Identifying Gaps and Opportunities for Maternal and Neonatal Immunization Research and Implementation in Latin America

Maternal and neonatal immunization (MNI) has emerged as a critical strategy for protecting both mothers and infants from vaccine-preventable diseases. Maternal immunization provides passive immunity to the infant through the transfer of pathogen-specific antibodies across the placenta.1 This approach is particularly vital in the early months of life when the infant’s immune system is still developing, and the risk of severe infections is high. The effectiveness of maternal immunization in preventing diseases, such as influenza, pertussis and tetanus, has been well-documented, leading to increased global efforts to optimize immunization schedules and harmonize them with routine infant vaccines.1–6 More recently, maternal COVID-19 vaccination proved to be an effective strategy to protect infants <6 months, reducing the risk of hospitalization due to coronavirus disease 2019 (COVID-19) and decreasing the likelihood of intensive care unit admission.7–9 In addition, recent clinical trials have demonstrated that maternal vaccination with the bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF, Pfizer, New York, NY, Abrysvo) was effective in preventing severe RSV disease in infants <6 months.10 Beyond reducing the risk of severe disease in pregnant women and their infants, maternal vaccination also addresses pregnancy-related complications, such as pregnancy loss and low birth weight associated with influenza, and the risk of stillbirth and preterm birth related to maternal COVID-19.2,3,8,9,11 In Latin America, where maternal, neonatal and infant morbidity and mortality rates remain a significant public health concern, maternal immunization offers a promising avenue for improving health outcomes. The Pan American Health Organization’s (PAHO) Regional Immunization Action Plan aims to establish and strengthen MNI platforms as part of broader efforts to enhance health services for more effective vaccine administration. This initiative has already led to significant public health achievements in the Americas, such as the elimination of congenital rubella syndrome in 2015 and the elimination of maternal and neonatal tetanus in 2017.12 Building on these successes, PAHO’s Technical Advisory Group recommends the use of tetanus-containing vaccines, influenza vaccines and acellular pertussis-containing vaccines for pregnant women. As a result of these recommendations, there is now increasing adoption of maternal immunization practices across the region: 32 of 52 countries and territories in the Americas recommend tetanus-containing vaccines for women of childbearing age, 34 countries advocate for the vaccination of pregnant women against influenza and 16 countries recommend the administration of the acellular pertussis-containing vaccine (Tdap) during every pregnancy.12 According to the World Health Organization, in 2023, the region reported administrative coverages for influenza vaccine in pregnant women that varied from 16.1% in Guatemala to more than 90% in Panama and Nicaragua (Figure, Supplemental Digital Content 1, https://links.lww.com/INF/F997). For pertussis-containing vaccines, coverages in the region were in general more homogeneous among the countries that already implemented this strategy, with only 3 countries, Uruguay, Honduras and El Salvador, achieving more than 80% coverage in 202313 (Figure, Supplemental Digital Content 2, https://links.lww.com/INF/F998). These efforts underscore the importance of the commitment to maternal and neonatal vaccination. However, there are gaps and opportunities that need to be addressed to fully realize the benefits of this strategy. On March 12–14, 2024, during the 6th International Neonatal & Maternal Immunization Symposium (INMIS), held in San Jose, Costa Rica, public health and medical experts from across Latin America participated in a scientific symposium focused on identifying gaps and opportunities for MNI in Latin America. The symposium had 3 core presentations followed by a panel discussion with the following objectives: (1) Discuss the status of MNI in Latin America. (2) Identify gaps and opportunities for research and implementation of vaccines in pregnancy and early childhood, (3) Action items and prioritization. This article reflects the discussions and the conclusions reached during the symposium, focusing on Latin American countries’ needs to improve surveillance and immunization coverage rates, lessons learned and recommendations for the future. MATERNAL IMMUNIZATION RESEARCH IN LATIN AMERICA Maternal immunization research in Latin America faces significant challenges despite its potential to improve maternal and child health outcomes. These challenges include limited and heterogeneous access to vaccines across the region, slow implementation in national policies, safety concerns among healthcare providers and pregnant women and disparities in healthcare infrastructure. In addition, there is a lack of robust surveillance systems to monitor vaccine coverage and adverse events following immunization, which is compounded by cultural beliefs, social norms and socioeconomic factors that affect vaccine acceptance among pregnant women and their families.14,15 The introduction of maternal vaccines in Latin America has been gradual, influenced by global health initiatives and regional efforts to improve maternal and child health. The tetanus toxoid vaccine was one of the earliest maternal vaccines introduced, with research from Colombia, Ecuador, Chile and Brazil providing initial evidence of its benefits for pregnant women and neonates in the region. The tetanus toxoid vaccination