, discarded COVID-19 vaccines in the United States rose into the millions, even as residents of other countries desperately sought them.⁴ By June, President Biden announced a “month of action” to try to improve waning vaccination numbers.⁵ Despite efforts ranging from vaccine lotteries and other financial incentives to celebrity endorsements and even door-to-door vaccine drives, the U.S. was unable to recover from the disastrous drop in desire for vaccines, and currently hovers around 38^th in the world for percent of the population fully vaccinated.^6,7 The greatest gulf exists between older and younger adults, with 57% of Americans under 30 vaccinated, compared to 85% of Americans over 65.⁸

Pregnant individuals fall squarely into the demographic of under-vaccinated adults. The viral spread of misinformation and disinformation on risks of the COVID vaccine to pregnant and reproductive-age individuals, together with the exclusion of pregnant and lactating individuals from the initial COVID vaccine trials and entrenched vaccine and medication hesitancy during pregnancy, have created a potent alchemy. This vaccine hesitancy has been difficult to combat, even with widespread dissemination of data demonstrating the safety and efficacy of COVID vaccines in pregnancy. According to the CDC’s Vaccine Safety Datalink, a collaboration between the CDC and multiple integrated health systems, only 16% of pregnant people had received at least one dose by May 2021, compared with 46% of all women ages 18–49.^9,10 By the end of September, at least 4 months after COVID-19 vaccine eligibility was expanded to all adults regardless of risk factors, and in the midst of the “fourth surge” driven by the Delta variant, vaccine coverage in pregnant people rose to only 31%.¹¹ The rise of the highly transmissible B.1.6.17.2 (Delta) SARS-CoV-2 variant has created the perfect storm from mid-summer into fall, resulting in a surge of cases among the unvaccinated, many of whom are pregnant individuals. In fact, August marked the deadliest month of the pandemic for pregnant individuals, with 22 dying from COVID-19 in August alone.¹² This led the CDC to issue an urgent public health advisory on September 28, noting that pregnant individuals have a 70% increased risk of mortality and urging people who are pregnant or considering pregnancy to get vaccinated.¹²

An irony not lost on clinical care providers is that data about the risks versus benefits of remdesivir, tocilizumab or other novel monoclonal antibody therapeutics in pregnancy are far more limited^13,14 than the data about COVID-19 vaccines in pregnancy. While the COVID vaccines have now been given to over 158,000 pregnant individuals in the United States,¹⁵ reports of remdesivir in pregnancy include patients in the tens to hundreds^13,16 and tocilizumab at the level of case reports.¹⁴ But in the summer and fall of 2021, unvaccinated pregnant patients are making these risk calculus adjustments on a daily basis, as they fight to avoid intubation, preterm delivery, extracorporeal membrane oxygenation (ECMO), and death.

Vaccine hesitancy in pregnant people

There is now substantial evidence that COVID-19 vaccines are safe and effective in preventing severe illness in pregnant and lactating people,^17–19 and that pregnant people mount a comparable, robust immune response compared to their non-pregnant counterparts.^20–22 It is unequivocal that pregnant individuals are at increased risk for severe illness from COVID-19 compared to non-pregnant people of reproductive age.^23–25 The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal Fetal Medicine (SMFM) have consistently voiced that the COVID-19 vaccines should not be withheld on the basis of pregnancy.²⁶ Mounting data affirming the safety of COVID vaccine use in pregnancy, continued evidence of harm from COVID-19 infection during pregnancy, a rise in cases driven by the highly-infectious Delta variant, and evidence of low vaccine uptake in pregnant women, all prompted ACOG and SMFM to issue a joint statement on July 30, 2021 firmly recommending COVID-19 vaccination in pregnant individuals.²⁷ On August 11, the CDC endorsed vaccination for all people aged 12 and older, including “people who are pregnant, lactating, trying to achieve pregnancy now, or who might become pregnant in the future,”²⁸ and on September 28, the CDC strengthened this recommendation through an urgent public health advisory.¹²

