Determinants of maternal immunization in developing countries

BackgroundMaternal immunization is an effective intervention to protect newborns and young infants from infections when their immune response is immature. Tetanus toxoid vaccination of pregnant women is the most widely implemented maternal vaccine in developing countries where neonatal mortality is the highest. We identified barriers to maternal tetanus vaccination in developing African and Asian countries to identify means of improving maternal immunization platforms in these countries.MethodWe categorized barriers into health system, health care provider and patient barriers to maternal tetanus immunization and conducted a literature review on each category. Due to limited literature from Africa, we conducted a pilot survey of health care providers in Malawi on barriers they experience in immunizing pregnant women.ResultsThe major barriers of the health system are due to inadequate financial and human resources which translate to inadequate vaccination services delivery and logistics management. Health care providers are limited by poor attendance of Antenatal Care and inadequate knowledge on vaccinating pregnant women. Patient barriers are due to lack of education and knowledge on pregnancy immunization and socioeconomic factors such as low income and high parity.ConclusionThere are several factors that affect maternal tetanus immunization. Increasing knowledge in health care providers and patients, increasing antenatal care attendance and outreach activities will aid the uptake of maternal immunization. Health system barriers are more difficult to address requiring an improvement of overall immunization services. Further analyses of maternal immunization specific barriers and the means of addressing them are required to strengthen the existing program and provide a more efficient delivery system for additional maternal vaccines.     

Understanding factors influencing vaccination acceptance during pregnancy globally: A literature review

Maternal vaccination has been evaluated and found to be extremely effective at preventing illness in pregnant women and new-borns; however, uptake of such programmes has been low in some areas.To analyse factors contributing to uptake of vaccines globally, a systematic review on vaccine hesitancy was carried out by The Vaccine Confidence Project in 2012. In order to further analyse factors contributing to uptake of maternal immunisation, a further search within the broader systematic review was conducted using the terms ‘Pregnan*’ or ‘Matern*’. Forty-two articles were identified. Pregnancy-related articles were further screened to identify those focused on concerns, trust and access issues regarding maternal vaccination reported by pregnant women and healthcare workers. Thirty-five relevant articles were included which were then searched using the snowballing technique to identify additional relevant references cited in these articles. A search alert was also conducted from February to April 2015 in PubMed to ensure that no new relevant articles were missed. A total of 155 relevant articles were included.Most of the literature which was identified on hesitancy surrounding vaccination during pregnancy reports on determinants of influenza vaccine uptake in North America. Research conducted in low-income countries focused primarily on tetanus vaccine acceptance. The main barriers cited were related to vaccine safety, belief that vaccine not needed or effective, not recommended by healthcare worker, low knowledge about vaacines, access issues, cost, conflicting advice. From the point of view of healthcare workers, barriers included inadequate training, inadequate reimbursement and increased workload. Twenty-seven out of 46 (59%) articles mentioning ethnicity reported lower rates of coverage among ethnic minorities.Barriers to vaccination in pregnancy are complex and vary depending on context and population. There are wide gaps in knowledge regarding the attitudes of healthcare workers and how ethnicity and gender dynamics influence a pregnant woman's decision to vaccinate.     

Factors influencing acceptance of vaccination during pregnancy in The Gambia and Senegal

