Questionnaire survey on maternal pertussis vaccination for pregnant women and mothers in Nara prefecture, Japan

ABSTRACT

Background: Infantile pertussis is a major concern and causes a significant health burden worldwide. Maternal adult tetanus, diphtheria, and acellular pertussis (Tdap) vaccination is very effective way of preventing infantile pertussis. However, Tdap has not been approved by the Japanese government or been included in Japan’s national immunization program (NIP). We carried out a questionnaire survey to investigate whether Japanese women would accept the Tdap vaccination if they were provided with appropriate information.

Methods: The questionnaire survey was administered to pregnant women who visited the Obstetrics and Gynecology Department and mothers who visited the Pediatrics Department of Nara Medical University, Kashihara City, Japan, between October 2018 and May 2019. The questionnaire included information about pertussis infection and maternal vaccination, followed by seven questions.

Results: A total of 943 participants answered the questionnaire (481 pregnant women and 462 mothers). Before reading the information, just 4.6% of participants knew that infantile pertussis can be prevented by maternal vaccination. After reading the information, 93.0% and 92.6% of participants thought that the maternal Tdap vaccine should be approved by the Japanese government and be included in the NIP, respectively. Although only 67.6% of participants wished to have the maternal Tdap vaccine without government financial support after reading the information, 92.5% said they would have the vaccine with government support (P < .001).

Conclusion: Most Japanese mothers and pregnant women would like the maternal Tdap vaccine to be approved by the government and included in the NIP, once they have been provided with appropriate information.

KEYWORDS:

• Immunization program
• Tdap vaccine
• neonatal pertussis
• policy-making
• questionnaire

Introduction

Pertussis causes a severe burden of disease worldwide despite pertussis-containing vaccines having been widespread for some considerable time. It was estimated that, worldwide, in 2014 there were 24.1 million pertussis cases and 160,700 deaths from pertussis in children aged less than 5 years.¹ In the U.S., approximately 18,000 cases of pertussis infection were reported in 2017, with 13 deaths.² Neonates infected with pertussis have a high mortality rate, and a significant burden of disease due to infantile pertussis infection has been reported by many countries.^3–5 In the U.S., from 2005 to 2010, the overall average incidence of infantile pertussis in children aged less than 12 months was 117.7/100,000 person-years, and the average incremental cost for each pertussis infection for a 1-month-old baby was $18,781.⁶ In Japan, only sentinel pertussis surveillance was conducted until 2017; notifiable pertussis surveillance began in 2018.⁷ During the first year of this surveillance program more than 11,900 pertussis cases were reported, including 530 cases of infantile pertussis in infants aged less than 6 months.⁸ Among 344 reported individuals hospitalized due to pertussis in 2018, 290 (84.3%) were infants aged less than 6 months.⁸ The possibility of underreported and undiagnosed cases suggests the actual disease burden of infantile pertussis may be higher.^9,10 Therefore, it is highly likely that the total burden of pertussis infection may have been underestimated in Japan.

Japan has yet to approve the adult tetanus, diphtheria, and acellular pertussis (Tdap) vaccine, nor has it included the vaccine in its national immunization program (NIP).¹¹ Although four doses of pediatric diphtheria, tetanus, acellular pertussis, and inactivated polio vaccine (DPT-IPV) during infancy and childhood have been included in the Japanese NIP (at 3, 4, 5 to 11, and 12 to 23 months), individuals or their families have to pay for additional booster doses.¹¹

Many countries offer the Tdap vaccine to women during pregnancy to prevent neonatal pertussis infections.^12,13 For example, maternal Tdap vaccination was introduced in England and was reported to be approximately 90% effective at preventing neonatal pertussis infections.¹³ It is widely recognized that Tdap vaccination during pregnancy is very safe both for pregnant women and their fetuses and is the most effective way to reduce neonatal pertussis infections.^14–16 Tdap vaccination has also been shown to be very cost-effective.¹⁷

Japan has been suffering from low coverage rates of several important vaccines, including the human papilloma virus (HPV) vaccine, partly because of public anxiety arising from excessive negative campaigns in the mass media and despite the lack of any scientific evidence of adverse events.^18–20 Investigating social attitudes is very important if vaccine coverage is to be improved. For example, the majority of parents found it acceptable for their children to have two doses of mumps vaccine (which has not been included in the Japanese NIP due to concerns over adverse events) if they were provided with appropriate information and the cost of vaccination was covered by the government.²¹

For the reasons stated above, investigating social attitudes toward Tdap vaccination during pregnancy to prevent neonatal pertussis may be necessary if Japan is to decrease its neonatal pertussis incidence and the burden of this disease in the near future. This study aimed to evaluate the acceptance of maternal Tdap vaccination, as well as willingness to have the vaccine with and without reimbursement of the vaccine’s cost, by administering a questionnaire to Japanese mothers and pregnant women while simultaneously providing them with accurate information.