became standard practice, leading to the elimination of maternal and neonatal tetanus in the Americas by 2017, as validated in Haiti. Rubella vaccination was incorporated into childhood immunization programs in the 1990s, and efforts beginning in 2005 led to widespread immunization of women of reproductive age, preventing an estimated 112,500 cases and eliminating congenital rubella syndrome in the Americas by 2015. These efforts have been complemented by increased interest in maternal immunization due to the impact of influenza on pregnant women and their children during the H1N1 pandemic in 2009, as well as the progressive implementation, since 2012, of acellular pertussis-containing vaccine programs for pregnant persons. Organizations such as the PAHO play a critical role in promoting maternal immunization by providing technical assistance, supporting vaccine procurement and promoting vaccination campaigns across the region.14–16 Despite these successes, research on maternal immunization remains limited in the region due to disparities in funding, infrastructure and access to vaccines.16 There is a growing need to study the impact of social determinants and specific population characteristics on the transfer of maternal antibodies to infants and the overall protection of the maternal-infant dyad. Research gaps persist, particularly in indigenous populations, which represent a significant portion of the population in some Latin American countries. The effects of malnutrition and environmental stresses, such as heat and pollution, also need to be addressed. Limited research capacity and expertise within academic and healthcare institutions further hinder the generation of local data and evidence. Collaboration with international partners is crucial but often challenging due to regulatory and logistical barriers. Strengthening coordination among stakeholders—including governments, healthcare providers, researchers and community leaders—is essential for the effective implementation and evaluation of maternal immunization programs. To address the current gaps in maternal immunization research and safety, several strategies are needed. Expanding participation in observational studies could track vaccinated pregnant women and their infants, evaluating safety and vaccine effectiveness in real-world settings. Training healthcare workers to monitor and report adverse events following immunizations is also crucial, as is aligning maternal vaccine schedules with infant schedules to optimize delivery and protection. Implementing these strategies requires collaborative efforts among healthcare providers, policymakers, researchers and public health organizations. Continuous evaluation is vital to ensure that maternal immunization programs are safe, effective and well-integrated with infant vaccination schedules. RESEARCH TO IMPROVE UPTAKE OF VACCINES DURING PREGNANCY AND EARLY INFANCY: AN UNMET NEED IN LATIN AMERICA Conducting research on pregnancy vaccination in Latin America is essential to identify barriers to immunization and develop strategies to enhance vaccine uptake in the region. Improving current immunization approaches and incorporating new tools against pathogens like RSV, chikungunya, cytomegalovirus and Group B streptococcus (GBS) could significantly reduce neonatal and infant mortality rates in the region and worldwide.2,17–21 To improve vaccine uptake among pregnant women and infants in Latin America, it is necessary to address factors such as misinformation and lack of awareness, poor access to quality healthcare, cultural beliefs and socioeconomic constraints. Many expectant parents may not fully understand the benefits and safety of vaccines, and misinformation, particularly through social media, can further deter vaccination. Limited access to healthcare facilities, especially in rural or indigenous areas, impedes good prenatal care and timely vaccination. In addition, cultural norms and socioeconomic factors can influence attitudes toward vaccination, with some communities having beliefs that discourage vaccine use. Economic challenges also limit a family’s ability to access vaccination programs, as low-income families may prioritize immediate needs over preventive measures like immunization. Recent studies have highlighted the first 1000 days of life as a crucial period for preventing the impact of infectious diseases on maternal and infant morbidity and mortality in Latin America. Findings reveal significant variability in prenatal care in the region, low rates of exclusive breastfeeding and suboptimal immunization coverage for essential vaccines.22 Several research-driven strategies can effectively address these barriers. Educational campaigns tailored to local contexts can improve awareness about the importance of vaccines and counteract misinformation. Improving access to healthcare through mobile clinics, telemedicine and outreach programs can ensure vaccines are readily available in all communities. Engaging local leaders and influencers can foster trust and acceptance, while financial support and incentives for vaccination can alleviate economic burdens on families. Research can also help design effective incentive programs that encourage higher vaccine uptake, remove regulatory barriers and implement confidential health record systems to link mother and infant information.23 In Panama, the Cevaxin model demonstrates how public–private partnerships can enhance clinical research as a care option, addressing obstacles to study participation and expanding healthcare access (https://cevaxin.com/en/). By focusing on participant needs, building trust and ensuring ethical standards, Cevaxin is a medical research center that promotes