The health risks for pregnant women who contract COVID-19 disease are concerning.  Unvaccinated pregnant women are more likely to require hospitalisation and treatment for COVID-19 compared to those vaccinated. 

Rania Mansour, Graduate Medical Student, Population Health Research Institute, St George’s, University of London, UK
Mohammad S. Razai, In-Practice Fellow, Population Health Research Institute, St George’s, University of London, UK
Fatima Husain, Consultant in Obstetrics & Gynaecology, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Berkshire, UK
Azeem Majeed, Professor of Primary Care & Public Health, Department of Primary Care and Public Health, Imperial College London, UK
Pippa Oakeshott, Professor of General Practice, Population Health Research Institute, St George’s, University of London, UK

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Moreover, multiple studies report higher rates of intensive care admissions, greater requirement for invasive ventilation, and higher risk of death compared to non-pregnant women who have COVID-19. Approved COVID-19 vaccines are safe, effective, necessary, and important in pregnancy. Despite the protective effects of COVID-19 vaccination, uptake is very low among pregnant women compared to non-pregnant women in the UK and globally. Causes for vaccine hesitancy include lack of long-term safety data for COVID-19 vaccines, mixed messaging from healthcare providers, and mistrust of healthcare providers and the pharmaceutical industry. Strategies to improve vaccine roll-out include transparent, empathetic dialogue with pregnant women, recommendation by trusted sources of information such as a GP or midwife, offering vaccination during routine antenatal clinics, and generally making vaccination more convenient.

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In April 2021, the UK’s Joint Committee on Vaccination and Immunisation (JCVI) recommended COVID-19 vaccination in pregnant women. Vaccination during pregnancy is safe and to date, the side effects of COVID-19 vaccines have been similar in pregnant and non-pregnant women (Shimabukuro et al., 2021). Furthermore, published studies have not identified safety concerns about COVID-19 vaccination in pregnancy (Shimabukuro et al., 2021; Kharbanda et al., 2021; Vousden et al., 2021). Rates of stillbirth, preterm birth and low birthweight following vaccination have been found to be similar among pregnant vaccinated and unvaccinated women (UK Health Security Agency, 2022; Blakeway et al., 2021). Previous studies have affirmed the safety and effectiveness of COVID-19 vaccines in preventing severe disease and death in pregnant women. 

In contrast, the health risks for pregnant women who contract COVID-19 are very concerning. The US Centers for Disease Control and Prevention (CDC) reports that the rates of intensive care unit admission and invasive ventilation are three times greater among pregnant women with COVID-19, with a 25% greater likelihood of dying, compared to non-pregnant women (Kadiwar et al., 2021). However, many pregnant women remain unvaccinated for COVID-19 and show high levels of vaccine hesitancy, defined as refusing or delaying a vaccination by the World Health Organization (MacDonald and the Sage Working Group on Vaccine Hesitancy, 2015). In this review, we explore the causes and consequences of vaccine hesitancy in pregnancy and make practical recommendations for increasing vaccine confidence and uptake in this group.

The efficacy of COVID-19 vaccination in pregnancy

Recent systematic reviews exploring the efficacy of COVID-19 vaccines in pregnancy have affirmed that robust humoral responses were mounted in maternal sera and transferred to cord blood and breast milk following vaccination (Fu et al., 2021; Falsaperia et al., 2021). COVID-19 vaccination confers high levels of protection against the serious outcomes of SARS-CoV-2 infection in pregnant women (Dagan et al., 2021; Goldshtein et al., 2021; Gray et al., 2021), and one study found evidence that higher antibody levels were induced following vaccination than when following disease (Gray et al., 2021). As such, it is crucial to delineate and tackle the reasons for vaccine hesitancy among pregnant women as there is growing evidence that pregnant women are at higher risk of developing severe COVID-19 disease and that vaccination against COVID-19 is protective (Abbas-Hanif e al., 2021).

Epidemiology of vaccine hesitancy in pregnancy

With all women in the UK now eligible for vaccination, more women will be receiving their COVID-19 vaccine before giving birth. The UK Health Security Agency (UKHSA) (2022) outlines this increase in vaccination:

• Approximately 3% of women who gave birth in May 2021 had received at least 1 dose of vaccine

• Increasing to 10% of women who gave birth in June 2021

• Increasing to 16% in July 2021

• And to 22% in August 2021. (see Figure 1)

A cohort study conducted at St George’s University Hospital in London between March and July 2021 found that less than one third of pregnant women (29%, n=140/491) who were eligible for COVID-19 vaccination had accepted the vaccination during pregnancy (Blakeway et al., 2021). Similarly, researchers in Scotland identified that of all 4,064 pregnant women who gave birth in October 2021, only 43% had received any COVID-19 vaccination, and only 32% were fully vaccinated (Stock et al., 2022). These rates are significantly lower than that in the general population, where 85% of women between the ages of 18 and 44 years had received any vaccination and 77% were vaccinated with two doses by October 2021 (Stock et al., 2022).

