To support the safe and timely use of vaccines in pregnancy and among lactating women, a comprehensive strategy is required that integrates clinical trial innovation, targeted observational studies, and robust pharmacovigilance systems. These approaches must be adapted to the characteristics of different pathogens, vaccine platforms and formulations and the realities of country contexts. They must also be aligned with regulatory and policy frameworks.

Clinical Trials

Adaptive trial designs, which allow protocols to evolve in response to emerging safety and immunogenicity data, can accelerate inclusion. These designs were effectively employed during COVID-19 and could be adapted for inclusion of pregnant and lactating women.

Adaptive trial design in pregnancy - Lessons from COVID-19 mRNA Vaccines

COVID-19 mRNA vaccine trials used an adaptive design that began with healthy, non-pregnant adults and expanded to pregnant women once short-term safety and immunogenicity data were reassuring. Predefined safety milestones triggered staged inclusion, starting with second- and third-trimester participants. In parallel, large observational pregnancy registries captured real-world safety data from pregnant women vaccinated outside of trials. Frequent interim analyses allowed rapid protocol adjustments, and harmonized maternal, fetal, and infant endpoints enabled pooled analyses.

This approach may be applied to other vaccines for use in pregnant and lactating women (e.g., malaria, TB, meningococcus) by:

• starting in non-pregnant adults but planning for inclusion of pregnant women early in the development programme;
• defining clear "go/no-go" criteria for expansion;
• include lactating women as part of expanded population;
• leveraging incidental pregnancy exposures for safety monitoring;
• aligning immunological endpoints to bridge data across populations.

Trimester-stratified enrolment is critical for understanding how maternal physiology and fetal development affect vaccine performance and safety across gestation.

• Example: GBS
  For GBS vaccines, which aim to prevent neonatal sepsis and meningitis, trials must consider the optimal timing of vaccination to maximize placental antibody transfer. Third-trimester immunization is expected to confer the highest level of neonatal protection, but data across trimesters are needed to support flexible policy implementation.


• Example: meningococcal disease
  Although several meningococcal vaccines (e.g., MenACWY, MenB) are licensed for adolescents and outbreak response, their use during pregnancy has not been formally studied in prospective trials. Vaccination during pregnancy could prevent early-onset neonatal disease through placental antibody transfer. Trials incorporating trimester-stratified enrolment—particularly in regions with high meningococcal transmission or epidemic risk—could help bridge this gap and inform maternal vaccine policy in endemic and epidemic-prone areas.

Observational studies

While randomized controlled trials remain the gold standard, observational studies can play an important role alongside vaccine trials. They are particularly useful for collecting data on groups often excluded from early trial phases, such as pregnant or lactating women. For example, observational cohorts within antenatal care can track women who are unintentionally vaccinated before knowing they are pregnant, or those enrolled later in maternal vaccine programmes. These studies provide valuable real-world evidence on safety and pregnancy outcomes, complementing trial data and helping to fill gaps that randomized studies cannot address (Table 3).

Table 3 Examples of observational studies for pipeline vaccines providing pregnancy-specific data