PREGNANT WOMEN’S COMPLIANCE WITH VACCINATION IN THE CONTEXT OF PANDEMICS: AN INTEGRATIVE REVIEW

ABSTRACT Objective: to analyze national and international publications regarding pregnant women’s compliance with vaccination in the context of pandemics. Method: this is an integrative literature review, carried out in August 2021 in the LILACS, MEDLINE, Web of Science and Scopus databases, without language and publication time restriction. The descriptors indexed in DeCS and MeSH, Immunization, Vaccination, Pregnancy and Pandemics, combined using the Boolean operator, were used. The results obtained were exported to the EndNote reference manager software and, later, to the Rayyan - Intelligent Systematic Review application. The sample consisted of 27 studies. Analysis considered frequency and similarities between the studies. Results: the factors that interfere with compliance with vaccination by pregnant women in pandemic times were highlighted: distrust of vaccines; concerns about vaccination safety in pregnancy or for the fetus’ health; lack of information and lack of knowledge about the benefits of vaccine. Moreover, the reasons for compliance were desire to protect the baby, knowledge about the pandemic, concern about the risk of infection, and recommendation and guidance on vaccination during prenatal care. Conclusion: the factors that may interfere with compliance with vaccination were verified, mainly in relation to new vaccines in the context of pandemics. It is considered that investments in strategies related to immunization during pregnancy can provide health benefits, preventing preventable diseases in pregnant women and their babies.


INTRODUCTION
A disease becomes a pandemic when it affects large proportions, i.e., when a certain agent spreads in several countries and in more than one continent, reaching a large number of people. 1 In recent years, the World Health Organization (WHO) has declared two pandemics: influenza A H1N1 (H1N1), on June 11, 2009 2 ; and Coronavirus Disease 2019 (COVID- 19), declared on March 11, 2020. 3 Influenza pandemic is a cyclical and unpredictable occurrence that is related to the emergence of a new viral subtype, resulting from mutations capable of generating a new virus. 4The COVID-19 pandemic, caused by coronavirus (SARS-CoV-2), is responsible for presenting a broad clinical chart, with complications in the respiratory tract and even death. 5regnant women represent a vulnerable group to outbreaks of infectious diseases due to the physiological changes typical of pregnancy, which make them more susceptible to infection. 6For this reason, they are included in priority groups for vaccination against influenza and COVID-19. 73] Therefore, vaccines are essential for disease prevention in large population groups and their aggravations, including the impacts on health in relation to COVID-19 and Influenza.6][17] Thus, guidance to pregnant women about vaccination is an essential element in immunization programs as it allows them to acquire knowledge about the benefits of immunization. 18n the last decade, there have been great advances in the development of new vaccines with the expansion of immunization programs. 19However, there is a need to know the factors that lead to compliance with vaccination and to consolidate immunization strategies in the population of pregnant and postpartum women, especially in pandemic contexts. 20Based on this assumption, this integrative review aims to analyze national and international publications regarding pregnant women's compliance in the context of pandemics.

METHOD
This is an integrative review (IR), which consists of a method that provides synthesis of knowledge, allowing the inclusion of experimental and non-experimental studies, for a complete understanding of the phenomenon or problem analyzed with discussions of results for application in evidence-based practice. 21he construction of this review covered six steps: 22 research question elaboration; sampling or literature search of primary studies; data extraction from selected studies; assessment of included studies; interpretation of results; and IR presentation.
The guiding question was elaborated based on the PICo strategy: with vaccination; and context, by pandemics.Based on the strategy, the following guiding question was generated: what evidence is available in the literature on pregnant women's compliance with vaccination in the context of pandemics?
For the survey of primary studies, an advanced search was carried out in August 2021, via electronic address, with access through the CAPES portal, in the following databases: Latin American and Caribbean Literature in Health Sciences (LILACS) via Virtual Health Library (VHL); Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed) via the National Library of Medicine); Web of Science via Clarinet Analytics; and Scopus via Elsevier.
To search for articles, the exact descriptors, Immunization, Vaccination, Pregnancy and Pandemics, were used, located in the Health Sciences Descriptors (DeCS)/Medical Subject Headings (MeSH), combined using Boolean operators "OR" and "AND", according to Chart 1.We included primary articles that addressed vaccination in pregnant women in the context of pandemics, published without language restriction and without time frame.We excluded literature review articles, reflections, guides, comments, abstracts of annals, theses, dissertations, course conclusion works, letters to the editor, reports, official documents of national and international programs, book chapters and e-books.
Database search identified 1,007 publications: 608 in Scopus; 329 in the Web of Science; 69 in MEDLINE; and one in LILACS (Table 1).The results obtained were exported to the EndNote reference manager software, in which 282 duplicate studies were excluded and, later, to the Rayyan application -Intelligent Systematic Review -in which 31 more duplicated studies were excluded, leaving 694 articles that were selected for the review reading of titles and abstracts by two independent reviewers.The titles and abstracts of 694 articles were read with the help of Rayyan application to verify their adequacy to the eligibility criteria, and 650 articles were excluded.From pre-selection, there were a total of 44 articles and, after reading the full texts, 27 were selected, which answered the review's 5/19 guiding question.Figure 1 shows the steps for selecting articles that were part of IR, following the Preferred Reporting Items for Systematic reviews and Meta Analyzes (PRISMA) recommendations. 24s for analysis, two independent reviewers blindly assessed the studies.In case of disagreement, a third reviewer's opinion was requested.The meetings for assessing the articles that would compose the IR took place via Google Meet.The inclusion process of articles was in accordance with the inclusion criteria and the research question; thus, an attempt was made to reduce the risk of selection bias, giving it methodological rigor in the inclusion of studies until the final sample.
Data from studies included in the IR were extracted using the instrument validated by URSI 25 , considering the following variables: article identification (journal title, authors, country, year of publication and language); study's host institution; methodological characteristics (study design, sample selection); performed interventions; results and implications; level of evidence; and methodological rigor assessment.The selected articles' methodological rigor was assessed according to the Critical Appraisal Skills Program (CASP) 26 criteria, and, to assess the strength of evidence of the research included, the classification of the seven levels proposed by Fineout-Overholt was used.

