Flu and pertussis vaccination during pregnancy in Geneva during the COVID-19 pandemic: A multicentric,prospective, survey-based study

ObjectiveTo determine pertussis and influenza vaccination coverage during pregnancy among women delivering in all the maternities of Geneva (Switzerland), during the COVID-19 pandemic.MethodsAll women delivering in all the maternity centres of the canton of Geneva from 1st November 2020 to 30th November 2020 (beginning of the flu vaccination season) and from 8th March 2021 to 7th April 2021 (end of the flu vaccination season) had their records checked upon admission to the labour ward regarding pertussis and influenza vaccination during pregnancy. Reasons for non-vaccination were recorded. Univariate and multivariate analyses were done to identify predictors of vaccine uptake.Results951 women delivered in Geneva during the two study periods, of which 950 were included in the study. 86.2% were vaccinated against pertussis, with no significant difference between the study periods (87.5% vs 85% at the beginning and end of the flu vaccination season respectively). 49.8% were vaccinated against influenza, with no significant difference between the study periods (48.8% vs 50.7% beginning and end of the flu vaccination season respectively). The influenza vaccine was 5 times more likely not to be proposed (8.9% vs. 1.7%) and 3 times more likely to be refused (26.6% vs. 8%) than the pertussis vaccine. Main reason for refusal was a lack of maternal desire for both vaccines, but not vaccine fear. Maternal parity ≥ 1 was significantly associated with pertussis vaccine uptake at univariate analysis. Women were significantly more likely to accept the influenza vaccine if they had a university degree or if they did not deliver in a midwife-only run delivery unit in both univariate and multivariate analysis.ConclusionsIn Geneva, most gynaecologists offer pertussis immunization during antenatal care and uptake is high, but more efforts must be done to increase influenza vaccination coverage. Education level impacts maternal flu vaccination uptake, but other social disparities did not.     

Declining responsiveness to influenza vaccination with progression of human pregnancy

BackgroundInfluenza immunization is universally recommended during pregnancy to protect mothers and their offspring. However, pregnancy-induced shifts in vaccine responsiveness remain poorly defined.MethodsQuantitative and qualitative shifts in the serological response to influenza vaccination were evaluated in healthy women throughout the course of pregnancy. Serum was obtained before and after vaccination among 71 pregnant and 67 non-pregnant women during the 2011–12 and 2012–13 influenza seasons. Serum hemagglutination inhibition (HAI) assay was used to investigate anti-influenza antibody responses by comparing pre-vaccine and post-vaccine geometric mean titers (GMTs) between groups for each antigen. IgG1, IgG2, IgG3, and IgG4 anti-influenza titers were also evaluated by enzyme-linked immunosorbent assay (ELISA). Pregnancy induced shifts in HAI titers and levels of each anti-influenza antibody isotype were evaluated using linear regression models.ResultsPost-vaccine GMTs at day 28 were significantly reduced for women vaccinated during pregnancy for A/California (H1N1) in 2011 (p = 0.027), A/Perth (H3N2) in 2011 (p = 0.037), and B/Wisconsin in 2012 (p = 0.039). Vaccine responses progressively declined with the initiation of vaccination later in pregnancy. Anti-H1N1 IgG1, IgG2, and IgG3 titers were reduced in pregnant women compared to non-pregnant controls, and these titers declined with pregnancy progression. The most striking differences were found for anti-H1N1 IgG1, where titers decreased by approximately 7% each week throughout pregnancy.ConclusionsHAI responses elicited by immunization were significantly reduced during pregnancy for three different influenza vaccine antigens. Anti-H1N1 IgG1 was significantly lower in pregnant women and decreased throughout the course of pregnancy. Waning serological responsiveness to influenza vaccination with the progression of human pregnancy has important translational implications for when immunization should be optimally administered during pregnancy.     

