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Byline: Chaur-Dong Hsu, Erika Meaddough, Kristen Aversa, Shih-Fen Hong, Li-Cheng Lu, David C. Jones, Joshua A. Copel Keywords: Amniotic fluid; interleukin 6; interleukin 8; intra-amniotic infection; leukemia inhibitory factor Abstract: Objective: The study's objective was to determine and correlate amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 in patients with and without intra-amniotic infection. Study Design: Amniocentesis was performed on 41 pregnant women with preterm contractions, labor, or premature rupture of membranes. Intra-amniotic infection was defined as the presence of a positive amniotic fluid culture result. Amniotic fluid tests for Gram stain, glucose, leukocyte counts, creatinine level, pH, and specific gravity were performed. Amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 were measured by an enzyme-linked immunoassay. Unlike in previous reports, cytokines were normalized by amniotic fluid creatinine levels. Results: Fifteen patients had intra-amniotic infection and 26 did not. Amniotic fluid median levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 were significantly higher in pregnant women with intra-amniotic infection than in those without intra-amniotic infection (leukemia inhibitory factor median 3912 pg/mg creatinine, range 0.0-199314, vs 56 pg/mg creatinine, range 0.0-12148, P = .01; interleukin 6 median 2005 ng/mg creatinine, range 27-4071, vs 990 ng/mg creatinine, range 7.5-3409, P = .005; interleukin 8: median 4933 ng/mg creatinine, range 0.0-55058, vs 61 ng/mg creatinine, range 0.0-2399, P = .005). Amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 were positively correlated. Conclusions: The data indicate that leukemia inhibitory factor plays an important role in the pathogenesis of intra-amniotic infection. In addition, significant elevations of and correlations among amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 suggest that measurements of these cytokines in amniotic fluid may be of diagnostic and prognostic importance. (Am J Obstet Gynecol 1998;179:1267-70.) Author Affiliation: New Haven, Connecticut Article Note: (footnote) [star] From the Department of Obstetrics and Gynecology, Yale University School of Medicine., [star][star] Reprint requests: Chaur-Dong Hsu, MD, MPH, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520-8063., a 0002-9378/98 $5.00 + 0 6/6/92026

Byline: Chaur-Dong Hsu, Erika Meaddough, Kristen Aversa, Joshua A. Copel Keywords: Intraamniotic infection; amniotic fluid; l-selectin; interleukin-8; GRO-[alpha] Abstract: OBJECTIVE: Our purpose was to compare and correlate amniotic fluid GRO-[alpha], interleukin-8, and l-selectin in patients with and without intraamniotic infection. STUDY DESIGN: Amniocentesis was performed on 45 pregnant women with preterm contractions, labor, or rupture of membranes. Fourteen patients had intraamniotic infection, and 31 did not. Intraamniotic infection was defined as the presence of a positive amniotic fluid culture. Amniotic fluid tests for Gram stain, glucose, neutrophil counts, creatinine, pH, and specific gravity were performed. Amniotic fluid levels of soluble l-selectin, interleukin-8, and GRO-[alpha] were measured by an enzyme-linked immunoassay and normalized by amniotic fluid creatinine levels. The Mann-Whitney U test and Spearman's rank correlation test were used for statistical analyses. RESULTS: Amniotic fluid median levels of soluble l-selectin, interleukin-8, and GRO-[alpha] were significantly higher in pregnant women with intraamniotic infection than in those without intraamniotic infection (soluble l-selectin: median 3334.6 ng/mg creatinine, range 408.4 to 15,956.8 vs 717.2 ng/mg creatinine, range 129.4 to 4601.9, p = 0.009; GRO-[alpha]: median 841.6 ng/mg creatinine, range 28.1 to 8591.7 vs 56.8 ng/mg creatinine, range 0.0 to 440.2, p < 0.0001; interleukin-8: median 4932.7 ng/mg creatinine, range 0.0 