COVID-19 Vaccine Knowledge, Attitude, Acceptance and Hesitancy among Pregnancy and Breastfeeding: Systematic Review of Hospital-Based Studies

The risk of unfavourable outcomes for SARS-CoV-2 infection is significant during pregnancy and breastfeeding. Vaccination is a safe and effective measure to lower this risk. This study aims at reviewing the literature concerning the anti-SARS-CoV-2 vaccine’s acceptance/hesitancy among pregnant and breastfeeding women attending hospital facilities. A systematic review of literature was carried out. Hospital-based observational studies related to vaccination acceptance, hesitancy, knowledge and attitude among pregnant and breastfeeding women were included. Determinants of acceptance and hesitancy were investigated in detail. Quality assessment was done via the Johann Briggs Institute quality assessment tools. After literature search, 43 studies were included, 30 of which only focused on pregnant women (total sample 25,862 subjects). Sample size ranged from 109 to 7017 people. Acceptance of the SARS-CoV-2 vaccine ranged from 16% to 78.52%; vaccine hesitancy ranged between 91.4% and 24.5%. Fear of adverse events for either the woman, the child, or both, was the main driver for hesitancy. Other determinants of hesitancy included religious concerns, socioeconomic factors, inadequate information regarding the vaccine and lack of trust towards institutions. SARS-CoV-2 vaccine hesitancy in hospitalized pregnant women appears to be significant, and efforts for a more effective communication to these subjects are required.


Introduction
Pregnant and breastfeeding women encounter distinct challenges concerning vaccine acceptance [1].Throughout this crucial period, women proactively seek information concerning their health and their child's well-being, with significantly impacts their medical decisions [2].Vaccination holds particular importance for this population group, as certain vaccine-preventable diseases can lead to severe outcomes during pregnancy or pose risks to the child both before and after birth [3].Various interconnected factors influence vaccine acceptance encompassing individual's knowledge and attitudes towards vaccination, societal norms, and perceptions of benefits and risks related to vaccination [4].Vaccine hesitancy, characterized by delays in completing vaccination schedules or in refusing vaccines, can emerge when individuals lack sufficient motivation to get vaccinated [5].Numerous factors contribute to this reluctance, including concerns about safety and effectiveness, as along with mistrust in vaccine development and regulatory processes [6,7].The emergence of the COVID-19 pandemic brought about additional uncertainties surrounding health choices and vaccination [8].During the initial months of the pandemic, there was a lack of both effective therapy and a safe and effective vaccine.This created substantial expectations within the general population for a vaccine capable to "restore normalcy" [9].Concurrently, as anti-SARS-CoV-2 vaccines became available, the distinctive characteristics of these vaccines, coupled with the limited initial data regarding their long-term safety and efficacy, along with the remarkably rapid pace of their development, engendered feelings of uncertainty and ambivalence toward vaccination.Pregnant and breastfeeding women, in particular, expressed concerned about possible side effects of the vaccine affecting either them or their child [10].Despite these concerns, subsequent data from the Centers for Disease Control and Prevention reassured the safety of COVID-19 vaccines for pregnant women, promoting public health programs to prioritize their vaccination [3,11].It is essential to recognize that vaccine hesitancy often varies depending on the specific vaccine and the socio-cultural background of the hesitant individual.Additionally, COVID-19 vaccines are relatively new, making it challenging to predict the evolution of hesitancy towards them.To gain a deeper understanding of the factors contributing to COVID-19 vaccine hesitancy among pregnant and breastfeeding women, we planned a systematic review.
The primary aim of this review is to synthesize existing literature on knowledge, beliefs, attitudes, barriers, and facilitators related to COVID-19 vaccine acceptance among pregnant and breastfeeding women.The review specifically seeks to address two key research questions: (1) What is the level of knowledge regarding COVID-19 vaccination among pregnant/breastfeeding women?(2) What are the facilitators and barriers to COVID-19 vaccine acceptance associated with pregnancy and/or breastfeeding?The findings from this review will provide valuable insights into the current landscape and help identify research gaps, informing public health strategies to promote vaccination in this population.For consistency, this review focuses on hospital-based studies, while population-based studies have been addressed separately, considering potential differences in health literacy, attitudes towards healthcare, and trust in medical professionals among women seeking medical support.