Methods

This study involved a questionnaire survey. The participants were pregnant women who visited the Obstetrics and Gynecology Department or mothers who visited the Pediatrics Department at Nara Medical University, Kashihara City, Japan, between October 2018 and May 2019. All individuals who agreed to participate in the study were included in our analysis. Participants were asked to read some information about Tdap vaccination during pregnancy and then answer seven questions. No participant completed the questionnaire more than once. No background information about the participants was collected for this study. The study was approved by the Institutional Review Board of Nara Medical University (IRB No. 1974). The content of the questionnaire is described in further detail below.

The information section provided the following information.

-Adults with pertussis infections usually present with a long-term cough, but infants with pertussis may have severe symptoms and often present with seizure and holding of their breath, especially if they are aged less than three months and have not received a pertussis vaccination. Approximately half of them need to be admitted. Infantile pertussis can be life-threatening.

-The most effective way to prevent pertussis is vaccination; however, infants aged less than three months are currently not eligible for the vaccination. The most effective way of preventing severe pertussis infections in these young infants is by pregnant women having the vaccine. For example, in England, the use of pertussis vaccination during pregnancy to prevent infantile pertussis infections was about 90% effective.

-Adult pertussis-containing vaccine (known as Tdap) has not been approved for use in Japan, which means no public compensation is available for individuals who experience adverse events. The vaccine is also currently not included in the NIP, which means no public funds are available to cover the cost of the vaccine. The cost of the Tdap vaccine is approximately JPY 6,000–11,000 (USD 54–100) per dose.

-Adverse reactions to the vaccine include local pain and swelling at the site of the injection. Tdap vaccination during pregnancy does not increase the risk of complications during the pregnancy.

The questionnaire itself comprised seven questions (Table 1). Questions 1 to 3 investigated participants’ knowledge of pertussis and its vaccine. Questions 6 and 7 asked how participants would behave if the vaccine were to be approved or included in the NIP. If the majority of participants answered “Yes” to question 6 and there was no difference between the rates of answering “Yes” to both questions 6 and 7, we could reasonably assume that many of them would opt to have the Tdap vaccine once it was approved, even if it were not included in the NIP. If, however, the proportion of positive answers to questions 6 and 7 was significantly different, we could assume that the lack of financial support would be a significant factor in not accepting the vaccination. No personal information, such as participants’ or their children’s ages were recorded in the questionnaire.

Table 1. Maternal Tdap vaccination questionnaire (n, %).

1. Before reading the information, did you know that whooping cough can be prevented by vaccination?
	Yes	No	Unsure	No answer	P-value
Ob/Gyn	90 (18.7%)	392 (81.3%)	0 (0.0%)	0 (0.0%)	0.007
Pediatrics	120 (26.0%)	340 (73.8%)	0 (0.0%)	1 (0.2%)
Total	210 (22.2%)	732 (77.6%)	0 (0.0%)	1 (0.1%)
2. Before reading the information, did you know that infantile whooping cough can be very severe and life-threatening?
	Yes	No	Unsure	No answer	P-value
Ob/Gyn	89 (18.5%)	393 (81.5%)	0 (0.0%)	0 (0.0%)	<0.001
Pediatrics	131 (28.4%)	329 (71.4%)	0 (0.0%)	1 (0.2%)
Total	220 (23.3%)	722 (76.6%)	0 (0.0%)	1 (0.1%)
3. Before reading the information, did you know that infantile whooping cough can be prevented by vaccination for pregnant women?
	Yes	No	Unsure	No answer	P-value
Ob/Gyn	19 (3.9%)	463 (96.1%)	0 (0.0%)	0 (0.0%)	0.352
Pediatrics	24 (5.2%)	436 (94.6%)	0 (0.0%)	1 (0.2%)
Total	43 (4.6%)	899 (95.3%)	0 (0.0%)	1 (0.1%)
4. After reading the information, do you hope that Tdap vaccine will be approved in Japan?
	Yes	No	Unsure	No answer	P-value
Ob/Gyn	450 (93.4%)	26 (5.4%)	3 (0.6%)	3 (0.6%)	0.658
Pediatrics	427 (92.6%)	25 (5.4%)	3 (0.7%)	6 (1.3%)
Total	877 (93.0%)	51 (5.4%)	6 (0.6%)	9 (1.0%)
5. After reading the information, do you hope that maternal Tdap vaccine will be included in the NIP?
	Yes	No	Unsure	No answer	P-value
Ob/Gyn	449 (93.2%)	25 (5.2%)	4 (0.8%)	4 (0.8%)	0.490
Pediatrics	424 (92.0%)	29 (6.3%)	2 (0.4%)	6 (1.3%)
Total	873 (92.6%)	54 (5.7%)	6 (0.6%)	10 (1.1%)
6. After reading the information, would you have the maternal Tdap vaccine in the case of voluntary vaccination (you need to pay)?
	Yes	No	Unsure	No answer	P-value
Ob/Gyn	326 (67.6%)	139 (28.8%)	13 (2.7%)	4 (0.8%)	0.955
Pediatrics	311 (67.5%)	135 (29.3%)	9 (2.0%)	6 (1.3%)
Total	637 (67.6%)	274 (29.1%)	22 (2.3%)	10 (1.1%)
7. After reading the information, would you have the maternal Tdap vaccine in the case of routine vaccination (the Government covers the cost)?
	Yes	No	Unsure	No answer	P-value
Ob/Gyn	444 (92.1%)	32 (6.6%)	2 (0.4%)	4 (0.8%)	0.673
Pediatrics	428 (92.8%)	24 (5.2%)	3 (0.7%)	6 (1.3%)
Total	872 (92.5%)	56 (5.9%)	5 (0.5%)	10 (1.1%)

