Elevated Amniotic Fluid Interleukin‐6 Levels During the Early Second Trimester Are Associated With Greater Risk of Subsequent Preterm Delivery

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Abstract
PROBLEM: Subclinical intra‐amniotic infection is often associated with preterm delivery and may precede it by several weeks. We tested the hypothesis that Interleukin‐6 (IL‐6) may be elevated in the midtrimester amniotic fluid of pregnancies destined to deliver preterm.METHODS: A historical cohort study was designed to compare the amniotic fluid (AF) concentrations of IL‐6 at 14–20 weeks in a group of women subsequently delivering at ≤ 34 weeks (n = 13) with those of women delivering at term (n = 166). Included were singleton gestations with no evidence of fetal structural or chromosomal abnormalities, or maternal conditions known to be associated with preterm delivery (n = 179). Levels of IL‐6 were measured by immunoassay and correlated with demographic and pregnancy outcome information. Statistical analysis included correlation, one‐way ANOVA after log‐transformation, contingency tables, logistic regression, and receiver operator characteristic (ROC) curve analysis.RESULTS: There was an inverse correlation between AF IL‐6 levels at 15–20 weeks and gestational age at delivery (r = −0.16, P = 0.03). Women delivering at ≤ 34 weeks had significantly higher median AF IL‐6 levels (570 pg/ml versus 330 pg/ml, P < 0.0001), rate of African American race (50% versus 12%, P = 0.004), and of infants with birth weights < 10th centile (31% versus 7%, P = 0.02) than women delivering at ≥ 37 weeks. Logistic regression analysis showed that IL‐6 was independently associated with PTD at ≤ 34 weeks after controlling for race and birth weight centiles (P = 0.039).CONCLUSIONS: AF IL‐6 at 15–20 weeks can identify patients at risk for PTD at ≤ 34 weeks, suggesting that a portion of PTD cases have inciting events that take place during the early second trimester.CAPSULE: Midtrimester amniotic fluid IL‐6 concentrations are significantly higher in women subsequently delivering preterm at ≤34 weeks compared with those delivering at term.