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

S. M. Lee, J. S. Park, E. R. Norwitz, S. Oh, E. J. Kim, S. M. Kim, J. Lee, B. J. Kim, C. W. Park, J. K. Jun

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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.

Original languageEnglish
Pages (from-to)542-546
Number of pages5
JournalJournal of Perinatology
Issue number8
Publication statusPublished - 2015 Aug 30

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Health R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI12C00240300) and by a grant of the Seoul National University Hospital Research Fund (03-2012-0160).

Publisher Copyright:
© 2015 Nature America, Inc.

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynaecology


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