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

Objective: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.