So why, then, do we continue to encounter profound vaccine hesitancy – defined as the delay in acceptance or refusal of vaccination despite availability of vaccination services²⁹ – in our pregnant patients, who are among the most vulnerable to severe COVID-19 illness, hospitalization, intubation, and even death? First described in 2011 by the Vaccine Communications Working Group to the WHO, the “3 Cs” framework identifies three key factors affecting vaccine hesitancy in adults: confidence, complacency, and convenience.²⁹ Vaccine hesitancy in pregnant people is not an unfamiliar challenge: prior to the H1N1 pandemic, seasonal influenza vaccine uptake in pregnancy hovered at a similarly low rate of 27%.³⁰ The H1N1 pandemic inspired targeted strategies to increase vaccination in pregnant people, and influenza vaccine coverage rose to 61% in 2020, comparable to the general adult population.^31,32 Although lessons learned from these efforts, and other vaccination campaigns, are valuable in countering vaccine hesitancy in pregnant people, there are ways in which the COVID-19 pandemic presents an entirely new challenge. In this commentary, we will use the “3 Cs” model to explore COVID-19 vaccine hesitancy in pregnant people, suggest why it may not fully capture the complexity of factors driving vaccine hesitancy in this population at this unique time in history, and propose a fourth “C” that incorporates the role of the provider in countering vaccine hesitancy: compassion.

Confidence

Not surprisingly, surveys of pregnant people’s attitudes about COVID-19 vaccination conducted prior to its release identified that the most common reasons for vaccine refusal were lack of data about COVID-19 vaccine safety in pregnant populations and the possibility of harm to the fetus.^33,34 Confidence in vaccine safety among pregnant people has been significantly hindered by the exclusion of pregnant individuals from initial COVID-19 vaccine clinical trials,³⁵ which would have provided much needed safety information to guide decision-making and inspire confidence. Changing and sometimes conflicting recommendations from public health authorities have also likely undermined vaccine confidence. For example, the WHO recommendation to withhold COVID-19 vaccines from pregnant individuals unless at high risk of exposure stood in contrast to CDC guidance that vaccines not be withheld on the basis of pregnancy alone.²⁶ The increasing power of social media to propagate misinformation on risks of the COVID vaccine to pregnant and reproductive-age individuals, illustrated by the recent rapid spread of myths about the risks of the COVID vaccine to male fertility,^36,37 is another key difference between the COVID pandemic era compared to H1N1. The resultant lack of confidence in COVID-19 vaccines among pregnant and reproductive-age individuals has been difficult to combat, even with concerted, public-facing attempts to refute myths and rumors with real data.^38,39 It may be that for some people, the damage to vaccine confidence incurred by this misinformation is irreparable. Continued support for research efforts into the impact of COVID-19 vaccination on pregnant women and their children – including long term outcomes of children born to women vaccinated during pregnancy - is likely necessary but may not be sufficient.

Importantly, the “3 Cs” framework does not explicitly acknowledge the complex history of racism and racial injustice in science and medicine in this country,^40,41 and the role this has played in vaccine hesitancy among subsets of the U.S. population, including among pregnant individuals in these groups. Racial and ethnic disparities in COVID-19 vaccination coverage in both pregnant and non-pregnant populations have been observed repeatedly.^41,42 According to the CDC MMWR report on vaccine coverage in pregnant people, only 6% of Black and 11.9% of Hispanic pregnant women had received 1 or more doses of the COVID-19 vaccine as of May 2021, compared to 19.7% of White and 24.7% of Asian pregnant women.⁹ If not corrected, these differences in vaccination rates could perpetuate already significant disparities in numbers of COVID-19 infections, hospitalizations and deaths in communities of color.^43,44 The impact of generations of medical racism and experimentation affecting communities of color, particularly women, on their confidence in and willingness to consider novel vaccines is important to maintain in the forefront of these conversations.^41,45 Eliciting the concerns of pregnant people of color and identifying the barriers that any individual may face to getting vaccinated, particularly those from underserved communities, is critical to achieving vaccine equity.