P-values were calculated by the proportion of questions answered “yes” in both departments.

Pregnant women who presented to the Obstetrics and Gynecology Department and participated in the study comprised the Ob/Gyn group, while mothers whose children presented to the Pediatric Department comprised the Pediatrics group.

Ob/Gyn; Obstetrics and Gynecology.

Statistical analysis

Based on a previous study that investigated vaccine acceptance in Japan, we expected that between 65% and 95% of subjects would wish to have the vaccine if appropriate information was provided.²¹ The required sample size to detect a 10% difference in the proportions of “yes” and “no” between two questions (for example 70% yes to one question and 80% yes to another question) was 784 with 0.9 of power. We used Pearson’s chi-squared test to compare opinions between pregnant women who visited the Obstetrics and Gynecology Department and mothers who visited the Pediatrics Department. We also used Pearson’s chi-squared test to compare the distribution of answers to questions 6 and 7 to assess if financial support would affect the coverage rate. Statistical analysis was performed using Stata release 14 (StataCorp, College Station, TX, USA).

Results

A total of 943 participants completed the questionnaire (481 pregnant women and 462 mothers). The results of the questionnaire survey are summarized in Table 1. A total of 90/481 (18.7%) pregnant women knew that pertussis is vaccine preventable, compared with 120/462 (26.0%) mothers (p = .007), while 89/481 (18.5%) pregnant women knew that infantile pertussis can be very severe and life-threatening compared with 131/462 (28.4%) mothers who stated they knew this (p < .001). Only a few respondents in either group knew that infantile pertussis can be prevented by maternal vaccination before they read the information; 19/481 (3.9%) and 24/462 (5.2%) (p = .352) pregnant women and mothers, respectively. For questions 4 and 5, 450/481 (93.4%) and 427/462 (92.6%) pregnant women and mothers, respectively, thought that the maternal Tdap vaccine should be both approved by the Japanese government and included in the NIP. Although only 637/943 (67.6%) participants answered that they would choose to have the maternal Tdap vaccine without government financial support even after reading the information, 872/943 (92.5%) stated that they would choose to have the vaccine if there was government support (P< .001). When comparing the results obtained from pregnant women and mothers, significant differences were seen in their responses to questions 1 and 2. Participants’ additional comments written in the questionnaire are listed in Table 2.

Table 2. Participant’s comments.

I would like more information, including about preservatives, additives, and any serious adverse events.

I will have the maternal vaccine once it is approved, included in the NIP, and has been to shown to have no adverse events.

I want to have the maternal vaccine if it has no side effects, like the HPV vaccine.

I will have the maternal vaccine, although the possibility of side effects is concerning.

I will have the maternal vaccine if it is proved to be safe.

I will not have the vaccine unless I have had known pertussis contacts.

I have not decided yet because it is too expensive.

I will have the vaccine, but I want the vaccine fee to be reduced.

I have not had the vaccine because the incidence rate of pertussis is not known.

I have not had the vaccine because the incidence rate of neonatal pertussis and the risk for maternal health is not known. It can be prevented by not taking babies outside.