妊娠期接种流感疫苗与不良妊娠结局的Meta分析

目的 系统评价妊娠期接种流感疫苗与不良妊娠结局的关系。方法 通过计算机检索结合手工检索PubMed、Embase、CNKI、VIP、WF等中英文数据库,查找关于妊娠期接种流感疫苗对妊娠结局影响且符合纳入排出标准的随机对照研究或队列研究,检索时限均从建库至2018年12月。由2位研究员筛选文献、提取资料并评价质量后,采用Stata 12.0软件进行Meta分析。结果 共纳入16个研究,共748 259例（试验组:145 980例;对照组:602 279例）。质量评价表明纳入文献质量较高。Meta分析结果显示,自然流产[OR = 0.14,95%CI(0.10,0.18),P＜0.001]、死产[OR = 0.71,95%CI(0.59,0.85),P＜0.001]、先天性畸形[OR = 0.84,95%CI(0.54,1.30),P = 0.427＞0.05]均低于对照组,表明妊娠期接种流感疫苗不会增加自然流产、死产和先天性畸形的风险,并在一定程度上能降低不良妊娠发生率,敏感性分析表明结果可信,Begg’s法所得P值均表明不存在发表偏倚（自然流产:P = 0.466;死产:P = 1.00;先天性畸形P = 0.175）。结论 现有证据未表明母体流感疫苗接种与自然流产、死产和先天性畸形的风险增加有关,妊娠期接种流感疫苗在妊娠结局方面安全性较高,但仍可开展更多高质量研究予以验证。     

Interventions to increase the uptake of seasonal influenza vaccination among pregnant women: A systematic review

BackgroundPregnant women and their infants under 6 months of age infected with influenza have a high risk of serious morbidity and mortality. Influenza vaccine during pregnancy offers 3-for-1 benefits to pregnant women, fetuses and newborn infants. Current vaccination uptake rates during pregnancy, however, are often lower than other high-risk groups and the general population.MethodsWe systematically reviewed evidence on the effectiveness of interventions to improve influenza vaccination coverage in pregnant women. Risk differences (RDs) were calculated from the included studies.ResultsEleven studies were included in the review, of which four were randomized controlled trials (RCTs). Three cohort studies assessed provider-focused interventions while four RCTs and one cohort study evaluated pregnant women-focused interventions. Two cohort studies and a prospective intervention study assessed the effectiveness of bundled interventions. No study solely assessed the effectiveness of interventions to enhance access to influenza vaccination. One moderate quality RCT showed that an influenza pamphlet, with or without a verbalized benefit statement, improved the vaccination rate (RD = 0.26; RD = 0.39). The other reviewed RCTs showed discordant results, with RDs ranging from −0.15 to 0.03. Although all observational studies significantly improved vaccination rates (RDs ranged from 0.03 to 0.44), the quality of the evidence varied.ConclusionsThere is a lack of effective interventions to increase the influenza vaccination rate in pregnant women. Based on the existing research, we recommend that clinicians provide influenza pamphlets to pregnant women with a verbalized statement about the benefits of influenza vaccine to newborns. Further high-quality RCTs are needed to develop successful maternal influenza vaccination programs. Increased clarity in reporting the content of interventions would help to improve the comparability and generalizability of the published studies.     

Optimizing benefits of influenza virus vaccination during pregnancy: Potential behavioral risk factors and interventions

Pregnant women and infants are at high risk for complications, hospitalization, and death due to influenza. It is well-established that influenza vaccination during pregnancy reduces rates and severity of illness in women overall. Maternal vaccination also confers antibody protection to infants via both transplacental transfer and breast milk. However, as in the general population, a relatively high proportion of pregnant women and their infants do not achieve protective antibody levels against influenza virus following maternal vaccination. Behavioral factors, particularly maternal weight and stress exposure, may affect initial maternal antibody responses, maintenance of antibody levels over time (i.e., across pregnancy), as well as the efficiency of transplacental antibody transfer to the fetus. Conversely, behavioral interventions including acute exercise and stress reduction can enhance immune protection following vaccination. Such behavioral interventions are particularly appealing in pregnancy because they are safe and non-invasive. The identification of individual risk factors for poor responses to vaccines and the application of appropriate interventions represent important steps towards personalized health care.     

Mandatory policies for influenza vaccination: Views of managers and healthcare workers in England

Introduction

Mandatory policies have the potential to increase uptake of influenza (‘flu’) vaccination among healthcare workers (HCWs), but concerns have been expressed about their acceptability and effectiveness. We explored views on three mandatory policies (declination forms, face masks or reduced patient contact, and mandatory vaccination) among both HCWs and flu vaccination programme managers in the National Health Service (NHS) in England.