6/19
In Figure 1, the screening and the process of selecting studies assessed to the final sample is presented following the PRISMA criteria. 24In Chart 2, there are the results presented descriptively aiming at synthesizing and fostering the discussion.Regarding the interpretation of results, they were analyzed qualitatively based on analysis of frequency and similarities between related studies, having as its central point the analysis of factors regarding pregnant women's compliance with vaccination.

RESULTS
Of the articles selected to compose the IR, 22 addressed vaccination in H1N1 pandemic, and five, the COVID-19 pandemic, and 26 studies were in English and published in 19 different journals.As for study origin, the commonly found countries were the United States, Canada, Turkey, China, South Korea, Australia and Switzerland.They were less often identified studies in Qatar, Iran, Morocco, Ivory Coast, Brazil, the United Kingdom and India.The articles were, in their entirety, classified as level six of evidence.As for methodological rigor, 24 articles were classified as level A, good methodological quality and reduced bias (Chart 2).
With regard to the reasons for vaccination compliance, evidence points to the desire to protect the baby, 31,38,48 knowledge about the pandemic and concern about the risk of infection, 36,43,[52][53] the recommendation and guidance on vaccination during prenatal care 29,47 and reading about vaccine efficacy or positive feedback from family or friends 28

(Chart 2).
Chart 2 -Synthesis of primary studies related to pregnant women's compliance regarding the vaccination offered in pandemic times.Recife, PE, Brazil, 2021.

Author/year/LoE* RM † Objective and sample Result
Mohan S, et al 28  67.6% of FG participants agreed "somewhat" about vaccine safety during pregnancy and, for most of the, the vaccine's unknown risks do not outweigh the benefits and were concerned about adverse effects of vaccination.
In the online survey, 42% of unvaccinated women did not feel informed enough to make the decision to receive the vaccine; 42% were concerned about safety; and 50% did not discuss vaccination with their health professional.
Jung EJ, et al 29  The reasons for seasonal flu vaccination were protection against the disease for themselves and their family (44% preand 45% post-pandemic) and health professionals' recommendation (19% pre and 38% post), reasons for vaccination H1N1 (48% and 20%, respectively).Reasons for not vaccinating against seasonal flu were that they did not need to receive immunization (36% pre and 70% post) and concern about side effects (5% and 26%); reasons also cited by women who did not receive the vaccine against the H1N1 pandemic (26% and 14%, respectively).
Lohiniva AL, et al 34 2014 LoE:6 MR: Level A -Describe pregnant women's perceptions related to H1N1 influenza, to identify the factors that encourage or discourage them to take the A(H1N1) monovalent vaccine pdm09 during the response to the pandemic (2009-2010), and the sources of information that influenced their process of decision-making.
-Sample of 123 pregnant women.
Women feared that the vaccine could negatively affect their health and that of their babies, and speech analysis identified the interference of the social network in the decision-making to receive the vaccine: discussions with health professionals were a positive factor for the decision-making for vaccination, while rumor-based discussions about complications and side effects with neighbors and friends often fuel the decision not to vaccinate.-Sample of 300 postpartum women.
95.7% received the vaccine against influenza during pregnancy and, of these, 73.2% knew that the vaccine would protect their child.Among those who did not receive it, all were unaware of the fact that the vaccine would protect the baby, and 69.2% would have been vaccinated if they had been informed of neonatal protection.
The main reason for refusing to receive the vaccine was concern about safety risks to the fetus (62%) and to herself (59%).
Pregnant women who knew that the H1N1 vaccine provided protection against H1N1 flu for their babies were more likely to receive the vaccine.
64% of participants received vaccination against seasonal flu, and 54%, against H1N1 flu during pregnancy.
Of women who did not receive both vaccines, 25% reported not being well-informed about the importance of the vaccine, 18% reported concern about the vaccine's effects on fetal health, and 9%, about maternal health.
Sakaguchi S, et al 43 2010 LOE:6 MR: Level A -Determine how many pregnant women received the H1N1 vaccine after their call to Motherisk and explore pregnant women's perceptions of the H1N1 vaccine and factors surrounding the decision to receive vaccination.
-Sample of 130 pregnant women.
Among pregnant women who received the vaccine, 73.1% reported concern about the risk of H1N1 infection in the fetus and/or themselves as a reason for their decision; 34.6% cited recommendations to encourage vaccination; and 3.8% mentioned a previous history of complication or illness due to influenza.Of those who did not receive the vaccine, 42.3% reported concerns about safety for themselves and/or their fetus, and 23.1% did not find the vaccine necessary.
Ozer A, et al 46

