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Abstract
Background
Respiratory syncytial virus (RSV) is a leading cause of infant respiratory disease. Recent approval of preventive measures like a long-acting monoclonal antibody and a maternal vaccine signals a potential shift in early-life RSV infection control. However, success hinges on acceptance.
MethodsWe conducted a cross-sectional survey among pregnant women and partners in the Netherlands, recruited via healthcare professionals, social media platforms, and the 9-Months Fair. The survey assessed willingness and motivation for maternal RSV vaccination and neonatal RSV immunization, including strategy preferences and informational needs.
ResultsIn total 1001 pregnant women (mean age: 31.1 years) and their partners (mean age: 33.2 years) completed the survey. On average, they were 24 weeks pregnant at the time, and 54.6 % had no other children yet. The majority was Dutch-born (95.2 % of women); with 68.3 % of women having completed higher education and with overall strong pro-vaccination attitudes (93.9 % of partners intended to vaccinate their expected newborn). The overall acceptability to vaccination and immunization was high, with 87 % of respondents indicating they would (likely) accept both strategies. A positive attitude towards both methods was associated with previous experience with severity of RSV, intention to vaccinate the newborn and parental vaccination status during childhood and current pregnancy. When the choice was given, the majority of participants, in particular those with children and the intention to breastfeed, favoured maternal vaccination over passive immunization of infants (75.3 % of the pregnant and 71.6 % of the partners). A majority of the respondents cited optimal protection for the child and knowledge of RSV as important factors for accepting RSV prophylaxis.
ConclusionsWhile most participants would accept both strategies for RSV protection of their infant, a majority, especially those with other children, favoured maternal vaccination, due to concerns about infant safety and awareness of RSV severity.
Full text
An infection with the respiratory syncytial virus (RSV) is the leading cause of global infant respiratory disease, affecting nearly all infants within their first two years [1,2]. Each winter, RSV presents a recurring challenge that overwhelms paediatric facilities and health care systems. While preterm births or certain high-risk conditions increase the risk of severe illness, the majority of children under 2 years hospitalized for RSV are healthy, term infants without an underlying condition [3,4]. In the Netherlands alone, 3.600 children are hospitalized annually due to an RSV-infection, generating healthcare costs of €6.5 million [5]. Beyond the acute respiratory infection experienced in early childhood, studies reveal a concerning link between early RSV infections and compromised respiratory health in older children, often leading to wheezing and asthma [6–8]. Thus, the consequences of an RSV-infection extend beyond infancy, with a broader impact on respiratory health.
Recently approved preventive measures indicate progress in protecting young infants from RSV. These measures include a long-acting monoclonal antibody [9] (la-mAB; Nirsevimab) that offers passive immunization for infants, as well as a maternal vaccine [10]. Both preventive measures exhibit good effectiveness for the first 6 months of life, with 76 % and 69 % effectiveness over a period of 150 and 180 days, respectively [10,11]. The European Medicines Agency (EMA) approved both measures in 2023, and immunization programs have already been implemented showing promising results in Luxembourg and Spain during the winter of 2023–2024 [12–14]. Various other European countries are willing to roll out protection programs against RSV in the near future as well. Subsequently, the Health Council in the Netherlands issued a recommendation for immunization with Nirsevimab in February 2024 [5].
There is no doubt that RSV prevention programs effectively decrease disease burden and healthcare costs [15,16]. Nevertheless, their success depends heavily on acceptance and willingness of pregnant women and their partners to choose for maternal vaccination or immunization of their child in the first days of life. Growing vaccine hesitancy worldwide is a serious threat to the efficacy of immunization programs affecting herd immunity and global health [17,18]. Pertussis and influenza prevention programs during pregnancy are in place in many countries, but show varying acceptance rates, alongside a decline in the number of children vaccinated through national immunization programs [19]. Limited research has explored acceptance of RSV prevention strategies, predominantly focusing on maternal vaccination, with varying results [20–26]. A few of these studies have concurrently evaluated both maternal vaccination and neonatal immunization [20,22,24], highlighting the need for comprehensive research.
Vaccine acceptance or hesitancy is the result of many factors, including cultural background, political influences and personal experience with vaccines and the preventable disease [21,26]. To enhance vaccine coverage and implement an effective prevention program for RSV, it is crucial to identify drivers and barriers influencing pregnant women and young (expectant) parents. The choices made by pregnant women and young (expectant) parents regarding a particular strategy are important for achieving good uptake and maximizing health benefits. Therefore, this study aims to investigate the perception and willingness of pregnant women and their partners regarding maternal vaccination and neonatal immunization by monoclonal antibodies for RSV, following approval of both these strategies by official health care institutes.
2 Material and methodsA cross-sectional survey study in pregnant women and partners (if present) was performed. A non-WMO (Medical Research Involving Human Subjects Act) declaration has been given by the Medical Ethics Committee of Leiden/The Hague/Delft (N23.094).
2.1 Study participants and recruitmentParticipants were considered eligible if they were pregnant at the time they filled out the survey, were proficient in Dutch or English, and possessed a cell phone, laptop, or tablet to complete the online survey. When applicable, partners were asked to complete an additional section of the questionnaire.
