Harmonized approaches for the vigilance of interventions during pregnancy

Extract from GACVS meeting of 15–17 May 2024, published in the WHO Weekly Epidemiological Record of 9 August 2024

Updates were provided on harmonization of data for monitoring maternal, fetal and newborn outcomes and on analysis of pregnancy exposure registries in low– middle-income countries. The WHO PVG provided an overview of a project for harmonizing data for monitoring maternal, fetal and newborn outcomes in a set of standardized indicators and data elements. An interdepartmental team comprising 12 WHO departments developed a minimum maternal and newborn health dataset (WHO mMNHDS), which comprises 15 core indicators to be collected in all WHO regions and countries and 62 complementary “catalogue” indicators. The next stage is to assess collection of the WHO mMNDHS in settings with limited resources. A pilot study is under way in nominated hospitals in 7 GAVI-eligible countries .

In 2013, GACVS examined the safety of the increasing number of vaccines intended for pregnant women as well as inadvertent vaccinations in pregnancy.¹⁶ The difficulty of differentiating the risks of pregnancy from the risks of interventions on pregnancy outcomes was noted. Given the limited amount of clinical trial data on pregnant women, risks should be closely assessed through enhanced pharmacovigilance in the post-licensure phase and in different geographical settings.

Several promising vaccines to protect mothers and infants in the first few weeks of life before infant vaccination are being developed. Safety monitoring of vaccines administered during pregnancy will require enhanced vigilance mechanisms and standardized case definitions of key events in pregnant women and newborns. In June 2016, GACVS reviewed the work conducted by the Global Alignment of Immunization Safety assessment in pregnancy (GAIA) project, and considered important not only the need for good health data, but also compatibility with the longstanding and established use of terminology coding underpinning disease monitoring (the International Classification of Diseases – ICD) or drug regulation (the Medical Dictionary for Regulatory Activities – MedDRA). The Committee also suggested that assessment of applicability of the case definition in different settings with limited health-care services be conducted. Immunization, however, is only one of many medical interventions during pregnancy and early childhood. Adequate vigilance requires that harmonization of methods be compatible with the work of other stakeholders including several WHO programmes.

During the meeting GACVS was informed of a stakeholders meeting on maternal interventions vigilance that took place in Geneva, 20–21 November 2017. The objectives of the meeting were to review current methods to monitor outcomes of maternal immunization and other interventions, with a particular focus on vigilance; assess available methodologies and identify where harmonization is needed; assess the global applicability of vigilance methodologies for maternal immunization and other interventions; and propose coordination mechanisms to support vigilance harmonization across programmes and partners working on improving pregnancy and early childhood health events. The stakeholders invited included WHO Collaborating Centres in pharmacovigilance, technical agencies with an interest in immunization in pregnancy;¹⁷ academic experts from all WHO regions;¹⁸ and regulatory experts with an interest in pregnancy interventions.¹⁹ Discussions addressed global applicability of vigilance methodologies for maternal health interventions during pregnancy. Several situations were highlighted that will affect the quantity and quality of data available; for example, during clinical research, there is likely to be a higher possibility of a specific diagnosis, compared with public health surveillance, where diagnoses may be based on minimal requirements. Likewise, weak civil registration systems can prevent the identification of vital events. It was therefore proposed that harmonized sets of data be collected so that studies and evaluations of the health of pregnant women can be developed. These sets should be tailored according to study characteristics, ranging from minimal to optimal infrastructure and clinical conditions.

GACVS noted the similar data needs for both clinical surveillance and public health vigilance, and that data coding and data systems should be usable for both purposes. The Committee agreed that minimal data elements will need to be assessed for their availability in different settings and for different types of studies. The November meeting has already resulted in plans for the GAIA definitions to be considered by those working on updating and refining ICD 11 as part of the ICD’s rolling programme for updating terms. ICD updates consider stakeholders, including obstetrics and gynaecology services, an essential part of the work in promoting ownership and use of ICD coding.

GACVS noted that as part of developing a roadmap for improving maternal, neonatal and child health programmes and assessments of vaccine safety in pregnancy, a WHO interdepartmental task force will be established to address harmonization of coding and data systems. The task force will include several stakeholders, including WHO regional and country offices and service providers. The aim of such a task force, over the next few years, is to establish a common platform to assess pregnancy related outcomes for any intervention delivered to women during pregnancy. GACVS welcomed this initiative and indicated that joint efforts to enhance access to quality data on pregnancy outcomes will benefit the broad community of stakeholders working to improve the health of mothers and their infants.

¹⁶ Global Advisory Committee on Vaccine Safety. Safety of Immunization during Pregnancy. A review of the evidence. World Health Organization, 2014. Available at: http://www.who.int/vaccine_safety/publications/safety_pregnancy_nov2014.pdf, accessed December 2017.

¹⁷ PATH, Brighton Collaboration, GAPPS, the US Centers for Disease Control and Prevention, INCLEN, INDEPTH, IMPRINT, CROWNE, IABS.

¹⁸ University of Witwatersrand, South Africa; Washington State University, USA; University of Washington, USA; Baylor College, USA; Johns Hopkins Bloomberg School of Public Health, USA; Makere University, Uganda; London School of Hygiene and Tropical Medicine, UK; Monash University, Australia; University of Alberta, Canada; University of Utrecht, the Netherlands; Liverpool School of Tropical Medicine, UK

¹⁹ US Food and Drug Administration, industry umbrella organizations and the the Council for International Organizations of Medical Sciences.

Full report of GACVS meeting of 6-7 December 2017, published in the WHO Weekly Epidemiological Record of 19 January 2018