Reported influenza in pregnancy and childhood tumour

The present study was conducted to test the hypothesis that exposure to influenza in pregnancy increases the risk of tumour of certain type in childhood. Children ages 17 years or less diagnosed in Greece with brain tumours or neuroblastomas from 1982 to 1993 (n=94) were contrasted to 210 controls selected from the same hospitals. Mothers of these children were interviewed about a variety of possible etiologic factors. The prevalence of influenza in Greece for each year during the period 1984–1992 was also compared with the number of children born during the same year who subsequently developed brain tumour or neuroblastoma. The results indicate a significant association between influenza in pregnant women and occurrence of tumour in index child (OR: 3.15, 95% CI: 1.13–8.77). These results persisted when adjustment for potential confounding factors was made. The findings should be interpreted cautiously because of lack of serologic documentation of information about infection obtained in interviews. A positive correlation (r = 0.74) of the number of tumour births by year of birth with the prevalence of influenza during the same year was also noted. This exploratory study is one of the few case-control studies of the epidemiology of childhood tumours in children, and the results suggest directions for future epidemiologic studies in this relatively uncharted field.     

Mild and asymptomatic influenza B virus infection among unvaccinated pregnant persons: Implication for effectiveness of non-pharmaceutical intervention and vaccination to prevent influenza

BackgroundWe estimated symptomatic and asymptomatic influenza infection frequency in community-dwelling unvaccinated pregnant persons to inform risk communication.MethodsWe collected residue sera from multiple antenatal-care blood draws during October 2016–April 2017. We determined influenza infection as seroconversion with ≥ 4-fold rise in antibody titers between any two serum samples by improved hemagglutinin-inhibition assay including ether-treated B antigens. The serology data were linked to the results of nuclei acid testing (rRT-PCR) based on acute respiratory illness (ARI) surveillance.ResultsAmong all participants, 43 %(602/1384) demonstrated serology and/or rRT-PCR evidenced infection, and 44 %(265/602) of all infections were asymptomatic. ARI-associated rRT-PCR testing identified only 10 %(61/602) of total infections. Only 1 %(5/420) of the B Victoria cases reported ARI and had a rRT-PCR positive result, compared with 33 %(54/165) of the H3N2 cases. Among influenza ARI cases with multiple serum samples, 19 %(11/58) had seroconversion to a different subtype prior to the illness.ConclusionsThe incidence of influenza B infection in unvaccinated pregnant persons is under-estimated substantially. Non-pharmaceutical intervention may have suboptimal effectiveness in preventing influenza B transmission due to the less clinical manifestation compared to influenza A. The findings support maternal influenza vaccination to protect pregnant persons and reduce consequent household transmission.     

Text messages for influenza vaccination among pregnant women: A randomized controlled trial

ObjectiveTo evaluate if text message reminders increase the likelihood of receiving the influenza vaccine among pregnant women.MethodsPregnant women were randomized to either receive or not receive weekly text messages. Women were told the messages would be about health-related behavior in pregnancy. Those randomized to the intervention group received two messages weekly for four consecutive weeks reinforcing that the influenza vaccine is recommended for all pregnant women and safe during pregnancy and breastfeeding. Women were contacted six weeks postpartum to determine if they had received the vaccine. Sample size calculation determined that 108 women were required in both groups to see a 75% increase in vaccination rates over baseline in the text message group compared to the control group.ResultsRecruitment began November 4, 2013, and 317 women were randomized. The mean gestational age at recruitment was 22 weeks. There were 40/129 (31%) women in the text message group and 41/152 (27%) women in the control group who received the vaccine (p = 0.51). Significant predictors of vaccine acceptance were being married compared to single (95% vs. 67%, p < 0.001), having higher household income (55% vs. 39%, p = 0.03) and having received the vaccine before (77% vs. 36%, p < 0.001). Among women receiving text messages, the majority were satisfied, with only 15/129 (12%) reporting that they did not like receiving the messages, and 24/129 (19%) stating that the information in the messages was not helpful.ConclusionWeekly text messages reinforcing the recommendation for and safety of the influenza vaccine in pregnancy did not increase the likelihood of actually receiving the vaccine among pregnant women. Overall vaccination rates were low, highlighting the need for patient education and innovative techniques to improve vaccine acceptance.Registered with ClinicalTrials.gov at http://www.clinicaltrials.gov, registration number NCT 02428738.     