Materials and Methods
The systematic review adhered to the guidelines established by the Cochrane Collaboration [12] and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines [13] for transparent reporting.

Search Strategy and Data Collection
To construct a comprehensive search strategy, we logically linked a combination of free text words and Medical Subject Headings (MeSH) terms using Boolean operators.This approach was implemented for each database, with simultaneous searches by two independent authors.In brief, keywords referred to breastfeeding/pregnant women (and synonyms) were combined with keywords related to knowledge, attitude, acceptance and hesitancy (and synonyms).A detailed search strategy has been previously published [14].Additionally, we screened the reference lists of included articles to identify potentially relevant studies that may have been missed.

Inclusion and Exclusion Criteria
Eligible studies met the following criteria: (i) original observational hospital-based studies (cross-sectional, case-control, or cohort studies), (ii) conducted after 2019, (iii) focusing on knowledge, attitudes, acceptance and hesitancy related to COVID-19 vaccination, (iv) involving pregnant or breastfeeding women, (v) published in English peer-reviewed international journals.The exclusion criteria encompassed: studies not conducted on humans or those involving a different population, studies combining data with different and multiple outcomes or assessing outcomes not listed in our inclusion criteria (e.g., vaccine efficacy/safety/development or collecting serological/immunological data); articles assessing acceptance/hesitancy/refusal against vaccines other than COVID-19; articles not written in English or not published in peer-reviewed international journals; non-observational studies, e.g., trials (randomized or non-randomized controlled trials); and, lastly, nonoriginal research papers, including reviews or meta-analyses, articles lacking quantitative information or details, and non-full-text papers (e.g., letters to the editor, conference papers, commentary notes, expert opinions, abstracts).The selected inclusion/exclusion criteria were established based on our research question.Specifically, original observational hospital-based studies were included because they provide valuable data on the knowledge, attitudes, acceptance, and hesitancy related to COVID-19 vaccination in pregnant or breastfeeding women focusing on the hospital setting.Secondly, we applied a time lag, selecting article published after 2019, given that the COVID-19 pandemic began at the end of 2019.This ensures that the data is current and relevant to the ongoing situation.Thirdly, we focused on knowledge, attitudes, acceptance and hesitancy to specify the topic of interest.Fourthly, we defined our population of interest as pregnant or breastfeeding women, ensuring that the selected studies include this specific population Additionally, we limited our selection to articles published in English and in peer-reviewed international journals because English is the internationally recognized language for scientific publication, and we have confidence that high-quality articles are typically published in peer-reviewed international journals.Peer-reviewed international journals that, in turn, usually offer a quality assurance measure.

Selection Process
The complete set of retrieved studies was imported into EndNote software (EndNote ® for Microsoft, X9 version, Redmond, WA, USA, 2020), and duplicates were initially removed using automated tools, followed by manual cross-checking.The remaining articles underwent a two-step evaluation: first based on title and abstract, followed by full-text assessment.

Data Extraction
Data extraction was carried out by two reviewers using a predefined Excel spreadsheet (Microsoft Excel ® for Microsoft 365 MSO, 17 version, Redmond, WA, USA, 2019).The extracted information included author details, study characteristics, study population, assessment tools, recruitment methods, outcomes, methodological details, and statistical analyses.Additional details about data extraction are reported into the protocol [14].If studies report data using risk estimates, for instance, odds ratio (OR), risk ratio (RR) or hazard ratio (HR), the maximally adjusted data, along with the list of variables used for the adjustment were recorded.Lastly, information on received research funding and conflict of interests was also extracted.

Quality Assessment
Two independent reviewers assessed the risk of bias using the Joanna Briggs Institute (JBI) quality assessment tools [15] which consists of eight items scored on a scale from −2 to 2. Based on the cumulative scores, studies were categorized as low (score from −16 to 4), moderate (score from 5 to 9), or high quality (score more than 10 and up to 16), based on the JBI instruction [15].

