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Group B Streptococcus (GBS) is a major cause of pneumonia, sepsis, and meningitis in infants younger than 3 months of age. Furthermore, GBS infection in pregnant women is associated with stillbirths and pre-term delivery. It also causes disease in immunocompromised adults and the elderly, but the highest incidence of the disease occurs in neonates and young infants. At this time, there are no licensed vaccines against GBS. Complete GBS genome sequencing has helped identify genetically conserved and immunogenic proteins, which could serve as vaccine immunogens. In this study, in silico reverse vaccinology method were used to evaluate the prevalence and conservation of GBS proteins in invasive and colonizing isolates from South African infants and women, respectively. Furthermore, this study aimed to predict potential GBS vaccine targets by evaluating metrics such as antigenicity, physico-chemical properties, subcellular localization, secondary and tertiary structures, and epitope prediction and conservation. A total of 648 invasive and 603 colonizing GBS isolate sequences were screened against a panel of 89 candidate GBS proteins. Ten of the 89 proteins were highly genetically conserved in invasive and colonizing GBS isolates, nine of which were computationally inferred proteins (gbs2106, SAN_1577, SAN_0356, SAN_1808, SAN_1685, SAN_0413, SAN_0990, SAN_1040, SAN_0226) and one was the surface Immunogenic Protein (SIP). Additionally, the nine proteins were predicted to be more antigenic than the SIP protein (antigenicity score of > 0.6498), highlighting their potential as GBS vaccine antigen targets. [ABSTRACT FROM AUTHOR]

Maternal vaccination is a safe and effective means of preventing infection in pregnant women, their fetuses, and infants after birth. Several vaccines are routinely administered in pregnancy as a valuable part of prenatal care with supporting recommendations from national and international health organizations. Fears concerning vaccine safety in pregnancy are pervasive despite sufficient available safety data to support their use, leading to underutilization of maternal immunization. Despite this hesitancy, the field of maternal vaccination is evolving to include more vaccines in the routine prenatal vaccination schedule, including the new RSV vaccine. This review discusses the currently recommended vaccines in pregnancy, evidence for their use, and an overview of ongoing clinical trials investigating prospective vaccines for pregnant women. [ABSTRACT FROM AUTHOR]

Abstract Group B Streptococcus (GBS) is a major cause of pneumonia, sepsis, and meningitis in infants younger than 3 months of age. Furthermore, GBS infection in pregnant women is associated with stillbirths and pre-term delivery. It also causes disease in immunocompromised adults and the elderly, but the highest incidence of the disease occurs in neonates and young infants. At this time, there are no licensed vaccines against GBS. Complete GBS genome sequencing has helped identify genetically conserved and immunogenic proteins, which could serve as vaccine immunogens. In this study, in silico reverse vaccinology method were used to evaluate the prevalence and conservation of GBS proteins in invasive and colonizing isolates from South African infants and women, respectively. Furthermore, this study aimed to predict potential GBS vaccine targets by evaluating metrics such as antigenicity, physico-chemical properties, subcellular localization, secondary and tertiary structures, and epitope prediction and conservation. A total of 648 invasive and 603 colonizing GBS isolate sequences were screened against a panel of 89 candidate GBS proteins. Ten of the 89 proteins were highly genetically conserved in invasive and colonizing GBS isolates, nine of which were computationally inferred proteins (gbs2106, SAN_1577, SAN_0356, SAN_1808, SAN_1685, SAN_0413, SAN_0990, SAN_1040, SAN_0226) and one was the surface Immunogenic Protein (SIP). Additionally, the nine proteins were predicted to be more antigenic than the SIP protein (antigenicity score of > 0.6498), highlighting their potential as GBS vaccine antigen targets.

Maternal vaccination is a safe and effective means of preventing infection in pregnant women, their fetuses, and infants after birth. Several vaccines are routinely administered in pregnancy as a valuable part of prenatal care with supporting recommendations from national and international health organizations. Fears concerning vaccine safety in pregnancy are pervasive despite sufficient available safety data to support their use, leading to underutilization of maternal immunization. Despite this hesitancy, the field of maternal vaccination is evolving to include more vaccines in the routine prenatal vaccination schedule, including the new RSV vaccine. This review discusses the currently recommended vaccines in pregnancy, evidence for their use, and an overview of ongoing clinical trials investigating prospective vaccines for pregnant women.

Group B streptococcus (GBS) poses a significant threat to neonates, leading to morbidity and mortality. Intrapartum antibiotics, although effective, have limitations, prompting the exploration of maternal vaccination. This study reviews the current evidence for maternal GBS vaccination in the prevention of early‐onset GBS disease in newborns. A search on Google Scholar, PubMed, and Scopus identified studies assessing the impact of maternal GBS vaccination on early‐onset GBS disease. Inclusion criteria comprised English‐language clinical trials or observational studies. Data extraction included study details, immunogenicity profiles, effectiveness, safety outcomes, and relevant findings. Qualitative synthesis was employed for data analysis. Five studies meeting the inclusion criteria were reviewed. Maternal GBS vaccines demonstrated efficacy with sustained immunogenicity. Adverse events, although documented, were predominantly non‐severe. Variability in immune responses and maternal‐to‐infant antibody ratios show the need for tailored vaccination approaches. Long‐term follow up and surveillance are essential to assess persistence and identify unintended effects. Positive outcomes in vaccine efficacy support GBS vaccination integration into maternal health programs. Implementation challenges in diverse healthcare infrastructures require tailored approaches, especially in resource‐limited settings. Overcoming cultural barriers and ensuring healthcare provider awareness are crucial for successful vaccination. Synopsis: Maternal GBS vaccination effectively prevents early‐onset group B streptococcus (GBS) disease in newborns, showing sustained immunogenicity. Although adverse events occurred, they were mostly non‐severe. [ABSTRACT FROM AUTHOR]

Newborns and young infants are at risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection. Passive immunity is the mainstay of infection prevention in this cohort. Transplacental transfer of maternal antibodies provides the newborn with immediate protection from life-threatening infections, however, is dependent upon gestational age, birth weight, mother's age, recent maternal vaccination, maternal nutritional status, maternal immunocompetence and medical conditions, and placental integrity. Efficient transplacental transfer of RSV-neutralizing antibodies have led to the development and approval of maternal RSV immunization for the protection of the newborn. Additionally, administration of RSV-specific antibodies to infants leads to high serum titers of RSV-neutralizing antibodies and further protection from severe disease. [ABSTRACT FROM AUTHOR]

Introduction: Although the safety and effectiveness of COVID-19 vaccination during pregnancy have been proven, there is still little data explaining neonatal outcomes of maternal pre-pregnancy vaccination. Methods: Here, we investigated the impact of vaccination and SARS-CoV-2 infection on maternal-neonate immune response in a cohort study involving 141 pregnant individuals, and defined the importance of maternal COVID-19 vaccination timing for its effectiveness. Results and discussion: Our data indicate that vertically transferred maternal hybrid immunity provides significantly better antiviral protection for a neonate than either maternal post-infection or post-vaccination immunity alone. Higher neutralization potency among mothers immunized before pregnancy and their newborns highlights the promising role of pre-pregnancy vaccination in neonatal protection. A comparison of neutralizing antibody titers calculated for each dyad suggests that infection and pre-/during-pregnancy vaccination all support transplacental transfer, providing the offspring with strong passive immunity against SARS-CoV-2. Analysis of neutralizing antibody levels in maternal sera collected during pregnancy and later during delivery shows that immunization may exert a positive effect on maternal protection. [ABSTRACT FROM AUTHOR]

• Point estimates of the half-life of transplacental anti-GBS IgG were 23–28 days. • Strong correlation between IgG concentrations at birth and one month of age. • Antibody kinetics may help in defining a correlate of protection against GBS LOD. Capsular polysaccharide (CPS) serotype-specific Immunoglobulin G (IgG) in cord blood has been proposed as a correlate of protection against invasive Group B Streptococcus (iGBS) disease. Although protective levels are required in infants throughout the window of vulnerability up to 3 months of age, little is known regarding the kinetics of GBS-specific IgG over this period. We enrolled 33 healthy infants born to mothers colonized with GBS. We collected cord blood and infant blood samples either at one (21–35 days), two (49–63 days), or three months of age (77–91 days). We measured GBS serotype-specific CPS IgG concentrations and calculated the decay rate using a mixed-effects model. We further explored whether the antibody kinetics were affected by common maternal and infant factors and estimated the correlation between IgG concentration at birth and one, two, and three months of age. The half-life estimate of IgG concentration for homologous and non-homologous GBS serotypes in paired samples with detectable IgG levels at both time points was 27.4 (95 % CI: 23.5–32.9) days. The decay rate did not vary by maternal age (p = 0.7), ethnicity (p = 0.1), gravida (p = 0.1), gestation (p = 0.7), and infant sex (p = 0.1). Predicted IgG titres above the assay lower limit of quantification on day 30 strongly correlated with titres at birth (Spearman correlation coefficient 0.71 [95 % CI: 0.60–0.80]). Our results provide a basis for future investigations into the use of antibody kinetics in defining a serocorrelate of protection against late-onset iGBS disease. [ABSTRACT FROM AUTHOR]

