Recommendations for vaccine safety data strategies across the different stages of the vaccine development pipeline for use in pregnant and lactating women

For all new vaccines entering early-stage development, WHO would recommend DART studies.  For those vaccines that are already in the market, however, and for which the developer does not intend to undertake DART studies, alternatives include: 

  • tracking incidental pregnancies during large-scale efficacy trials. Such pregnancies are especially likely given changes to the policy of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use for trials including women of reproductive age and/or in high-fertility settings;
  • post-marketing pregnancy registries to monitor outcomes among women vaccinated preconception or early in pregnancy;
  • retrospective data linkage with national health systems or birth registries to compare outcomes;
  • bridging studies using reproductive toxicology data from the same vaccine platform or adjuvant (e.g., AS01);
  • modelling studies to predict placental transfer and antibody kinetics. 

Box 3 provides additional information

Box 3 - Best Practice Checklist – Managing Incidental Pregnancies in Vaccine Trials 

Before the trial begins:
  • Anticipate the likelihood of incidental pregnancies in trials including women of reproductive age, especially in high-fertility settings.
  • Include pregnancy management plans in the protocol and ethics submission.
  • Define safety endpoints and follow-up procedures for pregnant participants and infants.
During the trial:
  • Obtain informed consent for continued participation if pregnancy occurs.
  • Offer appropriate medical care and counselling to pregnant participants.
  • Collect systematic safety data using harmonised definitions (e.g., GAIA, WHO MNHDS).
After pregnancy:
  • Follow mother–infant pairs through delivery and postpartum, ideally to 12 months.
  • Capture key outcomes (e.g., miscarriage, stillbirth, congenital anomalies, neonatal health).
  • Input pregnancy and lactation specific modules into pregnancy registries and post-marketing surveillance systems.