BackgroundVaccination during pregnancy can protect pregnant women and their babies from infectious diseases. Tetanus vaccine, also known as tetanus toxoid, is the only vaccine given to pregnant women in The Gambia and Senegal, where it is given by antenatal care providers as part of the Expanded Programme on Immunization. A qualitative study was undertaken to explore factors influencing acceptance of vaccination during pregnancy in The Gambia and Senegal.MethodsFocus group discussions and in-depth interviews were conducted across urban and rural settlements of The Gambia and Senegal. We explored the knowledge, attitudes, and perceptions of 152 women who were either pregnant or with an infant. NVivo 11 Qualitative Data Analysis Software was used for management and thematic analysis of the data.ResultsWomen had sufficient knowledge of the need for tetanus vaccine from different information sources but insufficient knowledge of tetanus causes, signs and symptoms. Tetanus vaccine was perceived to be safe and side effects such as pain and swelling at site of injection did not deter uptake of future doses. Women overall had confidence in their sources of vaccine information and the health care workers who administered maternal vaccinations. Their willingness to accept vaccination during pregnancy was particularly influenced by their husbands and trusted healthcare workers. Women across all sites mentioned they would accept new maternal vaccines if they are sensitized beforehand about any potential risks and benefits to them and their babies.ConclusionVaccine acceptance can be influenced by several factors including contextual, individual or group influences and vaccine or vaccination-specific issues. Women across The Gambia and Senegal are generally vaccine acceptors with confidence in the health care workers who vaccinate them and few concerns about maternal vaccines. Women’s acceptance of vaccination during pregnancy is based on previous vaccination experiences and individual weighing of risks and benefits.     

Safety of immunization during pregnancy: A review of the evidence of selected inactivated and live attenuated vaccines

Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. While there is emerging scientific evidence, as well as theoretical considerations, indicating that certain vaccines are safe for pregnant women and fetuses, policy formulation is challenging because of perceived potential risks to the fetus.This report presents an overview of available evidence on pregnant women vaccination safety monitoring in pregnant women, from both published literature and ongoing surveillance programs. Safety data were reviewed for vaccines against diseases which increase morbidity in pregnant women, their fetus or infant as well as vaccines which are used in mass vaccination campaigns against diseases. They include inactivated seasonal and pandemic influenza, mono- and combined meningococcal polysaccharide and conjugated vaccines, tetanus toxoid and acellular pertussis combination vaccines, as well as monovalent or combined rubella, oral poliomyelitis virus and yellow fever vaccines. No evidence of adverse pregnancy outcomes has been identified from immunization of pregnant women with these vaccines.     

Efficiency of placental transfer of vaccine-elicited antibodies relative to prenatal Tdap vaccination status

Administration of vaccines during pregnancy provides maternal protection against infectious diseases. This protection is extended to their infants during the first months of life, as pathogen-specific antibodies formed in response to maternal vaccination are transferred across the placenta to the fetus. Notably, Tdap (tetanus-diphtheria-acellular pertussis) vaccination booster is routinely administered to pregnant women both to prevent neonatal tetanus and to ensure that infants have protective levels of pertussis antibodies until they are able to establish their own vaccine-induced levels. Whether infant protection through maternal immunization is merely due to an increase in maternal antibody levels or whether maternal immunization enhances the transfer of vaccine-specific antibodies is unclear. Moreover, the potential impact of prenatal vaccinations on the transplacental transfer of other antibodies, such as antibodies raised as a result of infections or other vaccines administered prior to pregnancy, has not been studied.The goal of this study was to define the impact of maternal vaccination on IgG transplacental transfer efficiency. We analyzed antigen-specific antibody populations and IgG subclass distribution in maternal and cord blood samples from 58 mother-infant pairs. All women received the seasonal inactivated influenza vaccine during pregnancy and 25 women received the Tdap vaccine during the second or third trimester of gestation. Prenatal Tdap vaccination did not impact the efficiency of IgG transplacental transfer; however, it was associated with higher maternal and infant vaccine-elicited Tdap-specific antibody levels, and with a higher proportion of infants with protective levels of antibodies, especially against diphtheria. There was also no difference in the IgG transplacental transfer rate of antibodies against non-Tdap vaccines between the two groups of women. Our results confirm previous reports demonstrating the benefits of prenatal Tdap immunization and indicate that this strategy does not impede the transplacental transfer of other antibodies that are also important for infant protection.     

