Integrated review of cytokines in maternal, cord, and newborn blood: Part I-associations with preterm birth

Preterm birth (PTB; spontaneous delivery prior to 37 weeks gestation) affects one out of eight infants born in the United States and is the most common cause of neonatal morbidity and mortality. Although the pathogenesis of PTB is multifactorial, a growing body of literature supports the hypothesis that one cause of PTB is inflammation in pregnancy. Investigators have implicated mediators of inflammation, most notably proinflammatory cytokines, as being associated with and perhaps a playing a causal role in the pathogenesis of preterm labor and adverse early fetal outcomes. Though researchers have pursued the association of cytokines with preterm labor and subsequent early adverse fetal outcomes as a line of research, there has been little integration of diverse findings across studies. This systematic review appraises the empirical evidence from human studies for the association of levels of cytokines in blood with preterm labor and adverse early fetal outcome to examine the current state of the science in this important area of biobehavioral research. The most consistent finding is that increased levels of proinflammatory cytokines, particularly interleukin (IL) 6, IL-β1, and tumor necrosis factor α (TNF-α), are associated with PTB as compared to levels found at term birth. However, there have been relatively few studies and results have not been consistent. Therefore, further research is needed to elucidate the association of these inflammatory mediators with adverse pregnancy outcomes.