J. Perinat. Med. 39 (2011) 403–409 • Copyright  by Walter de Gruyter • Berlin • Boston. DOI 10.1515/JPM.2011.041 2010/210 Article in press - uncorrected proof Mid-trimester amniotic fluid concentrations of the proinflammatory cytokines IL-6, IL-8, TNF-a, and lipopolysaccharide binding protein in normal pregnancies: a prospective evaluation according to parity, gestational age, and fetal gender* Christian Bamberg 1, **, Christina Fotopoulou 2 , Mattea Linder 1 , Charles Christoph Roehr 3 , Joachim W. Dudenhausen 1 , Wolfgang Henrich 1 and Karim Kalache 1 1 Department of Obstetrics, Charite ´-University Hospital, Berlin, Germany 2 Department of Gynecology, Charite ´-University Hospital, Berlin, Germany 3 Department of Neonatology, Charite ´-University Hospital, Berlin, Germany Abstract Objective: To assess mid-trimester amniotic fluid concentra- tions of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-a, and lipopolysaccharide binding protein (LBP) in pregnancies with normal outcome and correlate them with gestational week (GW), parity, and fetal gender. Methods: Cytokine concentrations were measured within a week of amniocentesis during GW 15q0 to 20q6 and cor- related with GW at birth, parity, and fetal gender. Results: After exclusion of women with an adverse preg- nancy outcome or those lost to follow-up, 273 consecutive patients were evaluated (median parity: 1; range: 0–5). Rang- es for IL-6, IL-8, TNF-a, and LBP were 4.9–2620 pg/mL, 36.2–5843 pg/mL, 8.0–28.2 pg/mL, and 0.06–1.9 mg/mL, respectively. IL-6, IL-8, and LBP values did not respectively differ among time points, but TNF-a values did between the 15 th and 16 th and the 15 th and 18 th weeks of gestation (P- 0.05). No significant correlations between cytokine levels and parity or fetal gender were identified. Conclusions: Cytokine concentrations in amniotic fluid during the mid-trimester did not differ with parity or fetal gender. IL-6, IL-8, and LBP levels appeared stable with GW, whereas GW significantly influenced TNF-a concentrations. *Financial and funding disclosures: This study was supported by a research grant from DPC Biermann GmbH. **Corresponding author: Christian Bamberg, MD Department of Obstetrics Charite ´ Campus Virchow Clinic – University Hospital Augustenburger Platz 1 13353 Berlin Germany Tel.: q4930450664327 E-mail: christian.bamberg@charite.de Further analyses are warranted to establish the role of cyto- kines in predicting adverse pregnancy outcomes. Keywords: Amniotic fluid; cytokines; interleukin-6; inter- leukin-8; lipopolysaccharide binding protein; mid-trimester; reference values; tumor necrosis factor-a. Introduction Mid-trimester amniocentesis is the most widely used proce- dure for prenatal diagnosis of fetal cytogenetic abnormalities. About 0.5% of patients suffer spontaneous abortion after this invasive testing w 5x . Several studies have suggested that both preterm delivery and pregnancy losses after amniocentesis might result from a pre-existing subclinical intrauterine inflammation present very early in gestation w 29, 36–38x . Cytokines, powerful mediators of cell growth and regulators of immunological and inflammatory reactions, are thought to play an important role in pregnancy w 35x . The gestational tissues, including placenta, trophoblast, amnion, and mater- nal decidua, produce several cytokines that are considered to influence the outcome of pregnancy, but the function of cyto- kines in normal pregnancy and delivery is not fully estab- lished w 24x . They may be key mediators in the preterm labor mechanism associated with intrauterine infection by inducing prostaglandin synthesis in amnion and decidual cells w 23x . In intrauterine infection, the inflammatory cells, including neu- trophils, migrate through the epithelial cells of the amnion into the amniotic fluid, resulting in the production of various cytokines w 26x . A few studies have reported higher levels of inflammatory cytokines in the amniotic fluid of patients with infection compared to those without infection w 12, 23, 26x . Various authors have attempted to use mid-trimester cyto- kine concentrations in amniotic fluid as a prognostic marker and to derive conclusions about pregnancy outcome in terms of premature labor, abortion, preeclampsia, or infection w 9, 17, 25, 29, 36–38x . Nevertheless, insufficient data exist regarding the concentration of different cytokines in amniotic fluid during normal pregnancies. This lack also holds true for their natural pattern of concentration over time. Further- more, only scant data are available regarding the correlation of cytokine concentrations between fetal and maternal stages. The aim of our study was to evaluate prospectively the concentrations of four proinflammatory cytokines w interleu- kin (IL)-6, IL-8, tumor necrosis factor (TNF)-a, and lipo- Brought to you by | Simon Fraser University Authenticated Download Date | 6/6/15 2:03 PM