No association between influenza vaccination during pregnancy and adverse birth outcomes

BackgroundPregnant women are recommended to receive inactivated influenza vaccination anytime during pregnancy. Studies have investigated the impact of influenza vaccination during pregnancy on birth outcomes and results on preterm birth have been inconsistent.MethodsWe conducted a retrospective cohort study among children born at a gestational age ≥ 24 weeks from January 1, 2010 to December 31, 2015 at Kaiser Permanente Northern California facilities (KPNC). We evaluated the association between maternal influenza vaccination during pregnancy and risk of preterm birth, small and large for gestational age, admission to the neonatal intensive care unit (NICU), respiratory distress syndrome, low birth weight, and low Apgar score. We ascertained the dates of maternal influenza vaccination, conception, and delivery, as well as birth outcomes from KPNC inpatient and outpatient databases. Conditional multivariate Cox regression and logistic regression analyses were used to determine the association between maternal vaccination during pregnancy and risk of each birth outcome.ResultsThe study included 145,869 children. Maternal influenza vaccination during pregnancy was not associated with risk of small or large for gestational age births, preterm birth, need for mechanical ventilation at birth, respiratory distress syndrome, admission to the NICU, low birth weight, or low Apgar score. However, when we did not control for immortal time bias, the risk of preterm birth (odds ratio [OR] = 0.69, 95% confidence interval [CI] 0.66–0.72) was lower among infants of vaccinated mothers.ConclusionWe found no association between maternal influenza vaccination during pregnancy and adverse birth outcomes. When investigating preterm birth outcome in association with vaccination during pregnancy, immortal time bias should be taken into account in the analysis.     

Acceptance of vaccination during pregnancy: experience with 2009 influenza A (H1N1) in the Netherlands

Objectives

In 2009, the Dutch government advised pregnant women to get vaccinated against influenza A (H1N1). A study was set up to gain insight into vaccination coverage and reasons why pregnant women seek vaccination or not.

Methods

We invited 14,529 pregnant women to complete an internet survey on vaccination during pregnancy in general and against 2009 influenza A (H1N1). Differences in background characteristics between unvaccinated and vaccinated women were investigated. Prediction analyses were carried out to determine which survey statement had the greatest impact on vaccination status or intention to get vaccinated during pregnancy.

Results

Of the 2993 included respondents, 63% reported to be vaccinated against 2009 influenza A (H1N1). Vaccination coverage was higher among older birth cohorts, women who had been pregnant before, women with underlying medical conditions, and women who reported no defined ‘life philosophy’. Protection of the child (after birth), the government's advice and possible harmful effects of the vaccine for the unborn child had the greatest predictive value for vaccination status. With regards vaccination during future pregnancies, 39% had a positive intention to obtain vaccination and 45% were neutral. The government's advice was the strongest predictor for intention. Furthermore, women expressed concern over lack of sufficient knowledge about vaccine safety.

Conclusions

A considerable number of pregnant women in the Netherlands reported to be vaccinated against 2009 influenza A (H1N1). The challenge for the government in the future will be to provide pregnant women and health care professionals with sufficient and clear information about disease severity and the benefits and safety of vaccination.     

Inflammatory responses to trivalent influenza virus vaccine among pregnant women

Objective

In the U.S., seasonal trivalent influenza virus vaccine (TIV) is currently universally recommended for all pregnant women. However, data on the maternal inflammatory response to vaccination is lacking and would better delineate the safety and clinical utility of immunization. In addition, for research purposes, vaccination has been used as a mild immune trigger to examine in vivo inflammatory responses in nonpregnant adults. The utility of such a model in pregnancy is unknown. Given the clinical and empirical justifications, the current study examined the magnitude, time course, and variance in inflammatory responses following seasonal influenza virus vaccination among pregnant women.

Methods

Women were assessed prior to and at one day (n = 15), two days (n = 10), or approximately one week (n = 21) following TIV. Serum interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), and macrophage migration inhibitory factor (MIF) were determined by high sensitivity immunoassay.