Vaccine hesitancy and low COVID-19 vaccine coverage among pregnant women is a global phenomenon. Cross sectional studies on pregnant women’s opinions of vaccination against COVID-19 support this notion. A systematic review exploring  nine studies with cumulative data from more than 15 countries indicated that the percentage of pregnant women who accept the vaccine vary, and ranged between 30% and 77% among studies (Januszek et al., 2021). In a German study, 57% of 1,053 pregnant women were not in favour of receiving the vaccine; however, 47% would be in favour of receiving the vaccine if more scientific evidence on its impact, side effects, risks and benefits during pregnancy were available (Schaal et al., 2021). In a study exploring the intention of receiving the COVID-19 vaccine among pregnant and lactating women in the Czech Republic, only 3.6% of 362 participants indicated that they would immediately accept the COVID-19 vaccine and 30% would refuse it (Riad et al., 2021). Interestingly, approximately two-thirds of participants (67%) indicated they would have the COVID-19 vaccine but only after giving birth (Riad et al., 2021). Researchers in Turkey found that most pregnant women (63%, n=189/300) rejected a healthcare professional’s recommendation of vaccination (Goncu Ayhan et al., 2021).

Findings from studies in the USA also indicate that pregnant women are less likely to accept vaccination compared to non-pregnant women (Turocy et al., 2022; Siegel et al., 2021; Sutton et al., 2021). One study based in Massachusetts revealed that only half of 477 pregnant women surveyed reported receiving at least one dose of the vaccine; this was lower than the local adult vaccination rate of 64% at the time of the study and lower than the participants’ self-reported acceptance of influenza vaccination (75%) (Siegel et al., 2021). Similarly, in a study of more than 17,000 women from 16 countries, only 52% of pregnant women (n=2747/5282) reported that they would take the vaccine compared to 73% of non-pregnant women (n=9214/12562) (Skjefte et al., 2021) Additionally, low vaccine uptake in pregnancy is associated with younger age (Stock et al., 2022; UKHSA, 2022; Blakeway et al., 2021; Januszek et al., 2021; Skirrow et al., 2021; Woolf et al., 2021), higher levels of deprivation, lower socioeconomic status (Stock et al., 2022; UKHSA, 2022; Blakeway et al., 2021; Januszek et al., 2021; Skirrow et al., 2021) and minority ethnicities particularly Black and Latin (UKHSA, 2022; Blakeway et al., 2021; Crawshaw et al., 2021; Siegel et al., 2021; Skjefte et al., 2021; Woolf et al., 2021).

Consequences of vaccine hesitancy during pregnancy

Compared to non-pregnant women of reproductive age with COVID-19, pregnant women with COVID-19 are twice as likely to be admitted to critical care and receive invasive ventilation and extra-corporeal membrane oxygenation (Kadiwar et al., 2021; Allotey et al., 2020). In particular, contracting COVID-19 during pregnancy is associated with increased risk of pre-eclampsia, preterm birth, stillbirth, and early neonatal death (Mahase, 2022; Stock et al., 2022; Iacobucci, 2021). Additionally, unvaccinated pregnant women who have COVID-19 disease are at higher risk of needing hospitalisation for treatment compared to vaccinated women (UKHSA, 2022; Iacobucci, 2021; Vousden et al., 2021). The UK Obstetric Surveillance Study has reported that between February and September 2021, more than 98% of 742 pregnant women hospitalised with symptomatic COVID-19 were unvaccinated (Iacobucci, 2021; Vousden et al., 2021). Similarly, in a population-based study in Scotland, 77% of COVID-19 infections in pregnancy occurred in unvaccinated women (n=3833/4950); of pregnant women requiring hospitalisation, 91% (n=748/823) were unvaccinated as were 98% (n=102/104) of those needing critical care admission (Stock et al., 2022). These data highlight the increased risk from COVID-19 in unvaccinated pregnant women. It is therefore essential to identify reasons behind vaccine hesitancy and improve vaccine coverage in this population.

