Standardized tools and templates must be adapted for use across vaccine platforms (e.g., protein subunit, mRNA, viral vector), enabling harmonized data collection and regulatory comparability across diverse settings and products for pregnant and lactating women.

This section outlines key outcome domains and tools, drawing from experience with licensed vaccines (e.g., Tdap, COVID-19 mRNA, RSV, MenACWY) and vaccines in late-stage development (e.g., GBS, TB, malaria).  

Core outcome domains

Maternal outcomes

Robust assessment of maternal safety and immunogenicity is essential to determine the benefit–risk profile of any vaccine intended for use in pregnancy or lactation. 

Key endpoints include:

• Seroconversion and immunogenicity metrics
  • Measurement of specific antibody titers (e.g., IgG, neutralising antibodies) and functional responses (e.g., opsonophagocytic activity for GBS, IFN-γ ELISpot for TB) using harmonized assays.
  • Example: In COVID-19, vaccine trials, maternal seroconversion and antibody kinetics were used to model passive transfer and guide recommendations for timing of vaccination during pregnancy.
• Adverse obstetric event
  • Includes hypertensive disorders of pregnancy, gestational diabetes, preterm labour, placental abruption, and maternal mortality.
  • Example: In maternal RSV vaccine trials, obstetric complications were tracked systematically using GAIA definitions, enabling comparison across products and trials.
• Pregnancy outcomes
  • Miscarriage, stillbirth, and mode of delivery should be captured with precise gestational age data.
  • Example: Tdap vaccine safety monitoring has demonstrated no increased risk of adverse pregnancy outcomes when given in the third trimester. 
• Lactation outcomes
  • Assessment of vaccine impact on breast milk composition (e.g., antibody levels, cytokines, microbiome) and breastfeeding safety, including infant growth and feeding tolerance.
  • Example: Studies of influenza and COVID-19 vaccines have demonstrated robust antibody responses in breast milk without adverse effects on breastfeeding or infant health.

Fetal and neonatal outcomes

Evidence of fetal and neonatal protection is often a central goal of maternal immunization programmes and must be supported by well-defined, consistently measured endpoints.

Key endpoints include:

• Congenital anomalies and birth defects
  • Categorized using standardized systems such as MedDRA or the GAIA congenital anomaly definitions.
  • Example: Vaccine Adverse Event Reporting System (VAERS) data on COVID-19 mRNA vaccine exposure during pregnancy identified no safety signals for congenital anomalies, informing global recommendations. 
• Neonatal immune markers and antibody persistence
  • Measures of placental antibody transfer (e.g., cord:maternal ratio), duration of detectable antibody levels, and correlates of protection (if known).
  • Example: RSV and Tdap vaccine studies measured antibody half-life in infants to estimate duration of protection and guide scheduling of childhood vaccinations.
  • Assessment of potential immunomodulation of infant immune responses following maternal immunization, particularly in relation to routine childhood vaccines (e.g., diphtheria, tetanus, polio, measles).
  • Example: Studies of maternal pertussis vaccination showed transient reductions in infant antibody responses to primary series doses, though clinical protection remained uncompromised.
• Neonatal outcomes
  • Include birth weight, gestational age, Apgar scores, admission to neonatal intensive care unit, and early neonatal mortality.
  • Example: GBS vaccine trials are expected to use early-onset sepsis, birth weight, and gestational age as key endpoints aligned with GAIA and WHO MNHD standards.

Tools and templates for outcome measurement and regulatory alignment

To ensure consistency, transparency, and cross-study comparability, sponsors and regulators should adopt and adapt established tools. One such toolset is the BRAVATO (Benefit–Risk Assessment of VAccines by TechnolOgy) framework, which can be used to guide platform-specific evidence generation. 

BRAVATO templates (adapted for platform-specific use)

Originally developed through WHO and global expert consultation, BRAVATO templates provide a structured format for summarizing data on vaccine safety and effectiveness in pregnancy and lactation. These templates should be adapted to the biological features of different platforms, including:

• Protein-based vaccines
  • Emphasis on antibody isotype profiles, passive transfer efficiency, and adjuvant safety.
  • Example: RSV vaccines rely on BRAVATO-style tabulation of maternal-fetal antibody dynamics and potential reactogenicity.
• mRNA vaccines
  • Focus on systemic reactogenicity, placental biodistribution, and spike protein persistence.
  • Example: Moderna® and Pfizer® incorporated adapted BRAVATO formats in post-hoc reviews of pregnancy outcomes from clinical trials and real-world registries.
• Viral vector vaccines
  • Considerations include vector tropism, pre-existing immunity, and theoretical fetal exposure.
  • Example: Data on adenovirus-vectored Ebola vaccines have been summarized using BRAVATO-informed registries, despite limited data in pregnant populations.

Sponsors should work with regulators early in development to agree on platform-specific adaptations of BRAVATO templates and integrate them into clinical study reports, risk management plans, and WHO prequalification dossiers.