Literature Search
Initially, a total of 496 records were retrieved searching on PubMed/Medline, Scopus and EMBASE.Consultation with experts did not add any further eligible studies.After performing duplicate screening using Endnotes, 94 records were removed.Subsequently, based on language and on title/abstract screening, a total of 67 articles were considered eligible.However, after full-text assessment, three articles were removed due to aggre-gated data [16] and different comparison [17,18].Because of the high heterogeneity of the remaining 64 records, we chose to present results separately for population-based studies (21 records included; previously published [19]) and results of hospital-based studies (43 records included [2,; reported in the current manuscript).The disagreement about reviewers during the selection process was around 10%.All the disagreements were solved through discussion among the two.The final full screening process is detailed in Figure 1.
Regarding tools used to assess the outcome of interest, in the vast majority of the included studies, authors developed ad hoc questionnaire (n = 37/43).Eectronic medical records were used in two studies [23,59], while two studies used a pre-developed questionnaire (respectively the Vaccination Attitude Examination scale [28] and the Attitude toward COVID-19 vaccine scale [39]).Lastly, the remaining two studies did not provide the information [35,42].Regarding validation of the tools adopted, approximately half of the sample (n = 21/43) used validated tools, while five studies did not report the information [2,23,36,46,54].

Main Characteristics of Studied Population
The vast majority of included studies (n = 30/43) exclusively recruited pregnant women, while four studies focused solely on postpartum/breastfeeding women [25,41,48,50].The remaining studies included both pregnant and postpartum/breastfeeding women [20,22,24,39,40,51,52,57,61].Women's ages were reported as mean and standard deviation, or mean and interquartile range, or range, or percentage; however, the youngest women were 18 years old, while the oldest were 49 years old.The smallest sample size was 109 [53], whereas the largest was 7017 [59], and attrition rate ranged between 0% and 43%.Details can be found in Table 2.  remaining 64 records, we chose to present results separately for population-based studies (21 records included; previously published [19]) and results of hospital-based studies (43 records included [2,; reported in the current manuscript).The disagreement about reviewers during the selection process was around 10%.All the disagreements were solved through discussion among the two.The final full screening process is detailed in Figure 1.

Knowledge and Attitude toward COVID-19 Vaccine
Knowledge was assessed in 6 studies [21,26,36,42,43,57], and good level of knowledge ranged between 18.88% [57] to 88.2% of the populations under examination [21].However, it is important to note that none of the retrieved studies specifically focused solely on knowledge.Instead, knowledge assessment was part of a broader assessment, often combined with reasons for accepting or refusing the COVID-19 vaccine.Therefore, no information regarding potential predictor of level of knowledge has been retrieved.
Attitude toward COVID-19 vaccine was explored in 8 studies [21,25,26,39,[41][42][43]57].Among these, 5 studies reported positive attitude expressed as overall percentage of the populations being studied (ranging from 38.54% to 68.2%) [21,26,42,43,57].One study, reported percentage of attitude separated for each assessed aspect (level of immunity 60.8%, number of vaccination 60.3% and type of vaccine 53.3%) [25].One study expressed attitude as a mean score [41], and lastly one did not report the value [39].Out of 8 studies, only two of them explored potential predictors of attitude [39,41].Specifically, fear of getting the infection [41], pregnancy at risk [41], and consulting not official sources of data (sources of data different from, as for instance, Governmental or Health Agency/Authority) [41] were all associated with higher positive attitude.Not knowing the recommendation [41], lower level of education, and no history of COVID-19 infection were associated with a lower positive attitude [41], while living in urban area was associated with lower positive attitude in another study [39].Belief that COVID-19 vaccine is safe and postponing vaccination after delivery were all associated with lower rates of people reporting negative attitude [39].The need to receive information on COVID-19 vaccine [41], marital status [41], health status [41], and planned pregnancy [39] were not found to be associated with attitude.