Causes of vaccine hesitancy in pregnant women

Reasons for low COVID-19 vaccine uptake in the general population include:

• concerns about side- effects and long-term effects on health

• lack of confidence in vaccines and their importance, lack of trust owing to speed of development of COVID-19 vaccines

• lack of trust in the pharmaceutical industry (Razai et al., 2021).

Other factors include:

• concerns about vaccine congruence with religious beliefs

• previous side-effects from routine vaccines

• lack of communication from trusted providers

• negative experiences with the healthcare system such as racial discrimination

• inconvenient timing and location of vaccine delivery (Razai et al., 2021).

A systematic review exploring factors that influence vaccination acceptance during pregnancy revealed a range of barriers, including concerns about vaccine safety, lack of recommendations and conflicting advice from healthcare professionals (HCPs), lack of trust in HCPs and the pharmaceutical industry, lack of knowledge about vaccines, and practical issues such as accessibility and cost (Wilson et al., 2015). Recent cross-sectional and cohort studies have explored causes for COVID-19 vaccine hesitancy among pregnant women, and are summarised below.

Mixed messaging from government and healthcare bodies

Initially in February 2021, the UK JCVI cited a lack of evidence for the safety of COVID-19 vaccinations for pregnant women. Two months later, their advice changed with recommendation for pregnant women to be vaccinated alongside their age cohorts. Later still, all pregnant women were moved into clinical priority group 6 (People aged 16 to 64 considered to be at risk and adults who live with adults who are immune-suppressed). Without clear communication of the reasons behind the changes in messaging by a national institution, some women questioned and question the risks and benefits of vaccines. This seems also to be a concern among the general population and HCPs (Woolf et al., 2021)

Concerns about lack of long-term safety data in pregnancy

Pregnant women were excluded from COVID-19 vaccine trials and thus the lack of long-term safety data is one reason for vaccine hesitancy (Blakeway et al., 2021; Goncu Ayhan et al., 2021; Schaal et al., 2021; Siegel et al., 2021; Skjefte et al., 2021; Sutton et al., 2021). Indeed, one study in the USA found that unvaccinated pregnant women were more likely to agree that the vaccine was rushed, more likely to be worried about side-effects of the vaccine for themselves and their baby, and less likely to trust vaccine developers (Siegel et al., 2021). These concerns were also echoed by pregnant women in the UK (Skirrow et al., 2021). This was reiterated in another study looking at predictors of vaccine hesitancy, where a major reason for hesitancy among pregnant women included trust issues with pharmaceutical companies regarding safety data for pregnant women (Riad et al., 2021). This same study indicated that pregnant women’s primary concern regarding the COVID-19 vaccine was safety for their unborn baby (62%) followed by safety for the mother (47%). Another study focused on non-clinical healthcare workers in the UK has also indicated that safety concerns due to speed of vaccine development is a primary reason for vaccine hesitancy (Woolf et al., 2021).

Mistrust in government or healthcare professionals

A UK-based study found that mistrust in the wider healthcare system was another reason for declining COVID-19 vaccines among pregnant women (Skirrow et al., 2021). A global study found that lack of trust in government advice and guidelines was a significant indicator of rejecting vaccine uptake, specifically because vaccine approval would be rushed for political reasons (Skjefte et al., 2021). Other studies have highlighted that vaccine hesitancy may be because some HCPs are uncomfortable discussing benefits and risks of COVID-19 vaccination in pregnancy, leaving pregnant women uninformed and mistrusting of the vaccine (Blakeway et al., 2021; Wang et al., 2021).

Other reasons cited for vaccine hesitancy among pregnant women include the lack of explicit communication about the safety of COVID-19 vaccines for pregnant women and negative news in the media stating that the vaccinations are not safe (Januszek et al., 2021). Concerns of being exposed to COVID-19 if accessing hospital or clinical settings for vaccination have also been mentioned (Anderson et al., 2021; Blakeway et al., 2021). Additional barriers to vaccination include accessibility concerns, such as reduced public transport and difficulty finding child care to allow travel to a vaccination centre (Blakeway et al., 2021; Chmielewska et al., 2021), with one study indicating that unvaccinated pregnant women found it difficult to schedule COVID-19 vaccinations owing to missing work or time with family (Siegel et al., 2021).