Maternal benefits of immunization during pregnancy

The US Centers for Disease Control & Prevention currently recommend routine immunization to prevent 17 vaccine-preventable diseases that occur in infants, children, adolescents, or adults. Pregnant women are at particularly high risk for morbidity and mortality related to several vaccine-preventable diseases. Furthermore, such illnesses are also associated with adverse pregnancy outcomes such as spontaneous abortion, congenital anomalies, preterm birth, and low birthweight. In addition to directly preventing maternal infection, vaccination during pregnancy may offer fetal and infant benefit through passive immunization. Several vaccines aimed at providing passive immunity to neonates are either currently recommended or in development. This article specifically addresses maternal benefits of maternal immunization following (1) vaccines recommended for all pregnant women; (2) vaccines recommended for pregnant women with particular risk factors; and (3) novel vaccines currently under development that primarily aim to at reduce infant morbidity and mortality.     

‘My primary purpose is to protect the unborn child’: Understanding pregnant women’s perceptions of maternal vaccination and vaccine trials in Europe

Despite the important benefits of maternal vaccination for pregnant women and newborns, vaccination uptake is low in many European countries. Differences in vaccination policies and recommendations, as well as concerns about vaccine safety can partly explain inadequate coverage rates and women’s hesitancy to get vaccinated during pregnancy. This study aims to explore pregnant women’s experiences, decision-making processes and perceptions towards maternal vaccination and maternal vaccine trials in France, Germany, Italy, Spain and the United Kingdom. Qualitative interviews and focus groups were conducted with 258 pregnant women identified through local research panels and snowballing. Topic guides translated in local languages were designed to explore women’s awareness and perceptions of maternal vaccination, and willingness to participate in vaccine trials during pregnancy. A thematic analysis was conducted. Pregnant women were found to have low awareness about maternal vaccination, with many reporting not having received a recommendation to vaccinate from their doctors. Strong trust in health professionals indicate that strengthened recommendations could improve vaccination uptake. Vaccination decision-making in pregnancy was described in the context of a highly emotional period, generating anxiety and fears around the safety of vaccines. Pregnancy was also discussed as a period during which women develop nurturing and protective identities. However, depending on the information they received as well as influences from experts, families and peers, women either perceived vaccination as a threat to their babies’ safety or as a means to protect them. Attitudes towards maternal vaccine trials were less ambiguous, with most pregnant women strongly rejecting the notion of taking part in trials. While strategies to improve pregnant women’s awareness and perceptions of maternal vaccination are needed, it is equally important to understand why healthcare professionals may not be recommending vaccination. More coordinated strategies across Europe could help strengthen communication and trust in maternal vaccination.     

Maternal immunisation in developing countries

Maternal immunisation could help to prevent the 2-3 million neonatal and early infant deaths that occur in the developing world each year. Determining the causes of neonatal and early infant deaths in developing countries is difficult as most occur at home. However, it is likely that at least half are due to infections, several of which might be prevented by maternal immunisation. Even in poor countries with few health facilities, a high percentage of pregnant women attend an antenatal clinic at least once during pregnancy. Thus, an effective delivery system for maternal immunisation already exists and, because of the success of maternal tetanus immunisation, this approach to the prevention of serious illness or death in young infants is widely accepted by the general population. However, the high prevalence of HIV and malaria found in pregnant women in some parts of the developing world, especially sub-Saharan Africa, could have an effect on the efficacy of maternal immunisation as both of these infections adversely affect placental function. Nevertheless, the potential of maternal immunisation to prevent early infant deaths in developing countries needs to be fully explored. The incidence of pneumococcal infections is high in many developing countries and about 25% of these infections occur at an age before protection could be anticipated following vaccination with a pneumococcal conjugate vaccine in infancy. Thus, a strong case can be made for a trial of the effectiveness of maternal immunisation with a pneumococcal vaccine in preventing serious illness or death in young infants in developing countries.     