good patient satisfaction and encourages participation in vaccine trials. Engaging participants in study design and addressing their concerns about health risks and clinical research helps eliminate misconceptions and promote the ethical conduct of research. These strategies highlight the importance of collaboration and continuous investment in research to improve vaccine uptake during pregnancy and early infancy, ultimately benefiting maternal and child health.24 ADVANCING MATERNAL AND NEONATAL HEALTH: THE CLAP NETWORK’S PIONEERING JOURNEY The CLAP Network of Sentinel Centers for Maternal and Neonatal Health Surveillance and Research represents a pioneering collaboration among institutions across Latin America and the Caribbean, aimed at enhancing surveillance, training, and research to improve health outcomes for women and newborns. Established in 2015, the network includes 15 institutions from 8 countries and uses the Perinatal Information System (SIP) as a standardized platform for communication and data exchange. SIP captures clinical care data across prenatal, childbirth, postpartum and newborn stages and addresses broader issues such as contraception counseling and support for women facing violence. Data from network centers are shared through agreements for research purposes, with databases available to external researchers.25 The Perinatal Clinical Record, developed under the SIP framework, ensures meticulous documentation of care processes while aligning with evidence-based practices. SIP’s adaptability and interoperability with other electronic record systems enhance its versatility, and its adoption by 20 nations in the region demonstrates its effectiveness. The network also focuses on MNI, using SIP to enhance surveillance, monitoring and performance evaluation of immunization programs. Despite progress, challenges persist, particularly regarding immunization coverage during pregnancy. The introduction of COVID-19 vaccines has diverted resources from existing programs, leading to suboptimal coverage rates.26 Addressing these challenges requires proactive policies to promote vaccination among pregnant women and better integration of prenatal care and immunization services. PAHO’s study on maternal and neonatal adverse events following COVID-19 vaccination aims to generate critical insights into vaccine safety and efficacy in populations excluded from initial trials.27 Moving forward, inclusive clinical trials and collaboration among stakeholders are essential to achieving the CLAP Network’s vision of optimal maternal and neonatal health outcomes in the Americas. PANEL DISCUSSION Among the developments foreseen in Latin America, maternal and neonatal RSV immunization is considered a high priority. Despite all the progresses achieved with the current pertussis, tetanus and influenza maternal immunization programs implemented in Latin America, disparities in vaccine access and coverage persist. Moving forward, improving equitable access to vaccines in the region should be prioritized. In this regard, it would be important to address these disparities to accelerate the introduction of maternal RSV vaccines and infant RSV immunization.28–31 RSV is a leading cause of severe lower respiratory tract infections, particularly bronchiolitis and pneumonia, in infants worldwide. In Latin America, RSV contributes significantly to infant morbidity and mortality, placing a heavy burden on healthcare systems, including high economic costs.28,32,33 MNI against RSV has the potential to improve infant health outcomes by offering early protection to newborns during their most vulnerable months. The success of maternal immunization programs for other diseases, such as influenza and pertussis, highlights the effectiveness and safety of this approach, providing a strong foundation for RSV immunization efforts. However, several challenges must be addressed to implement an RSV maternal immunization program successfully in Latin America. One major challenge is the inconsistency in healthcare infrastructure across the region. Access to quality prenatal care varies widely, particularly in rural and underserved areas, making it difficult to ensure that all pregnant women receive the necessary vaccinations. Improving healthcare access and strengthening systems are crucial steps to overcoming this barrier. Argentina was the first country in Latin America to implement an RSV maternal immunization program, which became a priority as the country was able to highlight the burden of disease burden, the epidemiology and seasonality of the virus to adequately support the implementation of this strategy. Argentina also had historically good acceptance of maternal vaccination and an existing supporting partnership with antenatal care providers. Furthermore, the incorporation of a new vaccine must be followed by a comprehensive evaluation of its impact and effectiveness, as well as the establishment of a sustainable safety surveillance system over time.28 This might not be feasible in all countries in Latin America, where diagnostic, epidemiologic and safety surveillance capabilities are limited. Chile was the second country in the region to successfully implement a prevention strategy against RSV, with the use of a long-acting monoclonal antibody (nirsevimab) for all children at birth and in the first 6 months of life, starting in the winter of 2024. Similarly, having baseline disease burden information and surveillance infrastructure allowed Chile to successfully implement this highly effective strategy, but other countries in the region experienced challenges. Logistical and financial constraints further complicate the rollout of RSV vaccines. Ensuring a consistent