The challenges of pregnancy in clinical trials for vaccines

The study of vaccines during pregnancy is one of the most rapidly evolving fields in medicine today. Pregnant women and young infants are particularly at risk of acquiring and developing complications from infectious diseases [1]. Vaccines administered during pregnancy have the potential to benefit both the mother and her newborn infant [2,101]. Along with the active and ongoing development of safe and effective vaccines, the importance of including pregnant women in clinical research is increasingly recognized. The unique susceptibility of pregnant women and newborns to infections has been recognized for decades, and preventive interventions have been implemented, when available, based on their potential for benefit and the relatively low risk for the mother and fetus. Routine administration of tetanus vaccine during pregnancy was recommended by the WHO in the 1960s after a small study conducted in a high-risk region demonstrated a significant reduction in mortality from neonatal tetanus in infants born to vaccinated mothers. Tetanus vaccination during pregnancy has successfully reduced maternal and neonatal tetanus mortality worldwide [102]. Similarly, influenza vaccine was recommended for pregnant women in the USA after increased morbidity and mortality were documented in women who were pregnant during the influenza pandemics of the early twentieth century and during interpandemic periods [3]. However, it was the 2009 A/H1N1 influenza pandemic that served as a stark reminder of the severity of influenza in pregnancy, its impact on prematurity and fetal–neonatal mortality, and the need to improve influenza vaccine coverage in pregnant women [4]. More recently, the global resurgence of pertussis has resulted in risk-based recommendations to vaccinate pregnant women with tetanus-diphtheriapertussis vaccine in the USA and other countries, in order to provide protection during the period of highest vulnerability to pertussis by increasing the concentrations of maternally transmitted antibodies to the newborn [5]. While the impact of routine maternal immunization with influenza and pertussis vaccines remains to be determined, immunization during pregnancy is now a recognized and accepted strategy to provide protection against specific pathogens that are relevant to the mother and the newborn. These include tetanus, influenza and pertussis, and other infections for which vaccines are currently available, such as meningococcus and pneumococcus, or for which vaccines are in development, including group B streptococcus and respiratory syncytial virus [6,7]. The possibility to protect mothers and infants with vaccines against other relevant pathogens is evident. Maternal immunization is a high priority for research worldwide given its potential to significantly impact maternal and infant health. As interest in maternal immunization as a desirable and feasible strategy to reduce maternal and child morbidity and mortality increases, the challenges associated with vaccinating pregnant women also continue to evolve. Probably the most “The unique susceptibility of pregnant women and newborns to infections has been recognized for decades, and preventive interventions have been implemented, when available, based on their potential for benefit and the relatively low risk for the mother and fetus.”