Human perinatal immunity in physiological conditions and during infection

Gijs T. J. van Well, Leonie A. Daalderop, Tim Wolfs, Boris W. Kramer

The intrauterine environment was long considered sterile. However, several infectious threats are already present during fetal life. This review focuses on the postnatal immunological consequences of prenatal exposure to microorganisms and related inflammatory stimuli. Both the innate and adaptive immune systems of the fetus and neonate are immature, which makes them highly susceptible to infections. There is good evidence that prenatal infections are a primary cause of preterm births. Additionally, the association between antenatal inflammation and adverse neonatal outcomes has been well established. The lung, gastrointestinal tract, and skin are exposed to amniotic fluid during pregnancy and are probable targets of infection and subsequent inflammation during pregnancy. We found a large number of studies focusing on prenatal infection and the host response. Intrauterine infection and fetal immune responses are well studied, and we describe clinical data on cellular, cytokine, and humoral responses to different microbial challenges. The link to postnatal immunological effects including immune paralysis and/or excessive immune activation, however, turned out to be much more complicated. We found studies relating prenatal infectious or inflammatory hits to well-known neonatal diseases such as respiratory distress syndrome, bronchopulmonary dysplasia, and necrotizing enterocolitis. Despite these data, a direct link between prenatal hits and postnatal immunological outcome could not be undisputedly established. We did however identify several unresolved topics and propose questions for further research.