to 55,058.7 vs 28.3 ng/mg creatinine, range 0.0 to 1161.6, p = 0.0004). Patients with intraamniotic infection had significantly higher amniotic fluid leukocyte counts and leukocyte esterase activities and significantly lower amniotic fluid glucose concentrations compared with those without intraamniotic infection. Amniotic fluid GRO-a, interleukin-8, and soluble l-selectin were positively correlated, and each was positively correlated with amniotic fluid leukocytes and negatively correlated with amniotic fluid levels of glucose. CONCLUSIONS: Our data indicate amniotic fluid GRO-[alpha] and interleukin-8 may be two potent leukocyte chemoattractants and activators, and l-selectin is rapidly shed from leukocytes in the amniotic fluid in patients with intraamniotic infection. (Am J Obstet Gynecol 1998;178:428-32.) Author Affiliation: New Haven, Connecticut Article History: Received 3 June 1997; Revised 25 August 1997; Accepted 6 October 1997 Article Note: (footnote) [star] From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yale University School of Medicine., [star][star] Reprint requests: Chaur-Dong Hsu, MD, MPH, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520-8063., a 0002-9378/98 $5.00 + 0 6/1/86698

Byline: Chaur-Dong Hsu, Kristen Aversa, Erika Meaddough, In-Sik Lee, Joshua A. Copel Keywords: Nitric oxide; intraamniotic infection; cyclic guanosine monophosphate; nitrite; nitrate; amniotic fluid Abstract: OBJECTIVE: Our purpose was to compare amniotic fluid nitric oxide metabolites and cyclic guanosine 3',5'-monophosphate in pregnant women with and without intraamniotic infection. STUDY DESIGN: Amniocentesis was performed on 72 pregnant women with preterm contractions, labor, or rupture of membranes. Fourteen patients had intraamniotic infection and 58 did not. Intraamniotic infection was defined as the presence of a positive amniotic fluid culture. Amniotic fluid Gram stain, glucose, leukocyte counts, leukocyte esterase activity, creatinine, pH, and specific gravity were performed. Endogenous nitrite was determined using Griess reagent. Amniotic fluid nitric oxide metabolites (nitrite and nitrate) were measured after reduction of nitrate to nitrite with Aspergillus nitrate reductase. Tests for amniotic fluid cyclic guanosine monophosphate levels were determined by enzyme immunoassay. Two-tailed t test, contingency table methods, linear regression, and correlation were used for statistical analyses. RESULTS: Amniotic fluid levels of nitric oxide metabolites, endogenous nitrite, nitrate, and cyclic guanosine monophosphate were significantly higher in pregnant women with intraamniotic infection than in those without intraamniotic infection (2.66 [+ or -] 0.49 vs 1.77 [+ or -] 0.07 [mu]mol/mg creatinine, p = 0.002; 0.69 [+ or -] 0.15 vs 0.38 [+ or -] 0.03 [mu]mol/mg creatinine, p = 0.003; 1.99 [+ or -] 0.41 vs 1.38 [+ or -] 0.07 [mu]mol/mg creatinine, p = 0.02; and 1.47 [+ or -] 0.22 vs 0.90 [+ or -] 0.08 nmol/mg creatinine, p = 0.004, respectively). Both amniotic fluid nitric oxide metabolites and cyclic guanosine monophosphate were positively correlated with amniotic fluid leukocyte counts and leukocyte esterase activity and negatively correlated with amniotic fluid glucose concentrations. CONCLUSIONS: Our data indicate that amniotic fluid nitric oxide and cyclic guanosine monophosphate may play important roles in the pathogenesis of intraamniotic infection. Measurements of amniotic fluid nitric oxide metabolites and cyclic guanosine monophosphate may be part of a panel of tests that can be used to detect intraamniotic infection. (Am J Obstet Gynecol 1997;177:793-6.) Author Affiliation: New Haven, Connecticut Article Note: (footnote) [star] From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yale University School of Medicine., [star][star] Reprint requests: Chaur-Dong Hsu, MD, MPH, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520-8063., a 0002-9378/97 $5.00 + 0 6/6/84109