Objective: Due to lack of information regarding attitudes and behaviors of pregnant women towards vaccines, we sought to study the acceptability of influenza, pertussis and a hypothetical Group B Streptococcus (GBS) vaccine during pregnancy from a global perspective.

Method: Data were abstracted from responses of 782 pregnant women from North America, Europe and Brazil to an industry sponsored online survey in 2014. Participants were provided brief disease and vaccine synopses prior to completing the survey.

Results: Significant differences in vaccine acceptance were observed across regions and vaccine types. Women from Brazil had the highest rate while those from Europe had the lowest rate of acceptance for all vaccines. For all regions and all vaccine types, physician recommendation positively influenced patient acceptance of vaccines (p<0.05). The GBS vaccine was the highest rated for vaccine acceptance globally. Neonatal protection was a significantly stronger motivator compared to self-protection for each region and vaccine type. Working status, income, parity and compliance with medical care were significantly associated with vaccine acceptance but in an inconsistent manner for region and vaccine type. Health care providers were considered as the most credible source and medical and pregnancy specific websites were considered the most credible online source of pregnancy related information across all regions.

Conclusion: Understanding regional differences in the acceptability of vaccines among pregnant women, effective use of the internet and most importantly involvement of the physician in disseminating vaccine related information to the public is key to increasing the uptake of vaccines during pregnancy.

Keywords: Group B Streptococcus, Pregnancy, Global diversity, Vaccine

Abbreviations: GBS: Group B Streptococcus 

INTRODUCTION

We had the unique opportunity to examine globally acquired data extracted from an industry sponsored patient survey to address some of the above issues. We opted to examine three vaccines, two of which are already commercially available and one is a hypothetical vaccine in development. The influenza vaccine was selected because of the anticipated well-recognized disease burden and long established recommendation for use in pregnancy. This vaccine has been supported primarily for its benefit to maternal health, although benefits to the neonate have also been reported [8-12]. The second vaccine, the pertussis vaccine, is less recognized for its disease burden in adults and to the newborn, and has only recently been advocated for use in pregnancy. Although benefits to the mother from pertussis vaccination are identifiable, the main scope of the current recommendations focuses on protection of the newborn child [14,15]. The last (hypothetical) vaccine is directed against Group B Streptococcus (GBS) and is currently being investigated for use in pregnancy with an exclusive focus on neonatal benefit [22]. We sought to better understand the perspectives of pregnant patients for each of these vaccines and their willingness to receive them during pregnancy.

MATERIALS AND METHODS

A total of 782 women between 12 and 40 weeks of pregnancy from USA, Canada, Brazil, France, Germany, Ireland and the Netherlands participated in a twenty minute online survey in 2014. Written informed consent for participation in the study was obtained from participants. This industry sponsored survey was primarily focused on attitudes and behaviors of pregnant women regarding influenza, pertussis and GBS vaccination during pregnancy. It consisted of five sections with total 54 questions related to general prenatal health behavior, demographic data of participants, acceptability of the three vaccines, motivation for receiving these vaccines and sources of pregnancy related information. Being up-to-date with other vaccines and laboratory testing was considered as being compliant with healthcare. Participants were supplied disease profiles and vaccine synopses prior to completing the survey (available upon request). Questions related to the acceptability of the three vaccines were answered using a scale of 1 to 10, with 1 being “Not at all likely/strongly disagree” and 10 being “Extremely likely/strongly agree”. No exclusion criteria were applied. Willingness to undertake the online survey was the only requirement.

Hierarchical cluster analyses demonstrated that data from countries within each region e.g. countries within Europe as well as countries within North America exhibited similar patterns. Hence, further analysis was performed by grouping data into 3 regions– North America (USA and Canada - 400 women), Europe (France, Germany, Ireland and the Netherlands - 282 women) and Brazil (100 women). Acceptability of vaccines scored on a scale of 1 to 10, was divided into dichotomous variables: A score of 8-10 was considered as an affirmatory response and 1-3 was considered as declinatory response. Mean scores were also calculated for a comparison of acceptability of vaccines.

Descriptive statistical analysis was performed by utilizing a z test for dichotomous variables and a t test for continuous variables. Factors associated with acceptability of vaccines were analyzed using univariate linear and logistic regression analysis. Linear regression models were based on acceptability of vaccines as dependent variable (ranging from 1 to 10) with factors controlled for collinearity. A sample size calculation was not performed in this cross sectional survey study.