Introduction: Severe respiratory syncytial virus (RSV) disease is most prevalent during infancy, particularly in those born prematurely, who benefit least from maternal antibody transfers. Maternal immunization is an attractive prevention leading to vaccine clinical trials. This meta-analysis aimed to evaluate recent maternal RSV vaccine trials. Methods: Following PRISMA-P guidelines for systematic reviews and registered at https://www.crd.york.ac.uk/prospero, this study shortlisted six randomized clinical trials of suitable quality from four databases. Meta-analysis evaluated vaccine safety, immunogenicity, and efficacy in infants and their mothers. Results: From random-effects and fixed-effects meta-analysis between trial and control arms, the maternal post-vaccination geometric antibody (Ab) titers showed pooled standard mean differences (SMDs [95% CI]) at delivery of (4.14 [2.91–5.37]), (3.95 [2.79–5.11]), and (12.20 [7.76, 16.64]) for RSV neutralizing Ab A, B, and F IgG, respectively. Vaccine administration was more likely than placebo to cause local pain, erythema, swelling, and systemic myalgia. Furthermore, the Ab levels in infants at birth showed pooled SMDs of each RSV A (3.9 [2.81–4.99]), RSV B (1.86 [1.09–2.62]), and RSV F IgG (2.24 [1.24–3.23]). The overall reduction of RSV-related lower respiratory tract infections and hospitalizations in the first 6 months of life was 52% and 48%, respectively. Conclusions: Not only does antenatal RSV vaccination look safe and immunogenic in vaccinated mothers, but it also reliably provides effective antibody levels in infants and diminishes RSV-related severe disease in infants under 6 months of age. [ABSTRACT FROM AUTHOR]

We assessed the impact of respiratory syncytial virus (RSV) preventive characteristics on the intentions of pregnant people and healthcare providers (HCPs) to protect infants with a maternal vaccine or monoclonal antibodies (mAbs). Pregnant people and HCPs who treated pregnant people and/or infants were recruited via convenience sample from a general research panel to complete a cross-sectional, web-based survey, including a discrete choice experiment (DCE) wherein respondents chose between hypothetical RSV preventive profiles varying on five attributes (effectiveness, preventive type [maternal vaccine vs. mAb], injection recipient/timing, type of medical visit required to receive the injection, and duration of protection during RSV season) and a no-preventive option. A best–worst scaling (BWS) exercise was included to explore the impact of additional attributes on preventive preferences. Data were collected between October and November 2022. Attribute-level preference weights and relative importance (RI) were estimated. Overall, 992 pregnant people and 310 HCPs participated. A preventive (vs. none) was chosen 89.2% (pregnant people) and 96.0% (HCPs) of the time (DCE). Effectiveness was most important to preventive choice for pregnant people (RI = 48.0%) and HCPs (RI = 41.7%); all else equal, pregnant people (RI = 5.5%) and HCPs (RI = 7.2%) preferred the maternal vaccine over mAbs, although preventive type had limited influence on choice. Longer protection, protection starting at birth or the beginning of RSV season, and use for both pre-term and full-term babies were ranked highest in importance (BWS). Pregnant people and HCPs strongly preferred a preventive to protect infants against RSV (vs. none), underscoring the need to incorporate RSV preventives into routine care. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is the world's leading cause of viral acute lower respiratory infections (ALRI) in infants. WHO has identified maternal RSV vaccination a priority and candidate vaccines are in development; however, vaccine hesitancy remains an impediment to successful implementation of maternal immunization. This study, the largest antenatal survey conducted to‐date, aimed to examine maternal RSV awareness, likely acceptance of RSV vaccination in pregnancy, and attitudes to maternal vaccination. Methods: Pregnant women of all gestations attending antenatal clinic of a university maternity hospital in Ireland were invited to participate. An information leaflet provided, consent obtained, and survey administered examining RSV awareness, willingness to avail of antenatal RSV vaccination, factors influencing acceptability and preferred sources of assistance. Research Ethics Committee (REC) approval obtained, and general data protection regulation (GDPR) guidelines followed. Results: 528 women completed the survey. A large proportion (75.6%) had never heard of RSV, yet 48.5% would still avail of a vaccine, 45.8% were undecided and only 5.3% would not. The main factor making vaccination acceptable to women (76.4%) was that it protects their infant from illness (p <.001, CV 0.336 for association with acceptance) and general practitioner (GP) was the preferred guidance source in decision‐making (57.7%). Conclusions: Despite low levels of maternal awareness of RSV, pregnant women in Ireland are open to availing of antenatal vaccination. Maternal immunization strategies need to focus on infant's protection from RSV‐associated ALRI along with vaccine safety, and build on an interdisciplinary collaboration of maternal, neonatal, primary care and public health services. [ABSTRACT FROM AUTHOR]

This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children around the world. The post-pandemic era has resulted in a notable increase in reported cases of RSV infections, co-circulation of other respiratory viruses, shifts in epidemiology, altered respiratory season timing, and increased healthcare demand. Low- and middle-income countries are responsible for the highest burden of RSV disease, contributing significantly to health expenses during respiratory seasons and RSV-associated mortality in children. Until recently, supportive measures were the only intervention to treat or prevent RSV-infection, since preventive strategies like palivizumab are limited for high-risk populations. Advances in new available strategies, such as long-acting monoclonal antibodies during the neonatal period and vaccination of pregnant women, are now a reality. As the Regional Expert Group of the Latin American Pediatric Infectious Diseases Society (SLIPE), we sought to evaluate the burden of RSV infection in Latin America and the Caribbean (LAC) region, analyze current strategies to prevent RSV infection in children, and provide recommendations for implementing new strategies for preventing RSV infection in children in LAC region.

IntroductionAlthough the safety and effectiveness of COVID-19 vaccination during pregnancy have been proven, there is still little data explaining neonatal outcomes of maternal pre-pregnancy vaccination.MethodsHere, we investigated the impact of vaccination and SARS-CoV-2 infection on maternal-neonate immune response in a cohort study involving 141 pregnant individuals, and defined the importance of maternal COVID-19 vaccination timing for its effectiveness.Results and discussionOur data indicate that vertically transferred maternal hybrid immunity provides significantly better antiviral protection for a neonate than either maternal post-infection or post-vaccination immunity alone. Higher neutralization potency among mothers immunized before pregnancy and their newborns highlights the promising role of pre-pregnancy vaccination in neonatal protection. A comparison of neutralizing antibody titers calculated for each dyad suggests that infection and pre-/during-pregnancy vaccination all support transplacental transfer, providing the offspring with strong passive immunity against SARS-CoV-2. Analysis of neutralizing antibody levels in maternal sera collected during pregnancy and later during delivery shows that immunization may exert a positive effect on maternal protection.

Tetanus, pertussis, influenza, and COVID-19 vaccines are recommended for the prevention of related morbidity and mortality during pregnancy and postpartum. Despite the established benefits of vaccination for prenatal and postnatal women, maternal vaccination is not universally included in routine antenatal programs, especially in low- and middle-income countries. Furthermore, the uptake of recommended vaccines among pregnant and postpartum women remains below optimum globally. This review aimed to map the evidence on interventions to improve knowledge, attitudes, and uptake of recommended vaccines among pregnant and postpartum women. We conducted a comprehensive and systematic search for relevant literature in PubMed, Scopus, Web of Science, EBSCOhost, and Google Scholar. Overall, 29 studies published between 2010 and 2023 were included in this review. The majority (n = 27) of these studies were from high-income countries. A total of 14 studies focused on the influenza vaccine, 6 on the Tdap vaccine, 8 on both influenza and Tdap vaccines, and only one study on the COVID-19 vaccine. Patient-centered interventions predominated the evidence base (66%), followed by provider-focused (7%), health system-focused (10%), and multilevel interventions (17%). Overall, the effect of these interventions on knowledge, attitudes, and uptake of maternal vaccines was variable. [ABSTRACT FROM AUTHOR]

Abstract Background Respiratory syncytial virus (RSV) is the world's leading cause of viral acute lower respiratory infections (ALRI) in infants. WHO has identified maternal RSV vaccination a priority and candidate vaccines are in development; however, vaccine hesitancy remains an impediment to successful implementation of maternal immunization. This study, the largest antenatal survey conducted to‐date, aimed to examine maternal RSV awareness, likely acceptance of RSV vaccination in pregnancy, and attitudes to maternal vaccination. Methods Pregnant women of all gestations attending antenatal clinic of a university maternity hospital in Ireland were invited to participate. An information leaflet provided, consent obtained, and survey administered examining RSV awareness, willingness to avail of antenatal RSV vaccination, factors influencing acceptability and preferred sources of assistance. Research Ethics Committee (REC) approval obtained, and general data protection regulation (GDPR) guidelines followed. Results 528 women completed the survey. A large proportion (75.6%) had never heard of RSV, yet 48.5% would still avail of a vaccine, 45.8% were undecided and only 5.3% would not. The main factor making vaccination acceptable to women (76.4%) was that it protects their infant from illness (p