Results

Significant increases in CRP were seen at one and two days post-vaccination (ps < 05). A similar effect was seen for TNF-α, for which an increase at two days post-vaccination approached statistical significance (p = .06). There was considerable variability in magnitude of response; coefficients of variation for change at two days post-vaccination ranged from 122% to 728%, with the greatest variability in IL-6 responses at this timepoint.

Conclusions

Trivalent influenza virus vaccination elicits a measurable inflammatory response among pregnant women. There is sufficient variability in response for testing associations with clinical outcomes. As adverse perinatal health outcomes including preeclampsia and preterm birth have an inflammatory component, a tendency toward greater inflammatory responding to immune triggers may predict risk of adverse outcomes, providing insight into biological mechanisms underlying risk. The inflammatory response elicited by vaccination is substantially milder and more transient than seen in infectious illness, arguing for the clinical value of vaccination. However, further research is needed to confirm that the mild inflammatory response elicited by vaccination is benign in pregnancy.     

H7N9 influenza and its impact on pregnancy

This short article specifically focuses on the new emerging H7N9 influenza which has just been observed since early 2013. As a new disease, it is lack for the knowledge on the new H7N9 influenza. Here, the author will discuss on the impact of emerging H7N9 influenza on pregnancy.     

The effectiveness of influenza vaccination in pregnancy in relation to child health outcomes: Systematic review and meta-analysis

ObjectivesTo determine the effectiveness of influenza vaccination during pregnancy on child health outcomes.DesignSystematic review/meta-analysis.Data sourcesClinical Trials.gov, Cochrane Library, EMBASE, Medline, Medline in process, PubMed and Web of Science, from 1st January 1996 to 29th June 2018. An updated Medline search was performed 30th June 2018 to 31st October 2019.MethodsRandomised controlled trials (RCTs) and observational studies reporting health outcomes of infants and children born to women who received inactivated influenza vaccine during pregnancy. The primary outcome was infant laboratory confirmed influenza (LCI). Secondary outcomes included influenza-like illness (ILI), other respiratory illnesses, primary care, clinic visit or hospitalisations due to influenza illness and long-term respiratory childhood outcomes.Results19 studies were included; 15 observational studies and 4 primary RCTs with an additional 3 papers reporting secondary outcomes of these RCTs. In a random effects meta-analysis of 2 RCTs including 5742 participants, maternal influenza vaccination was associated with an overall reduction of LCI in infants of 34% (95% confidence interval 15–50%). However, there was no effect of maternal influenza vaccination on ILI in infants ≤6 months old. Two RCTs were excluded from the meta-analysis for the outcome of LCI in infants (different controls used). Both of these studies showed a protective effect for infants from LCI, with a vaccine efficacy of up to 70%.Overall observational studies showed an inverse (protective) association between maternal influenza vaccination and infant LCI, hospitalisation and clinic visits due to LCI or ILI in infants and other respiratory illness in infants ≤6 months old.ConclusionsThis systematic review supports maternal influenza vaccination as a strategy to reduce LCI and influenza-related hospitalisations in young infants. Communicating these benefits to pregnant women may support their decision to accept influenza vaccination in pregnancy and increase vaccine coverage in pregnant women.RegistrationPROSPERO CRD42018102776.     

A prospective cohort study assessing the reactogenicity of pertussis and influenza vaccines administered during pregnancy

BackgroundPertussis vaccination during pregnancy can prevent 91% of infant infections. In 2015, antenatal pertussis vaccination programs were introduced across Australia.MethodsTo monitor the safety of this program, pregnant women who received trivalent influenza vaccine (TIV) and/or diphtheria-tetanus-acellular pertussis vaccine (dTpa) were surveyed by text message seven days post-vaccination about possible adverse events following immunization (AEFI). Univariate logistic regression models were used to calculate the odds of reporting an AEFI following dTpa compared to TIV. Similar analyses were used to compare AEFI reported by women who received a previous dose of dTpa in 2011/2012 as part of a state-wide cocooning program.ResultsOf 5155 women, 4347 (84.3%) replied; 10.8% indicated they experienced an AEFI. There was no difference in the proportion of women who reported any reaction by vaccine; however, women who received dTpa were more likely to report a local reaction than women who received TIV (7.1% and 3.2%, respectively; OR: 2.29; 95% CI: 1.61–3.26). There was evidence suggesting local reactions were more common among women with a previous dose of dTpa (11.4%) compared to women with no previous dose (6.0%; OR: 2.00; 95% CI: 0.95–4.25); 11 (0.3%) women reported attending a hospital emergency department. Subsequent follow-up indicated symptoms resolved and mother and infant were healthy. There was no difference in the proportion of women attending hospital by vaccine (p > 0.05).DiscussionData on systemic and local reactions following receipt of TIV and dTpa during pregnancy support the safety of antenatal vaccination.     