Pregnant women were recruited through multiple channels across the Netherlands to ensure diverse representation. Recruitment took place during appointments with midwives from various locations and gynecologists at the Spaarne Gasthuis Hospital in Haarlem, as well as through Youth Health Care centers in the Haarlem region where vaccinations (e.g., 22-week pertussis, COVID-19, or influenza) are offered. Additional recruitment efforts included social media platforms (Instagram, LinkedIn, and Facebook) and the nationally popular 9-Months Fair, a large pregnancy and baby event that attracts over 30,000 visitors from across the Netherlands over a four-day period. Posters and flyers with a QR code provided direct access to the anonymized questionnaire via SurveyMonkey. Electronic consent was obtained at the start of the survey, which was available in Dutch and English. The surveys were conducted between February and April 2024.
While we did not perform a formal power calculation, we aimed to recruit approximately 1.000 participants. This target was set to allow for meaningful subgroup analyses and to ensure robust representation across various demographic groups, reflecting the diversity of the Dutch pregnant population.
2.2 Study parametersThe questionnaire was divided into three parts. The first part involved questions about the background and vaccination status of the pregnant woman and, if present, other children. Study parameters included age, number of weeks pregnant at the time of the survey, number of pregnancies, number of children, country of birth, cultural or religious background, level of education, occupation, smoking/vaping habits, intention to breastfeed, vaccinations received as a child, maternal vaccination, and vaccination status of siblings. At the end of Part 1, questions about relationship status and whether a partner was actively involved were asked. If a partner was involved, the same background questions applicable to the partner were asked in Part 2. Part 3 included questions for both the expectant women and their partners (if present), who completed the questionnaire jointly, regarding their knowledge and opinions on RSV and its preventive methods in more detail. Expectant parents were asked about their intentions to immunize their newborn according to the national immunization program, their knowledge regarding and experience with RSV infections, their willingness to accept maternal vaccination and neonatal immunization as prevention strategy against RSV, their reasoning behind their choice and their (possible) preference for one of the two strategies. Finally, respondents were asked what information they needed to make a well-informed choice. Answers were categorized per question, as listed in Table S1. When a question aimed at inventorying motivations for a choice, the open option ‘Other, namely…’ was provided.
The primary objective was to understand the willingness of pregnant women to consider RSV preventive options. Respondents could indicate their willingness for maternal vaccination by selecting one of the following options: ‘yes’ (indicating direct agreement), ‘doubt, likely yes’ (indicating hesitation but leaning towards agreement), ‘doubt, likely no’ (indicating hesitation but leaning towards refusal), ‘no’ (indicating direct refusal), or ‘I don't know’. The ‘I don't know’ option was available only for maternal vaccination responses. For neonatal immunization, the answer options were ‘yes’, ‘doubt, likely yes’, ‘doubt, likely no’, and ‘no’.
2.3 Statistical analysisStatistical analyses were conducted using SPSS Statistics (IBM, version 26). A significant portion of the study yielded primarily descriptive data. Categorical variables are presented as numbers with percentages, while continuous data are reported as mean ± SD or as median with the first to third quartile [Q1-Q3] in case of non-normality. Normality of variables was assessed through visual inspection of histograms and normality plots.
Univariate logistic regression was employed to analyse the characteristics of respondents who indicated ‘doubt, likely yes’ or ‘(likely) no’ in comparison to those who answered ‘yes’ for both maternal vaccination and neonatal immunization, examined separately. To address the issue of small sample sizes, the responses categorized as ‘doubt, likely no’ and ‘no’ were combined into a single category labelled ‘(likely) no’. Additionally, responses indicating ‘I don't know’ for maternal vaccination (n = 13) were excluded from the analysis to ensure the accuracy and reliability of the results. Variables were combined when possible if the groups were too small for accurate analysis, specifically if they had fewer than 5–10 participants per group. This was the case, for example, with religious background.
A multivariate logistic regression model was employed to examine the relationship between various characteristics and respondents' likelihood of indicating hesitation (“doubt, likely yes”) or refusal (“(likely) no”) regarding maternal vaccination and neonatal immunization. The expression of hesitation or refusal was compared to the group respondents that agreed with the proposed prevention strategy. This analysis included all variables with p ≤ 0.2 from the univariate logistic regression analyses, which assessed the two groups classified as “doubt, likely yes” and “(likely) no” for both maternal vaccination and neonatal immunization. Certain variables were excluded from the analysis to enhance model accuracy and reduce multicollinearity. For instance, gravidity was removed from the multivariable model due to multicollinearity with number of current children. The vaccination status of current children was also excluded because less than half of the respondents currently had no children, and those respondents would otherwise be removed from the analysis. Moreover, there was multicollinearity between vaccination status of current children and the parental intention to vaccinate the newborn for the national immunization program. Additionally, the variables related to Influenza and COVID-19 vaccination during pregnancy were also eliminated from the multi-variate model, as these vaccines are only offered during the winter period for pregnant women in the Netherlands. Statistical significance for the multivariate model was determined using a threshold of p ≤ 0.05. The results include adjusted odds ratios (aOR) and 95 % confidence intervals (CI), which indicate the strength and direction of the association between the selected characteristics and the likelihood of respondents expressing hesitation or refusal towards maternal vaccination and neonatal immunization.
3 ResultsA total of 1228 started the survey and 1079 completed the survey (survey completion rate of 87.9 %, 1064 in Dutch, 15 in English). 78 respondents were excluded because they answered not applicable or 0 weeks when asked how many weeks they were pregnant, resulting in an overall analytic sample size of 1001 respondents.