Abstract Background Maternal vaccinations against Influenza, Pertussis, and Covid-19 are recommended in the UK, and vaccines against further infections may become available soon. However, many pregnant women, especially in socially and ethnically diverse areas, have low vaccine uptake. Qualitative studies on the reasons and possible solutions are needed that are inclusive of disadvantaged and minority ethnic groups. We therefore aimed to understand the complex interplay between structural and behavioural factors contributing to the low maternal vaccine uptake in socially and ethnically diverse areas in London in the Covid-19 context. Methods In 2022, we conducted semi-structured interviews and a focus group discussion among a purposive sample of 38 pregnant/recently pregnant women and 20 health service providers, including 12 midwives. Participants were recruited in ethnically diverse London boroughs. We followed a critical realist paradigm and used a thematic analysis approach. Results The sample included participants who took all, some or none of the maternal vaccines, with some participants unsure whether they had taken or been offered the vaccines. Decision-making was passive or active, with the expectation for pregnant women to do their 'own research'. Participants described various individual, social and contextual influences on their decision-making as they navigated the antenatal care system. Missing or conflicting information from providers meant knowledge gaps were sometimes filled with misinformation from unreliable sources that increased uncertainties and mistrust. Both pregnant women and providers described structural and organisational factors that hindered access to information and vaccinations, including lack of training, time and resources, and shortcomings of health information systems and apps. Some participants described factors that facilitated vaccination uptake and many made recommendations for improvements. Conclusions Our study showed how structural and organisational factors can compound uncertainties around maternal vaccination among socially and ethnically diverse populations. Results highlight the need for more reliable resources, streamlined workflows, improved electronic information systems and training in their use. Roles and responsibilities should be clarified with potential greater involvement of nurses and pharmacists in vaccine provision. Education and communication should consider individual (language/digital) skills and needs for information and reassurance. Further research is needed to co-produce solutions with service users and providers.

Background: Pregnancy is associated with a higher risk of adverse symptoms and outcomes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for both mother and neonate. Antibodies can provide protection against SARS-CoV-2 infection and are induced in pregnant women after vaccination or infection. Passive transfer of these antibodies from mother to fetus in utero may provide protection to the neonate against infection. However, it is unclear whether the magnitude or quality and kinetics of maternally derived fetal antibodies differs in the context of maternal infection or vaccination. Objective: We aimed to determine whether antibodies transferred from maternal to fetus differed in quality or quantity between infection- or vaccination-induced humoral immune responses. Methods: We evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from New Orleans, Louisiana, with histories of SARS-CoV-2 infection and/or vaccination. Plasma was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. Responses were compared between 4 groups according to maternal infection and vaccination. Results: We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies compared to naive subjects. Vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. Conclusions: These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women.

Background: Respiratory syncytial virus (RSV) is a leading cause of childhood mortality in infants below 6 months of age. In low-income and middle-income countries (LMICs), the public health burden is substantial and resources are limited. It is critical to inform decision makers about effectiveness of new interventions. Methods: We developed a mathematical model where individual RSV subtype A (RSV-A) and B (RSV-B) maternally derived neutralizing titers were predicted at time of birth after maternal vaccination with the RSV prefusion F protein-based vaccine. We estimated the subsequent duration of vaccine-induced immunity and compared this to the age at time of death distribution in the RSV GOLD Mortality Database to predict the potential impact of maternal vaccination on RSV-related childhood mortality. We used country-specific timing of antenatal care visits distributions and mortality estimates to make country-specific predictions for number of cases averted. Findings: The model predicts that on average a neonate born at 40 weeks gestational age will be protected between 6 and 7 months from RSV-A and approximately 5 months from RSV-B related mortality. We estimated the potential impact of RSV-related mortality for in-hospital and out-of-hospital cases in LMICs and predicted that in 51 GAVI-eligible countries maternal vaccination could avert between 55% and 63% of the RSV-related in-hospital mortality cases below 6 months of age. Interpretation: We show that maternal vaccination could substantially decrease RSV-A and RSV-B related in-hospital and out-of-hospital mortality in LMICs in the first 6 months of life.

Objective: To explore beliefs and attitudes toward the COVID-19 vaccine among vaccinated and unvaccinated pregnant persons in order to identify reasons for both vaccine hesitancy and vaccine uptake. Methods: From June–August 2021, we conducted a qualitative study consisting of semi-structured interviews with pregnant persons (n = 30). Participants were recruited from university-owned obstetric practices during prenatal and ultrasound appointments. Interviews were audio recorded and transcribed; transcripts were coded and analyzed to identify themes and subthemes. Results: Of the participants, one-third (n = 10) had received the COVID-19 vaccine, while two-thirds (n = 20) were unvaccinated. Primary themes for unvaccinated participants were concern about the paucity of research on the vaccine in pregnancy and potential impact of the vaccine on both fetal development and maternal health. For vaccinated participants, main themes included potential maternal and fetal protection from COVID-19 and anticipated health complications from contracting COVID-19 as their motivations to get vaccinated. While most participants cited healthcare providers as the most trusted source of vaccine information, a majority reported that the internet was their primary source of vaccine information. Many participants wanted to learn more about the COVID-19 vaccine from their obstetric providers, and notably, most vaccinated participants reported the importance of their obstetrician in their vaccine decision-making process. Conclusions: COVID-19 vaccine hesitancy is prevalent among pregnant persons, with concerns for vaccine safety for their fetus, as well as for themselves, being common. Obstetric providers must therefore be prepared to address common concerns with patients during prenatal appointments, taking the time to actively recommend vaccination. Significance: At a time of high vaccine hesitancy, this study demonstrates the importance of the patient-physician relationship in influencing patients towards vaccination. [ABSTRACT FROM AUTHOR]

While the influenza vaccine is recommended for all pregnant women, influenza vaccine coverage among this high-risk population remains inadequate. Factors associated with vaccine coverage among pregnant women, including insurance status, are poorly understood. In a cross-sectional study of the National Health Interview Survey (NHIS) data from 2012 to 2018, we evaluated predictors of self-reported influenza vaccine coverage in pregnant women. Among 1,942 pregnant women surveyed, 39% reported receiving the influenza vaccine in accordance with national recommendations. Influenza vaccine coverage increased by 8 percentage points from 2012 to 2018. Only 15% of uninsured pregnant women received the influenza vaccine, compared to 41% of those with insurance (design-corrected F-test, p-value

Abstract Background There are limited data describing adverse infant outcomes in infants born to women with a low risk of complications during pregnancy, such as those who may be enrolled in maternal immunization trials. This retrospective study estimated incidence proportions of infant outcomes in different cohorts of liveborn infants in England between 2005 and 2017. Methods The incidence proportions of 10 infant outcomes were calculated for liveborn infants from pregnancies represented in the Clinical Practice Research Datalink (CPRD) Mother-Baby Link (MBL) and linkage to Hospital Episode Statistics (HES). Three infant cohorts were designed: (1) the all pregnancies infants cohort (N = 185,119), (2) the all pregnancies with a gestational age (GA) ≥ 24 weeks infants cohort (N = 183,869), and (3) the low-risk pregnancies infants cohort (LR infants cohort, N = 121,871), which included pregnancies with a GA ≥ 24 weeks and no diagnosis of predefined high-risk medical conditions until 24 weeks GA. Results The most common adverse infant outcome in the three infant cohorts was macrosomia (e.g., 1,085.9/10,000 live births in the LR infants cohort), followed by minor congenital anomalies (e.g., 800.6/10,000 in the LR infants cohort), very low/low birth weight (e.g., 400.6/10,000 in the LR infants cohort), and major congenital anomalies (e.g., 270.4/10,000 in the LR infants cohort). The incidence proportions for early-onset sepsis, very low/low birth weight, and minor and major congenital anomalies were lower in the LR infants than in the other cohorts (non-overlapping confidence intervals [CIs]). The incidence proportions of neonatal death, infant death, late-onset sepsis, macrosomia, small for GA, and large for GA were similar between cohorts (overlapping CIs). Conclusions This study generated background rates of adverse infant outcomes from liveborn infants of all and low-risk pregnancies represented in the CPRD Pregnancy Register MBL and linkage to HES. The results indicate lower incidence proportions of several adverse infant outcomes in infants from low-risk pregnancies compared to all pregnancies, illustrating the importance of considering maternal risk factors. These background rates may facilitate the interpretation of safety data from maternal immunization trials and of pharmacovigilance data from maternal vaccines. They may also be of interest for other interventions studied in pregnant women.