Cross-sectional study on factors associated with influenza vaccine uptake and pertussis vaccination status among pregnant women in Germany

Pregnant women and their newborns are at increased risk for influenza-related complications; the latter also have an increased risk for pertussis-related complications. In Germany, seasonal influenza vaccination is recommended for pregnant women since 2010. A dose of pertussis-containing vaccine has been recommended since 2004 for women of childbearing age if they have not been vaccinated within the past 10 years. We conducted a nationwide cross-sectional survey among pregnant women in February/March 2013 to assess knowledge, attitudes, and practices related to influenza vaccination during pregnancy and to identify factors associated with their pertussis vaccination status. In total, 1025 pregnant women participated and provided information through a self-administered questionnaire. Of these, 23.2% were vaccinated against seasonal influenza during the 2012/13 season; 15.9% during their pregnancy. Major reasons for being unvaccinated (n = 686 respondents) were lack of confidence in the vaccine (60.4%) and the perception that vaccination was not necessary (40.3%). Influenza vaccination during pregnancy was independently associated with having received influenza vaccine in the previous season, having received a recommendation from a physician, a high level of vaccine-related knowledge and of perceived disease severity. In contrast, knowledge of the recommendation for regular hand-washing to prevent influenza and the perception that vaccine-related side effects were likely to occur or likely to be severe were negatively associated with vaccine uptake. Receipt of a pertussis vaccine in the past 10 years was reported by 22.5% of participants. Pertussis vaccine uptake was independently associated with living in the Eastern federal states and receiving seasonal influenza vaccination annually, while a migration background was associated with a lower uptake. To enhance vaccine uptake in pregnant women and women of childbearing age, special efforts must be undertaken to improve knowledge of both recommendations and the benefits of vaccination. Gynecologists could serve as important facilitators.     

Measuring maternal Tdap and influenza vaccination rates: Comparison of two population-based methods

Pregnant women are routinely recommended to receive Tdap and influenza vaccines to prevent disease and complications among mothers and newborns. Monitoring population trends in maternal vaccination is important in order to evaluate the implementation of these recommendations and to identify pockets of need. We present two methods for measuring maternal vaccination among a state population and discuss the strengths and drawbacks of each method. First, we matched maternal information from records of Wisconsin births during 2013–2015 with maternal vaccination records in the Wisconsin Immunization Registry. Second, we used an all-payer health insurance claims database to identify Wisconsin women with deliveries during 2013–2015 and vaccinations received during pregnancy. Both methods produced similar trends and indicated a substantial increase in the percentage of women receiving Tdap during pregnancy, and lower vaccination rates among women who were Medicaid-insured. When available and timely, both methods are useful for monitoring maternal vaccination.     

妊娠合并甲型H1N1流感患者的预后随访分析

目的:研究妊娠期甲型H1N1流感对母儿的长期影响.方法:收集16例妊娠合并甲型H1N1流感患者的临床资料,随访5年后的临床症状、胸部CT检查及肺功能检测,探讨各项检查指标的变化.结果:随访5年后,16例患者存在临床慢性呼吸道症状3例,胸部CT异常8例,肺功能异常9例;轻症与重症(包括危重症)甲型H1N1流感患者的胸部CT及肺功能随访结果对比,差异有统计学意义(P＜0.05).10例新生儿未发现H1N1流感病毒感染,在随后的5年随访中,生长发育与其他婴幼儿无异.结论:妊娠合并甲型H1N1流感患者出院5年后,仍有部分患者残留胸部CT异常和肺功能障碍,应重视对此类患者临床检查,以指导长期治疗.