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

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.