Extract from the second joint meeting of WHO GACVS and WHO ACSoMP, published in the WHO Weekly Epidemiological Record of 3 March 2023

The Pregnancy Exposure Registries Landscape Analysis (PERLA) is a landscape analysis to identify registries, databases, surveys, etc., in LMICs that record exposure to drug and vaccine products during pregnancy and subsequent maternal and perinatal outcomes. This is a collaborative project involving the WHO-HQ PVG team and the University of Washington and is part of a larger Bill and Melinda Gates Foundation (BMGF)-funded project to advance maternal immunization implementation in LMICs. A literature search,a key informant survey and interviews have been used to gather information. From the original 116 resources identified in the literature review, 71 resources were retained for analysis. An additional seven registries were identified in the key informant survey and interviews. The registries have categorized by type: exposure to vaccine or medication; observational cohorts; outcomes registries; maternal health conditions; manufacturer-, product- or class-specific registries and others. It is planned to finalize the report in Q1 2023 and to submit a manuscript describing the project in Q2-Q3 2023.

The WHO COVID-19 pregnancy cohort study is one of several early investigation protocols posted on the WHO website, that were developed early in the COVID-19 pandemic to ensure standardized data collection in studies were addressing important issues.[1] The original protocol, which involved outcomes in pregnant women with COVID-19 infections, was updated in November 2022 to include vaccine-related endpoints, data collection forms and analyses. This is a longitudinal cohort study of consecutively recruited pregnant women being conducted in eight countries in five WHO regions.

Enrolment started in June 2021 and mostly ended in December 2022. The enrolled women will be followed every 4–6 weeks  and up to 6 weeks postpartum, and the neonates are followed for 4 weeks postpartum. The primary objectives are to compare the risk of adverse outcomes for SARS-CoV-2 infected and uninfected pregnant women, to estimate how many neonates born from SARS-CoV-2 infected women have detectable SARS-CoV-2 infections and to describe pregnancy-related outcomes among women who receive ≥1 dose of a COVID-19 vaccine during pregnancy. The secondary objectives are to assess COVID-19 vaccine uptake during pregnancy, to describe symptoms and non-pregnancy-related events following COVID-19 vaccination during pregnancy and, if feasible, to determine if the risk of adverse outcomes differs in women receiving COVID-19 vaccine during pregnancy compared with pregnant women not receiving COVID-19 vaccine during pregnancy.

The overall target sample size is 16 312 with 2700 vaccinated pregnant women. As of 2 December 2022, 15 538 and 8143, respectively have been enrolled. Over 60% of the vaccinated pregnant women have received non-mRNA vaccines. Enrolment will be terminated by Q2 2023 follow-up by Q1 2024.

Report of the second joint meeting (hybrid) of the WHO Global Advisory Committee on Vaccine Safety and the WHO Advisory Committee on Safety of Medicinal Products, 14–16 December 2022 (WER 98, No 9)

With increased attention to the benefits of some vaccines administered to pregnant women there is also a need to better understand safety implications. GACVS noted the new work to harmonize case definitions for AEFI related to vaccination in pregnancy by an ad hoc voluntary group of experts, the Brighton Collaboration working jointly with WHO. The Committee welcomed the ongoing work to strengthen relevant research and communication in maternal immunization safety. The proposed activities build on previous successful work based on a stakeholder review, collation of currently used terms and definitions and a series of Brighton Collaboration working group meetings, to produce a set of definitions and application of terms for vaccine pharmacovigilance. GACVS identified the regulatory needs to map these definitions to MedDRA codes, the existence of case definitions already in use, for instance in pregnancy registers, and electronic health and vital statistics datasets. It is recognized that it will be challenging to reach a consensus and it will be difficult to apply these definitions in epidemiological studies in low- and middle-income settings given limited resources and health capacity. Capacity-building for AEFI monitoring in low-income settings requires ongoing support and will facilitate the use of these case definitions.

Full report of GACVS meeting of 3-4 December 2014, published in the WHO Weekly Epidemiological Record of 23 January 2015

Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. Maternal immunization can protect the mother directly against vaccine-preventable infections, and provide a cocooning effect that can potentially protect the fetus. It can also provide further direct fetal/infant protection against infection via the transport of specific antibodies to the fetus prior to birth.

At its meeting in December 2011, the Strategic Advisory Group of Experts (SAGE) asked GACVS to provide support to the review of current evidence on the safety of vaccinations in pregnant and lactating women. This request related to uncertainties about the safety of vaccination – whether intended or inadvertent – of pregnant women during mass vaccination campaigns. Such evidence would be particularly important in situations where manufacturers do not recommend the vaccination of pregnant women on precautionary grounds.

Given the broad spectrum of vaccines currently available, GACVS prioritized vaccines for review based on 2 key criteria: their potential to reduce morbidity for the pregnant woman and her fetus; and their use (or projected use) in vaccination campaign settings, which have the potential for inadvertent vaccination of pregnant women. GACVS evaluated relevant data from interventional and non-interventional studies and spontaneous reporting systems on the safety of immunization of pregnant women for several viral, bacterial inactivated vaccines, toxoid and live attenuated vaccines.

Based on the reviewed data, GACVS concluded that there is no evidence of adverse pregnancy outcomes from the vaccination of pregnant women with inactivated virus, bacterial, or toxoid vaccine. Therefore, pregnancy should not preclude women from immunization with the assessed vaccines if medically indicated.

Live vaccines may pose a theoretical risk to the fetus. However, there is substantial literature available describing the safety of live attenuated vaccines including monovalent rubella vaccines, combined measles-mumps-rubella vaccines, and oral polio vaccines. No significant adverse effects to the fetus following these live attenuated vaccines have been reported. Thus, the contraindication of measles-mumps-rubella (MMR)-containing vaccines is considered a purely precautionary measure. Inadvertent vaccination of pregnant women with MMR-containing vaccines is not considered an indication for pregnancy termination.

The benefits of vaccinating pregnant women generally outweigh the potential risks of exposure to a particular infection to the mother or her fetus/newborn if the vaccine is unlikely to cause harm. The use of selected vaccines in pregnancy is an important aspect of prenatal care, which not only improves maternal health but also benefits the neonate.

Full report of GACVS meeting of 12-13 June 2013, published in the WHO Weekly Epidemiological Record on 19 July 2013