Discussion

The majority of participants were unaware that pertussis is vaccine-preventable or that infantile pertussis can be very severe, including those mothers whose children should have had pertussis-containing vaccines. The reason for statistically significant differences between the answers of pregnant women compared with mothers in questions 1 and 2 was that mothers had more previous opportunities to learn about pertussis and its vaccine because their children received the DPT-IPV vaccine via the NIP. Although we did not ask pregnant women if they were primiparous or parous, it can be inferred that primiparous women would be less likely to know these facts about pertussis. In addition, few participants in either group knew that infantile pertussis can be prevented by maternal vaccination. This study found that many women, both those who were pregnant and those who were mothers, wished to have the maternal vaccine once they had been offered the appropriate information. In addition, our study revealed that government funding would be likely to significantly increase the coverage rate if the vaccine were to be approved in Japan.

As a very important first step to eliminate infantile pertussis, Japan has implemented notifiable surveillance for this disease, beginning in 2018.⁷ The source of infection for reported cases of infantile pertussis varied, and included mothers, fathers, siblings, grandparents, and others according to the data of the notifiable surveillance in 2018.⁸ These data support the suggestion that maternal vaccination is crucial if cases of neonatal and infantile pertussis are to be effectively reduced in Japan. While many countries have already implemented maternal pertussis vaccination and as a result reduced infantile pertussis, a large gap persists between Japan and those countries where pertussis reduction has been successful; therefore, we need to address this issue immediately.^13–15 Since family members have been identified as the most common source of pertussis infection, vaccinating family members (known as a “cocooning strategy”) has been suggested as a possible option.²² While a study from New South Wales, Australia showed a 51% reduction in infantile pertussis when this strategy was adopted, another study from the U.S. was unable to detect any reduction.^23,24 Therefore, the WHO position paper concluded that the impact of a cocooning strategy would be lower than that of employing a maternal Tdap vaccination approach.²²

A significant difference in the positive proportion of responses to question 6 (parents who would accept vaccination without financial support) and question 7 (parents who would accept vaccination with financial support) was observed in this study. Other recent data from Italy and Spain relating to the Tdap vaccine in a cocooning context noted that the cost of vaccine coverage was a significant determiner of acceptance.²⁵ Our study also revealed that the cost of coverage was a crucial determinant in optimizing the coverage rate in the context of maternal vaccination. Considering the huge burden of infantile pertussis and the effectiveness of the maternal Tdap vaccination, in addition to the approval of the Tdap vaccine from the Japanese government, the inclusion of Tdap in the NIP is necessary to further decrease infantile pertussis and the burden of this disease.^25,26

In our study, some opinions about safety concerns were raised (Table 2). Previous studies also found that safety concerns for mothers, fetuses, and newborns were a significant barrier for maternal vaccination.^27,28 An explanation of safety information from health care providers, based on evidence, to mothers is essential if the acceptance rate of maternal vaccination is to be increased. Studies investigating real opinions that people hold about vaccines, and the acceptability of vaccines based on the provision of proper information, are extremely important, especially in Japan where several fundamental vaccines have not been delivered partly because of the mass media’s biased exaggeration of adverse events and a lack of governmental support.^18–20,29 We have shown that most Japanese women would choose to have the maternal Tdap vaccine if provided with appropriate information and governmental support. This theory can be applied to other vaccines in which Japan suffers from low coverage rates, including HPV and mumps vaccines.

There were some limitations to the present study. First, we provided only basic information about infantile pertussis and the maternal Tdap vaccine. We did not provide detailed information such as mortality rates with infantile pertussis and the cost-effectiveness of the vaccine. However, it was difficult for participants to read and understand detailed and complicated information while waiting in outpatient departments, and it was not clear that more detailed information would have changed their opinion. Second, this was a single-center study, performed at Nara Medical University Hospital. Therefore, we need to consider the possibility that the results were affected by selection bias; we do not think that this was significant, however, and feel that the present results can be generalized to the nation because we included all participants irrespective of their and their children’s medical condition. Third, no background demographic data, such as a participant’s age, their number of children/pregnancies, or their socioeconomic status were collected in this study. Had they been collected, these factors may have revealed different levels of acceptance among individuals of different backgrounds.

In conclusion, most women in a sample from Nara, Japan said they would wish to have the Tdap vaccine during pregnancy if appropriate information and financial support were given. Considering the heavy burden of neonatal pertussis in the nation, the Japanese government should discuss the inclusion of the maternal Tdap vaccine in the NIP.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We would like to express our gratitude to all members in the Obstetrics and Gynecology Department and the Pediatric Department at Nara Medical University for their very kind help during this study.