COVID-19 Vaccine Acceptance
A total of 33 articles estimated the COVID-19 vaccination acceptance among pregnant/ breast-feeding women, with rates ranging from 16% [56] to 78.52% [40].Out of these 33 articles, 27 studies further explored the association/correlation/differences between vaccine acceptance and several predictors, as detailed in Table 3. Specifically, we identified socio-demographic data, lifestyle factors, health-related aspects, pregnancy characteristics and COVID-19 related aspects as topics studied in association with COVID-19 vaccine hesitancy among pregnant/breastfeeding women.
Regarding maternal age, half of the retrieved studies did not find any significant association, whereas the remaining 5 studies found that age ≥ 35 years was significantly associated with higher COVID-19 vaccine acceptance.Out of a total of 13 studies, 8 reported a statistically significant association: higher education was linked to higher acceptance, while lower education was linked to lower acceptance (the association was not significant in the remaining 5 studies).Considering ethnicity, all three studies identified a significant association between being a member of a minority group and higher COVID-19 vaccine acceptance.Most included studies (6 out of 8) did not detect an association between acceptance and employment, while the remaining two found a positive association between being employed and COVID-19 vaccine acceptance.Moreover, feeling overloaded [54] but not work-related stress [54] was associated with higher acceptance rate.Living in urban area was associated with higher acceptance, except in one study that did not find a significant association between living in rural area and vaccine acceptance [34].Income was not associated with acceptance, except in one study that found a significant association between lower income and lower COVID-19 vaccine acceptance [23].Marital status was directly assessed in one study that did not find an association with acceptance.However, husband's educational level [58], living with husband and children [47], and having a husband who favoured COVID-19 vaccination [49] were all significantly associated with a higher rate of acceptance.Moreover, living with or being in contact with people vaccinated against COVID-19 or being in favour of receiving the vaccine was significantly associated with COVID-19 vaccine acceptance in all the included studies, except in one study [21].Furthermore, living with people older than 65 years or the number of householder members in general were not associated with acceptance [35].

Health Related Aspects
Only one study assessed the association between BMI and acceptance, but no significant association was found [23].Comorbidities/health status was explored in 10 studies, half of them found a significant association between a history of chronic diseases and higher acceptance, while the remaining studies did not find an association.Having a private health insurance was explored in one study, which found an association with a lower acceptance rate [47].A history of COVID-19 infection was assessed in 6 studies, but only one found an association with higher acceptance [41].All the remaining did not find a significant association.Moreover, a high level of perceived susceptibility was assessed in one study and appeared to be significantly associated with higher acceptance rate [55].Lastly, higher adherence to mitigation measures against COVID-19, having received information/recommendations about COVID-19 vaccine, and having received other vaccinations (such as influenza or pertussis) during pregnancy were significantly associated in all the assessed studies (3, 4 and 3 studies, respectively).

Pregnancy Characteristics
Gestational week was assessed in 8 studies, of which 6 studies found an association between a later gestational week and higher COVID-19 acceptance, whereas two studies failed to find a statistically significant association [35,45].Parity was assessed in 8 studies but only one study found a statistical association between a higher number of pregnancy and higher acceptance [40]; all the remaining studies did not find a significant association.Pregnancy at risk was only assessed in one study and was not found to be associated with acceptance [41].History of abortion was explored in two studies, of which one study found an inverse association with acceptance [59], while the second did not find an association [21].Lastly, a poor obstetric history was associated with lower acceptance rate, insufficient prenatal care was in one study associated with lower acceptance [59] but was not significant in another study [21]; while infertility treatment was associated with higher acceptance [59].