Abstract Background Immunization of pregnant women with a tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccine is an effective and safe way to protect infants from pertussis before their primary vaccinations. Vaccine uptake among pregnant women is influenced by their care providers’ attitudes toward maternal vaccination. This qualitative study aimed to evaluate the implementation of the maternal Tdap vaccination under the National Immunization Program of the Netherlands from the perspective of obstetric care providers. Methods In this qualitative and explorative study, we conducted in-depth interviews by telephone with obstetric care providers who were selected from a pool of respondents (convenience sampling) to a questionnaire in a previous study. The interviews were based on a semi-structured interview guide that covered three aspects of the implementation strategy: providers’ overall experience with the implementation of maternal Tdap vaccination in the Netherlands; implementation logistics and counseling, and pregnant women referrals to municipal Youth Healthcare Centers. The interviews were recorded, pseudonymized and transcribed verbatim. Transcripts were analyzed according to the Thematic Analysis approach by two researchers independently in two phases of iterative coding, categorizing, reviewing and redefining until ultimately, emergent themes regarding maternal Tdap vaccination implementation were identified. Results Interviews with 11 midwives and 5 OB-GYN physicians yielded 5 major themes regarding the Tdap vaccination implementation strategy: challenges throughout the implementation process, views on maternal Tdap vaccination, general versus tailored counseling, provider responsibilities in vaccine promotion, and impact of materials for information delivery. Participants indicated that to improve provider attitudes toward Tdap vaccination, its implementation requires clear and transparent information about what is entailed, i.e., what is expected from obstetric care providers, how they can obtain information, and when their actions must be initiated. Participants demanded involvement throughout the implementation planning process. They preferred tailored communication with pregnant women over a generalized approach. Conclusion This study emphasized the importance of involving all relevant healthcare professionals in planning the implementation of maternal Tdap vaccination. Possible barriers perceived by these professionals should be taken into account in order to improve their attitudes toward vaccination, thus to increase uptake among pregnant women.

Abstract Background Respiratory syncytial virus (RSV) causes a substantial burden of acute lower respiratory infection in children under 5 years, particularly in low- and middle-income countries (LMICs). Maternal vaccine (MV) and next-generation monoclonal antibody (mAb) candidates have been shown to reduce RSV disease in infants in phase 3 clinical trials. The cost-effectiveness of these biologics has been estimated using disease burden data from global meta-analyses, but these are sensitive to the detailed age breakdown of paediatric RSV disease, for which there have previously been limited data. Methods We use original hospital-based incidence data from South Africa (ZAF) and Kenya (KEN) collected between 2010 and 2018 of RSV-associated acute respiratory infection (ARI), influenza-like illness (ILI), and severe acute respiratory infection (SARI) as well as deaths with monthly age-stratification, supplemented with data on healthcare-seeking behaviour and costs to the healthcare system and households. We estimated the incremental cost per DALY averted (incremental cost-effectiveness ratio or ICER) of public health interventions by MV or mAb for a plausible range of prices (5–50 USD for MV, 10–125 USD for mAb), using an adjusted version of a previously published health economic model of RSV immunisation. Results Our data show higher disease incidence for infants younger than 6 months of age in the case of Kenya and South Africa than suggested by earlier projections from community incidence-based meta-analyses of LMIC data. Since MV and mAb provide protection for these youngest age groups, this leads to a substantially larger reduction of disease burden and, therefore, more favourable cost-effectiveness of both interventions in both countries. Using the latest efficacy data and inferred coverage levels based on antenatal care (ANC-3) coverage (KEN: 61.7%, ZAF: 75.2%), our median estimate of the reduction in RSV-associated deaths in children under 5 years in Kenya is 10.5% (95% CI: 7.9, 13.3) for MV and 13.5% (10.7, 16.4) for mAb, while in South Africa, it is 27.4% (21.6, 32.3) and 37.9% (32.3, 43.0), respectively. Starting from a dose price of 5 USD, in Kenya, net cost (for the healthcare system) per (undiscounted) DALY averted for MV is 179 (126, 267) USD, rising to 1512 (1166, 2070) USD at 30 USD per dose; for mAb, it is 684 (543, 895) USD at 20 USD per dose and 1496 (1203, 1934) USD at 40 USD per dose. In South Africa, a MV at 5 USD per dose would be net cost-saving for the healthcare system and net cost per DALY averted is still below the ZAF’s GDP per capita at 40 USD dose price (median: 2350, 95% CI: 1720, 3346). For mAb in ZAF, net cost per DALY averted is 247 (46, 510) USD at 20 USD per dose, rising to 2028 (1565, 2638) USD at 50 USD per dose and to 6481 (5364, 7959) USD at 125 USD per dose. Conclusions Incorporation of new data indicating the disease burden is highly concentrated in the first 6 months of life in two African settings suggests that interventions against RSV disease may be more cost-effective than previously estimated.

We assessed the impact of respiratory syncytial virus (RSV) preventive characteristics on the intentions of pregnant people and healthcare providers (HCPs) to protect infants with a maternal vaccine or monoclonal antibodies (mAbs). Pregnant people and HCPs who treated pregnant people and/or infants were recruited via convenience sample from a general research panel to complete a cross-sectional, web-based survey, including a discrete choice experiment (DCE) wherein respondents chose between hypothetical RSV preventive profiles varying on five attributes (effectiveness, preventive type [maternal vaccine vs. mAb], injection recipient/timing, type of medical visit required to receive the injection, and duration of protection during RSV season) and a no-preventive option. A best–worst scaling (BWS) exercise was included to explore the impact of additional attributes on preventive preferences. Data were collected between October and November 2022. Attribute-level preference weights and relative importance (RI) were estimated. Overall, 992 pregnant people and 310 HCPs participated. A preventive (vs. none) was chosen 89.2% (pregnant people) and 96.0% (HCPs) of the time (DCE). Effectiveness was most important to preventive choice for pregnant people (RI = 48.0%) and HCPs (RI = 41.7%); all else equal, pregnant people (RI = 5.5%) and HCPs (RI = 7.2%) preferred the maternal vaccine over mAbs, although preventive type had limited influence on choice. Longer protection, protection starting at birth or the beginning of RSV season, and use for both pre-term and full-term babies were ranked highest in importance (BWS). Pregnant people and HCPs strongly preferred a preventive to protect infants against RSV (vs. none), underscoring the need to incorporate RSV preventives into routine care.

Antepartum maternal vaccination can protect highly sensitive newborns before they are old enough to receive their own vaccines. Two vaccines are currently recommended during pregnancy: the flu vaccine and the Tdap vaccine against tetanus, diphtheria, and pertussis. Although there is strong evidence that maternal vaccination works to protect the offspring, limitations in the understanding of vaccines and of maternal transfer of immunity compound to obscure our understanding of how they work. Here we focus on the example of pertussis to explore the possible mechanisms involved in the transfer of protection to offspring and how these may impact the newborn's response to future exposure to pertussis. For example, Tdap vaccines induce pathogen specific antibodies, and those antibodies are known to be transferred from mother to the fetus in utero and to the newborn via milk. But antibodies alone have modest impact on pertussis disease, and even less effect on colonization/transmission. Maternal immune cells can also be transferred to offspring and may play a direct role in protection from disease and/or influence the developing neonatal immune system. However, some of the transferred immunity may also blunt the offspring's response to subsequent vaccination. In this review we will summarize the protection conferred to offspring by maternal vaccination against pertussis and the likely mechanisms by which protection is transferred, identifying the many knowledge gaps that limit our most effective application of this approach. [ABSTRACT FROM AUTHOR]

Background: Maternal vaccinations against Influenza, Pertussis, and Covid-19 are recommended in the UK, and vaccines against further infections may become available soon. However, many pregnant women, especially in socially and ethnically diverse areas, have low vaccine uptake. Qualitative studies on the reasons and possible solutions are needed that are inclusive of disadvantaged and minority ethnic groups. We therefore aimed to understand the complex interplay between structural and behavioural factors contributing to the low maternal vaccine uptake in socially and ethnically diverse areas in London in the Covid-19 context. Methods: In 2022, we conducted semi-structured interviews and a focus group discussion among a purposive sample of 38 pregnant/recently pregnant women and 20 health service providers, including 12 midwives. Participants were recruited in ethnically diverse London boroughs. We followed a critical realist paradigm and used a thematic analysis approach. Results: The sample included participants who took all, some or none of the maternal vaccines, with some participants unsure whether they had taken or been offered the vaccines. Decision-making was passive or active, with the expectation for pregnant women to do their 'own research'. Participants described various individual, social and contextual influences on their decision-making as they navigated the antenatal care system. Missing or conflicting information from providers meant knowledge gaps were sometimes filled with misinformation from unreliable sources that increased uncertainties and mistrust. Both pregnant women and providers described structural and organisational factors that hindered access to information and vaccinations, including lack of training, time and resources, and shortcomings of health information systems and apps. Some participants described factors that facilitated vaccination uptake and many made recommendations for improvements. Conclusions: Our study showed how structural and organisational factors can compound uncertainties around maternal vaccination among socially and ethnically diverse populations. Results highlight the need for more reliable resources, streamlined workflows, improved electronic information systems and training in their use. Roles and responsibilities should be clarified with potential greater involvement of nurses and pharmacists in vaccine provision. Education and communication should consider individual (language/digital) skills and needs for information and reassurance. Further research is needed to co-produce solutions with service users and providers. [ABSTRACT FROM AUTHOR]