Maternal immunization in Malawi: A mixed methods study of community perceptions,programmatic considerations,and recommendations for future planning

BackgroundSafe, effective vaccines are given to pregnant women to protect their infants and/or themselves against certain infectious agents; however, apart from tetanus vaccination, maternal immunization in low- and middle-income countries (LMICs) remains low. Tetanus toxoid vaccine is integrated into antenatal care services in Malawi with high coverage and provides an opportunity to identify factors that facilitate successful immunization delivery to pregnant women in LMICs.MethodsPATH and the University of Malawi’s Centre for Social Research conducted a mixed-methods study in 2015 to document community perceptions of maternal immunization, using tetanus vaccine as an example, and to identify factors perceived to be important to successfully introducing other maternal vaccines, such as influenza vaccine, in Malawi. We conducted 18 focus group discussions with pregnant and recently pregnant women and their family members and 76 semi-structured interviews with pregnant and recently pregnant women, community leaders, health workers, public health program managers, non-governmental partners, and policy makers.ResultsWe identified factors perceived to support the introduction of new maternal vaccines, including strong maternal vaccine acceptance in the community, an existing strategy for maternal tetanus vaccine delivery, and positive health workers’ views about the introduction of additional maternal vaccines. Potential challenges to adoption and acceptance included identifying and tracking the target population and monitoring adverse events, and the need to ensure operational capacity of the health system to support the introduction and wide-scale use of an additional vaccine. For influenza vaccine specifically, additional challenges included limited awareness of influenza disease and its low prioritization among health needs.ConclusionsLessons from the successful delivery of maternal tetanus immunization in Malawi may be informative for similar countries considering new vaccines for pregnant women or striving to optimize the delivery of those currently provided.     

Vaccination for Group B Streptococcus during pregnancy: attitudes and concerns of women and health care providers

Group B Streptococcus (GBS) is the leading infectious cause of neonatal morbidity and mortality. Although intrapartum antibiotic prophylaxis (IAP) strategies are effective in preventing GBS transmission from mothers to newborns, there are growing concerns about adverse effects, and the development of antibiotic resistance. GBS vaccines targeting the most virulent neonatal disease serotypes are currently under development and may be used during pregnancy. The objective of this study was to explore the key issues and concerns that would be associated with GBS vaccination during pregnancy from the perspectives of pregnant women and health care providers. Twenty-two women and 25 health care professionals in Alberta, Canada participated in 10 focus groups, each group ranging from 2 to 20 participants. Valuable information emerged from the focus groups about the factors that would affect acceptance of a maternal GBS vaccine. This information will be essential for health systems to consider in the introduction, promotion and delivery of such a vaccine. The data may help optimize education about GBS and a putative vaccine to pregnant women.     

A review of the costs of delivering maternal immunisation during pregnancy

BackgroundRoutine maternal immunisation against influenza and pertussis are recommended by the WHO to protect mother and child, and new vaccines are under development. Introducing maternal vaccines into national programmes requires an understanding of vaccine delivery costs – particularly in low resource settings.MethodsWe searched Medline, Embase, Econlit, and Global Health for studies reporting costs of delivering vaccination during pregnancy but excluded studies that did not separate the vaccine purchase price. Extracted costs were inflated and converted to 2018 US dollars.ResultsSixteen studies were included, of which two used primary data to estimate vaccine delivery costs. Costs per dose ranged from $0.55 to $0.64 in low-income countries, from $1.25 to $6.55 for middle-income countries, and from $5.76 to $39.87 in high-income countries.ConclusionsMore research is needed on the costs of delivering maternal immunisation during pregnancy, and of integrating vaccine delivery into existing programmes of antenatal care especially in low and middle-income countries.     

