Integrated Review of Cytokines in Maternal, Cord, and Newborn Blood: Part I—Associations With Preterm Birth

Abstract

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-beta1, and tumor necrosis factor alpha (TNF-alpha), 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.

Microbiologic and Inflammatory Markers of Periodontitis are Different to those of Preterm Birth

“…Unlike other published studies, we did not find significantly increased levels of IL-6, IL-8 and TNF-α in women delivering preterm [47,48]. There is a vast controversy in the literature regarding cytokine profiles and PTB.…”

Relationships among psychosocial factors, biomarkers, preeclampsia, and preterm birth in African American women: A pilot

“…High cortisol levels (Erickson et al, 2001;Field et al, 2004;Hobel, Dunkel-Schetter, Roesch, Castro, & Arora, 1999;Kramer et al, 2010;Sandman et al, 2006) and a state of low grade inflammation characterized by higher serum levels of IL-1β, IL-6, IL-8 and TNF-α (Hasegawa et al, 2003;Vogel et al, 2007) have been associated with increased risk for preterm birth. Indeed, a recent systematic review found that women with preterm birth have increased levels of pro-inflammatory cytokines during pregnancy, particularly IL-6, IL-1β and TNF-α compared with women with full term birth (Lyon et al, 2010). Such a pro-inflammatory environment, due to either increased production of pro-inflammatory cytokines or decreased production of anti-inflammatory cytokines, may be instrumental in the etiology of preterm birth (Mulherin .…”

Early pregnancy vitamin D and patterns of antenatal inflammation in African–American women

“…In addition to an essential role in bone health, growing evidence shows that vitamin D is involved in the inflammatory response (Adams and Hewison, 2008). Although inflammation has been linked to poor birth outcomes (Lyon et al, 2010), little is known about the relationship between vitamin D and inflammation during pregnancy. In the nonpregnant state, vitamin D is important in the regulation of the immune system and inflammation.…”