vaccine supply and maintaining cold chain logistics in remote areas can be difficult. In addition, limited financial resources may hinder the expansion of immunization programs. Collaborative efforts with international organizations and donor agencies will be essential to address these challenges. New maternal vaccines are currently in various stages of research and development, targeting diseases that represent significant risks to pregnant women and their infants. In this regard, maternal immunization against GBS is crucial for protecting newborns from severe infections that can occur during the first weeks of life. GBS is a leading cause of neonatal sepsis, meningitis and pneumonia, conditions that can lead to long-term complications or even death. Currently, the primary strategy to prevent GBS infection involves administering antibiotics to pregnant women during labor, but this approach has limitations, including the potential for antibiotic resistance and limited effectiveness in preventing late-onset disease. This strategy is not yet incorporated in most Latin American countries, where rates of maternal genital colonization have been reported to range from 2% to 20.4% in studies conducted in Mexico, Argentina, Colombia and Brazil, and where the incidence of neonatal invasive disease has been estimated to affect 0.3%–1% of live births.34,35 A maternal vaccine against GBS would provide more comprehensive protection by enabling the transfer of protective antibodies from the mother to the baby through the placenta.36 This could significantly reduce the incidence of GBS infections in newborns, offering a safer and more effective method to prevent these life-threatening conditions and improve overall neonatal health outcomes. Other pathogens associated with significant burden in young infants as well as pregnant persons could be considered for future maternal immunization, including arboviral infections (Zika, Dengue and Chikungunya), cytomegalovirus, malaria, Herpes simplex virus, hepatitis E among several others.1,2,18,37 There is also a need to enhance the public’s education and awareness about the benefits and safety of maternal immunization. Vaccine hesitancy, fueled by misinformation and cultural beliefs, poses a significant challenge to future immunization programs. communication strategies and approaches are to trust and encourage vaccine acceptance among both healthcare providers and the The of maternal and infant immunization schedules is crucial for the protective effects of vaccines while the risk of adverse involves aligning the and of vaccines during pregnancy with to infants This ensures that the antibodies by maternal immunization not with the infant’s immune to vaccinations. Research into the optimal and of vaccines is essential to develop schedules that provide the most effective and protection for both mothers and their infants. Furthermore, more and comprehensive immunization programs, reducing the burden on healthcare systems and improving vaccine OF AND TO MATERNAL IMMUNIZATION RESEARCH IN LATIN AMERICA Despite the benefits of maternal immunization, several gaps in research and implementation particularly in Latin America. gaps and opportunities in Latin America are in Digital Content One significant is the lack of data on the burden of as well as on the safety and efficacy of maternal vaccines. studies on maternal immunization have been conducted in countries, where the healthcare infrastructure and population significantly from in Latin America. To ensure the implementation of maternal immunization programs in the region, there is a need for local research that the needs and challenges of Latin American This includes the burden of diseases in country and the safety of maternal vaccines in populations with of access to healthcare, as well as the potential maternal and infant vaccines in these in the integration of maternal immunization into existing public health In Latin American countries, maternal and child health programs are not fully with immunization leading to opportunities for vaccination. Strengthening the integration of these services could improve vaccine uptake among pregnant women and ensure that infants receive timely In addition, public awareness and education campaigns are to address misconceptions about vaccine safety and which remain a to maternal immunization in of the region. opportunities for improving MNI in Latin America is essential for public health outcomes. include existing healthcare such as antenatal and care to identify cases of maternal vaccines and promote immunization with international and local communities can help to develop that address the specific needs and concerns of Latin American By addressing these gaps and these Latin America can enhance the impact of maternal immunization programs, ultimately reducing the burden of vaccine-preventable diseases among mothers and infants. Continuous investment in research and collaboration among governments, healthcare providers and international organizations is crucial to address these gaps and enhance vaccine uptake during pregnancy and early infancy, improving health outcomes for mothers and infants across the region. In maternal immunization and its with infant vaccines a significant to improve health outcomes for mothers and their infants in Latin America. However, this potential requires addressing and research enhancing public health and promoting education and By focusing on these areas, stakeholders can develop more effective and sustainable MNI programs across the region. The and Latin American Symposium the for their support and help in the and conduct of this symposium, as well as and Costa and their for their administrative and