Mid-trimester amniotic fluid pro-inflammatory biomarkers predict the risk of spontaneous preterm delivery in twins: A retrospective cohort study

To evaluate the association between the concentrations of immune-related proteins in mid-trimester amniotic fluid (AF) and the subsequent risk of spontaneous preterm delivery in twins.Study Design:The study population consisted of consecutive women with a twin pregnancy who underwent clinically indicated genetic amniocentesis at 15 to 20 weeks, and had a subsequent spontaneous delivery in the early preterm period (<32 weeks (cases)) or at term (37 to 42 weeks (controls)). AF was analyzed for cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13 and IL-15, interferon-γ, tumor necrosis factor-α), matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-12), and chemokines (complement factor-D/Adipsin, Serpin E1/PAI-1, Adiponectin/Acrp30, C-Reactive Protein, CCL2/MCP-1, Leptin, Resistin) using multiplex immunoassay kits. The association between AF protein levels and subsequent early preterm birth were examined.Result:A total of 96 sets of twins were enrolled, including 17 early preterm birth cases and 79 term controls. AF concentrations of IL-6, IL-8, MMP-3, MMP-8 and MMP-9, and CCL2/MCP-1 were significantly higher in cases than controls. Among these analytes, the combination of AF IL-8 and MMP-9 values had the highest predictive value for early preterm birth. The risk was 8% (10/132) for IL-8<1200 pg ml^-1 and MMP-9<1000 pg ml^-1, 30% (15/50) for IL-8>1200 pg ml^-1 or MMP-9>1000 pg ml^-1, and 90% (9/10) for IL-8>1200 pg ml^-1 and MMP-9>1000 pg ml^-1 (P<0.001).Conclusion:High concentrations of IL-8 and MMP-9 in mid-trimester AF in twins predicted well the risk of early preterm birth.