COVID-19 Related Aspects
Regarding COVID-19 related aspects, we detected the following topics: fear of COVID-19, knowledge, attitude toward vaccination, perceived barrier, safety and benefit of vaccination, vaccine efficacy, facility, data availability and source of data, and trust in authorities.
Fear of COVID-19 infection was assessed in 5 studies, of which three found an association with higher vaccine acceptance, while this association was not found in the other two studies [41,61].A higher level of knowledge on COVID-19 or its vaccine was associated with a higher acceptance rate in 6 studies, except in one that failed to find a statistical association [45], 2022.Attitude toward COVID-19 vaccination was assessed in 6 studies.Positive attitude was associated with higher acceptance in 5 out of 6 studies; only one study did not detect a significant association [43].Perceived barriers were explored in one study, which found a positive association between lower level of perceived barriers and higher acceptance rate.The perception of vaccine benefits was assessed in three studies, all of which concurred in finding an association between higher benefit perception and higher acceptance rates.COVID-19 vaccine safety for women or fetus was explored in 6 studies.Fear of side effects, vaccine's toxicity, or belief that vaccine can cause the infection were all associated with lower acceptance, except in one study where fear of side effects was not associated with acceptance [36].General confidence in vaccine safety was also not associated with acceptance [49].On the contrary, confidence in vaccine efficacy was assessed in three studies and all of them found a significant association with higher acceptance.Similarly, access to vaccination centres was also associated with acceptance [27].Regarding data availability and the source of data, studies found that the perceived unavailability of data on COVID-19 vaccines, the feeling that trials were rushed, and the belief that people from minority groups were not adequately represented in trials were all associated with lower acceptance.On the contrary being exposed to official source of data was associated with higher acceptance.Lastly, trust in authorities (government and vaccine features) was associated with higher acceptance.
Considering maternal age, three out of five studies did not find any significant association, whereas the remaining two found a significant associated between older age and a lower rate of hesitancy.Educational level was also not statistically significantly associated with hesitancy in most of the retrieved studies (5 out of 7).In the remaining two studies, one found an association between higher level of education and lower level of hesitancy [2], whereas the last one found an inverse association [41].Ethnicity (minorities) was associated with lower rate of hesitancy in two out of three study, but DesJardin et al. [30] failed to find a significant association.On the contrary, employment was not associated with hesitancy in all the three retrieved studies [30,31,38].Similarly, area of residency [46] and income [30,31,46] were not associated with hesitancy.Marital status [30] and husband's level of education [46] were also not significantly associated with hesitancy.Lastly, the number of household members and in particular living with school children, significantly differed among hesitant and not hesitant women [48], as well as being in contact with other pregnant women vaccinated was significantly associated with lower rate of hesitancy.However, living with people affected by comorbidities did not predict COVID-19 vaccine hesitancy [48].

Lifestyle Factors
Drugs consumption [30] and smoking habit [2,31] were explored in one and two studies, respectively.However, only one study found a significant association between smoking habit and higher rate of hesitancy [2], while all the other did not find an association.Lastly, a high level of perceived cues to action, but not self-efficacy [32], was associated with lower hesitancy [32].

Health Related Aspects
Comorbidities/health status [2,32] and a history of COVID-19 infection [30,50] were each examined in two studies, and no association was detected with COVID-19 vaccine hesitancy.Having a health insurance was explored in two studies, obtaining contrasting results [2,30].Moreover, a high level of perceived susceptibility was assessed in one study, according to which not being aware that pregnancy increases the risk of severe illness and not being aware that pregnant women represent a priority group were more frequently reported by hesitant women [60].Having received other vaccines was assessed in two studies, yielding contrasting results.Sutanto et al. found a significant association between having planned to receive flu vaccine or diphtheria-tetanus-pertussis vaccine and lower hesitancy.However, the other study [30] failed to find the association.Lastly, not having received a healthcare worker's (HCWs) recommendation was more frequently reported by hesitant individuals [60]; conversely, consulting one's own physician significantly reduced hesitancy [44].

Pregnancy Characteristics
Gestational week was not associated with hesitancy in all the three retrieved studies [2,46,48].Parity was assessed in four studies, obtaining contrasting results (half of them found a significant association with hesitancy [2,48], while half of them did not [38,46]).Pregnancy at risk was only assessed in one study and was not found to be associated with hesitancy [31].Lastly, no pregnancy related issues [44] and history of reproductive issues were associated with higher rate of hesitancy [32].

COVID-19 Related Aspects
Regarding COVID-19 related aspects, we detected the following topics: fear of COVID-19, knowledge, perceived barrier, safety and benefit of vaccination, vaccine efficacy, source of data.
Fear of COVID-19 infection was assessed in three studies, of which two found an association between no fear (or anxiety/obsession with COVID-19 symptoms) and higher hesitancy [28,50], whereas one study found an inverse association [41].The level of knowledge on COVID-19 [31,32] and level of perceived barriers [32] did not differ among groups.High perceived vaccine benefit and trust in COVID-19 vaccine were associated with a lower rate of hesitancy [32,53]; on the contrary, distrust in vaccines was associated with a higher rate of hesitancy [28], while the perceived inefficacy of the vaccine was not associated [41].Fear of side effects, considering both women and babies was more frequently reported by the hesitant group [60].Lastly, the source of data was another relevant predictor factor of hesitancy: trusting rumours on social media [28] or not consulting official sources of information both increase hesitancy [41].