Trust,emotions and risks: Pregnant women’s perceptions,confidence and decision-making practices around maternal vaccination in France

Maternal vaccination is an important strategy to reduce maternal and newborn mortality and morbidity. Yet, vaccination uptake is suboptimal in many countries, including France. This mixed-method study aimed to identify factors influencing maternal vaccination, exploring pregnant women’s perceptions, confidence, and decision-making processes in France. Maternal vaccination uptake was positively associated with awareness of maternal vaccines, confidence in vaccine effectiveness and receiving a recommendation from a healthcare professional. A trusting relationship with healthcare professionals was observed as crucial for women during pregnancy. Even if women considered themselves as sole decision-makers, healthcare professionals’ role in decision-making was viewed as substantial. Pregnancy can be a complex time for assessing risks, which was evident in the strong emotional reactions to maternal vaccination and anxieties about safety. As new maternal vaccines are developed, it is crucial to consider women’s values, risk perceptions and emotions in the development of strategies to support acceptance of maternal vaccination.     

Pertussis vaccination during pregnancy in Belgium: Results of a prospective controlled cohort study

Vaccination during pregnancy has been recommended in some countries as a means to protect young infants from severe infection. Nevertheless, many aspects are still unknown and possible blunting of the infant's immune responses by maternal antibodies, is one of the concerns with maternal vaccination. We report the first prospective controlled cohort study in women and infants on the effects of using Boostrix^®, a combined tetanus, diphtheria and acellular pertussis vaccine, during pregnancy. The primary aim was to measure the influence of this booster dose on the titer and duration of the presence of maternal antibodies in the infants and assess possible interference with infant immune responses.In a controlled cohort study, 57 pregnant women were vaccinated with Tdap vaccine (Tetanus Diphtheria acellular Pertussis, Boostrix, GSK Biologicals), at a mean gestational age of 28.6 weeks. A control group of pregnant women (N = 42) received no vaccine. Antibody geometric mean concentrations (GMCs) against tetanus (TT), diphtheria (DT), pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (Prn) were measured with commercial ELISA tests in samples taken preceding maternal vaccination and one month afterwards, at delivery and from the cord blood, and in infants before and 1 month after the primary series of 3 pertussis containing hexavalent vaccines.Infants born to vaccinated women had significantly higher GMC at birth and during the first 2 months of life for all vaccine antigens compared to the offspring of unvaccinated women, thereby closing the susceptibility gap for pertussis in infants. However, blunting was noticed for infant diphtheria and pertussis toxin vaccine responses (p < 0.001) in the infants from vaccinated women after the primary vaccination schedule (weeks 8,12 and 16).Since pertussis vaccination has been recommended during pregnancy already, the results of this study support that recommendation and provide additional scientific evidence to document possible interference by maternal antibodies.     

An investment case for maternal and neonatal tetanus elimination

IntroductionGlobally, 13 countries have yet to eliminate maternal and neonatal tetanus. While efforts have improved access to tetanus toxoid containing vaccines (TTCVs) and increased clean delivery practices, reaching elimination targets (<1 case of neonatal tetanus per 1000 live births per district per year) may require significant resources to reach the remaining high risk and hard-to-reach districts.MethodsWe estimated the cost to achieve maternal and neonatal tetanus elimination (MNTE) in three years in the remaining 13 countries: Afghanistan, Angola, Central African Republic, Democratic Republic of the Congo, Guinea, Mali, Nigeria, Pakistan, Papua New Guinea, Somalia, South Sudan, Sudan, and Yemen. Costs were estimated for: (1) vaccination campaigns using standard TTCVs and TT-Uniject™ targeting women of reproductive age in high risk areas, (2) additional vaccinations delivered to pregnant women at antenatal care (ANC) clinics, (3) clean delivery and umbilical cord care promotion, (4) neonatal tetanus surveillance strengthening, and (5) validation activities. We forecasted the averted mortality to assess the cost-effectiveness of achieving MNTE.ResultsIt will cost an estimated US$197.7 million to realize MNTE over three years. These costs include $161.4 million for vaccination campaigns, $6.1 million for routine vaccination during ANC, $23.3 million for promotion of clean delivery practices, $4 million for surveillance, and $3 million for validation of MNTE. Achieving MNTE will avert approximately 70,000 neonatal deaths over ten years of vaccine protection, resulting in approximately 4.4 million life years gained. It will cost $2,900 per death averted and $45 per life year gained.ConclusionMaternal and neonatal tetanus can be eliminated with significant financial investment, high prioritization, and strong political will. While substantial costs must be incurred to reach hard-to-reach populations, MNTE should be accomplished as a matter of health equity, and will significantly contribute to reaching the United Nations' Sustainable Development Goals.     