In 2014, the Global Alignment on Immunization safety Assessment in pregnancy consortium (GAIA) was formed, with the goal of developing a harmonized, globally‐concerted approach to actively monitor the safety of vaccines in pregnancy. A total of 26 standardized definitions for the classification of adverse events have been developed. The aim of this review was to identify and describe studies undertaken to assess the performance of these definitions. A literature search was undertaken to identify published studies assessing the performance of the definitions, and reference lists were snowballed. Data were abstracted by two investigators and a narrative review of the results is presented. Four studies that have evaluated 13 GAIA case definitions (50%) were identified. Five case definitions have been assessed in high‐income settings only. Recommendations have been made by the investigators to improve the performance of the definitions. These include ensuring consistency across definitions, removal of the potential for ambiguity or variations in interpretation and ensuring that higher‐level criteria are acceptable at lower levels of confidence. Future research should prioritize the key case definitions that have not been assessed in low‐ and middle‐income settings, as well as the 13 that have not undergone any validation. Synopsis: This review paper summarizes the research conducted assessing performance of standardized case definitions developed to actively monitor the safety of maternal vaccines globally. [ABSTRACT FROM AUTHOR]

Objective: The authors investigated tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccination during pregnancy following Advisory Committee on Immunization Practices' (ACIP's) recommendation for antenatal pertussis vaccination. Methods: A retrospective chart review was performed in 2019 of women receiving prenatal care at our institution between January 1, 2014 and December 31, 2018. Receipt of ACIP‐recommended vaccines were examined using Current Procedural Terminology codes to identify initiation of prenatal care, then administration of Tdap and influenza vaccines. Data were examined by individual practice (university faculty, community physicians, obstetrics and gynecology (OBGYN) residents, and family medicine residents, practice staff composition, vaccination protocol use, and insurance status. Statistical analyses were performed using χ2 testing and χ2 testing of linear trend. Results: Within our cohort (n = 17 973), highest vaccination uptake occurred in the university‐based OBGYN faculty practice (Tdap = 58.2%, influenza = 56.5%) with lowest uptake in the OBGYN resident practice (Tdap = 28.6%, influenza = 18.5%). Higher uptake occurred in practices with standing orders, more advanced practice providers, lower provider to nursing ratios, and lower rates of Medicaid insurance. Conclusion: These data demonstrated higher vaccination uptake with standing orders, more advanced practice providers, and lower provider to nurse ratios. Future work optimizing practice staff composition and vaccination protocols may increase vaccine uptake. Synopsis: Vaccination uptake is most successful in practices with standing orders, lower rates of non‐Medicaid insurance, low provider to nurse ratios, and proportionally more advanced practice providers. [ABSTRACT FROM AUTHOR]

Background: Maternal influenza vaccination has been introduced in several countries to prevent influenza‐related morbidity and mortality in pregnant women, fetuses, and infants too young to be vaccinated. Objectives: To analyze the available randomized controlled trials (RCTs) on the effectiveness of pregnant women‐focused interventions to increase influenza vaccination uptake during pregnancy. Search Strategy: Medline, CINAHL, Scopus, Web of Science, and Cochrane Trial were searched on August 25, 2021. Selection Criteria: RCTs assessing the effectiveness of pregnant women‐focused interventions in increasing influenza vaccination among pregnant women were included. Data Collection and Analysis: Two independent reviewers extracted data. A random‐effects meta‐analysis was conducted to estimate pooled odds ratios (ORs). Main Results: Seven RCTs were selected. Overall, the interventions had a significant effect in increasing influenza vaccination during pregnancy compared with standard care (OR 1.78, 95% confidence interval [CI] 1.25–2.54; P = 0.001; I2 = 67%). However, subgroup analysis suggested that influenza vaccination uptake only was associated with educational interventions (OR 2.71, 95% CI 1.93–3.81; P < 0.001; I2 = 0%). Conclusions: We found that several educational interventions for pregnant women can effectively increase influenza vaccination uptake in this population. Specifically, pamphlets, websites, and brief one‐to‐one education can be effective tools. Registration: CRD42021269478. Synopsis: This systematic review identified the effectiveness of some educational interventions in increasing influenza vaccination during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate hemagglutinin stem‐specific antibody response to the influenza vaccine during pregnancy and its transfer to the infant. Methods: The authors assessed antibody titers among maternal participants and their paired neonate's cord blood (CB) using enzyme‐linked immunoassay. Fifteen pregnant participants pre‐2019 and post‐2019 seasonal influenza vaccine were compared with 18 prenatally vaccinated participants with paired neonatal CB samples. Total IgG and IgG subclass titers specific for whole vaccine antigens versus recombinant hemagglutinin stem–specific antigen were compared using Wilcoxon exact test. Results: Hemagglutinin stem–specific IgG was boosted more robustly than whole vaccine titers when comparing postvaccine versus prevaccine log2 IgG ratios (P = 0.04). Hemagglutinin stem–specific IgG titers were boosted postvaccination (prevaccine: 14.5 [95% confidence interval, 13.8–15.2] vs. postvaccine: 16 [95% confidence interval, 15.2–16.8], P = 0.004). While IgG to whole vaccine was similar in neonatal CB and maternal plasma (P = 0.09), hemagglutinin stem–specific IgG concentrated in CB (P = 0.002), which was dominated by IgG1 subclass (analysis of variance P < 0.05). Conclusion: These data demonstrate the ability of pregnant women to generate a more robust antibody response to the stem region compared with the head region of hemagglutinin with transplacental transfer of IgG. Synopsis: Influenza vaccination during pregnancy elicits robust anti‐hemagglutinin stem antibody response, which is IgG1 dominant and transfers efficiently to the fetus. [ABSTRACT FROM AUTHOR]

Abstract Background Vaccination of pregnant patients with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccine during influenza season can reduce maternal and fetal morbidity and mortality; nevertheless, vaccination rates remain suboptimal in this patient population. To investigate the effect of a brief educational counseling session on maternal Tdap and influenza vaccination and determine factors influencing women’s decision in regards to receiving Tdap and or influenza vaccine during their pregnancy. Methods A face-to-face semi-structured cross-sectional survey was administered to postpartum patients on their anticipated day of discharge (June 11-August 21, 2018). A brief educational counseling session about maternal pertussis and Tdap vaccine was provided to interested patients after which the Tdap vaccine was offered to eligible patients who did not receive it during their pregnancy or upon hospital admission. Medical records were reviewed to determine if surveyed patients were vaccinated prior to discharge. Results Two hundred postpartum patients were surveyed on their day of anticipated discharge. Of those who were surveyed, 103 (51.5%) had received Tdap and 80 (40.0%) had received influenza vaccinations prior to hospitalization. Among immunized patients, the common facilitators were doctor’s recommendation (Tdap: 68, 54.4%; influenza: 3, 6.0%), to protect their baby (Tdap: 57, 45.6%; influenza: 17, 34.0%) and for self-protection (Tdap: 17, 13.6%; Influenza: 17, 34.0%). Of the 119 participants who had not received either Tdap or influenza vaccine prior to the survey, the barriers cited were that the vaccine was not offered by the provider (Tdap: 36, 52.2%; influenza: 29, 27.6%), belief that vaccination was unnecessary (Tdap: 5, 7.2%; influenza: 9, 8.5%), safety concerns for baby (Tdap: 4, 5.8%; influenza: 2, 1.9%). Of 97 patients who were not immunized with Tdap prior to admission but were eligible to receive vaccine, 24 (25%) were vaccinated prior to survey as part of routine hospital-based screening and vaccination program, 29 (38.2%) after our survey. Conclusion Interventions to educate pregnant patients about the benefits of vaccination for their baby, addressing patient safety concerns, and vaccine administration in obstetricians’ offices may significantly improve maternal vaccination rates.

• Intention is most predictive for second trimester Tdap vaccine acceptance. • Second vs third trimester Tdap vaccine acceptance yields comparable predictors. • Rejection of maternal vaccination as opposed to acceptance remains hard to predict. A maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccine is offered to all pregnant women in the Netherlands in their second trimester since December 2019. However, former studies solely investigated the socio-psychological factors that influence vaccine acceptance among pregnant women in the third trimester. We identified predicting factors for attitude, intention and acceptance of maternal Tdap vaccination during the second trimester of pregnancy. As part of a large prospective cohort study, women early in pregnancy completed a questionnaire on determinants regarding acceptance of maternal Tdap vaccination between 20 and 24w of gestation. The vaccine was offered after completion of the questionnaire. A random forest model and Receiver Operating Characteristics (ROC) analyses were carried out to identify the factors most predictive for vaccine acceptance on the whole data set, and also in sensitivity analysis on a subset reflecting the annual nationwide 70% vaccination uptake. Among 1158 participants who were offered a Tdap vaccination between 20 and 24w of gestation, 1098 (94.8%) accepted and 60 (5.2%) rejected the vaccine. Random forest analyses identified intention as most predictive for acceptance, followed by attitude towards vaccination, beliefs regarding safety, risk perception of severity of side effects, moral responsibility, beliefs regarding effectiveness and risk perception of susceptibility of side effects, with a sensitivity of 100% and a specificity of 40%, for which this combination could be improved by the ROC analysis to 82% and 67%, respectively. The sensitivity analysis yielded an order of predictors that generally corresponded with the initial model. Intention, attitude, beliefs on safety and effectiveness, risk perception of side effects and moral responsibility were most predictive for maternal Tdap vaccine acceptance during the second trimester of pregnancy, in accordance with studies regarding third trimester vaccination. These should be discussed by healthcare professionals early in pregnancy to provide an informed choice towards vaccine acceptance. [ABSTRACT FROM AUTHOR]