Quality Assessment
Approximately one third (n = 16) of the included studies scored equal or more than 10 and were therefore classified as high quality.Similarly, 16 studies scored equal or below 4 and were classified as low quality, while 11 studies scored between 5 and 9 and were classified as moderate quality.Quality assessment for each included study, reported itemby-item, is detailed in Supplementary Table S2.Inter-rater reliability was assessed, and discrepancy between the two reviewers was 10%.Disagreements were solved through discussion, reaching the final agreement for all the included studies.

Discussion
The systematic review of literature raises concerns about the low anti-SARS-CoV-2 vaccination coverage in pregnant and breastfeeding patients attending healthcare facilities.The more consistently cited causes of vaccine hesitancy in pregnant and breastfeeding women appear to be safety concerns and lack of causal association analysis [3].Many included studies indicate that women are particularly concerned that vaccines might cause biological damages to either themselves [46,48,53], their child [40,41,51] or both [20,22,34,37,38].The findings of Riad et al. [51] are suggestive, highlighting that over 60% of their sample population continued to refuse vaccination even after their physician's recommendation and the vaccination offer in hospital setting.
These data are especially significant in consideration that these studies were carried out in hospitals or other healthcare facilities.Patients accessing healthcare would be expected to be more compliant to HCWs' recommendations than subjects who refuse or do not actively seek medical care [62,63].However, the included studies showed a significant level of vaccine hesitancy even in this "privileged" population.This is likely related to the multifaceted nature of vaccine hesitancy [5,64], as confirmed by several studies that have highlighted a diverse pattern of the determinants for vaccine hesitancy in this population In addition to the previously mentioned safety concerns, these reasons included religious issues [58], social disadvantage and a lack of trust in institutions [51], as well as factors related to education and occupational status [42,44,59] and misinformation about COVID-19 and its risks for pregnant women [21,27,28,39].Older women were generally observed to have a significantly higher degree of acceptance and trust in vaccination [21,42,53,59].Additionally, ethnicity is another factor associated with higher acceptance and lower hesitancy in the majority of included studies.However, it is important to note that the association between ethnicity and vaccine hesitancy/acceptance can depend on the specific ethnic group, cultural factors, historical experiences, and access to healthcare resources.According to our results, Afro-Caribbean, Asian ethnicity and Bedouin pregnant/breastfeeding women were more accepting, while, Asian and Sindhi pregnant/breastfeeding women were less hesitant.
These results appear to contrast with previous evidence regarding ethnicity and vaccine hesitancy/acceptance in general.These seemingly contrasting results might be due to the fact that a global vaccination campaign for COVID-19 has been launched.As a result, more language and culturally adapted communication materials have been developed by each country worldwide, as well as by international health authorities/agencies, including the World Health Organization.Moreover, free of charge access to the vaccine, and the prioritization of specific vulnerable group in terms of health condition (including pregnancy), may have facilitated the acceptancy among minorities.
From this perspective, the findings of Premji et al. [50] are particularly intriguing, as they pertain to a population of Pakistani women and also included their spouses in the data collection.According to the results of this study, the acceptance of vaccination among women in Pakistan appears to be significantly influenced by their husband's opinion.This might be related to the religious and cultural background of these individuals.Notably, husbands of pregnant women were observed to be more supportive of COVID-19 vaccination when they had no safety concerns regarding both the woman and the child.Doubts about the efficacy of COVID-19 vaccine were also identified as a cause of vaccine hesitancy in some studies [34,48,56].Chronic medical illness was also found to increase vaccination uptake in pregnant and breastfeeding women [45,58].This might be attributable to a heightened awareness of morbidity and mortality associated with vaccine preventable diseases, a phenomenon observed in other populations as well [65].
Several other factors influencing vaccine hesitancy were identified, although their presence was less consistent across the included studies.Education was significantly associated with lower hesitancy levels in eight different studies, while only two identified current employment as a facilitator for vaccine acceptance.Islamic faith subjects reported higher hesitancy in one study, although the exact causes of this behaviour were not investigated.Older maternal age was investigated as a possible determinant by only ten studies, only half of which observed a consistent increase in vaccine acceptance for pregnant/breastfeeding women over 35 years of age.
In-hospital vaccination has been identified as a possible solution to low vaccination coverage [66].Apart from the convenience of administering vaccines during a hospital stay, which eliminates the need for patients to travel long distances to access vaccination services, the idea of being constantly monitored by HCWs often serves as a facilitator of vaccine acceptance among patients, particularly in emergency areas [67][68][69].Hospital staff also generally support this practice [70].However, the case of COVID-19 vaccination is peculiar.The rapid development of the currently available vaccines has mitigated the growing burden of COVID-19, reducing the risk of infection, with a specific impact on symptomatic and severe disease, and has increased confidence of HCWs and the general population [71].Despite benefits of immunization programs, hesitancy persists in specific subgroups [72][73][74] during the first phases of vaccination campaigns [75].
Our review identified an insufficient level of knowledge regarding anti-SARS-CoV-2 vaccination among pregnant women, underscoring the critical role of reliable information sources in shaping individuals' attitude towards vaccination [43].The widespread dissemination of misinformation concerning both COVID-19 and its vaccines could un-dermine vaccination coverage [76,77].Given this complex landscape, the conventional recommendations for clearer communication with patients by HCWs [78,79] may prove inadequate to address vaccine hesitancy and promote acceptance.A structured approach, considering the level of education [55,56] is especially needed when assisting pregnant and breastfeeding women, whose acceptance of vaccination is often lower than average even for "common" vaccines [80].It is also crucial to involve spouses and other family members in the communication process, as their opinion can be pivotal in determining the woman's final decision regarding vaccination.This new approach to vaccination would require the use of multiple tools in a standardized manner while allowing room for personalization to accommodate various social and cultural backgrounds.The quality and quantity of information must be tailored to the patient's ability to understand, avoiding information overload that could lead to anxiety and, ultimately, refusal [81].Finally, when interacting with patients in a post-primary healthcare setting, emphasis should be placed on creating a safe and controlled environment where potential side effects can be handled more effectively, thereby encouraging women to accept timely vaccination.

