Vaccine safety in pregnancy and lactation

Extract from the first joint meeting of WHO GACVS and WHO ACSoMP, published in the WHO Weekly Epidemiological Record of 26 August 2022

WHO has 3 ongoing initiatives to improve safety monitoring during pregnancy. The first is a collaborative project between the Pharmacovigilance team and PATH aiming to map and assess the strengths and limitations of pregnancy exposure registries available in LMICs. The second is an internal WHO project, to map various WHO initiatives to assess the availability of minimal data elements to study pregnancy and neonatal outcomes in LMICs and to propose methods to harmonize these data elements. The third project is the monitoring of the safety of COVID-19 vaccines during pregnancy, which is a collaboration with the WHO Sexual and Reproductive Health and Research team.

An Expert Steering Committee (ESC), set up to oversee the first 2 projects, will provide independent, authoritative, and scientific advice to WHO on the safety of health interventions in pregnancy, and for the implementation of pregnancy exposure registries and other methods for monitoring the safety in pregnancy in LMICs. This will be critical for the preparation of LMICs for the safe introduction and use of health products in pregnant women. The ESC will also provide best practice guidance on the safety monitoring of health interventions in pregnancy.

The third initiative, the WHO COVID-19 pregnancy cohort study, is a longitudinal cohort study that comprises about 21 000 consecutively recruited pregnant women who will be followed every 4 to 6 weeks up to 6 weeks postpartum, to capture information on maternal, pregnancy, perinatal, neonatal and postpartum outcomes as well as non-pregnancy related outcomes. Information on COVID-19 vaccination status, when and which vaccine was administered will also be collected. Consistency between countries and study sites for outcome definitions, such as gestational age, and the data collected will be maximized by the use of standardized case report forms and standardized training provided to the investigators

As of June 2022, over 10 000 women have been recruited in 8 countries, including about 4500 vaccinated women, of whom about 1700 and 1300 were exposed and unexposed, respectively, to SARS-CoV-2 infection. This study is very labour, time and resource intensive and the rapidly evolving pandemic adds to the challenges for running this type of study, but it is hoped that this initiative will help to strengthen the existing infrastructure for the future.

The Committees discussed the importance of collecting comorbidity data and to control for confounding factors, sample size, consistency between countries and complexities around the determination of SARS-CoV-2 infections during pregnancy. The Committees suggested that the cohorts and the infrastructure should be continued after the end of this study so that important safety data on maternal and neonatal outcomes can continue to be collected.

Several available vaccines have the potential to reduce maternal and fetal morbidity and mortality from preventable diseases. Thus, optimal protection against preventable diseases that pose a higher risk for disease and death in pregnant woman and their offspring should be balanced against the risk of malformations, abortions, stillbirth or other adverse outcomes that theoretically could affect the fetus as a result of vaccination in pregnancy. Maternal antibodies induced by vaccination during pregnancy are actively transferred to the fetus and confer passive protection in the infant after birth. GACVS recently established a subgroup to review the safety profile of several important vaccines for pregnant and lactating women. In addition to the review of available data on influenza vaccines described below, the committee also reviewed the accumulated safety data for rubella-containing vaccines when inadvertently administered to pregnant women to complement the review conducted in June 2008. GACVS concludes that the data remain very reassuring for the use of vaccines during pregnancy, with no evidence of adverse fetal outcomes identified. Protection of mothers at risk and their young infants will be critical to attain the reduction of morbidity and mortality due to infections that affect many populations around the world.

Full report of GACVS meeting of 6-7 June 2012, published in the WHO Weekly Epidemiological Record on 27 July 2012

Significant morbidity due to vaccine-preventable diseases among women and infants could be prevented by immunization of pregnant women. Policy formulation regarding vaccination during pregnancy is challenging because the evidence base to guide decisions is extremely limited. SAGE recently requested GACVS to provide guidance on the safety of vaccines used among pregnant and lactating women.

The concerns include risks to the fetus because there have been a small number of demonstrated instances of live vaccine transmission. For other live vaccines and all inactivated vaccines no evidence of such risk exists. For newer vaccines, several of which are used primarily in low- and middle-income countries, there is no evidence of pregnancy-related harm. Despite of the lack of apparent safety issues for many vaccines, precautions and contraindications are often included in product labelling with respect to immunization during pregnancy and lactation, thereby limiting their benefit to women. In developing countries, pregnancy is one of the few opportunities for women to be in contact with the health care system.

Several important questions need to be addressed. These include the possibility of assessing safety of vaccines in pregnancy and lactation during the vaccine development process and additional opportunities for generating post-licensure data. Adverse events may occur with vaccination only coincidentally, giving rise to a false perception of increased risk from vaccination during pregnancy. Better understanding and analysis of the frequency of occurrence of adverse events that occur during pregnancy in the absence of vaccination («background rates») would be of great benefit. An agenda for continued monitoring, better definitions, availability of background rates, inclusion of pregnant women in cohort studies, and collaboration with regulatory authorities could be developed and proposed. Likewise, since labelling of vaccines package inserts is highly variable around the world, there is a possible role for WHO to help harmonize practices in this area.

Based on the presentation and discussion, GACVS recognizes the need to address safety issues related to the use of vaccines during pregnancy and lactation. GACVS proposes to review the relevant evidence. It will also consider including methodological points for planning and analysis of clinical trials and post-marketing studies.

Full report of GACVS meeting of 7-8 December 2011, published in the WHO Weekly Epidemiological Record on 10 February 2012