3.1 Patient characteristicsAmong 1001 pregnant women (mean age 31.1 ± 4.3 years), 978 had involved partners during their pregnancy (mean age 33.2 ± 5.0 years) (Table 1). On average, women were 24 weeks pregnant, with a median gravidity of two, with over half (54.6 %; 547/1001) the pregnancies in mothers who had no other (biological) children. Almost all respondents were Dutch-born (95.2 % pregnant women; 953/1001, and 92.4 % of partners; 904/978), and the respondents' education levels were high compared to the average in the Netherlands, with 68.3 % (683/1001) of the pregnant women and 56.6 % (553/978) of their partners having completed higher education.
As seen in Table 1, the studied group exhibited strong pro-vaccination attitudes: 94.3 % (944/1001) of pregnant women and 91.2 % (892/978) of all partners had received all childhood vaccinations, 97.1 % of their current children were partially or fully vaccinated, and 93.9 % (940/1001) of respondents intended to vaccinate their expected newborn. Moreover, 90.7 % (908/1001) of pregnant women were either vaccinated or intended to be vaccinated against pertussis during the current pregnancy. However, the maternal vaccination rates or intention to vaccinate during pregnancy for Influenza and COVID-19 were lower, at 34.3 % (343/1001) and 9.2 % (92/1001), respectively.
RSV awareness was high, with 46.3 % of respondents (463/1001) reporting a good understanding of RSV, 40.8 % (408/1001) having some knowledge, and 13.0 % (130/1001) having no knowledge of it (Table 1). However, nearly half (48.7 %, 487/1001) had no prior experience with children affected by RSV. Pregnant women with RSV experience were significantly older (31.5 years vs. 30.8 years; p = 0.007) and more often had children (54.4 % vs. 35.6 %; p < 0.001). The majority of respondents with at least some experience (n = 514) reported that children required hospitalization at a paediatric ward (64.2 %; 330/514) or paediatric intensive care unit (18.5 %; 95/514).
3.2 Factors influencing acceptance of maternal RSV vaccinationThe majority of the participants had a positive attitude towards maternal vaccination, with 66.6 % (658/988) saying ‘yes’ and 24.6 % (243/988) saying ‘doubt, likely yes’ to this strategy (Fig. 1). Table 2A summarizes the associations between respondent characteristics and expressing ‘doubt, likely yes,’ or ‘(likely) no’ regarding the acceptance of future maternal RSV vaccination compared with the respondents who answered ‘yes’, in the adjusted overall model. The corresponding univariate analyses are shown in Table S2.
It was clear from our results that respondents who were uncertain about vaccinating the newborn according to the national immunization program (NIP) were also unsure about maternal vaccination (OR 10.39, 95 %CI 2.8–38.4) or were refusing this (OR 8.15, 95 %CI 1.58–42.01) (Table 2A). Moreover, skipping pertussis vaccination during pregnancy increased the odds of refusing maternal vaccination (OR 17.74; 95 % CI 7.09–44.41). A similar pattern was seen for breastfeeding; doubt about breastfeeding was associated with a higher odd of being apprehensive about maternal vaccination (OR 2.75, 95 %CI 1.30–5.79). No clear effect of educational level was found, but a trend towards an association between more doubt and lower education was observed. Additional associations were found between familiarity and experience with RSV-severity and acceptance of maternal vaccination. There was a significantly higher likelihood of hesitancy towards maternal vaccination among those with little knowledge on the RS-virus (OR 1.89 95 %CI 1.29–2.78) or no knowledge about it (OR 2.20 95 %CI 1.24–3.90). Experience with severity of RSV-disease represented as PICU-admission, was associated with decreased likelihood of doubting maternal vaccination (OR 0.37, 95 % CI 0.17–0.83). Furthermore, experience with severity of RSV-disease represented as hospital-admission, was associated with decreased likelihood of refusing maternal vaccination (OR 0.47, 95 % CI 0.22–0.99).
3.3 Factors influencing acceptance of neonatal RSV immunization with la-mABA large majority of participants expressed a positive attitude towards neonatal immunization, which was comparable to their acceptance of maternal vaccination. Specifically, 63.8 % (632/988) of participants indicated acceptance (‘yes’) and 26.6 % (272/688) expressed uncertainty but leaning towards acceptance (‘doubt, likely yes’) (Fig. 1). Table 2B summarizes the associations between respondent characteristics and expressing ‘doubt, likely yes,’ or ‘(likely) no’ regarding the acceptance of future neonatal RSV immunization compared with the respondents who answered ‘yes’. The corresponding univariate analyses are shown in Table S3.
The overall adjusted model (Table 2B) showed a significant association between already having children and a higher likelihood of declining neonatal immunization compared to those without children (1 child: OR 2.6 95 %CI 1.40–4.82; ≥2 children: OR 2.77 95 %CI 1.17–6.57). Intention to breastfeed or uncertainty about breastfeeding increased the refusal odds for neonatal immunization. Furthermore, associations were found between (likely) no and an unvaccinated mother, doubt about the NIP for the newborn and refusal of the NIP.
Significant associations were found between acceptance and RSV-familiarity and experience, in line with maternal vaccination (Table 2A an 2B). There was a higher likelihood of hesitancy for la-mAB among those with little knowledge (OR 2.29, 95 %CI 1.60–3.29) or no knowledge about RSV (OR 1.94, 95 %CI 1.11–3.37). Although univariate analyses indicated that a child's hospitalization (in general ward or PICU) was associated with decreased likelihood of doubting neonatal immunization (Tables S3), multivariate analysis could not confirm this effect. Familiarity and experience with RSV had little impact on refusal of neonatal immunization.
Further exploration provided more information on the optimal timing of neonatal immunization according to the 632 pregnant women and partners that would accept this strategy if offered, see Fig. 2. Of this group, 20.1 % (127/632) indicated that the best timing for immunization was within the first week after birth, and 41.1 % (260/632) opted for one week after birth. Of the remaining 38.8 % (245/632) who preferred a later timing or had no preference, two-thirds indicated they might still accept it within the first week (165/245), while 22.1 % would probably refuse (54/245).
3.4 Intentions and preferences regarding RSV prevention methodsFig. 1 summarizes respondents' intentions regarding RSV-prophylaxis. Of all pregnant women and partners who were asked how they viewed both possible RSV vaccination and immunization independently, 87 % (859/988) responded that they would (likely) say yes to both strategies. In contrast, only 5.3 % (53/988) indicated that they were most likely refusing both strategies.
Next, the questionnaire explored the most preferable option according to all pregnant women and their partners (if present), summarized in Fig. 3. A majority of the pregnant women (75.3 %; 754/1001) indicated that they would choose maternal vaccination, 8.1 % (81/1001) opted for a combination of both, and only 2.6 % (26/1001) preferred neonatal immunization alone. A small group (2.4 %; 24/1001)) indicated that they would refuse both options. Furthermore, a large proportion of partners reported agreeing with the pregnant woman's choice (71.6 %; 704/983), while only 2.1 % (21/983) reported having a different preference.
3.5 Motivation and requirements for decision-making for RSV prophylaxisTable 3 summarizes the motivation, with corresponding distribution, behind decision-making for RSV prophylaxis of all respondents. When asked about their choice to accept maternal vaccination or neonatal immunization, respondents choose very similar for both options. A majority cited optimal protection for the child (maternal vaccination: 86.8 %; 571/658, neonatal immunization: 86.6 %; 547/632) and knowledge of RSV-severity (maternal vaccination: 75.5 %; 497/658, neonatal immunization: 75.4 %; 471/632) as important factors. Additionally, approximately one-third indicated that a recommendation by an expert influenced their decision, while only about one-tenth opted for a recommendation by the government or a public health institute. Furthermore, main reasons for refusal of maternal vaccination included lack of RSV knowledge (42.9 %; 15/35), fear for the unborn child's safety (34.3 %; 12/35), and a preference for a natural RSV infection for the child (25.7 %; 9/35). Among hesitant respondents for maternal vaccination, insufficient RSV knowledge (56.3 %; 143/254) and fear for the unborn child's safety post-vaccination (23.2 %; 59/254) were important factors contributing to their doubts. Additionally, a sizable portion of this group cited lack of coverage by their insurance as an important reason for doubt (34.6 %; 88/254).
Finally, we asked respondents what was required to make an adequate decision (Table 4). Pregnant women and partners indicated that they considered more information about both methods (74.9 %; 750/1001), expert advice (58.5 %; 586/1001), and information about RSV and its effects on young children (57.9 %; 580/1001) to be important factors. Government advice was mentioned less frequently but was still deemed necessary by 17.6 % (176/1001) of respondents to decide.
4 DiscussionWith two promising new strategies to reduce RSV-infections in the most vulnerable population under consideration by healthcare institutes, we are on the verge of major transformation in the landscape of RSV-infections in early life. The success of national strategies highly depends on uptake by the target group. With this questionnaire study among 1001 pregnant women and their partners, we explored acceptance of maternal vaccination and neonatal immunization by monoclonal antibodies and showed that 87 % of all pregnant women would say yes or likely yes to both strategies to protect their infants from RSV. The most frequently mentioned reason for a positive attitude towards both methods is infant protection, followed by knowledge on the severity of an RSV-infection. While both strategies are highly accepted, if given the choice, a majority of women, especially those with previous children, would opt for maternal vaccination over neonatal immunization. Uptake is highly dependent on maternal vaccination state and that of previous children, the acceptance of pertussis vaccination during pregnancy, experience with severity of RSV and the intention to breastfeed. Participants with the intention to breastfeed would (likely) say no to neonatal immunization and prefer maternal vaccination.
To date, most studies exploring the acceptance of RSV prophylactic strategies have primarily focused on maternal vaccination alone [21,23,25,26], despite the fact that most countries are willing to implement neonatal immunization. A small number of recently published studies did evaluate the acceptability of both strategies among parents of children <2 years old, pregnant women and health care professionals [20,22,24]. However, this study is the first to ask pregnant women and their partners for their opinion on both strategies at the same time and explores this question in the year that implementation of RSV-protection will follow approval of these strategies by official health care institutes. Early after the start of this study, the Health Council in the Netherlands came out with a recommendation for neonatal immunization, which may have influenced the outcomes of the study. However, we observed a preference for the maternal vaccination instead, similar to other recently published questionnaire studies [20,24]. Therefore, the influence of this recommendation is considered small. When comparing our study population with previous studies and national records, it should be noted that our group has a relatively high overall vaccination willingness, a high education level and is mainly born in the Netherlands [21,24,26,27]. This could affect the outcome, resulting in a relatively positive representation of the findings. Another notable difference with previous reports is the high familiarity with RSV, which might reflect increased public awareness and media attention around RSV or selection bias in our cohort [28]. Still, we believe that this survey provides healthcare professionals and policy makers with important information to improve the enrolment of RSV protection in the coming years.
Maternal vaccination protects the infant directly from birth until at least 6 months of age, with still effective but waning immunity until 1 year of age and the highest gain found in the first months of life when infants are most vulnerable [16,28,29]. Parents have become more familiar with this strategy for infant protection since pertussis vaccination is part of the standard National Immunization Program (NIP) in many countries. Therefore, the high number of pregnant women that opts for pertussis vaccination in our cohort might also explain the high number of respondents favouring maternal vaccination over neonatal immunization. A high proportion of our study population (91.2 %) showed willingness to maternal vaccination which was much higher compared to previous reports that ranged from 48.5 to 77 % [21,23,25,26]. Reasons for this could be the overall high vaccination willingness and high familiarity with RSV in this study, which has been suggested as a strong predictor for vaccine uptake before [25]. This finding is consistent with a recent published survey showing 88 % acceptance of maternal vaccination [24]. Here, vaccination rates and RSV awareness were also higher compared to the other studies. These compelling results suggest a preference for maternal vaccination over neonatal immunization, as is also supported by both our survey and another study, in which most participants preferred maternal vaccination (75 % and 83 %, respectively) if asked to make the choice [24]. Nevertheless, national immunization programs in other countries, for example Spain, Luxembourg, and the USA, have not included maternal vaccination but have successfully rolled out a neonatal immunization program [12,13,30,31]. This might be explained by safety concerns that were formed after one RCT with another maternal vaccine from a different pharmaceutical (GSK) that observed an increase in premature births in the vaccine arm of a study [29,32]. Despite a possible difference in preterm births in the trial of Pfizer's vaccine (Abrysvo), it was not significantly different [10,32] and was not confirmed by a recent study [33].
Neonatal immunization by la-mAB for all newborns is a relatively new concept for many (expectant) parents [34,35]. It is a form of passive immunization, which is different from regular vaccinations that are part of the NIP. Palivizumab, a short-acting monoclonal antibody administered monthly, has been offered to infants at risk for a severe RSV-infection before, but it was never accessible to all children [36]. The la-mAB can be administered within the first 2 weeks after birth and can be repeated or used as catch-up immunization at the start of the RSV season. One dose is considered to protect an infant for at least 5 months, but some breakthrough cases within the first month after immunization have been reported [31,35]. In many settings, including the Netherlands, the NIP starts with vaccinating infants at 8 or 12 weeks. Injecting a newborn child earlier might be challenging for parents, especially in the Netherlands where there is no familiarity with routine vitamin K injection after birth. This and the relative unfamiliarity with neonatal immunization using la-mAB could contribute to why respondents in this study preferred maternal vaccination when given the choice. Although the introduction of immunization in one Spanish region showed high uptake (93 %) when administered within 24 h of birth [12], this cannot be directly translated to the Netherlands because of the high rate of home births. Additionally, this number is higher compared to Luxembourg where the uptake was 84 % for hospital births and in Great Britain where a survey found 78 % acceptance for neonatal immunization [13,24]. Nevertheless, other preventive measures, including Bacillus Calmette-Guérin (BCG) vaccination and hepatitis B vaccination administered shortly after birth, show good uptake. More importantly, the protective results of the la-mAB are very promising [37,38]. An early estimate of the effect of Nirsevimab introduction in Spain shows a reduction of 74–75 % in hospital admissions due to RSV in children <1 year old [12,30]. This suggests that this strategy could be rolled out successfully.
It appears that policymakers currently have the option to choose between two distinct strategies. However, what seems overlooked is the possibility of implementing a combination of both approaches. Each strategy has its own set of advantages and disadvantages, and they could potentially complement each other. With maternal vaccination, the coverage is not guaranteed for the entire RSV season for women who give birth outside of this period. Moreover, premature babies are not adequately protected with maternal vaccinations since antibodies are primarily transferred during the latter part of the third trimester [39]. Then again, with administering la-mAB, children born before the season can be immunized just prior to it for optimal coverage (catch-up immunization). However, for children born during the RSV season, monoclonal antibodies can only provide protection after the immunization has taken place and not directly after birth, as is the case with maternal vaccination. Moreover, research indicates that some children can still get an RSV infection during the first month after immunization with la-mAB [31]. Therefore, the chance of neonatal RSV infections, which can be probably more severe compared to older children, is probably higher when neonatal immunization is used. Exploring the integration of both strategies could offer a more comprehensive and effective solution to address the issues at hand. Furthermore, using a combination makes it also possible that expectant parents can choose their preferred strategy, potentially resulting in the highest uptake.
In a time with declining vaccination rates, understanding and addressing the reasons for vaccine hesitancy are more important than ever. Main reasons for a negative attitude towards maternal vaccination found in our cohort included lack of knowledge on RSV and/or the vaccination and fear of harmful vaccine-related side effects for the unborn child. The importance of awareness of RSV-infection severity communicated by a trained professional has been shown in previous reports [25,40–42] and repeating this message might be key to emphasize the importance [43]. However, promotional campaigns should perhaps shift their focus towards the protectiveness and safety of the prophylactic method, as shown by two recently published studies [20,22] and confirmed in our study. This is also supported by the COVID-19 pandemic, which was one of the main reasons for the strongest decline in vaccine acceptance in years [44]. One of the things this pandemic has taught us is that healthcare professionals' recommendations can be ignored if people fear the vaccine might be harmful.
Taken together, this study highlights important factors that could be beneficial or obstructive in a successful RSV-prevention program. Next steps should include a detailed cost-effectiveness analysis of a potential combination program, determining the optimal timing for providing information, investigation the most suitable execution and timing of implementation, and develop a comprehensive plan for adequate vaccine stocking in practice [15,42,45]. In depth discussions should include pregnant women, healthcare professionals and policy makers.
FundingThe research was supported by a research fund of the Spaarne Gasthuis Academy.
Statements & declarationsAll authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organization for the submitted work: no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work. Transparency declaration: the lead author (M.A. van Houten) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
CRediT authorship contribution statementLisette M. Harteveld: Writing – original draft, Software, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Lisanne M. van Leeuwen: Writing – original draft, Visualization, Software, Project administration, Methodology, Investigation, Formal analysis, Conceptualization. Sjoerd M. Euser: Writing – review & editing, Validation, Formal analysis. Lucy J. Smit: Writing – review & editing, Resources, Methodology, Conceptualization. Karlijn C. Vollebregt: Writing – review & editing, Resources, Methodology. Debby Bogaert: Writing – review & editing, Methodology, Conceptualization. Marlies A. van Houten: Writing – review & editing, Validation, Supervision, Resources, Methodology, Investigation, Funding acquisition, Conceptualization.
Declaration of competing interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
AcknowledgementsWe would like to thank the midwives, gynecologists and doctors and nurses of the Youth Health Care that contributed to recruitment of participants. Additionally, we thank the scientific department of Spaarne Gasthuis for their help with recruitment and organization of the study.
Appendix A Supplementary dataSupplementary materialImage 1
Appendix A Supplementary dataSupplementary data to this article can be found online at https://doi.org/10.1016/j.vaccine.2024.126541.
| Pregnant women ( | Partners ( | |
| Age | 31.1 (4.3) | 33.2 (5.0) |
| Area of birth | ||
| 953 (95.2) | 904 (92.4) | |
| 48 (4.8) | 74 (7.8) | |
| Cultural or religious background | ||
| 225 (22.5) | 196 (20.0) | |
| 116 (11.6) | 108 (11.1) | |
| 660 (65.9) | 674 (68.9) | |
| Highest level of education | ||
| 41 (4.1) | 81 (8.3) | |
| 277 (22.7) | 344 (35.2) | |
| 390 (39.0) | 303 (31.0) | |
| 293 (29.3) | 250 (25.6) | |
| Employed | ||
| 476 (47.6) | 851 (87.0) | |
| 472 (47.2) | 117 (12.0) | |
| 53 (5.3) | 10 (1.0) | |
| Smoking/vaping | ||
| 22 (2.2) | 143 (14.6) | |
| 298 (29.8) | 308 (31.5) | |
| 681 (68.0) | 527 (53.9) | |
| Gestational age during questionnaire | 23.8 (8.7) | |
| Gravidity | 2 [1–2] | |
| Number of children | ||
| 547 (54.6) | ||
| 324 (32.4) | ||
| 130 (13.0) | ||
| Intention to breastfeed | ||
| 791 (79.0) | ||
| 137 (13.7) | ||
| 73 (7.3) | ||
| Having received childhood vaccination according to NIP or a similar program abroad | ||
| 944 (94.3) | 892 (91.2) | |
| 19 (1.9) | 24 (2.5) | |
| 14 (1.4) | 36 (3.7) | |
| Vaccinated or intention to vaccinate during pregnancy | ||
| 908 (90.7) | ||
| 343 (34.3) | ||
| 92 (9.2) | ||
| 17 (1.7) | ||
| Previous children vaccinated | ||
| 443 (97.1) | ||
| 10 (2.2) | ||
| 3 (0.7) | ||
| Parental intent to vaccinate newborn according to NIP* | ||
| 940 (93.9) | ||
| 17 (1.7) | ||
| 44 (4.4) | ||
| Familiarity* | ||
| 463 (46.3) | ||
| 408 (40.8) | ||
| 130 (13.0) | ||
| Experience* | ||
| 487 (48.7) | ||
| 514 (51.3) | ||
| 89 (17.3) | ||
| 330 (64.2) | ||
| 95 (18.5) | ||
| A Maternal vaccination | B Neonatal immunization | |||||||||||
| Doubt, likely yes | (Likely) No | Doubt, likely yes | (Likely) No | |||||||||
| Age | 0.99 | 0.93–1.05 | 0.662 | 0.91 | 0.82–1.00 | 0.055 | 1.02 | 0.97–1.08 | 0.449 | 0.95 | 0.87–1.03 | 0.198 |
| Weeks currently pregnant | 0.99 | 0.96–1.00 | 0.078 | 1.04 | 1.00–1.08 | 0.055 | 0.99 | 0.98–1.01 | 0.524 | 0.99 | 0.96–1.02 | 0.608 |
| Current number of children | ||||||||||||
| Reference | ||||||||||||
| 0.70 | 0.47–1.05 | 0.085 | 1.33 | 0.66–2.68 | 0.423 | 1.07 | 0.73–1.55 | 0.735 | 2.60 | 1.40–4.82 | ||
| 1.02 | 0.59–1.75 | 0.958 | 1.65 | 0.63–4.36 | 0.311 | 1.31 | 0.79–2.19 | 0.298 | 2.77 | 1.17–6.57 | ||
| Cultural or religious background | ||||||||||||
| Reference | ||||||||||||
| 1.17 | 0.68–2.01 | 0.569 | 1.23 | 0.48–3.15 | 0.664 | 1.12 | 0.69–1.85 | 0.643 | 0.68 | 0.27–1.68 | 0.403 | |
| 1.24 | 0.55–2.80 | 0.613 | 2.71 | 0.93–7.93 | 0.068 | 1.09 | 0.52–2.27 | 0.818 | 1.91 | 0.63–5.52 | 0.254 | |
| Level of education | ||||||||||||
| Reference | ||||||||||||
| 1.34 | 0.85–2.12 | 0.205 | 1.65 | 0.70–3.90 | 0.258 | 1.23 | 0.81–1.88 | 0.331 | 3.84 | 1.59–7.66 | ||
| 1.77 | 1.04–30.4 | 1.30 | 0.47–3.62 | 0.618 | 1.08 | 0.64–1.81 | 0.786 | 2.54 | 1.00–6.44 | |||
| 1.58 | 0.57–4.33 | 0.378 | 2.89 | 0.56–15.03 | 0.206 | 2.88 | 1.22–6.80 | 1.64 | 0.34–7.93 | 0.539 | ||
| Smoking/vaping | ||||||||||||
| Reference | ||||||||||||
| 0.81 | 0.54–1.20 | 0.286 | 0.69 | 0.33–1.41 | 0.306 | 1.22 | 0.84–1.76 | 0.300 | 0.65 | 0.34–1.26 | 0.200 | |
| 1.29 | 0.35–4.79 | 0.700 | 0.56 | 0.09–3.71 | 0.551 | 1.60 | 0.48–5.27 | 0.444 | 0.69 | 0.12–4.00 | 0.674 | |
| Intention to breastfeed | ||||||||||||
| Reference | ||||||||||||
| 1.59 | 0.93–2.71 | 0.089 | 2.57 | 0.87–7.59 | 0.089 | 2.05 | 1.21–3.46 | 4.16 | 1.40–12.32 | |||
| 2.75 | 1.30–5.79 | 3.47 | 0.82–14.68 | 0.091 | 1.82 | 0.84–3.94 | 0.131 | 10.09 | 2.80–36.46 | |||
| Age | 1.03 | 0.98–1.08 | 0.253 | 1.04 | 0.96–1.13 | 0.349 | 0.99 | 0.95–1.04 | 0.750 | 1.05 | 0.99–1.12 | 0.125 |
| Born in the Netherlands | 1.03 | 0.47–2.24 | 0.949 | 0.61 | 0.19–1.97 | 0.408 | 0.95 | 0.47–1.94 | 0.888 | 0.89 | 0.30–2.66 | 0.836 |
| Cultural or religious background | ||||||||||||
| Reference | ||||||||||||
| 0.83 | 0.47–1.49 | 0.538 | 1.59 | 0.61–4.18 | 0.347 | 1.24 | 0.74–2.09 | 0.422 | 1.20 | 0.58–3.09 | 0.705 | |
| 0.62 | 0.26–1.46 | 0.273 | 1.12 | 0.35–3.58 | 0.850 | 1.14 | 0.54–2.39 | 0.730 | 1.85 | 0.58–5.84 | 0.298 | |
| Level of education | ||||||||||||
| Reference | ||||||||||||
| 1.00 | 0.61–1.64 | 0.999 | 1.72 | 0.66–4.47 | 0.268 | 1.03 | 0.65–1.64 | 0.886 | 0.68 | 0.31–1.48 | 0.330 | |
| 1.29 | 0.76–2.18 | 0.340 | 1.61 | 0.58–4.49 | 0.361 | 1.56 | 0.95–2.58 | 0.080 | 0.70 | 0.31–1.59 | 0.393 | |
| 1.13 | 0.54–2.33 | 0.752 | 0.78 | 0.18–3.43 | 0.745 | 1.20 | 0.61–2.37 | 0.593 | 0.51 | 0.15–1.81 | 0.298 | |
| Employed | ||||||||||||
| Reference | ||||||||||||
| 0.75 | 0.44–1.29 | 0.304 | 0.21 | 0.04–1.01 | 0.051 | 1.11 | 0.69–1.77 | 0.672 | 0.45 | 0.16–1.26 | 0.128 | |
| 0.14 | 0.01–2.11 | 0.155 | 2.44 | 0.20–29.13 | 0.481 | 2.98 | 0.41–21.93 | 0.283 | 3.64 | 0.31–43.28 | 0.307 | |
| Smoking/vaping | ||||||||||||
| Reference | ||||||||||||
| 0.82 | 0.56–1.21 | 0.320 | 0.79 | 0.38–1.65 | 0.530 | 0.65 | 0.45–0.94 | 1.18 | 0.63–2.18 | 0.609 | ||
| 0.75 | 0.42–1.33 | 0.316 | 1.71 | 0.72–4.05 | 0.221 | 0.51 | 0.30–0.89 | 1.36 | 0.60–3.09 | 0.458 | ||
| Pregnant women NOT vaccinated as a child | 1.05 | 0.15–7.50 | 0.960 | 0.55 | 0.03–9.91 | 0.682 | 3.21 | 0.62–16.58 | 0.165 | 14.82 | 1.38–159.12 | |
| Partner NOT vaccinated as a child | 1.79 | 0.45–7.18 | 0.414 | 3.09 | 0.58–16.49 | 0.186 | 0.34 | 0.08–1.46 | 0.148 | 0.22 | 0.03–1.71 | 0.148 |
| No pertussis vaccination during pregnancy | 1.24 | 0.57–2.74 | 0.589 | 17.74 | 7.09–44.41 | 1.11 | 0.56–2.22 | 0.763 | 2.39 | 0.98–5.86 | 0.057 | |
| Parental vaccination intent for newborn for NIP | ||||||||||||
| Reference | ||||||||||||
| 2.41 | 0.11–51.38 | 0.573 | 16.77 | 0.83–337.67 | 0.066 | – | – | – | 20.08 | 3.13–128.6 | ||
| 10.39 | 2.82–38.36 | 8.15 | 1.58–42.01 | 2.50 | 0.93–6.73 | 0.069 | 7.07 | 2.28–21.94 | ||||
| Familiarity | ||||||||||||
| Reference | ||||||||||||
| 1.89 | 1.29–2.78 | 1.22 | 0.62–2.42 | 0.568 | 2.29 | 1.60–3.29 | 1.23 | 0.67–2.24 | 0.506 | |||
| 2.20 | 1.24–3.90 | 1.05 | 0.38–2.96 | 0.921 | 1.94 | 1.11–3.37 | 0.94 | 0.36–2.46 | 0.902 | |||
| Experience | ||||||||||||
| Reference | ||||||||||||
| 1.02 | 0.55–1.89 | 0.950 | 0.51 | 0.15–1.68 | 0.267 | 0.92 | 0.52–1.63 | 0.763 | 0.48 | 0.17–1.38 | 0.173 | |
| 0.94 | 0.63–1.41 | 0.777 | 0.47 | 0.22–0.99 | 0.88 | 0.60–1.29 | 0.513 | 0.56 | 0.29–1.07 | 0.079 | ||
| 0.37 | 0.17–0.83 | 0.64 | 0.22–1.88 | 0.421 | 0.72 | 0.39–1.34 | 0.302 | 0.44 | 0.16–1.23 | 0.118 | ||
| Maternal vaccination ( | Neonatal immunization (n = 632) | |
| Optimal protection child | 571 (86.8) | 547 (86.6) |
| Knowledge on severity of RSV | 497 (75.5) | 471 (74.5) |
| Recommendation by an expert (midwife, obstetrician, general practitioner, youth health doctor, paediatrician) | 209 (31.8) | 208 (32.9) |
| Recommendation by government or public health institute | 81 (12.3) | 69 (10.9) |
| Advise friends and/or family | 35 (5.3) | 27 (4.3) |
| Advise expert in the media | 15 (2.3) | 12 (1.9) |
| People in the surrounding opt for prophylaxis | 4 (0.6) | 4 (0.6) |
| Recommendation by influencers or other public figures | 2 (0.3) | 2 (0.3) |
| Other* | 9 (1.4) | 6 (0.9) |
| * Other: | ||
( | ||
| Not enough knowledge on RSV or the vaccination | 15 (42.9) | 143 (56.3) |
| Afraid that something happens to unborn child after vaccination | 12 (34.3) | 59 (23.2) |
| Wishes that infant experiences a natural RSV infection | 9 (25.7) | 17 (6.7) |
| No insurance coverage | 4 (11.4) | 88 (34.6) |
| Believe that infant will not become seriously ill from RSV | 4 (11.4) | 18 (7.1) |
| Afraid of side effects of vaccination | 4 (11.4) | 27 (10.6) |
| Too many other vaccinations recommended during pregnancy | 4 (11.4) | 20 (7.9) |
| Afraid of shot/needle | 0 (0.0) | 13 (5.1) |
| Other** | 5 (14.3) | 11 (4.3) |
| ** Other: | ||
| More information about both shots, especially regarding their effectiveness and safety | 750 (74.9) |
| Advice from an expert, such as the midwife, gynaecologist, general practitioner, youth health doctor, or paediatrician | 586 (58.5) |
| Information about the RS-virus and its effects on young children | 580 (57.9) |
| Information about whether the vaccine is covered by insurance | 277 (27.7) |
| Advice from the government, for example through commercials or the RIVM website | 176 (17.6) |
| Advice from an expert in the media | 36 (3.6) |
| Information via (social) media such as TV, magazines, podcasts, and Instagram | 34 (3.4) |
| Advice from friends and/or family | 27 (2.7) |
| Advice from well-known individuals (for example, influencers) | 4 (0.4) |
| Other⁎ | 2 (0.2) |
Copyright Elsevier Limited Jan 12, 2025