RESULTS

The results of this survey demonstrate a relatively strong, positive attitude towards acceptability of the influenza, pertussis and the hypothetical GBS vaccines in North America and Brazil, with more of a restrained response from women in Europe. However, no region in our study achieved a level of acceptability comparable to that anticipated if pediatric vaccination was being discussed [23]. These numbers also fall short of Healthy People 2020 and WHO goals related to adult vaccination [24,25]. Physician recommendation appears to be an important factor in acceptability of vaccines in all regions evaluated. This is consistent with previous studies that have reported increased acceptability to vaccination during pregnancy when a health care provider was involved in the process [19,26,27].

This study has demonstrated that there are striking regional variations in acceptability of vaccines during pregnancy despite the fact that the same information regarding these diseases and vaccines was provided to all the study participants. Generally, women in North America accepted all vaccines at similar rates and did not discriminate between the types of vaccines. This likely reflects a general positive attitude toward vaccination in this region. Furthermore, women in North America, who were compliant with their health, were more receptive toward vaccination.

Similarly, there was a strong positive response in favor of all three vaccines among women in Brazil. Along with protection of baby, there was an increase in vaccine acceptability in these women due to concerns of risk to self-health. Thus the very high rate of vaccine acceptance in this region could be a reflection of dual motivation for protecting baby as well as self.

Women vaccine acceptance during pregnancy was the lowest in Europe. Although they followed similar trends toward the desire to protect their neonates via maternal vaccination, their negativity towards vaccine uptake may be reflected in overall attitudes toward health care, in that, these same individuals reported reduced compliance with health related concerns.

Although there were no regional differences in demographic factors like age and parity, women in the study differed with respect to their education, working status, household income and area of residence. These demographic differences were associated with and may have contributed to the regional variations in vaccine acceptance.

Several studies have looked at potential barriers for vaccination. It seems clear that physician knowledge and positive attitude towards vaccination is an important contributor for increasing vaccine uptake among women [19,20,27-33]. Fear of vaccines and lack of disease-related knowledge in the pregnant population have been shown as hindrances to vaccine uptake [34,35]. It is not only the provision of information but also its content that is crucial. For example, women were more willing to accept the influenza vaccine when they were informed about a “two for one” benefit of the vaccine [36]. There is a need for health messages like these to be efficiently conveyed to women.

Communication strategies to improve vaccination rates among pregnant women are being evaluated with randomized controlled trials [37-39]. Patient targeted educational interventions through verbal discussion, information pamphlets, and text messaging [35,37,40-42] have made moderate improvements in vaccination uptake rates in regional studies, yet there is a need for continued efforts to achieve additional advancements on a more global level. Our study demonstrated that the internet was the second most common resource that many women relied upon for pregnancy related information. Updating medical websites with maternal immunization topics and using the internet as a means of propagation of relevant vaccine information, their availability and cost should be a focused initiative. Although these resources were viewed by many participants in our study as credible to obtain health related information, health professionals were still prioritized as the most reliable resource. Thus, dissemination of relevant risk vs. benefit information of maternal immunization towards fetal and neonatal disease prevention by health care providers remains key to increasing vaccine uptake among pregnant women globally. Most importantly, understanding regional variations during such efforts may yield better results than the adoption of universal policies and campaigns to promote the use of vaccines during pregnancy.

ACKNOWLEDGEMENT

We acknowledge Borislav Domuschiev (Managing Partner, cQuest Ltd.) and Martin Dimov (Director, Data Science, cQuest Ltd.) for their assistance with statistical analysis of the data. cQuest is a market research and consulting service located in Amsterdam, Netherland). Dr. Bernard Gonik and Dr. Manasi Patwardhan have no financial disclosures pertaining to this study or manuscript development.

We also acknowledge Elvira Ponce, MD and Catalina Rios Driscoll, MBA from GlaxoSmithKline LLC, Cambridge, MA 02139 for their contribution with providing the questionnaire and editing the manuscript.

DISCLOSURE

Novartis Vaccines and Diagnostics, Inc. provided unrestricted access to the global survey database referred to in this paper and also provided financial support for the independent statistical analysis of data cited on this manuscript. On March 2, 2015, GlaxoSmithkline completed acquisition of Novartis Vaccines Non-flu vaccines business and now owns the data cited.

CONSENT TO PARTICIPATE

Written informed consent for participation in the study was obtained from participants.

ETHICS APPROVAL

We have used already existing data that has no identifiers attached.

This falls under the Exemption categories according to Wayne State University IRB.