DISCUSSION
This IR presented articles on compliance with vaccination in pregnant women in two pandemics that occurred in the last ten years: the Influenza A/H1N1 pandemic, which occurred in 2009, and the current COVID-19 pandemic, which started in 2019 (2,3) .
When analyzing the vaccination coverage rate evidence in the H1N1 pandemic, studies showed that 95.7% of pregnant women were vaccinated in 2013 in Brazil, 47 Canada (80%), 43 USA (76.9% to 38.8%), [37][38][39][40][41]52 Australia (6.9%) and 44 Turkey (8.9%) 46 ; however, in Iran, there was 92.06% refusal of influenza vaccination by pregnant women. 32Regarding the COVID-19 pandemic, in studies carried out before the vaccine was available, the proportion of acceptance/willingness to receive the vaccine by pregnant women ranged from 29.7% to 77.4% 30,45,51,53 .However, a study in Qatar showed a 75% rate of vaccine hesitancy, in which 25% of women reported that they would probably or definitely not accept vaccination; 25.9% remained insecure; and 28.3% would not have their children vaccinated. 28Vaccine hesitancy is defined as delay in accepting or refusing vaccines despite the availability of vaccination services.It is a behavioral phenomenon that varies across time, place and types of vaccines and includes factors such as complacency, convenience and trust. Coplacency results from low perceived risk of contracting vaccine-preventable disease.Convenience considers physical and financial availability, geographic accessibility, ability to understand and access health information. Ulmately, trust is about vaccine efficacy and safety, health services' and professionals' competence and managers' motivations to recommend them.55 Concerns about vaccine safety and efficacy, distrust of vaccines, lack of knowledge about vaccines during pregnancy as well as the lack of recommendations by health professionals were some of the factors that influenced vaccine acceptance and/or hesitation.30,36,42,45,48,51 Although vaccines are safe, effective and recommended by health policies 7 , vaccine hesitancy is often cited as a particularly present problem during pregnancy, as pregnant women are encouraged to avoid medications with known or uncertain risks to the fetus.56 In this IR, studies showed that women choose not to vaccinate during pregnancy because they are not usually vaccinated during pregnancy 37,49 and that unvaccinated pregnant women were more likely to agree that vaccines should not be taken during pregnancy because they believe that the risk would be greater in receiving vaccination during pregnancy than in developing the disease.41 Authors stated that most pregnant women indicate their intention to receive COVID-19 vaccines, but they prefer to wait until the end of pregnancy so as not to expose their baby or after weaning their children because the COVID-19 vaccine safety is relatively new and, probably, not yet widespread.57,58 Distrust of vaccination ranks second in predicted reasons for not wanting to be Chart 2 -Cont.
12/19 vaccinated during pregnancy. 59Strengths cited in the study with regard to vaccine acceptance and confidence were perception of virus and disease risk, public trust, belief in the importance of having a COVID-19 vaccine, and vaccine efficacy during pregnancy. 58verall, pregnant and breastfeeding women reported vaccine safety for the child and the mother as top priorities in relation to the COVID-19 vaccine and had a higher level of acceptance in the third trimester of pregnancy, as a series of vaccines, including influenza (H1N1) and Tdap vaccines, is particularly recommended during the third trimester. 57rom the studies that were part of the IR sample, it was observed that the lack of recommendation by health professionals about vaccination and/or insufficient information were reasons for not vaccinating pregnant women. 29,33,37,40,44,48,52On the other hand, there was compliance with vaccination by pregnant women who received recommendations or face-to-face discussions with health professionals during the gestational period. 31,34,36,38herefore, it is important that health professionals take advantage of vaccination experiences on previous occasions and the perception that women have about vaccines, to provide effective advice to increase vaccination coverage during pregnancy. 59Health professionals have a relevant role in prenatal care as providers of information and encouragers for vaccination, with an impact on women's compliance with vaccines in the pregnancy-postpartum period. 7nformation support and provision about vaccination by health professionals is a great opportunity to achieve a complete vaccination history of women.Thus, vaccination during pregnancy should be analyzed as an opportunity to improve vaccination coverage of all vaccines, which are low in the general population. 60he studies included in the IR stated that pregnant women who had knowledge about the pandemic and the perception that they were susceptible to infection were more likely to accept vaccination. 35,52,53Women who believed they were at high risk of serious illness or complications, if infected with H1N1, had a higher prevalence of vaccination. 36,49However, the level of perceived knowledge regarding the COVID-19 vaccine alone cannot predict vaccine acceptance. 5743]52 However, a study carried out in the USA showed that women with complete higher education and aged over 35 years were more likely to have been vaccinated against the H1N1 flu. 35ith regard to the COVID-19 pandemic, it was found that greater COVID-19 vaccine acceptance was associated with young age, low level of education and high score of knowledge about COVID-19. 53owever, another study pointed out that age over 40 years and educational level higher than high school are associated with a higher rate of COVID-19 vaccine acceptance. 30However, women who claimed to have a low economic situation and concern about the risks of vaccination had a high vaccine hesitancy rate. 45vidence indicates that women had opinions and attitudes favorable to the vaccine when a health professional was the main source of information 38,39,45,49 , positive experience of personal vaccination or those close to them 34,50 , previously vaccinated family members 41 or when agreed with the benefits of vaccination in the gestational period 34 and for advice and incentives for vaccination by others. 32,43n addition to this, women with a previous vaccination history are more likely to be vaccinated in pandemic situations.Thus, having received influenza vaccination in the previous year was a positive predictor for accepting H1N1 ,54 and SARS-CoV-2 vaccines 49 . 30However, rumor-based discussions about complications and side effects with neighbors and friends discouraged the decision to be vaccinated. 34