The present study examined the role of the perception of risks and benefits for the mother and her babies in deciding about the COVID-19 vaccination. In this cross-sectional study, five hypotheses were tested using data from a convenience sample of Italian pregnant and/or breastfeeding women (N = 1104, July–September 2021). A logistic regression model estimated the influence of the predictors on the reported behavior, and a beta regression model was used to evaluate which factors influenced the willingness to become vaccinated among unvaccinated women. The COVID-19 vaccination overall risks/benefits tradeoff was highly predictive of both behavior and intention. Ceteris paribus, an increase in the perception of risks for the baby weighed more against vaccination than a similar increase in the perception of risks for the mother. Additionally, pregnant women resulted in being less likely (or willing) to be vaccinated in their status than breastfeeding women, but they were equally accepting of vaccination if they were not pregnant. COVID-19 risk perception predicted intention to become vaccinated, but not behavior. In conclusion, the overall risks/benefits tradeoff is key in predicting vaccination behavior and intention, but the concerns for the baby weigh more than those for the mother in the decision, shedding light on this previously neglected aspect. [ABSTRACT FROM AUTHOR]

Background: There are limited data describing adverse infant outcomes in infants born to women with a low risk of complications during pregnancy, such as those who may be enrolled in maternal immunization trials. This retrospective study estimated incidence proportions of infant outcomes in different cohorts of liveborn infants in England between 2005 and 2017. Methods: The incidence proportions of 10 infant outcomes were calculated for liveborn infants from pregnancies represented in the Clinical Practice Research Datalink (CPRD) Mother-Baby Link (MBL) and linkage to Hospital Episode Statistics (HES). Three infant cohorts were designed: (1) the all pregnancies infants cohort (N = 185,119), (2) the all pregnancies with a gestational age (GA) ≥ 24 weeks infants cohort (N = 183,869), and (3) the low-risk pregnancies infants cohort (LR infants cohort, N = 121,871), which included pregnancies with a GA ≥ 24 weeks and no diagnosis of predefined high-risk medical conditions until 24 weeks GA. Results: The most common adverse infant outcome in the three infant cohorts was macrosomia (e.g., 1,085.9/10,000 live births in the LR infants cohort), followed by minor congenital anomalies (e.g., 800.6/10,000 in the LR infants cohort), very low/low birth weight (e.g., 400.6/10,000 in the LR infants cohort), and major congenital anomalies (e.g., 270.4/10,000 in the LR infants cohort). The incidence proportions for early-onset sepsis, very low/low birth weight, and minor and major congenital anomalies were lower in the LR infants than in the other cohorts (non-overlapping confidence intervals [CIs]). The incidence proportions of neonatal death, infant death, late-onset sepsis, macrosomia, small for GA, and large for GA were similar between cohorts (overlapping CIs). Conclusions: This study generated background rates of adverse infant outcomes from liveborn infants of all and low-risk pregnancies represented in the CPRD Pregnancy Register MBL and linkage to HES. The results indicate lower incidence proportions of several adverse infant outcomes in infants from low-risk pregnancies compared to all pregnancies, illustrating the importance of considering maternal risk factors. These background rates may facilitate the interpretation of safety data from maternal immunization trials and of pharmacovigilance data from maternal vaccines. They may also be of interest for other interventions studied in pregnant women. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) causes a substantial burden of acute lower respiratory infection in children under 5 years, particularly in low- and middle-income countries (LMICs). Maternal vaccine (MV) and next-generation monoclonal antibody (mAb) candidates have been shown to reduce RSV disease in infants in phase 3 clinical trials. The cost-effectiveness of these biologics has been estimated using disease burden data from global meta-analyses, but these are sensitive to the detailed age breakdown of paediatric RSV disease, for which there have previously been limited data. Methods: We use original hospital-based incidence data from South Africa (ZAF) and Kenya (KEN) collected between 2010 and 2018 of RSV-associated acute respiratory infection (ARI), influenza-like illness (ILI), and severe acute respiratory infection (SARI) as well as deaths with monthly age-stratification, supplemented with data on healthcare-seeking behaviour and costs to the healthcare system and households. We estimated the incremental cost per DALY averted (incremental cost-effectiveness ratio or ICER) of public health interventions by MV or mAb for a plausible range of prices (5–50 USD for MV, 10–125 USD for mAb), using an adjusted version of a previously published health economic model of RSV immunisation. Results: Our data show higher disease incidence for infants younger than 6 months of age in the case of Kenya and South Africa than suggested by earlier projections from community incidence-based meta-analyses of LMIC data. Since MV and mAb provide protection for these youngest age groups, this leads to a substantially larger reduction of disease burden and, therefore, more favourable cost-effectiveness of both interventions in both countries. Using the latest efficacy data and inferred coverage levels based on antenatal care (ANC-3) coverage (KEN: 61.7%, ZAF: 75.2%), our median estimate of the reduction in RSV-associated deaths in children under 5 years in Kenya is 10.5% (95% CI: 7.9, 13.3) for MV and 13.5% (10.7, 16.4) for mAb, while in South Africa, it is 27.4% (21.6, 32.3) and 37.9% (32.3, 43.0), respectively. Starting from a dose price of 5 USD, in Kenya, net cost (for the healthcare system) per (undiscounted) DALY averted for MV is 179 (126, 267) USD, rising to 1512 (1166, 2070) USD at 30 USD per dose; for mAb, it is 684 (543, 895) USD at 20 USD per dose and 1496 (1203, 1934) USD at 40 USD per dose. In South Africa, a MV at 5 USD per dose would be net cost-saving for the healthcare system and net cost per DALY averted is still below the ZAF's GDP per capita at 40 USD dose price (median: 2350, 95% CI: 1720, 3346). For mAb in ZAF, net cost per DALY averted is 247 (46, 510) USD at 20 USD per dose, rising to 2028 (1565, 2638) USD at 50 USD per dose and to 6481 (5364, 7959) USD at 125 USD per dose. Conclusions: Incorporation of new data indicating the disease burden is highly concentrated in the first 6 months of life in two African settings suggests that interventions against RSV disease may be more cost-effective than previously estimated. [ABSTRACT FROM AUTHOR]

Background: Immunization of pregnant women with a tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccine is an effective and safe way to protect infants from pertussis before their primary vaccinations. Vaccine uptake among pregnant women is influenced by their care providers' attitudes toward maternal vaccination. This qualitative study aimed to evaluate the implementation of the maternal Tdap vaccination under the National Immunization Program of the Netherlands from the perspective of obstetric care providers. Methods: In this qualitative and explorative study, we conducted in-depth interviews by telephone with obstetric care providers who were selected from a pool of respondents (convenience sampling) to a questionnaire in a previous study. The interviews were based on a semi-structured interview guide that covered three aspects of the implementation strategy: providers' overall experience with the implementation of maternal Tdap vaccination in the Netherlands; implementation logistics and counseling, and pregnant women referrals to municipal Youth Healthcare Centers. The interviews were recorded, pseudonymized and transcribed verbatim. Transcripts were analyzed according to the Thematic Analysis approach by two researchers independently in two phases of iterative coding, categorizing, reviewing and redefining until ultimately, emergent themes regarding maternal Tdap vaccination implementation were identified. Results: Interviews with 11 midwives and 5 OB-GYN physicians yielded 5 major themes regarding the Tdap vaccination implementation strategy: challenges throughout the implementation process, views on maternal Tdap vaccination, general versus tailored counseling, provider responsibilities in vaccine promotion, and impact of materials for information delivery. Participants indicated that to improve provider attitudes toward Tdap vaccination, its implementation requires clear and transparent information about what is entailed, i.e., what is expected from obstetric care providers, how they can obtain information, and when their actions must be initiated. Participants demanded involvement throughout the implementation planning process. They preferred tailored communication with pregnant women over a generalized approach. Conclusion: This study emphasized the importance of involving all relevant healthcare professionals in planning the implementation of maternal Tdap vaccination. Possible barriers perceived by these professionals should be taken into account in order to improve their attitudes toward vaccination, thus to increase uptake among pregnant women. [ABSTRACT FROM AUTHOR]

Stillbirth is a recognized complication of COVID-19 in pregnant women that has recently been demonstrated to be caused by SARS-CoV-2 infection of the placenta. Multiple global studies have found that the placental pathology present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition that typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. These 3 pathologic lesions, collectively termed SARS-CoV-2 placentitis, can cause severe and diffuse placental parenchymal destruction that can affect >75% of the placenta, effectively rendering it incapable of performing its function of oxygenating the fetus and leading to stillbirth and neonatal death via malperfusion and placental insufficiency. Placental infection and destruction can occur in the absence of demonstrable fetal infection. Development of SARS-CoV-2 placentitis is a complex process that may have both an infectious and immunologic basis. An important observation is that in all reported cases of SARS-CoV-2 placentitis causing stillbirth and neonatal death, the mothers were unvaccinated. SARS-CoV-2 placentitis is likely the result of an episode of SARS-CoV-2 viremia at some time during the pregnancy. This article discusses clinical and pathologic aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitis, and perinatal death. [ABSTRACT FROM AUTHOR]

