A systematic review of adverse events following immunization during pregnancy and the newborn period

Abstract

In 2013, the WHO Strategic Advisory Group of Experts on Immunization (SAGE) requested WHO to develop a process and a plan to move the maternal immunization agenda forward in support of an increased alignment of data safety evidence, public health needs, and regulatory processes. A key challenge identified was the continued need for harmonization of maternal adverse event following immunization (AEFI) research and surveillance efforts within developing and developed country contexts. We conducted a systematic review as a preliminary step in the development of standardized AEFI definitions for use in maternal and neonatal clinical trials, post-licensure surveillance, and other vaccine studies. We documented the current extent and nature of variability in AEFI definitions and adverse event reporting among 74 maternal immunization studies, which reported a total of 240 different types of adverse events. Forty-nine studies provided explicit AEFI case definitions describing 35 separate types of AEFIs. We identified variability in how AEFIs were determined to be present, in how AEFI definitions were applied, and in the ways that AEFIs were reported. Definitions for key maternal/neonatal AEFIs differed on four discrete attributes: overall level of detail, physiological and temporal boundaries and cut-offs, severity strata, and standards used. Our findings suggest that investigators may proactively address these inconsistencies through comprehensive and consistent reporting of AEFI definitions and outcomes in future publications. In addition, efforts to develop standardized AEFI definitions should generate definitions of sufficient detail and consistency of language to avoid the ambiguities we identified in reviewed articles, while remaining practically applicable given the constraints of low-resource contexts such as limited diagnostic capacity and high patient throughput.

Maternal vaccination for the prevention of influenza: current status and hopes for the future

“…Perhaps the most important limitation of existing studies of the association between influenza and adverse pregnancy outcomes is the inconsistency in case definitions of these adverse outcomes [65]. Even during the most recent pandemic in 2009 only a small number of studies actually specified the definitions used to classify gestational age dependent outcomes (e.g.…”

A systematic review of ethical issues in vaccine studies involving pregnant women

“…Selected published works include randomized controlled vaccine trials, observational studies, and review articles, identified in a previous review 32 . A detailed search strategy and study inclusion criteria for this review was derived from previous work, including a systematic review of vaccine safety data reporting 34 and a systematic review documenting the extent and variability in adverse events following immunization (AEFIs) in maternal and neonatal clinical trials 32,34 . Study selection criteria are presented in Table 3.…”

“…Additional research, review of supplementary materials, and correspondence with study investigators could produce new categories of ethical issues that were not included in this report. Third, this review was limited to publications that met the inclusion criteria from a previous systematic review of AEFIs in vaccine studies involving pregnant women 32 . Publications meeting the inclusion criteria consisted largely of RCTs, cohort studies, and literature reviews, and do not include any editorial or commentary pieces published in peer-reviewed journals or other sources (Table S1).…”

Maternal immunization: where are we now and how to move forward?

“…Indeed, the absence of global standard definitions for adverse events following immunization in pregnant women limits comparisons between safety data across studies and regions and, therefore, the performance of meta-analyses [100,101]. To facilitate comparison of data across clinical trials and observational studies, the Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) initiative was launched by the Brighton Collaboration Foundation and the WHO [102].…”