Safety in pregnancy: the Global Vaccine Safety Multi-country Collaboration Project
Extract from GACVS meeting of 1-3 December 2020, published in the WHO Weekly Epidemiological Record of 22 January 2021
Global efforts are under way to develop new vaccines targeted specifically for use in pregnant women in LMIC. Appropriate surveillance systems with standard tools and methods are critical for monitoring the safety of maternal immunization in LMIC to ensure public confidence and programme success.
In response to the call from WHO for a globally concerted approach to monitoring the safety of vaccines in pregnancy, the Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project was launched in 2015. The aim of GAIA, managed by the Brighton Collaboration, was to improve data to facilitate comparability and interpretation among surveillance systems, ultimately leading to strengthened programmes of immunization in pregnancy. Standardized, harmonized definitions of obstetric and neonatal health outcomes were developed to increase meaningful comparisons of safety data among studies. Multiple “levels of diagnostic certainty” are recognized in each case definition, so that the definitions are globally applicable for all immunization safety purposes and in settings with different diagnostic capacity. Use of GAIA case definitions might be challenging in LMIC, as the proposed criteria for some definitions may exceed clinical capacity at some sites. The GACVS stressed the need for field testing and review to test and facilitate their implementation.5
A global network of hospital-based sentinel sites was established in 4 the WHO regions, including in LMIC, to assess the applicability of GAIA case definition for selected neonatal outcomes (congenital microcephaly, low birth weight, neonatal death, neonatal infection, preterm birth, small for gestational age and stillbirth). The network was set up according to the model of the proof-of-concept project of the Global Vaccine Safety Multi-country Collaboration6 and comprised 21 sites in 7 countries (Ghana, India, Islamic Republic of Iran, Nepal, Spain, United Republic of Tanzania, Zimbabwe). During this prospective observational study, more than 84 000 births were recorded over 1 year, and detailed information was recorded on over 8000 outcomes of interest to assess the applicability of GAIA case definitions, which was assessed by measuring the proportion of cases recruited that could be classified at any level of diagnostic certainty. The project also assessed the sites’ capacity for identifying and collecting data on maternal immunization status.
The results showed that the case definitions for preterm birth, low birth weight, neonatal death, bloodstream infections and respiratory infections were applicable at all study sites, whereas those for stillbirth, congenital microcephaly, neonatal meningitis and small for gestational age had limited applicability.
The vaccination status of 26% of the recruited mothers was unknown, and only 2 sites were able to classify the immunization status of most mothers to level 1.
The GACVS recognized the effort involved in conducting such a complex study. The GACVS noted the inconsistencies between case definitions (e.g. different gestational age and birth weight requirements for some definitions) identified by the study team. Some case definitions would also benefit from further details (e.g. case definition of stillbirth) and guidance (e.g. neonatal death, congenital microcephaly) to facilitate their application without subjective interpretation.
The project contributed to the development of expertise in participating hospitals and countries and built collaboration among maternal and child health programmes, immunization programmes and national regulatory agencies.
GACVS reiterated that the results were a promising proof of principle, even as many challenges were identified that require further consideration. It encouraged the planned workshops for disseminating the study results in participating countries and sites, during which institutional development plans will be developed to address observed site-specific limitations to qualitative and quantitative data. The next steps will include publication of the results and identification of relevant projects to further support the sites in preparing for the introduction of new vaccines.
5 See No. 28/29, 2016, pp. 341–348
6 Guillard-Maure C, et al. Operational lessons learned in conducting a multi-country collaboration for vaccine safety signal verification and hypothesis testing: The
global vaccine safety multi country collaboration initiative. Vaccine. 2018;36(3):355–362.