Cytokines and the Risk of Preterm Delivery in Twin Pregnancies |
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| Authors: | Line Rode Katharina Klein Helle Larsen Anni Holmskov Kirsten Riis Andreasen Niels Uldbjerg Jan Ramb Birgit Bødker Lillian Skibsted Lene Sperling Stefan Hinterberger Lone Krebs Helle Zingenberg Eva-Christine Weiss Isolde Strobl Lone Laursen Jeanette Tranberg Christensen Kristin Skogstrand David Michael Hougaard Elisabeth Krampl-Bettelheim Susanne Rosthøj Ida Vogel Ann Tabor |
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| Institution: | From the Department of Fetal Medicine and Ultrasound 4002, Copenhagen University Hospital, Rigshospitalet, and the University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark; the Departments of Obstetrics and Gynecology, Medical University of Vienna, Vienna, General Hospital of Klagenfurt, Klagenfurt, the Medical University of Graz, Graz, and the Medical University Hospital Innsbruck, Innsbruck, Austria; ?lborg Hospital, ?lborg, Viborg Hospital, Viborg, Hvidovre Hospital, Hvidovre, Aarhus University Hospital, Skejby, S?nderborg Hospital, S?nderborg, Hiller?d Hospital, Hiller?d, University Hospital Roskilde, Roskilde, Herlev Hospital, Herlev, University of Copenhagen, Holbaek Hospital, Holbaek, Glostrup Hospital, Glostrup, Odense University Hospital, Odense, and Gentofte Hospital, Gentofte, Denmark; and the Department of Clinical Biochemistry and Immunology, Statens Serum Institut, the Department of Biostatistics, Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen, and the Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark. |
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| Abstract: | OBJECTIVE:: To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment. METHODS:: 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. RESULTS:: 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). CONCLUSION:: 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. CLINICAL TRIAL REGISTRATION:: EudraCT, https://eudract.ema.europa.eu, 2006-000503-41, and ClinicalTrials.gov, www.clinicaltrials.gov, NCT00329914. LEVEL OF EVIDENCE:: II. |
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