Inflammatory and Procoagulant Cytokine Levels During Pregnancy As Predictors of Adverse Complications

Adverse complications of pregnancy include preterm delivery resulting from preterm labor, preeclampsia, and postpartum hemorrhage. Plasma cytokine levels and immunoregulatory proteins that are produced by gestational tissues and involved in inflammatory processes of pregnancy, have shown that perturbation of cytokine signaling networks is associated with preterm labor and preeclampsia. The purpose of this study was to identify the levels of various cytokines and other analytes associated with tissue damage, inflammation, and ischemia in maternal plasma samples taken throughout pregnancy and to determine whether these levels correlate with adverse conditions. Methods: This study examined plasma samples collected from populations of women (Hilleroed Hospital, Copenhagen, Denmark) with high-risk pregnancy complications such as postpartum hemorrhage, preeclampsia, and multiple gestations (n=16), preterm delivery (n=20), and normal pregnancy (n=20). Citrated plasma samples were analyzed at different time points during pregnancy (< 21 weeks, 21–32 weeks, 33+ weeks). Maternal cytokine levels — IL-1β, IL-6, IL-8, IL-10, and TNF-α— were measured by ELISA (R&D Systems Quantikine®, Minneapolis, MN). The Hyphen Biomed (Paris, France) ZYMUTEST Anti-Protein Z, IgG ELISA assay was used to determine maternal levels of auto-antibodies to Protein Z. Results: IL-6 levels were elevated over the course of pregnancy in the preterm delivery group compared to the normal pregnancy, high-risk pregnancy, and normal control groups. Statistical differences were found between the preterm delivery group and the other groups at 21–32 weeks (P < 0.01) and 33+ weeks (P < 0.001). IL-10 was elevated in normal pregnancy and was statistically different compared to other patient groups at all time points (P < 0.05). TNF-α levels were elevated in the high-risk pregnancy group versus normal controls (P < 0.001 at < 21 weeks and P < 0.05 at 21–32 weeks). Statistical differences for TNF-α levels were also found between high-risk pregnancy and preterm delivery patients at < 21 weeks (P < 0.01). No statistical differences between patient groups were found for maternal plasma levels of IL-1β, IL-8, and auto-antibodies to Protein Z, IgG. Conclusion: Our results suggest that analysis of maternal plasma for IL-6 and IL-10 may be of value in the early prediction of pregnancy complications such as preterm delivery and other high-risk conditions. Elevated IL-6 levels can be measured in preterm delivery pregnancy patients as early as 21–32 weeks; thus, examining plasma IL-6 levels over the course of pregnancy may be beneficial for identifying pregnancies at risk for preterm delivery. Detecting reduced maternal plasma IL-10 levels compared to normal pregnancy may identify patients at risk for preterm delivery and high-risk pregnancy complications such as postpartum hemorrhage, preeclampsia and related vascular complications.

No relevant conflicts of interest to declare.