CONSENT TO PUBLISH

Not applicable

COMPETING INTERESTS

1.       Swamy GK, Heine RP (2015) Vaccinations for pregnant women. Obstet Gynecol 125: 212-226.

2.       Cantu J, Tita AT (2013) Management of influenza in pregnancy. Am J Perinatol 30: 99-103.

3.       Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR (1998) Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 148: 1094-1102.

4.       Centers for Disease C Prevention (2011) Maternal and infant outcomes among severely ill pregnant and postpartum women with 2009 pandemic influenza A (H1N1)--United States, April 2009-August 2010. MMWR Morbid Mortal Wkly Rep 60: 1193-1196.

5.       Louie JK, Acosta M, Jamieson DJ, Honein MA; California Pandemic Working Group (2010) Severe 2009 H1N1 influenza in pregnant and postpartum women in California. N Engl J Med 362: 27-35.

6.       Pierce M, Kurinczuk JJ, Spark P, Brocklehurst P, Knight M, et al. (2011) Perinatal outcomes after maternal 2009/H1N1 infection: National cohort study. BMJ 342: d3214.

7.       Varner MW, Rice MM, Anderson B, Tolosa JE, Sheffield J, et al. (2011) Influenza-like illness in hospitalized pregnant and postpartum women during the 2009-2010 H1N1 pandemic. Obstet Gynecol 118: 593-600.

8.       Lu PJ, Santibanez TA, Williams WW, Zhang J, Ding H, et al. (2013) Surveillance of influenza vaccination coverage--United States, 2007-2008 through 2011-2012 influenza seasons. Morbid Mortal Wkly Rep 62: 1-28.

9.       Bridges CB, Thompson WW, Meltzer MI, Reeve GR, Talamonti WJ, et al. (2000) Effectiveness and cost-benefit of influenza vaccination of healthy working adults: A randomized controlled trial. JAMA 284: 1655-1663.

10.    Kissling E, Valenciano M; Team IMC-CS (2012) Early estimates of seasonal influenza vaccine effectiveness in Europe among target groups for vaccination: Results from the I-MOVE multicentre case-control study, 2011/2012. Euro Surveill 17: pii: 20146.

11.    Jimenez-Jorge S, de Mateo S, Pozo F, Casas I, Garcia Cenoz M, et al. (2012) Early estimates of the effectiveness of the 2011/2012 influenza vaccine in the population targeted for vaccination in Spain, 25 December 2011 to 19 February 2012. Eur Communicable Dis Bull 1.

12.    Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, et al. (2008) Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med 359: 1555-1564.

13.    Tanaka M, Vitek CR, Pascual FB, Bisgard KM, Tate JE, et al. (2003) Trends in pertussis among infants in the United States, 1980-1999. JAMA 290: 2968-2975.

14.    Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-Sanchez I, et al. (2006) Preventing tetanus, diphtheria and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recomm Rep 55: 1-37.

15.    Centers for Disease Control and Prevention (CDC) (2011) Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant aged <12 months --- Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep 60: 1424-1426.

16.    Van Dyke MK, Phares CR, Lynfield R, Thomas AR, Arnold KE, et al. (2009) Evaluation of universal antenatal screening for group B streptococcus. N Engl J Med 360: 2626-2636.

17.    Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases NCfI; Respiratory Diseases CfDC Prevention (2010) Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Morb Mortal Wkly Rep 59: 1-36.

18.    Fiore AE, Uyeki TM, Broder K, Finelli L, Euler GL, et al. (2010) Prevention and control of influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep 59: 1-62.

19.    Blanchard-Rohner G, Meier S, Ryser J, Schaller D, Combescure C, et al. (2012) Acceptability of maternal immunization against influenza: The critical role of obstetricians. J Matern Fetal Neonatal Med 25: 1800-1809.

20.    Clark SJ, Adolphe S, Davis MM, Cowan AE, Kretsinger K (2006) Attitudes of US obstetricians toward a combined tetanus-diphtheria-acellular pertussis vaccine for adults. Infect Dis Obstet Gynecol 2006: 87040.

21.    McQuaid F, Jones C, Stevens Z, Plumb J, Hughes R, et al. (2014) Attitudes towards vaccination against group B streptococcus in pregnancy. Arch Dis Childhood 99: 700-701.

22.    Madhi SA, Dangor Z, Heath PT, Schrag S, Izu A, et al. (2013) Considerations for a phase-III trial to evaluate a group B Streptococcus polysaccharide-protein conjugate vaccine in pregnant women for the prevention of early- and late-onset invasive disease in young-infants. Vaccine 31: D52-57.