13/19
The information found in the media for compliance with vaccination was rarely cited by studies 43,45,49,50 as well as the recommendations from the official government campaign. 31,47However, hearing or reading negative news in the media can be a factor in vaccine hesitancy. 45he internet is an increasingly used tool for obtaining information.Social media platforms such as Facebook, Twitter and Instagram are complex and fluid ecosystems in which vaccine-related misinformation can spread widely. 61Additionally, mobile applications, considering the epidemiological scenario of COVID-19 in the world, are an innovative digital technology that offers convenience and benefit to the population and managers in accessing knowledge and an attractive alternative for health professionals' continuing education. 62egarding the vaccine against COVID-19, the dissemination of correct information in a transparent manner must be reinforced, in order to avoid giving wrong or worrying information as a resource to increase vaccine acceptance, especially for vulnerable populations 53 , since fake news circulate more easily and because politicians with national visibility issue personal opinions against vaccines. 63he main limitation of this IR is the possibility of losing relevant studies indexed in other databases.Furthermore, the analysis performed on the publications is related to the search selection criteria proposed in this study.However, it was possible to infer the factors related to pregnant women's compliance with vaccination in the context of pandemics.It should be noted that publication biases may be related to the particularities of each host institution where the studies included in the review were carried out.

CONCLUSION
The main factors in the vaccine decision of pregnant women in pandemic situations are related to concerns about vaccine safety, fear of complications and its side effects, lack of information about the vaccine and lack of recommendation by health professionals.Moreover, the desire to protect the baby, knowledge about the pandemic and the recommendation and guidance on vaccination are factors for compliance with vaccination during the gestational period.
In view of this, it can be considered that investments in strategies related to immunization during pregnancy provide health benefits, preventing preventable diseases in pregnant women and their babies.Strengthening immunization programs as an advanced practice and having prenatal care as a window of opportunity for compliance with vaccines is considered relevant in vaccination acceptance among pregnant and postpartum women, especially in the context of pandemics.

Table 1 -
Publications found from the combination of descriptors according to database.Recife, PE, Brazil, 2021.