Vaccine safety in pregnancy
The safety of each vaccine platform must be carefully assessed in pregnancy. Evidence needs depend on the platform, available data, and how the vaccine is intended to be used (8). For newer platforms, DART studies and evaluations of antibody transfer across the placenta are essential to understand both maternal safety and potential protection for the fetus and infant. These data also guide the best timing for vaccination during pregnancy. Table 2 summarizes key safety considerations for different vaccine platforms.
Table 2 Vaccine platforms and safety considerations in pregnancy
| Vaccine platform | Examples | Typical safety considerations in pregnancy | Evidence needs for maternal use |
|---|---|---|---|
| Protein subunit | RSV F protein, HepB, recombinant influenza | Generally considered low theoretical risk, no live pathogen. Safety profile may be influenced by adjuvant choice (e.g., AS01, alum). | DART data for novel adjuvants; immunogenicity and placental transfer studies; trimester-specific safety monitoring. |
| Messenger ribonucleic acid (mRNA) | Pfizer-BioNTech COVID-19, Moderna COVID-19 | Non-replicating; transient expression; no integration into genome. Limited long-term pregnancy data but reassuring post-marketing experience. | Large pregnancy registries; antibody transfer kinetics; real-world safety data across trimesters and lactation. |
| DNA | Investigational Zika DNA vaccines | Non-replicating: theoretical concern about genomic integration is minimal in current platforms. Sparse pregnancy-specific data. | Preclinical DART studies; safety/immunogenicity in pregnant models; early-phase maternal trials. |
| Viral vector – non-replicating | ChAdOx1 COVID-19, adenovirus-vectored Ebola | Non-replicating vectors generally low risk: reactogenicity profile may be higher than subunit platforms; limited pregnancy-specific trial data. | DART data for vector and adjuvant; observational safety data from outbreak use; immunogenicity and transfer studies. |
| Viral vector – replicating | Vesicular stomatitis virus Ebola vaccine | Potential for low-level replication; theoretical fetal exposure risk; usually avoided in pregnancy unless outbreak risk is high. | Robust preclinical teratogenicity studies; risk–benefit modelling for outbreak scenarios; closely monitored emergency-use protocols. |
| Live attenuated | Measles, rubella, BCG | Contraindicated in pregnancy due to theoretical risk of fetal infection; post-exposure pregnancy outcomes generally reassuring but not risk-free. | Live vaccines are generally avoided in pregnancy but may warrant evaluation when disease risks are high and supportive reproductive toxicology and safety data exist; establish surveillance systems for inadvertent exposure. |
| Inactivated (killed) | Inactivated polio vaccine, whole-cell pertussis | No replication risk; generally safe in pregnancy; reactogenicity depends on formulation. | Immunogenicity and transfer studies; platform-specific pregnancy safety confirmation. |
| Virus-like particles | Human papillomavirus vaccine, Hepatitis B virus-like particles | Non-replicating; mimic natural virus structure; adjuvant-related safety profile is key. | Pregnancy registries for inadvertent exposure; lactation antibody transfer studies. |
| Conjugate | Haemophilus influenzae type b, Group B Streptococcus (GBS) conjugate, pneumococcal conjugate | No live pathogen; safety profile driven by carrier protein and adjuvant. | DART data for novel carrier proteins; immunogenicity across gestation; neonatal protection studies. |
Post-licensure pharmacovigilance
Even when vaccines are approved, ongoing monitoring is critical to detect rare or delayed effects in pregnancy and newborns, such as stillbirth, preterm birth, or congenital anomalies. Standardized pregnancy registries and data-sharing systems are needed, using harmonized tools such as the WHO MNHD templates, integrated into national adverse event monitoring systems.
Example: respiratory syncytial virus vaccines
As respiratory syncytial virus vaccines are rolled out for maternal use, regional pharmacovigilance networks are being set up to track outcomes. These systems can also support safety monitoring for other vaccines used in pregnancy, including those given off-label in outbreaks.
Example: malaria
If malaria vaccines are introduced for pregnant populations, low- and middle-income countries will require integrated maternal pharmacovigilance systems linked to malaria surveillance. WHO and national regulatory authorities can play a key role in supporting streamlined safety monitoring tailored to resource-limited settings.
References
- Kochhar S, Bauwens J, Bonhoeffer J. Safety assessment of immunization in pregnancy Vaccine. 2017;35(48Part A):6469–6471. doi: 10.1016/j.vaccine.2017.09.033