Pertussis is a serious and potentially fatal disease in infants too young for vaccination. Despite a high vaccine coverage in children, pertussis continues to occur in unvaccinated infants in the Kingdom of Saudi Arabia (KSA). Available data supports the use of maternal pertussis immunization for preventing pertussis in young infants. In June 2019, the Saudi Ministry of Health recommended maternal pertussis immunization with combined tetanus-diphtheria-acellular pertussis vaccine (Tdap) during every pregnancy. To understand barriers to maternal immunization and identify strategies to improve maternal immunization, we conducted an online survey in November and December 2020, asking 60 obstetricians/gynecologists about their attitudes to maternal pertussis immunization. Fewer than 50% survey respondents considered maternal immunization as part of their role, and only 47% were aware of the national recommendation. Consequently, the uptake of maternal vaccination in KSA may be sub-optimal. The key barriers that hinder obstetricians/gynecologists from recommending maternal Tdap immunization were the anticipation of patient refusal, and their own need for more information/experience about the disease and the national recommendation. Vaccine availability and supply were important barriers, whereas cost/reimbursement and resource issues were of lesser concern. Disseminating evidence based information to physicians, educating pregnant women and addressing public misconceptions.

Antepartum maternal vaccination can protect highly sensitive newborns before they are old enough to receive their own vaccines. Two vaccines are currently recommended during pregnancy: the flu vaccine and the Tdap vaccine against tetanus, diphtheria, and pertussis. Although there is strong evidence that maternal vaccination works to protect the offspring, limitations in the understanding of vaccines and of maternal transfer of immunity compound to obscure our understanding of how they work. Here we focus on the example of pertussis to explore the possible mechanisms involved in the transfer of protection to offspring and how these may impact the newborn’s response to future exposure to pertussis. For example, Tdap vaccines induce pathogen specific antibodies, and those antibodies are known to be transferred from mother to the fetus in utero and to the newborn via milk. But antibodies alone have modest impact on pertussis disease, and even less effect on colonization/transmission. Maternal immune cells can also be transferred to offspring and may play a direct role in protection from disease and/or influence the developing neonatal immune system. However, some of the transferred immunity may also blunt the offspring’s response to subsequent vaccination. In this review we will summarize the protection conferred to offspring by maternal vaccination against pertussis and the likely mechanisms by which protection is transferred, identifying the many knowledge gaps that limit our most effective application of this approach.

ABSTRACTIntroduction Despite high vaccination coverage among children and adolescents, pertussis remains a public health problem, with large outbreaks occurring periodically in the US and other developed countries.Areas covered We examine lessons learned more than 20 years after implementation of programs which use only acellular pertussis vaccines and propose avenues for possible effective use of acellular pertussis vaccine to prevent large outbreaks.Expert Opinion Acellular pertussis vaccines were introduced more than 20 years ago, yet the incidence of pertussis has been increasing over the past decade, with periodic large outbreaks marked by notable shifts in disease burden from infants and young children toward fully vaccinated adolescents and young adults. This age shift is mainly driven by the waning of vaccine immunity. To better protect adolescents against pertussis, modification of the current acellular pertussis vaccination schedule or adoption of new vaccination strategies should be considered. For infants not yet eligible to be vaccinated, maternal vaccination against pertussis during pregnancy is an effective way to protect infants from infection, severe disease and death. Implementation of maternal vaccination programs should be encouraged in countries without one or efforts to improve coverage should be supported in countries with existing program.

Abstract Background Maternal characteristics like medical history and health-related risk factors can influence the incidence of pregnancy outcomes and pregnancy-related events of interest (EIs). Data on the incidence of these endpoints in low-risk pregnant women are needed for appropriate external safety comparisons in maternal immunization trials. To address this need, this study estimated the incidence proportions of pregnancy outcomes and pregnancy-related EIs in different pregnancy cohorts (including low-risk pregnancies) in England, contained in the Clinical Practice Research Datalink (CPRD) Pregnancy Register linked to Hospital Episode Statistics (HES) between 2005 and 2017. Methods The incidence proportions of 7 pregnancy outcomes and 15 EIs were calculated for: (1) all pregnancies (AP) represented in the CPRD Pregnancy Register linked to HES (AP cohort; N = 298 155), (2) all pregnancies with a gestational age (GA) ≥ 24 weeks (AP24+ cohort; N = 208 328), and (3) low-risk pregnancies (LR cohort; N = 137 932) with a GA ≥ 24 weeks and no diagnosis of predefined high-risk medical conditions until 24 weeks GA. Results Miscarriage was the most common adverse pregnancy outcome in the AP cohort (1 379.5 per 10 000 pregnancies) but could not be assessed in the other cohorts because these only included pregnancies with a GA ≥ 24 weeks, and miscarriages with GA ≥ 24 weeks were reclassified as stillbirths. Preterm delivery (

Abstract Background Maternal vaccinations for influenza and pertussis are recommended in New Zealand to protect mothers and their infant from infection. However, maternal immunisation coverage in New Zealand is suboptimal. Furthermore, there is unacceptable inequitable maternal immunisation rates across the country with Māori and Pacific women having significantly lower maternal immunisation rates than those of other New Zealanders. Methods This research set out to explore what pregnant/recently pregnant Māori and Pacific women knew about immunisation during pregnancy and what factors influenced their decision to be vaccinated. A semi-structured interview guide was developed with questions focusing on knowledge of pertussis and influenza vaccination during pregnancy and decision-making. Māori and Pacific women aged over 16 years were purposively sampled and interviewed in Dunedin and Gisborne, New Zealand between May and August 2021. Interviews were analysed following a directed qualitative content approach. Data were arranged into coding nodes based on the study aims (deductive analysis) informed by previous literature and within these participant experiences were inductively coded into themes and subthemes. Results Not all women were aware of maternal vaccine recommendations or they diseases they protected against. Many underestimated how dangerous influenza and pertussis could be and some were more concerned about potential harms of the vaccine. Furthermore, understanding potential harms of infection and protection provided by vaccination did not necessarily mean women would choose to be vaccinated. Those who decided to vaccinate felt well-informed, had vaccination recommended by their healthcare provider, and did so to protect their and their infant’s health. Those who decided against vaccination were concerned about safety of the vaccines, lacked the information they needed, were not offered the vaccine, or did not consider vaccination a priority. Conclusions There is a lack of understanding about vaccine benefits and risks of vaccine-preventable diseases which can result in the reinforcement of negative influences such as the fear of side effects. Furthermore, if vaccine benefits are not understood, inaccessibility of vaccines and the precedence of other life priorities may prevent uptake. Being well-informed and supported to make positive decisions to vaccinate in pregnancy is likely to improve vaccine coverage in Māori and Pacific Island New Zealanders.

Background Few studies have examined influenza vaccine effectiveness (VE) among women during pregnancy in middle-income countries. We used data from a prospective cohort of women who were pregnant in Peru to estimate effectiveness of the 2018 Southern Hemisphere influenza vaccine. Methods Women at <28 weeks gestation were enrolled from 4 tertiary level hospitals in Lima, Peru at the start of the 2018 influenza season and followed until the end of their pregnancies. Participants had mid-turbinate nasal swabs collected and tested for influenza by reverse-transcription polymerase chain reaction (RT-PCR) with onset of ≥1 of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing. Time-varying Cox proportional hazard regression models were used to estimate the risk of RT-PCR-confirmed influenza infection after adjusting for inverse probability treatment weight. Results We followed 1896 women for a median of 127 days (interquartile range [IQR], 86–174). Participants had a median age of 29 years (IQR, 24–34). Among the 1896 women, 49% were vaccinated with the 2018 influenza vaccine and 1039 (55%) developed influenza-like illness, 76 (7%) of whom had RT-PCR-confirmed influenza. Incidence rates of RT-PCR-confirmed influenza were 36.6 and 15.3 per 100 000 person-days among women who were unvaccinated and vaccinated, respectively. Adjusted influenza VE was 22% (95% confidence interval, −64.1% to 62.9%). Conclusions Participants vaccinated against influenza had more than 50% lower incidence of RT-PCR-confirmed influenza illness. Although the VE estimated through propensity weight-adjusted time-varying Cox regression did not reach statistical significance, our findings provide additional evidence about the value of maternal influenza vaccination in middle-income countries. [ABSTRACT FROM AUTHOR]