23.    Smith PJ, Singleton JA; National Center for I, Respiratory D; Centers for Disease C, Prevention (2011) County-level trends in vaccination coverage among children aged 19-35 months - United States, 1995-2008. MMWR Surveill Summ 60: 1-86.

24.    Centers for Disease C, Prevention (2011) Ten great public health achievements--United States, 2001-2010. MMWR Morb Mortal Wkly Rep 60: 619-623.

25.    Koh HK, Blakey CR, Roper AY (2014) Healthy People 2020: A report card on the health of the nation. JAMA 311: 2475-2476.

26.    Maher L, Hope K, Torvaldsen S, Lawrence G, Dawson A, et al. (2013) Influenza vaccination during pregnancy: Coverage rates and influencing factors in two urban districts in Sydney. Vaccine 31: 5557-5564.

27.    Tong A, Biringer A, Ofner-Agostini M, Upshur R, McGeer A (2008) A cross-sectional study of maternity care providers' and women's knowledge, attitudes and behaviors towards influenza vaccination during pregnancy. J Obstet Gynecol Can 30: 404-410.

28.    Ahluwalia IB, Jamieson DJ, Rasmussen SA, D'Angelo D, Goodman D, et al. (2010) Correlates of seasonal influenza vaccine coverage among pregnant women in Georgia and Rhode Island. Obstet Gynecol 116: 949-955.

29.    Eppes C, Wu A, Cameron KA, Garcia P, Grobman W (2012) Does obstetrician knowledge regarding influenza increase HINI vaccine acceptance among their pregnant patients? Vaccine 30: 5782-5784.

30.    Maher L, Dawson A, Wiley K, Hope K, Torvaldsen S, et al. (2014) Influenza vaccination during pregnancy: A qualitative study of the knowledge, attitudes, beliefs and practices of general practitioners in Central and South-Western Sydney. BMC Fam Pract 15: 102.

31.    Schrag SJ, Fiore AE, Gonik B, Malik T, Reef S, et al. (2003) Vaccination and perinatal infection prevention practices among obstetrician-gynecologists. Obstet Gynecol 101: 704-710.

32.    Davis MM, Ndiaye SM, Freed GL, Kim CS, Clark SJ (2003) Influence of insurance status and vaccine cost on physicians' administration of pneumococcal conjugate vaccine. Pediatrics 112: 521-526.

33.    Arao RF, Rosenberg KD, McWeeney S, Hedberg K (2015) Influenza vaccination of pregnant women: Attitudes and behaviors of oregon physician prenatal care providers. Matern Child Health J 19: 783-789.

34.    Fisher BM, Scott J, Hart J, Winn VD, Gibbs RS, et al. (2011) Behaviors and perceptions regarding seasonal and H1N1 influenza vaccination during pregnancy. Am J Obstet Gynecol 204: S107-111.

35.    Yudin MH, Salripour M, Sgro MD (2010) Impact of patient education on knowledge of influenza and vaccine recommendations among pregnant women. J Obstet Gynecol Can 32: 232-237.

36.    Meharry PM, Colson ER, Grizas AP, Stiller R, Vazquez M (2013) Reasons why women accept or reject the trivalent inactivated influenza vaccine (TIV) during pregnancy. Matern Child Health J 17: 156-164.

37.    Meharry PM, Cusson RM, Stiller R, Vazquez M (2014) Maternal influenza vaccination: Evaluation of a patient-centered pamphlet designed to increase uptake in pregnancy. Matern Child Health J 18: 1205-1214.

38.    Wong VW, Fong DY, Tarrant M (2014) Brief education to increase uptake of influenza vaccine among pregnant women: A study protocol for a randomized controlled trial. BMC Pregnancy Childbirth 14: 19.

39.    Moniz MH, Hasley S, Meyn LA, Beigi RH (2013) Improving influenza vaccination rates in pregnancy through text messaging: A randomized controlled trial. Obstet Gynecol 121: 734-740.

40.    Ogburn T, Espey EL, Contreras V, Arroyo P (2007) Impact of clinic interventions on the rate of influenza vaccination in pregnant women. J Reprod Med 52: 753-756.

41.    Stockwell MS, Westhoff C, Kharbanda EO, Vargas CY, Camargo S, et al. (2014) Influenza vaccine text message reminders for urban, low-income pregnant women: A randomized controlled trial. Am J Public Health 104: e7-12.

42.    Kharbanda EO (2015) Helping mothers to get the message about influenza: Are texts the future for increased immunization? Expert Rev Vaccines 14: 333-335.