Obstetrical and neonatal case definitions for immunization safety data

Administering vaccines specifically to pregnant women as part of a disease prevention strategy has not been routinely practiced, with the major exception of protecting against neonatal tetanus. Pregnancy continues to be a contraindication for receipt of most live viral (e.g., measles, mumps, rubella, varicella) vaccines. In the wake of the thalidomide tragedy [1], real or perceived risks of ter-atogenicity have served as a deterrent to administration of many medicines during pregnancy. Little is known about the effects of new medications or vaccines on pregnant women since they are often excluded from clinical research designed to determine safety. In recent years, however, a groundswell of public and provider opinion has developed urging reconsideration of the practice of excluding pregnant women from drug safety studies for some vaccines. The morbidity and mortality following some infections (e.g., influenza and pertussis) can be disproportionally greater among infants and pregnant women [2,3]. Consequently, the Advisory Committee on Immunization Practices (ACIP) has recommended routine immunization of pregnant women with influenza vaccine since 1997 [2] and a dose of Tdap during every pregnancy since 2012 [4]. Future vaccines for use in pregnancy may include group B streptococcal, Zika, and respiratory syncytial virus vaccines. The challenges and opportunities for maternal immunization have begun to be addressed in various vaccine stakeholder meetings. For example, the US National Vaccine Advisory Committee (NVAC formed a Maternal Immunization Working Group in 2012 and issued a report in 2014 on ''Reducing Patient and Provider Barriers to Maternal Immunizations " [6]. Post-marketing surveillance of adverse events in pregnant women is warranted, not only because of the lack of pre-licensure vaccine safety data in pregnancy, but also to assess for rarer adverse events in pregnant women or their infants. Unlike efficacy or effectiveness, however, safety cannot be assessed directly. The relative safety of a vaccine can only be inferred indirectly from the absence of multiple possible adverse events following immunizations (AEFI) that have been assessed in a relatively large population. Historically, there was relatively little standardization of case definitions for AEFI [7]. This resulted in a huge missed opportunity for meaningful comparison of safety data across vaccine trials and studies in pre-and post-licensure settings, which in turn hindered our ability to advance the science of vaccine safety. The Brighton Collaboration was formed in 2000 to help overcome these shortcomings [7]. Over 30 standardized case definitions (with accompanying guidelines on data collection) have since been developed …