Many leaders in the medical and public health communities including the U.S. Surgeon General have identified that conversations with trusted health care providers are critical to counteracting health misinformation and increasing vaccine confidence.^46,47 This is particularly true in pregnant populations, where trust between a pregnant patient and the obstetrician is usually high and can significantly impact vaccine acceptance.⁴⁸ While the primary impetus for COVID vaccination in pregnancy is to protect the pregnant individual, reframing the conversation from potential harms to the fetus or child to potential benefits may be persuasive for some. The transfer of COVID-19 vaccine-generated, neutralizing antibodies from the maternal circulation to neonatal cord blood and breastmilk has been repeatedly demonstrated.^20–22,49 Neonatal antibody levels are dependent on maternal levels, and higher transfer ratios are observed when the full vaccine series has been completed before delivery.^20,49–51 Although the longevity of such protection is not known, with the rise of the highly infectious Delta variant leading to more cases in unvaccinated pediatric populations,⁵² vaccination during pregnancy represents a unique opportunity to provide the newborn with some immune protection, particularly relevant if unvaccinated children live in the same household.

Complacency

Complacency – the second “C” in the vaccine hesitancy model, defined as the perception that one’s individual risk for vaccine-preventable disease is low – may also be contributing to the plateau of vaccination rates in recent months. Before widespread vaccine availability in the US, pregnant individuals did express significant concern about their risk for COVID-19: of 915 pregnant people surveyed in December of 2020, 72% stated they were worried about getting sick with COVID-19, and 92% worried about harm to their pregnancy if they were to get sick, yet only 41% stated they would consider vaccination, the remainder primarily citing concerns about lack of safety data.³⁴ According to recent data from the CDC, of unvaccinated adults who state no intent to pursue vaccination, those that feel concerned about their risk for contracting COVID-19 has risen from only 14.9% to 19.5% from July 4 to August 28, during the “fourth surge” – evidence that the unvaccinated general adult population continues to lack concern about their individual risk.⁵³ Today the extent to which unvaccinated pregnant women’s attitudes may have shifted to reflect those of the general unvaccinated adult population is not known. It is possible that the persistently low vaccination rate in pregnant women – hovering now at 30% - reflects an overall decline in perceived risk, and a hopeful reliance on increased vaccination rates in the community to provide some level of protection through herd immunity. Further probing unvaccinated pregnant people’s attitudes could be informative and guide efforts to re-educate, if indicated. Publicizing the recent public health advisory from the CDC strongly recommending vaccination for people who are pregnant or considering pregnancy may help in countering complacency.⁵⁴

Convenience

Can increasing vaccine convenience significantly impact vaccination rates in pregnant people? Offering to administer the COVID-19 vaccine at the time of a prenatal appointment in which a provider recommends the vaccine would likely increase vaccination rates, as it has for the influenza vaccine.^48,55 However, factors unique to some of the COVID-19 vaccines – such as storage requirements and local availability – may make stocking vaccine doses in prenatal clinics untenable for the foreseeable future. All unvaccinated pregnant women who are hospitalized for non-COVID indications could routinely be offered the COVID vaccine, as well, to increase access. Strategies to increase vaccine access for pregnant people who face barriers to obtaining care – including access to reliable transportation, childcare, or work limitations –are important to consider, as these women, particularly those from underserved communities, may also face challenges that also make them more likely to contract COVID-19 and less likely to present early for care in the course of illness. Identifying an individual’s barriers to obtaining the vaccine and making efforts to remove or circumvent them will remain important. Targeting vaccination efforts for people that are immediately postpartum⁵⁶ or contemplating pregnancy may also be a key part of the strategy to increase vaccine coverage in hesitant patients before and after pregnancy.