• Maternal Tdap vaccination between 20 and 24 weeks of gestation is well-tolerated. • 67.5 % of pregnant women experienced ≥ 1 local reaction and 63.6 % ≥1 systemic AE. • 0.6 % of pregnant women reported mild-to-moderate fever (≥38.0˚C) post-vaccination. • Tdap vaccination between 20 and 24 vs 30-33w GA shows no increased reactogenicity. • Maternal Tdap vaccination yields no increased risks adverse pregnancy outcomes. Maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination is offered to all pregnant women during their second trimester in the Netherlands since December 2019. We assessed second trimester Tdap vaccination reactogenicity and compared with third trimester data from a similar study. For safety assessment, adverse pregnancy outcomes were compared with national data from 2018, before Tdap vaccine-introduction. Pregnant women were included between August 2019-December 2021 and received Tdap vaccination between 20 and 24w gestational age (GA). Participants completed a questionnaire on solicited local reactions and systemic adverse events (AEs) within one week after vaccination. Results were compared with historical data on reactogenicity from women vaccinated between 30 and 33w GA (n = 58). Regarding safety-related outcomes, each participant was matched to four unvaccinated pregnant women from the Dutch Perinatal Registry, based on living area, parity and age. Among 723 participants who completed the questionnaire, 488 (67.5 %) experienced ≥ 1 local reaction with pain at the injection site as most reported reaction (62.3 %), and 460 (63.6 %) experienced ≥ 1 systemic AE with stiffness in muscles/joints (38.9 %), fatigue (28.9 %), headache (14.5 %) and common cold-like symptoms (11.0 %) most frequently reported. 4 women (0.6 %) reported fever (≥38.0˚C). Symptoms were considered mild and transient within days. No difference in AEs were found between vaccination at 20-24w versus 30-33w GA. 723 participants were matched to 2,424 unvaccinated pregnant women with no increased rates of premature labor, small-for-gestational-age, or other adverse pregnancy outcomes. Second trimester maternal Tdap vaccination appears safe and well-tolerated. Comparison between second versus third trimester vaccination yielded no reactogenicity concerns. [ABSTRACT FROM AUTHOR]

Background: Vaccination of pregnant patients with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccine during influenza season can reduce maternal and fetal morbidity and mortality; nevertheless, vaccination rates remain suboptimal in this patient population. To investigate the effect of a brief educational counseling session on maternal Tdap and influenza vaccination and determine factors influencing women's decision in regards to receiving Tdap and or influenza vaccine during their pregnancy. Methods: A face-to-face semi-structured cross-sectional survey was administered to postpartum patients on their anticipated day of discharge (June 11-August 21, 2018). A brief educational counseling session about maternal pertussis and Tdap vaccine was provided to interested patients after which the Tdap vaccine was offered to eligible patients who did not receive it during their pregnancy or upon hospital admission. Medical records were reviewed to determine if surveyed patients were vaccinated prior to discharge. Results: Two hundred postpartum patients were surveyed on their day of anticipated discharge. Of those who were surveyed, 103 (51.5%) had received Tdap and 80 (40.0%) had received influenza vaccinations prior to hospitalization. Among immunized patients, the common facilitators were doctor's recommendation (Tdap: 68, 54.4%; influenza: 3, 6.0%), to protect their baby (Tdap: 57, 45.6%; influenza: 17, 34.0%) and for self-protection (Tdap: 17, 13.6%; Influenza: 17, 34.0%). Of the 119 participants who had not received either Tdap or influenza vaccine prior to the survey, the barriers cited were that the vaccine was not offered by the provider (Tdap: 36, 52.2%; influenza: 29, 27.6%), belief that vaccination was unnecessary (Tdap: 5, 7.2%; influenza: 9, 8.5%), safety concerns for baby (Tdap: 4, 5.8%; influenza: 2, 1.9%). Of 97 patients who were not immunized with Tdap prior to admission but were eligible to receive vaccine, 24 (25%) were vaccinated prior to survey as part of routine hospital-based screening and vaccination program, 29 (38.2%) after our survey. Conclusion: Interventions to educate pregnant patients about the benefits of vaccination for their baby, addressing patient safety concerns, and vaccine administration in obstetricians' offices may significantly improve maternal vaccination rates. [ABSTRACT FROM AUTHOR]

Introduction. Uptake of maternal vaccinations (MVs) is suboptimal in Aotearoa New Zealand, particularly for Māori. Aim. To describe Māori women’s journeys regarding maternal pertussis and influenza vaccinations and explore influences on uptake. Methods. Semi-structured interviews were conducted in Waikato, Aotearoa New Zealand, with pregnant or recently pregnant Māori women, and separately with Māori healthcare professionals (HCPs) to understand women’s decisions regarding MVs and enablers and barriers to uptake. Results. Nine women and nine HCPs were interviewed. Verbal communications from midwives, general practice and pharmacy strongly influenced women’s journeys. Women’s decisions appeared largely straight-forward, with influences including awareness, knowledge, underlying beliefs and previous MVs. Enablers for MV uptake included HCPs’ discussions, pro-vaccination beliefs, and accessibility. Barriers for MV uptake included poverty (and transport), lack of awareness, insufficient knowledge of benefits, late presentation to the midwife and other commitments or challenges in the women’s lives affecting prioritisation of the vaccine. Misconceptions, seasonality, and lower HCP emphasis impaired influenza vaccination uptake. Discussion. With multiple barriers to accessing MVs, HCPs who see pregnant women are the primary resource to improve awareness, knowledge, and access through kōrero (discussions) with the woman and, where possible, being able to administer the vaccinations. These HCPs need to be well-informed, aware of likely concerns women may have and how to address them, encourage these discussions and preferably be trusted. [ABSTRACT FROM AUTHOR]

Maternal vaccination with respiratory syncytial virus prefusion F vaccine (RSVpreF) is effective at preventing RSV-associated lower respiratory tract illness (LRTI) in newborns/infants. This subgroup analysis from the global, phase 3, randomized, double-blind, placebo-controlled MATISSE (Maternal Immunization Study for Safety and Efficacy) trial evaluated participants enrolled in Japan. Pregnant women 24–36 weeks' gestation were randomized 1:1 to receive RSVpreF or placebo. Maternal safety endpoints included local reactions/systemic events within 7 days, adverse events (AEs) through 1 month, and serious AEs (SAEs) through 6 months after vaccination. In infants born to maternal participants, safety endpoints included specific birth outcomes, AEs through 1 month after birth, and SAEs and newly diagnosed chronic medical conditions through 12 or 24 months after birth. Vaccine efficacy in infants was assessed against RSV-positive, medically attended LRTI (RSV-MA-LRTI) and severe RSV-MA-LRTI through 180 days after birth. In Japan, 230 maternal participants received RSVpreF and 232 received placebo; 218 and 216 infants born to these mothers, respectively, were analyzed. Observed vaccine efficacy (95 % CIs) against infant RSV-MA-LRTI within 90 and 180 days after birth was 100.0 % (30.9, 100.0; RSVpreF, 0 cases; placebo, 7 cases) and 87.6 % (7.2, 99.7; RSVpreF, 1 case; placebo, 8 cases), respectively. Vaccine efficacy (95 % CIs) against severe RSV-MA-LRTI within 90 and 180 days was 100.0 % (−140.9, 100.0; RSVpreF, 0 cases; placebo, 3 cases) and 75.1 % (−151.5, 99.5; RSVpreF, 1 case; placebo, 4 cases), respectively. No safety concerns were identified. AE rates ≤1 month after vaccination/birth were similar in the RSVpreF (maternal, 16.1 %; infant, 48.6 %) and placebo (19.8 %; 50.5 %) groups. Preterm birth rates were also similar (RSVpreF, 3.2 %; placebo, 6.0 %). Safety and efficacy data in Japanese participants were consistent with overall MATISSE results, supporting the efficacy of maternal RSVpreF vaccination against severe MA-RSV-LRTI/MA-RSV-LRTI in infants, with no safety concerns. NCT04424316. [ABSTRACT FROM AUTHOR]

Special populations, particularly pregnant women, are uniquely susceptible to infectious diseases due to alterations in their immunological, respiratory, and cardiovascular systems during gestation. Influenza infections during the perinatal period have been associated with more severe maternal and perinatal outcomes, underscoring the critical importance of vaccination data for pregnant women. According to the World Health Organization (WHO), all pregnant women and those of childbearing age should receive the inactivated influenza vaccine, irrespective of their pregnancy stage. This study aimed to elucidate factors influencing neonatal antibody presence following maternal influenza vaccination. Conducted through convenience sampling in Athens, Greece, this study involved 78 pregnant women who received flu vaccinations. The participants completed questionnaires covering demographics, obstetric history, attitudes toward influenza vaccination, and knowledge about the influenza virus and pregnancy vaccination. Blood samples were collected from 83 neonates to assess IgG antibody presence. Five of the surveyed women had twin pregnancies. The statistical analysis employed IBM SPSS-Statistics version 26.0. This study revealed the presence of positive influenza A and B antibodies in neonates following maternal immunization. Furthermore, it identified factors such as the gestational week and timing of vaccination during pregnancy that influenced the transfer of antibodies from mother to fetus. These findings offer valuable insights for healthcare professionals to provide informed recommendations on influenza vaccination during pregnancy and empower expectant mothers to make informed decisions about the benefits of immunization.