Vaccine implementation factors affecting maternal tetanus immunization in low- and middle-income countries: Results of the Maternal Immunization and Antenatal Care Situational Analysis (MIACSA) project

ObjectivesTo examine the characteristics of existing maternal tetanus immunization programmes for pregnant women in low- and middle-income countries (LMICs) and to identify and understand the challenges, barriers and facilitators associated with maternal vaccine service delivery that may impact the introduction and implementation of new maternal vaccines in the future.DesignA mixed methods, cross sectional study with four data collection phases including a desk review, online survey, telephone and face-to-face interviews and in country visits.SettingLMICs.ResultsThe majority of countries (84/95; 88%) had a maternal tetanus immunization policy. Countries with high protection at birth (PAB) were more likely to report tetanus toxoid-containing vaccine (TTCV) coverage targets > 90%. Less than half the countries included in this study had a TTCV coverage target of > 90%. Procurement and distribution of TTCV was nearly always the responsibility of the Expanded Programme on Immunization (EPI), however planning and management of maternal immunization was often shared between EPI and Maternal, Newborn and Child Health (MNCH) programmes. Receipt of TTCV at the same time as the antenatal care visit correlated with high PAB. Most countries (81/95; 85%) had an immunization safety surveillance system in place although only 11% could differentiate an adverse event following immunization (AEFI) in pregnant and non-pregnant women.ConclusionsRecommendations arising from the MIACSA project to strengthen existing services currently delivering maternal tetanus immunization in LMICs include establishing and maintaining vaccination targets, clearly defining responsibilities and fostering collaborations between EPI and MNCH, investing in strengthening the health workforce, improving the design and use of existing record keeping for immunization, adjusting current AEFI reporting to differentiate pregnant women and endeavoring to integrate the provision of TTCV within ANC services where appropriate.     

Elucidating the difference in the kinetics of antibody titres of infants in Belgium and Vietnam

Serological results obtained in a single laboratory from twin-studies on maternal immunisation, in Vietnam and Belgium offer the opportunity to compare antibody kinetics in infants before and after infant vaccination in the presence of vaccine-induced maternal antibodies. Nonlinear mixed-effects models (NLMMs) making use of a hypothesised dynamic evolution that captures the change in antibody titres over time, were employed to model anti-PT and anti-Prn antibody dynamics. Our proposed modelling approach provided useful insight into understanding the differences in the infants’ antibody kinetics in both countries since NLMMs offer the possibility of pooling all data in one analysis and incorporate relevant covariates of interest.In both controlled cohort studies, pregnant women were vaccinated with a tetanus, diphtheria, acellular pertussis (Tdap) vaccine (Boostrix®, Belgium; Adacel®, Vietnam), and children were followed before and after primary vaccination, and before and after booster vaccination (Infanrix hexa®). From our models, both anti-PRN and anti-PT antibody titres at birth of Vietnamese infants were significantly lower than those of Belgian infants born to vaccinated women groups. Even though the antibody titres in the cord at birth of Belgian infants were also higher than those of Vietnamese infants born to the control women groups, the difference was not significant. The significant difference between infants born to vaccinated women in the two countries was likely due to the use of different vaccine brands in pregnant women and the different vaccination histories of women in these two countries.Our analyses also suggested that the blunting effect was present during the primary immunisation but went away afterward for anti-PT data. In contrast, for anti-PRN antibodies, the blunting effect persisted after the primary vaccination and possibly went away after the booster dose. Countries should be aware of the regional situation in view of recommending maternal immunization.     