Apart from the benefits to the individual, increasing vaccination among pregnant individuals has the potential for significant cost savings for the healthcare system. Preventable COVID-19-related hospitalizations of unvaccinated individuals have already cost our healthcare system over 5 billion dollars between June and August 2021.⁵⁷ A hospital stay for severe COVID-19 in a pregnant individual also has the potential to double (or more) the costs to the healthcare system, due to the potential for both the pregnant women and neonate to be affected: if the average length of stay in the ICU for a pregnant patient with COVID-19 illness is estimated at 5 days,⁵⁸ the cost of an ICU admission with mechanical ventilation is conservatively estimated at $55,000 ($11,000 per day).⁵⁹ A course of remdesivir is estimated to cost $2,500.⁶⁰ A single dose of tocilizumab is $5,000.⁶¹ Although charges vary widely by state, hospital, and insurance status, the average cost of a cesarean delivery – often necessary if delivery is indicated in an unstable pregnant patient – could range from $10,000 to $22,000.⁶² An average NICU admission and cost for care during the first six months of life for a preterm newborn is $76,000.⁶³ In sum, the cost of critical COVID-19 disease in a pregnant patient that includes the items listed above is over $160,000. Allocating resources to improve vaccine convenience for pregnant people may be cost-effective and warrants further investigation.

Compassion

For pregnant people, there are strong data from over 158,000 women that the benefits of vaccination (avoiding severe disease, hospitalization, intubation, preterm delivery, and death) outweigh any theoretical risks of vaccination itself. The onus is on obstetric care providers to continue to be compassionate in our conversations with vaccine-hesitant pregnant people – while simultaneously recognizing and validating our feelings of frustration and “compassion fatigue” that may affect those conversations.⁶⁴ Most pregnant people who refuse vaccination do so because they believe that they are doing the best thing for the health and well-being of their pregnancy. The obstetrician should explicitly acknowledge this protective impulse, while presenting contradictory evidence of the available science. Guidelines for these conversations – including tools to combat misinformation and share empiric data – are readily available from ACOG, SMFM and the CDC (Table 1, adapted from ACOG).^28,65,66 Harnessing motivational interviewing skills used frequently in other conversations, such as smoking cessation or exercise counseling, may increase the effectiveness of those conversations.⁶⁷ Adopting a clinic-wide strategy to address COVID-19 vaccination with every obstetric patient (and to consistently document those conversations in the medical record) should be considered. Engaging with social media platforms may also be impactful in reaching vaccine-hesitant people outside of the healthcare setting.⁶⁸ We must continue to work to identify and overcome barriers pregnant people, particularly pregnant people of color and those in underserved communities, may face to getting vaccinated. While it is demoralizing and fatiguing to find ourselves in the midst of a regrettably preventable fourth surge in the COVID-19 pandemic, and “compassion fatigue” and burnout are real and tangible entities affecting healthcare workers throughout our U.S. system and the world,^69–71 now is a critical time to rise to the challenge of the present moment and address vaccine hesitancy with all available resources.

Table 1.

Talking points for counseling unvaccinated pregnant women

Risk of COVID-19	COVID-19 in pregnancy is associated with higher rates of maternal complications, including hospital admission, ICU admission, intubation, and death This is particularly true in patients with other high-risk conditions (diabetes, obesity, cardiovascular disease) This risk is increased with the emergence of more contagious strains like the Delta variant.
Safety of Vaccination	There are no data showing increased risk of ANY maternal or fetal complication with COVID-19 vaccination in pregnancy. Similarly, none of the vaccines have been shown to effect fertility. While any of the three available vaccines can be given in pregnancy, pregnant and lactating patients should be made aware of the increased risk of thrombosis with thrombocytopenia syndrome (TTS) observed with the Janssen vaccine (although absolute risk remains extremely low).
Effectiveness of Vaccination	All of the vaccines have been shown to effective in pregnant patients and reduce their risk of contracting COVID-19. The vaccines work equally well to produce antibodies in pregnant and non-pregnant patients. In patients who do become infected after receiving the COVID vaccines, they remain at low risk of hospitalization, intubation, and death. Additionally, maternal antibodies have been shown to pass through the placenta and breast milk to help protect the newborn.
Safe Practices	For patients who decline vaccination or who are not fully vaccinated, they should continue practicing safe measures, including hand washing, social distancing, and wearing a mask in crowded settings

Adapted from ACOG: COVID-19 Vaccines and Pregnancy: A Conversation Guide for Clinicians.⁶⁵

Key points:

• Low COVID-19 vaccination coverage in pregnant people is a major public health problem in the US

• COVID-19 vaccine hesitancy in pregnancy is multifactorial

• The 4 “C”s framework may be useful in countering COVID-19 vaccine hesitancy