Abstract
To assess deviations in longitudinally measured cytokines with preterm birth (PTB). Prospective longitudinal study targeting 80 subjects. Phlebotomy specimens for broad panel of cytokine analysis were obtained at three time (T)intervals: first trimester (T1: 8-14weeks' gestation), second trimester (T2: 18-22weeks' gestation), and third trimester (T3: 28-32weeks' gestation). Important demographics and outcomes were tracked. Data were stratified and the target groups were analyzed as follows: "Uncomplicated" (delivered≥37weeks) or "Preterm Birth" (<37weeks). Generalized Linear Modeling determined rate of change T1-T3 by outcome. Complete data replete with phlebotomy at all three visits were obtained on 80 women. Birth outcomes were as follows: 11 Uncomplicated Term Birth (UTB), 28 PTB, 4 low birth weight (LBW), 16 OB complications (OBC), 11 current infections (IFN), and 10 mixed complications (MC=2 or more of the above). 28 PTB were compared to 11 uncomplicated term deliveries. In both groups, T helper type 1 (TH1) cytokine (IL-1β), pleiotrophic pro-inflammatory cytokine (IL-6), and counter-regulatory cytokine (IL-10) responses decreased over gestation, but rates of change in IL-1β, IL-6, and IL-10 were significantly different. Stratification of women by smoking status additionally demonstrated significant variance in immune status over the course of pregnancy. Women delivering PTB demonstrated significant differences in cytokine trajectory over pregnancy; these data further validate key role played by immune regulation in directing pregnancy outcome. Likewise, smoking impacts longitudinal trajectory of cytokines over pregnancy.
Highlights
Shifts in immune parameters in pregnancy have been implicated in pregnancy outcomes
Denney et al.: Cytokine profiling identifies signals associated with preterm birth pathogenesis markers exist, cytokines are a diverse family of soluble small proteins, expressed by various cells and tissue types; these proteins act as immune mediators and the mapping corresponding expression profile may be important in predicting at risk pregnancies
Our data indicate there are critical variations in cytokine networks leading to preterm delivery
Summary
A number of adverse pregnancy outcomes like preeclampsia, preterm premature rupture of membranes, and miscarriage have all been hypothesized to have a strong association with increases in systemic inflammation as demonstrated by various serum markers. Denney et al.: Cytokine profiling identifies signals associated with preterm birth pathogenesis markers exist, cytokines are a diverse family of soluble small proteins, expressed by various cells and tissue types; these proteins act as immune mediators and the mapping corresponding expression profile may be important in predicting at risk pregnancies. Maternal immune responses are modified during pregnancy. Prior data indicate a trend over gestation toward a dampened T helper type 1 (Th1)-associated and pleiotrophic cytokine expression; such data implicate enhanced counter regulatory cytokine expression as instrumental in decreasing inflammatory responses and, in effect, tolerance to fetal tissues [5]. Other data further support the belief that maternal immune modulation plays a vital role for both establishment of and maintenance of a viable pregnancy [6, 7]
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