Cytokines and the Risk of Preterm Delivery in Twin Pregnancies

Abstract

To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment. This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay. Cytokine levels in spontaneous preterm delivery at 34-37 weeks of gestation and spontaneous preterm delivery before 34 weeks of gestation were compared with delivery at 37 weeks of gestation or more for placebo-treated women. The association between interleukin (IL)-8 and risk of spontaneous preterm delivery before 34 weeks of gestation was estimated further, including comparison according to treatment. Statistical analyses included Kruskal-Wallis test, Mann-Whitney U test, linear regression, and Cox regression analysis. We found a statistically significant association between IL-8 and spontaneous preterm delivery. At 23-33 weeks of gestation, the median IL-8 level was 52 pg/mL (interquartile range 39-71, range 19-1,061) for term deliveries compared with 65 pg/mL (interquartile range 43-88, range 14-584) for spontaneous preterm delivery at 34-37 weeks of gestation and 75 pg/mL (interquartile range 57-102, range 22-1,715) for spontaneous preterm delivery before 34 weeks of gestation (P<.001). Risk of spontaneous preterm delivery was associated with a large weekly increase in IL-8 (hazard ratio 2.0, 95% confidence interval [CI] 1.2-3.3). There was no effect of progesterone treatment on IL-8 levels. Levels of IL-8 at 18-24 weeks of gestation were associated with a cervix less than 30 mm (odds ratio 1.8, 95% CI 1.2-2.7). Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels.