ABSTRACT
Maternal vaccination for seasonal influenza is currently not listed as a routine vaccination in the national vaccination schedule of Japan. However, many pregnant women voluntarily receive an influenza vaccination. We explored the factors related to influenza vaccine uptake. We particularly focused on factors related to any recommendation, such as advice or suggestions from another individual. We conducted a cross-sectional web-based questionnaire survey in Japan among pregnant women or mothers who had recently given birth in March 2017 and 2018. Logistic regression models were used to determine the factors influencing vaccination uptake. Key individuals regarding maternal vaccination were examined using the network visualization software Gephi. The total number of valid responses was 2204 in 2017 and 3580 in 2018. Over 40% of respondents had been vaccinated with the seasonal influenza vaccine at some point in both years. Of the vaccinated respondents, over 80% received advice regarding the influenza vaccination. Obstetricians were the most common source of advice in both years. Among respondents who chose more than two sources, the largest link in the network of sources was found between the obstetrician and family members. Attention to public concern or potential recommenders, by public health authorities, not just pregnant women, about the benefits of maternal influenza vaccination is important.
Introduction
Influenza infection in pregnant women is associated with an increased risk of severe disease resulting in hospitalization or death.1,Citation2 In many countries, public health authorities recommend that pregnant women should be a priority group for seasonal influenza vaccination.Citation3 In 2012, the World Health Organization recommends in a position paper that pregnant women should be the highest-priority recipients for the seasonal influenza vaccination.Citation1
A 2018 Cochrane Review examined influenza vaccination among healthy adults and reported modest effectiveness of the vaccine for protecting pregnant women.Citation4 Some previous studies reported that the influenza vaccine reduced infection among pregnant women in Japan in the 2009 H1N1 pandemic.Citation5 Ohfuji et al. recently reported that maternal influenza vaccination decreased influenza occurrence and hospitalization among infants in Japan.Citation6
Previous studies in some countries showed that pregnant women were less likely to have received the seasonal influenza vaccination compared with other risk groups.Citation7,Citation8 Various strategies for diffusion of the vaccine have been explored.Citation7-Citation9
In Japan, the seasonal influenza vaccine is a voluntary vaccine except in persons older than 65 years. Maternal influenza vaccination is also voluntary and is not listed in the routine vaccination schedule. That is, the vaccination is not officially recommended as a routine vaccination and involves a financial cost for pregnant women. The instructions included in the package insert of the influenza vaccine for medical staff state, “Pregnant women should be administered only if the potential benefits outweigh the risks.” The estimated influenza vaccine uptake rate in people aged 13 to 65 years was 24.1% during the 2009–2010 influenza season and 28.6% during the 2010–2011 season.Citation10 In contrast, according to a pilot survey among 11 hospitals conducted during the 2013–2014, 2014–2015 influenza season, 51% of pregnant women were vaccinated for influenza.Citation11,Citation12 Thus, pregnant Japanese women can actively choose to receive the influenza vaccination.
The purpose of this study was to explore the factors related to the active decision to undertake influenza vaccination among pregnant women in Japan despite its not being included in the routine vaccination schedule. We also investigated multiple recommendations regarding maternal influenza vaccination, such as advice or suggestions received by the respondents from another individual.
Methods
We conducted a cross-sectional web-based questionnaire survey in Japan among pregnant women or mothers. This survey was specifically designed for this study of maternal vaccination and conducted using a survey panel of a private research company because there is no official panel of pregnant women in Japan. The survey was closed; i.e., it was only open to respondents targeted by the survey.Citation13 We calculated the necessary sample size as 1605 (assuming P1 = 0.50 and P2 = 0.45, with the significance level α set at 0.05 and power set at 0.80) to detect a difference in vaccine uptake rate in each year.Citation14 P1 was based on the findings of Yamada et al.Citation11 and P2 assumed a 10% decrease in vaccine uptake rate based on the findings of Ohfuji et al.Citation6 in this survey.
The survey was conducted in March 2017 and March 2018. The 2017 and 2018 questionnaires were almost identical, but with some minor improvements in the 2018 version. We used a survey company that maintains a database of potential respondents for many kinds of market research surveys. The participants had independently registered with the research company prior to the study. In return for their participation in surveys such as ours, they are eligible to receive incentives from the survey company in the form of points that are exchangeable for gift cards once they reach a certain threshold. In the current study, only women who had reported pregnancy on the routine registration survey were invited to participate. Invitations were sent by e-mail and via a notification on each invitee’s personal homepage on the survey company’s website. The respondents were then able to access the questionnaire site.
This questionnaire was developed in a pretest to identify any problems or areas of misunderstanding. The pretest was carried out with a group of mothers independent of those who subsequently took the web-based survey. This study was approved by the ethics committee of Meiji Pharmaceutical University. Respondents answered the questionnaire via a website. Only respondents who provided informed consent answered the questionnaire. Respondents who completed the questionnaire were included in the total number of respondents.
The questionnaire included queries relating to the respondents’ basic characteristics and vaccination-related questions. The questions gathered information about age, working status, pregnancy status (including month of pregnancy), educational background, and household income. The vaccination-related questions examined annual influenza vaccination status (every year, sometimes, never), knowledge about the influenza vaccine for pregnant women, whether respondents had received advice about the vaccine, and whether respondents had received the influenza vaccination during pregnancy. In the 2017–2018 season, there was a temporary shortage in the supply of influenza vaccine in Japan.Citation15 Therefore, in the 2018 survey, the response “could not be vaccinated because of the vaccine shortage” was included in the question about receiving the influenza vaccination during pregnancy, in addition to the “yes” or “no” response options. Differences between the 2017 and 2018 results were examined with the chi-squared test, t-test, and one-way analysis of variance (ANOVA). To determine the factors influencing vaccination during pregnancy, we analyzed bivariate and multivariate logistic models for the following variables: age, homemaker, pregnancy at the survey point, having annual influenza vaccinations, having other child/children, education period (years), awareness of influenza vaccination for pregnant women (yes), having received a recommendation about vaccination (yes) and income. We conducted analyzes on the pooled population and subgroups in the 2017 and 2018 surveys.
Regarding recommendation such as advice or suggestions, we included a question about the source of advice or suggestions directly regarding the influenza vaccination during pregnancy. Multiple answers to this question were allowed, and the options were as follows: obstetrician, general practitioner, pediatrician, nurse or midwife, friend, family member, and other. Using Gephi 0.9.2 software,Citation16 we conducted a network analysis of this question to assess the relationship among key individuals who might influence a pregnant woman’s decisions about vaccination, and created a graphic visualization of these relationships. We used the ForceAtlas2 algorithm in Gephi for the layout. This is a special force-directed algorithm, and the graphs are shown as nodes and edges based on the data.Citation17 The visualizations are useful to find network structure among the options and data. In health research, the method is used in the health informatics field.Citation18
We identified and included women who were pregnant or mothers within 3 months after delivery at the time of the survey to assess vaccine uptake during pregnancy. If participants did not meet the criteria, their responses were excluded from the analysis.
Results
The total number of valid responses was 2204 (29% of total invited population) in 2017 and 3580 (48% of total invited population) in 2018. The mean age of respondents was 32.5 years in 2017 and 32.3 years in 2018. The basic characteristics of the study respondents are listed in .
Table 1. Characteristics of respondents in the survey conducted in 2017 and 2018, in Japan.
Table 2. The key sources who might influence a pregnant woman’s decisions about vaccination in the survey conducted in 2017 and 2018, in Japan.
Over 30% of respondents had been vaccinated with the seasonal influenza vaccine annually (38.7% in 2017 and 34.9% in 2018). Over 40% of respondents had been vaccinated with the seasonal influenza vaccine at some point (41.2% in 2017 and 44.1% in 2018). Approximately 20% of respondents had never been vaccinated with the seasonal influenza vaccine (20.1% in 2017 and 21.0% in 2018). Approximately half of the respondents were vaccinated during pregnancy (53.5% in 2017 and 47.4% in 2018). In 2018, 173 respondents (4.8% of the total respondents in 2018) were not able to be vaccinated because of the vaccine shortage.
Several factors, including pregnancy status, other children, recommendation, and influenza vaccine uptake, showed significant differences between 2017 and 2018. More than the half of the respondents had a recommendation regarding the influenza vaccination (58.7% [1293/2204] in 2017 and 55.9% [2000/3580] in 2018). Of those who received advice, 1018 (78.7% [1018/1293]) and 1456 (72.8% [1456/2000]) respondents in 2017 and 2018, respectively, were vaccinated (). Of the vaccinated respondents (1180 in 2017 and 1697 in 2018), 86.3% (1018/1180) in 2017 and 85.8% (1456/1697) in 2018 received advice regarding the influenza vaccination. Obstetricians were the most common source of advice in both years (77.9% [793/1018] in 2017 and 79.9% [1164/1456] in 2018) (). Of vaccinated respondents who received advice, 73.8% (751/1018) and 73.1% (1064/1456) in 2017 and 2018, respectively, reported a single source of advice. The remaining respondents chose two or more options. The links between the categories of sources of advice were visualized using graphics created in Gephi 0.9.2 for both vaccinated and non-vaccinated respondents ( and ). The size of the circles shows the frequency of appearance and the lines connecting the nodes show the weighting of the relationships. A line weight between options in the graphic was added if respondents chose more than two options. Among respondents who chose more than two options, the link shown as the line weight between the obstetrician and family members was largest in both 2017 and 2018. The combination of obstetrician and family member was the most common, followed by obstetrician and either midwife/nurse or friend, in both years.
Figure 1. Sources who gave recommendation regarding vaccination among vaccinated respondents in 2017.
Figure 2. Sources who gave recommendation regarding vaccination among vaccinated respondents in 2018.
In contrast, among non-vaccinated respondents, 31.2% (181/581) and 26.5% (454/1710) had received advice regarding vaccination in 2017 and 2018, respectively. Of these respondents, 81.2% (147/181) and 78.6% (357/454) in 2017 and 2018, respectively, reported a single source of advice. The links among non-vaccinated respondents who received advice regarding vaccination are shown in and .
Figure 3. Sources who gave recommendation regarding vaccination among non-vaccinated respondents in 2017.
Figure 4. Persons who gave recommendation regarding vaccination among non-vaccinated respondents in 2018.
Three logistic regression models (pooled analysis and independent analyses) in 2017 and 2018 were examined with bivariate and multivariate analyses to determine the factors influencing vaccination uptake (). In the pooled model, pregnancy at the survey point (no), education period (longer), having annual received influenza vaccination (yes), awareness of influenza vaccination for pregnant women (yes), and received recommendation (yes) were significantly related to vaccine uptake in both the bivariate and multivariate models (). Age (older), homemaker (no), income (higher), and survey in 2017 were significantly related to vaccine uptake only in the bivariate model. Having other child/children was significantly related to vaccine uptake only in the multivariate model.
Table 3. Logistic regression model in the survey conducted in 2017 and 2018, in Japan.
In the 2017 model, having annual received influenza vaccination (yes), awareness of influenza vaccination for pregnant women (yes), and received recommendation (yes) were significantly related to vaccine uptake in both the bivariate and multivariate models. Age (older), homemaker (no), pregnancy at the survey point (no), education period (longer), and income in 2017 were significantly related to vaccine uptake only in the bivariate model. Having other child/children was significantly related to vaccine uptake only in the multivariate model.
In the 2018 model, pregnancy at the survey point (no), having other child/children, education period (longer), having annual received influenza vaccination (yes), awareness of influenza vaccination for pregnancy (yes), and received recommendation (yes) were significantly related to vaccine uptake in both the bivariate and multivariate models. Age (older), homemaker (no), and income (higher) were significantly related to vaccine uptake only in the bivariate model.
Discussion
Maternal vaccination for seasonal influenza is currently not listed as a routine vaccination in the national vaccination schedule of Japan. However, many pregnant women make an active decision to receive an influenza vaccination.Citation11 In this study, we explored the factors associated with influenza vaccine uptake in pregnant women. We also used a network analysis approach to explore and visualize the relationships of key individuals influencing the decision of whether to undergo maternal influenza vaccination.
Yamada et al. reported that the vaccination coverage of pregnant women was approximately 50% in the 2013–2014 and 2014–2015 influenza seasons in Japan.Citation11,Citation12 In the current study, approximately half of pregnant women (53.5% in 2017 and 47.4% in 2018) were vaccinated for seasonal influenza. Although the influenza vaccination is voluntary and not a routine vaccination, most pregnant women surveyed knew that the influenza vaccination was available for pregnant women in Japan. Knowledge of influenza and/or the benefits of vaccination were found to be important factors in vaccine acceptance in a review of previous studies.Citation9,Citation19 Most unvaccinated respondents in the current study had not received information regarding vaccination. These results suggest that information regarding influenza vaccination during pregnancy should be made widely available to pregnant women. Subsidy of vaccination for pregnant women might be a potential method of improving their awareness.
Markers of social status, such as education period, were identified as a significant factor in the univariate and/or multivariate model in this study. A relationship between education and vaccine uptake has been reported in previous studies,Citation20,Citation21 and more highly educated populations may have more opportunities to get information on influenza infection in pregnancy.Citation20 In Japan, influenza vaccination is voluntary and is provided at a cost of around 3500 JPY (approximately 30 USD) for a single injection.Citation22 A previous study in Belgium reported that lower income was strongly correlated with non-vaccination, even when vaccines were available free of charge.Citation21 However, in the current study, we found no clear relationship between education period or income and vaccine uptake. The effect of those factors should be explored carefully in future studies to examine the existence of biases related to income.
The results of the present study indicate the possibility that obstetricians are strong influencers of maternal influenza vaccine uptake because pregnant women in Japan usually see obstetricians during pregnancy.Citation20 The guidelines for obstetric practice in Japan established by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists show evidence for the effectiveness of vaccination for preventing severe influenza infection.Citation23 Since the influenza A (H1N1) pandemic in 2009, considerable evidence related to the safety and effectiveness of this vaccination has emerged.Citation23 Pregnant women tend to place a great deal of trust in obstetricians’ advice supported by the guidelines and current evidence. Furthermore, about 30% of vaccinated respondents had received more than two kinds of recommendation regarding influenza vaccine uptake. The combination of obstetricians’ advice and social relationships, such as family and friends, was also influential. In future, it will be important for public health authorities to inform the wider general public about the benefits of maternal influenza vaccination.
In the current study, some respondents who had received more than two kinds of recommendation were not vaccinated, in both study years. This finding indicates that hesitation regarding vaccination during pregnancy can remain despite receipt of advice.Citation21 Provision of information regarding the safety of vaccination during pregnancy may also be effective for increasing uptake.
This study had several limitations that should be considered. First, the surveys were conducted in both 2017 and 2018. Because of technical issues, the duration of pregnancy in different groups of respondents differed between groups. Additionally, the 2018 result may have been affected by the nationwide shortage of the vaccine that year. Second, the survey was performed using a cross-sectional web survey with a closed design. Therefore, the survey population in this study may have been biased. However, the proportional influenza vaccine uptake was similar to that reported in a previous study.Citation11,Citation12 Third, although the questionnaire in the current study included 10 questions, there are many factors that could potentially influence vaccine uptake. We focused on the key individuals who provided information via their recommendations in this study. However, possible information sources were not limited to the options included in the questionnaire. For example, we did not ask respondents about information obtained via social media, such as social networking services, or web services for questions and answers provided by private companies.Citation24 Thus, other information sources may also have influenced vaccine uptake.
Conclusion
It is important for public health authorities to inform the wider general public including potential recommenders, not just pregnant women, about the benefits of maternal influenza vaccination. Recommendations regarding maternal influenza vaccination from key individuals such as obstetricians, friends, and family members are important for increasing vaccination uptake.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Additional information
Funding
References
- World Health Organization. Weekly epidemiological record. No.47, 2012, 87:461–76. Vaccines against influenza WHO position paper November 2012. [accessed 2018 Dec 11]. https://www.who.int/wer/2012/wer8747.pdf?ua=1.
- Center for Disease Control and Prevention. Influenza (Flu) ACIP Recommendations and pregnancy (Flu) [accessed 2018 Dec 11]. https://www.cdc.gov/vaccines/pregnancy/hcp-toolkit/acip-recs.html
- Steinhoff MC, MacDonald N, Pfeifer D, Muglia LJ. Influenza vaccine in pregnancy: policy and research strategies. Lancet. 2014;383(9929):1611–13. doi:10.1016/S0140-6736(14)60583-3.
- Demicheli V, Jefferson T, Ferroni E, Rivetti A, Di Pietrantonj C. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2018:CD001269.
- Nakai A1, Saito S, Unno N, Kubo T, Minakami H. Review of the pandemic (H1N1) 2009 among pregnant Japanese women. J Obstet Gynaecol Res. 2012;38:757–62. doi:10.1111/jog.2012.38.issue-5.
- Ohfuji S, Deguchi M, Tachibana D, Koyama M, Takagi T, Yoshioka T, Urae A, Ito K, Kase T, Maeda A, et al. Osaka pregnant women influenza study group. Protective effect of maternal influenza vaccination on influenza in their infants: A prospective cohort study. J Infect Dis. 2018;217:878–86.
- Wong VW, Lok KY, Tarrant M. Interventions to increase the uptake of seasonal influenza vaccination among pregnant women: A systematic review. Vaccine. 2016;34:20–32. doi:10.1016/j.vaccine.2015.11.020.
- Yuen CY, Tarrant M. Determinants of uptake of influenza vaccination among pregnant women - a systematic review. Vaccine. 2014;32:4602–13. doi:10.1016/j.vaccine.2014.06.067.
- Bisset KA, Paterson P. Strategies for increasing uptake of vaccination in pregnancy in high-income countries: A systematic review. Vaccine. 2018;36:2751–59. doi:10.1016/j.vaccine.2018.04.013.
- Nobuhara H, Watanabe Y, Miura Y. Wagakuni ni okeru influenza vaccine sesshuritsu no suikei. Jnp. J. Public Health. 2014;61:354–59. in Japanese.
- Yamada T, Abe K, Baba Y, Inubashiri E, Kawabata K, Kubo T, Maegawa Y, Fuchi N, Nomizo M, Shimada M, et al. Vaccination during the 2013–2014 influenza season in pregnant Japanese women. Eur J Clin Microbiol Infect Dis. 2015;34:543–48. doi:10.1007/s10096-014-2259-8.
- Yamada T, Kawakami S, Yoshida Y, Kawamura H, Ohta S, Abe K, Hamada H, Dohi S, Ichizuka K, Takita H, et al. 2014–2015 among pregnant Japanese women: primiparous vs multiparous women. Eur J Clin Microbiol Infect Dis. 2016;35(4):665–71. doi:10.1007/s10096-016-2585-0.
- Eysenbach G. Improving the quality of Web surveys: the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). J Med Internet Res. 2004;6:e34. doi:10.2196/jmir.6.3.e34.
- Fleiss JL, Levin B, Paik MC. Statistical methods for rates and proportions. 3rd ed. New Jersey, USA: Wiley-Interscience. 2003.
- Japan times [accessed 2019 Jan 6]. https://www.japantimes.co.jp/news/2017/10/14/national/science-health/nation-bracing-for-tight-supply-of-flu-vaccines-this-winter/#.XDFlmmlUuCo.
- Bastian M, Heymann S, Jacomy M Gephi: an open source software for exploring and manipulating networks. International AAAI Conference on Weblogs and Social Media. 2009 [accessed 2019 Oct 18]. https://gephi.org/publications/gephi-bastian-feb09.pdf
- Jacomy M, Venturini T, Heymann S, Bastian M. ForceAtlas2, a continuous graph layout algorithm for handy network visualization designed for the Gephi software. PLoS One. 2014;9(6):e98679. doi:10.1371/journal.pone.0098679.
- Saheb T, Saheb M. Analyzing and visualizing knowledge structures of health informatics from 1974 to 2018: A bibliometric and social network analysis. Healthc Inform Res. 2019;25(2):61–72. doi:10.4258/hir.2019.25.2.61.
- Poliquin V, Greyson D, Castillo E. A systematic review of barriers to vaccination during pregnancy in the Canadian context. J Obstet Gynaecol Can. 2018;pii: S1701–2163(18)30515–2.
- Laenen J, Roelants M, Devlieger R, Vandermeulen C. Influenza and pertussis vaccination coverage in pregnant women. Vaccine. 2015;33:2125–31. doi:10.1016/j.vaccine.2015.03.020.
- Maertens K, Braeckman T, Blaizot S, Theeten H, Roelants M, Hoppenbrouwers K, Leuridan E, Van Damme P, Vandermeulen C. Coverage of recommended vaccines during pregnancy in Flanders, Belgium. Fairly good but can we do better? Vaccine. 2018;36(19):2687–93. doi:10.1016/j.vaccine.2018.03.033.
- Q life. [in Japanese]. [accessed 2018 Dec 11]. https://www.qlife.co.jp/news/7713.html.
- Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists - 2017 edition. Japan society of obstetrics and gynecology and Japan association of obstetricians and gynecologists In Japanese.
- Nawa N, Kogaki S, Takahashi K, Ishida H, Baden H, Katsuragi S, Narita J, Tanaka-Taya K, Ozono K. Analysis of public concerns about influenza vaccinations by mining a massive online question dataset in Japan. Vaccine. 2016;34:3207–13. doi:10.1016/j.vaccine.2016.01.008.