Updating the evidence on brighton collaboration's GAIA maternal immunisation case definitions: a systematic review of performance and implementation challenges.

Abstract

The Brighton Collaboration's GAIA initiative developed harmonised case definitions (CDs) to standardise safety monitoring for maternal immunisation studies globally. These definitions use levels of diagnostic certainty (LOC) to support use across settings with differing diagnostic capacity, but their real-world performance and applicability have remained uncertain. A 2023 review found that around half of GAIA CDs had not been evaluated and that several key outcomes performed poorly with high rates of cases that could not be classified at LOC 1-3 (achieving only LOC-4). Ovid MEDLINE, EMBASE, and Web of Science databases were searched for research studies in English-language publications from 2014 to May 5th, 2025, that assessed the performance of the GAIA case definitions in routine care or research. Two reviewers independently screened studies and extracted data, resolving any discrepancies through consensus. The review protocol was registered with PROSPERO (CRD42025620433). Database searches identified 4260 records; after deduplication and two-stage screening, 10 studies including 42,587 cases were eligible. Three definitions had not been evaluated (ectopic pregnancy, postpartum endometritis, neurodevelopmental delay), and several others have only been assessed in high-income settings. While CDs for maternal death, neonatal death, and preterm birth performed well, others had high proportions of unclassifiable cases, achieving only LOC-4. Variability was seen with some studies able to classify 100% of potential cases, whilst others were only able to classify 50% at LOC 1-3. Although progress has been made in evaluating GAIA case definitions, challenges remain in understanding their applicability across settings and data sources. Variability likely reflects differences in setting-level resources, data availability and documentation quality, as well as limitations inherent to the definitions themselves, highlighting the need for targeted refinement and broader validation to support robust, standardised, and comparable maternal immunisation safety surveillance globally.