Addressing vaccine hesitancy

Much of the evidence on facilitators of vaccination in pregnancy predates the COVID-19 pandemic (Castillo et al., 2021; Lilich et al., 2020; Bisset & Paterson, 2018), and most studies to date have focused on improving uptake of influenza and pertussis vaccination in pregnancy in high-income countries, with a dearth of evidence in low- and middle-income countries (Ransing et al., 2022). However, successful strategies to increase COVID-19 vaccination in the general population include:

• offering tailored communication from trusted sources, especially HCPs including GPs and midwives (Bisset & Paterson, 2018)

• improving access to vaccines

• increasing community engagement

• training and educating those involved with engagement activities (Razai et al., 2021).

Similarly, it is important to understand the contextual barriers and facilitators of vaccination in pregnant women and tailor interventions accordingly (Castillo et al., 2021).

Improving the practicalities of vaccine roll-out

In Manchester, UK, antenatal clinics offering COVID-19 vaccinations have shown an uptake rate of greater than 60% among pregnant women (Iacobucci, 2021). Expanding vaccine delivery to include hospital-based antenatal clinics as well as community clinics not only makes it accessible for women with regards to location and timing, but also ensures that pregnant women can be provided with information by their obstetrician, midwife, or general practitioner with adequate follow-up (Crawshaw et al., 2021; Siegel et al., 2021). This would also allow for targeted repeat messaging and reminders which also improves vaccine uptake. Offering booster doses for pregnant women specifically may also encourage vaccine uptake (Iacobucci, 2021). Additionally, vaccination should be targeted to geographic areas with low vaccine uptake (i.e., areas with higher rates of ethnic minority patients and/or deprived areas) in collaboration with leaders in the local community. This enhances familiarity and builds trust (Razai et al., 2021a).

Transparent dialogue

A key component of reducing vaccine hesitancy is through non-judgemental, open and transparent dialogue with pregnant women. It is also necessary to address misinformation on side-effects of vaccines, particularly in relation to fertility, menstruation, pregnancy and the impact of the vaccine on the health of the foetus and the mother. Pregnant women could be offered vaccination as they receive routine antenatal care when a dialogue needs to take place on risks of COVID-19 infection and benefits of vaccination (Razai et al., 2021; Razai et al., 2021a). Such a dialogue can occur at different levels such as through women’s HCPs (individual level), through community initiatives (community level), and by promoting evidence-based science for the public such as via regional/national vaccination campaigns and through social media (systems level) (Salmon et al., 2015). In addition, HCPs must be aware of the evidence behind vaccinating pregnant women. This would ensure that they can provide either direct information or refer women to the right resources to make an informed decision regarding vaccination (Razai et al., 2021).

Inclusivity and understanding

Approaches to addressing vaccine hesitancy are multifaceted and complex. As such, it is important to recognise that inclusivity and understanding should be at the core of all strategies. This means respectful and open communication, co-creating strategies with community members to ensure they are locally tailored, and joint decision-making based on individual circumstances (Schaal et al., 2021). A systematic review exploring vaccine uptake among migrants highlights the importance of culturally tailored and community-based interventions, appropriate messaging, and provision of recommendation for vaccination through a trusted HCP (Crawshaw et al., 2021). Such inclusive measures could also be applied to improve vaccine uptake among pregnant women, particularly among those more likely to be vaccine hesitant such as younger pregnant women, those from ethnic minorities, and pregnant women living with higher levels of deprivation.

Because one of the main reasons for vaccine hesitancy among pregnant women is the lack of safety data, it is crucial to share the evidence of the safety of COVID-19 vaccination in pregnancy through motivational and participatory interviewing, where these concerns can be addressed (Castillo et al., 2021). There is also a call for the inclusion of low-risk pregnant women in vaccine trials (Stock et al., 2022; Blakeway et al., 2021; Iacobucci, 2021). Such studies would allow governments and physicians to make recommendations to pregnant women regarding the safety and efficacy of vaccines for them and their babies.

Conclusion

COVID-19 vaccine hesitancy in pregnancy is a serious threat to the health of pregnant women and their babies. Approaches for improving vaccine uptake include optimising the vaccination roll-out process to increase accessibility for pregnant women, facilitating a dialogue between the healthcare professional and the pregnant woman, transparent and open communication about risk, and tackling contextual barriers to improve vaccine confidence in pregnancy. Offering access to vaccination in antenatal clinics is an intervention that should be considered for wider implementation by health systems such as the UK’s NHS.

Acknowledgements

MSR is funded by the National Institute for Health Research (NIHR) as an In-Practice Fellow. AM is supported by the NIHR Applied Research Collaboration NW London. The views and opinions expressed are those of the authors and do not necessarily reflect those of the NHS, the NIHR or the Department of Health and Social Care.

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