Integrated review of cytokines in maternal, cord, and newborn blood: part II-- associations with early infection and increased risk of neurologic damage in preterm infants.

A growing body of literature supports the relationship of maternal inflammation with preterm birth and adverse neonatal outcomes, including infection and central nervous system (CNS) dysfunction. Mediators of inflammation, most notably proinflammatory cytokines, have been implicated as having an association with and perhaps playing a causal role in the pathogenesis, leading to adverse neonatal outcomes. Even though the association of cytokines with early adverse neonatal outcomes has been actively pursued as a line of research, there has been little integration of diverse findings across studies. Therefore, the purpose of this systematic review was to appraise and classify empirical evidence from human studies for the association of cytokine levels in blood (serum, plasma, or cells; maternal, cord, or neonatal) with two adverse early outcomes in preterm infants: early infection and increased risk of neurologic damage. The review revealed that the proinflammatory cytokines most frequently linked with sepsis are in the interleukin (IL) 1 family as well as tumor necrosis factor alpha (TNF-alpha) and IL-6. The proinflammatory cytokines most frequently linked to neurologic insult in the reviewed studies were IL-1beta, IL-6, and IL-8. In all cases where IL-1beta was studied, the levels were increased when there was neurologic insult. A better understanding of the relationship of these inflammatory substances with these adverse conditions is needed for the future development of maternal and neonatal biobehavioral nursing research.