Implications for Policies and Practices
The current research indicates that vaccine acceptance/hesitancy among pregnant/ breastfeeding women is largely influenced by several factors, which significantly impact the final vaccine coverage rate.Therefore, our results should be taken into account to inform strategies related to public health policies and procedures.While reluctance toward vaccines primarily stems from concerns about their safety, whether considering women, the, fetus/newborn or both, many other aspects, such as educational level, source of information, and having received previous vaccination during pregnancy or at least recommendation from HCWs to receive the vaccines, positively influence acceptancy.In this perspective, simultaneously work on health education (among general public or, as in this case specific target populations) and HCWs' training (and re-training) is of paramount importance to concurrently and correctly inform people and ensure an updated and timely education of HCWs [82].This dual action allows, on the one hand, facilitating the public's access to appropriate sources of information, and on the other hand, dispelling doubts among HCWs [83], especially in the case of vaccine administration among pregnant women.This is particularly important given the novelty of the vaccine and the subsequent influx of new available information [84][85][86][87].
The uncertainty among HCWs about administering vaccinations to pregnant and breastfeeding women could significantly impact their acceptance and attitudes toward vaccination.As a consequence, HCWs should equip themselves with effective informationsharing and risk communication skills [88,89].Transparent, up-to-date, trustworthy, and timely communication is crucial for addressing concerns and misconceptions within the population [90,91].At the same time, easy access to and understandable information about COVID-19 vaccines and vaccination might largely impact vaccine acceptance [92,93].Therefore, taking into account our results, promoting targeted education campaigns addressing the main concerns of pregnant/breastfeeding women regarding COVID-19 safety is another aspect that healthcare systems and policymakers should consider in order to increase COVID-19 coverage and ensure the well-being of women and their child.
Given the aforementioned points, HCWs, both from the current and future generations, must stay informed about the prevailing guidelines for vaccinating pregnant women, receive training in effective communication strategies, and be actively encouraged to recommend necessary vaccines to their patients [94].HCWs are engaged to promote immunization in different healthcare settings and to develop effective communication toolkits and educational programs about vaccination [95,96].Moreover, fostering collaborations among HCWs, public health agencies, and citizen organizations (specialized in maternal and child health) should be encouraged and promoted to develop holistic strategies ensuring women have access to the most up-to-date evidence, policies and vaccines when recommended.