Maternal pertussis and influenza immunization coverage and attitude of health care workers towards these recommendations in Flanders,Belgium

In Belgium, pertussis vaccination is recommended for all pregnant women in every pregnancy. Adults in close contact with young infants are equally advised to receive a pertussis containing booster dose. Maternal influenza vaccination is likewise recommended in Belgium in the second or third trimester of pregnancy, within the influenza season.A quantitative multicenter survey study has been performed between October 2014 and May 2015 in both postpartum women (N = 823, response rate = 89.2%) and health care workers (HCWs) (N = 261) to assess the coverage of both vaccines during pregnancy along with the coverage of the pertussis cocoon strategy, and to evaluate the knowledge and recommending attitude of HCWs towards the maternal vaccination strategies and the cocoon strategy among surveyed women and HCWs.Overall coverage of pertussis vaccination during pregnancy was 64.0%. Most women were vaccinated by their general practitioner (GP) (82.4%), and most often in the third trimester (74.0%) of pregnancy. Overall coverage of influenza vaccination during pregnancy was 45.0%. Again the GP administered most vaccines (67.6%); vaccines were equally administered in the second or third trimester of pregnancy. Educational level had a significant influence on both the pertussis and influenza vaccination coverage during pregnancy while working situation and parity had only an influence on the maternal pertussis vaccination coverage and country of birth only on the maternal influenza vaccination coverage.Overall, 78.4% of gynecologists and GPs recommends both maternal pertussis and influenza vaccination and 67.0% recommends both maternal vaccination strategies and the cocoon strategy. Within the group of the midwives, only 23.7% recommends both maternal pertussis and influenza vaccination and 10.5% recommends both maternal vaccination strategies and the cocoon strategy.High coverage is reached among pregnant women for pertussis and influenza vaccination. Several underserved populations of pregnant women regarding maternal immunization, are identified.     

Antenatal care service delivery and factors affecting effective tetanus vaccine coverage in low- and middle-income countries: Results of the Maternal Immunisation and Antenatal Care Situational analysis (MIACSA) project

ObjectivesTo map the integration of existing maternal tetanus immunization programmes within antenatal care (ANC) services for pregnant women in low- and middle-income countries (LMICs) and to identify and understand the challenges, barriers and facilitators associated with high performance maternal vaccine service delivery.DesignA mixed methods, cross sectional study with four data collection phases including a desk review, online survey, telephone and face-to-face interviews and in country visits was undertaken between 2016 and 2018. Associations of different service delivery process components with protection at birth (PAB) and with country groups were established. PAB was defined as the proportion of neonates protected at birth against neonatal tetanus. Regression analysis and structural equation modelling was used to assess associations of different variables with maternal tetanus immunization coverage. Latent class analysis (LCA), was used to group country performance for maternal immunization, and to address the problem of multicollinearity.SettingLMICs.ResultsThe majority of LMICs had a policy on recommended number of ANC visits, however most were yet to implement the WHO guidelines recommending eight ANC contacts. Countries that recommended > 4 ANC contacts were more likely to have high PAB > 90%. Passive disease surveillance was the most common form of disease surveillance performed but the maternal and neonatal morbidity and mortality indicators recorded differed between countries. The presence of user fees for antenatal care and maternal immunization was significantly associated with lower PAB (<90%).ConclusionsRecommendations include implementing the current WHO ANC guideline to facilitate increased opportunities for vaccination during each pregnancy. Improved utilisation of ANC services by increasing the demand side by increasing the quality of services, reducing any associated costs and supporting user fee exemptions, or the supply side can also enhance utilisation of ANC services which are positioned as an ideal platform for delivery of maternal vaccines.