Strenghts and Limitations
Before we draw generalized conclusions from our findings, it is important to acknowledge certain limitations.Firstly, this is a review and, therefore, it inherited all the limitations from each primary study included.In detail, exposures and outcomes were defined and measured using different methods, increasing heterogeneity and uncertainty around the strengths of the associations.Associations were measured using different statistical methods, limiting the comparability of the results.Moreover, many studies did not report data when associations were not statistically significant, preventing the possibility to perform a statistical pooling of the results.When performing a meta-analysis, both positive and negative data should be combined in order to compute the new estimate.Furthermore, several studies did not adjust their results for potential confounders, or different confounders were considered among studies, or in some cases they didn't explicitly delineate them.Therefore, the differences in results could be due to many methodological aspects, including sampling methods, or to real dissimilarities in study populations.Another limitation in the data is the wide variability in terms of results.This might attributable not only to methodological aspects but also the setting-country where the study was conducted.Having included subjects attending hospital or healthcare facilities might have selected those less reluctant toward vaccinations or healthcare assistance in general, thereby potentially introducing bias.Lastly, most of the included studies were cross-sectional in nature, limiting the possibility to identify a causal association.Moreover, it should be considered that studies from different countries were considered altogether.This might simultaneously represent a strength and a limitation.Actually, one hand it offers a broad overview of the state of the art, but on the other hand, it loses the specificity of each country, which is known to be peculiar in terms of vaccine hesitancy/acceptance reasons.Furthermore, we did not stratify our results based on risk of bias assessment.It implies that moderate-to-low quality studies have been compared with high quality ones.However, despite these limitations, this review boasts several merits.First, this is a systematic review conducted adhering to the PRISMA guidelines, which help in ensuring a comprehensive approach.Secondly, the protocol of the current review has been published in advance, increasing transparency.Thirdly, several outcomes were considered, offering a broad assessment of the phenomenon.Fourthly, no limits were posed about exposures, contributing to a comprehensive and exhaustive overview of predictors of vaccine acceptance/hesitancy among pregnant/breastfeeding women.Lastly, we consulted three distinct databases to capture all eligible studies, surpassing the minimum requirements set by guidelines.

Conclusions
Vaccine hesitancy in pregnant and breastfeeding women is an especially serious issue to be tackled by healthcare professionals.It is a multifaceted problem, stemming from various factors regarding women, their health and their pregnancy.While improving knowledge about vaccines in general seems fundamental to increase the public's trust in vaccination, other interventions are required.Irrational factors such as fear of adverse events or religious concerns have been identified as important determinants of hesitancy.These issues are to be faced with personalized interventions aimed at improving communication and building a trust relationship between physicians and patient.HCWs have experienced substantial workload changes and attitude towards vaccine because of their role in managing measures to limit the spread of COVID-19.
It should also be considered that, as we have observed through our review of studies conducted in various socioeconomic and cultural settings, the reasons for hesitancy can vary significantly among different individuals.Future vaccination policies should prioritize communication on a broad range of topics to address the concerns and doubts of as many people as possible.

Figure 1 .
Figure 1.PRISMA flow diagram detailing the selection process.

Figure 1 .
Figure 1.PRISMA flow diagram detailing the selection process.

Table 1 .
Main characteristics of included studies.

Table 2 .
Main characteristics of studied population.

Table 3 .
Predictors of vaccine acceptance and vaccine hesitancy.