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Giannella L1, Giulini S, Cerami LB, La Marca A, Forabosco A, Volpe A. Abstract OBJECTIVES: The aims of the study were to evaluate the possible association between periodontal disease (PD) and preterm labor (PTL), to assess whether the presence of periodontal disease in women with PTL increases the risk of preterm birth (PTB), and to evaluate the role of nitric oxide (NO) in this possible association. STUDY DESIGN: This study included 820 nulligravid women with low risk socioeconomic status: 400 cases with PTL and 420 controls with normal pregnancy, between 25 and 33 weeks+6 days of weeks’ gestation. At enrollment, periodontal examination and detection of plasma, gingival and cervical NO levels were performed. We compared the periodontal status of the two groups; we detected the presence of PD and compared NO levels. We then followed the outcome of women with PTL and compared obstetric status and PTB rate between patients with and without PD. RESULTS: Logistic regression analysis revealed a strong association between PD and PTL (adjusted odds ratio: 2.83, 95% confidence interval (CI) 1.86-4.23; P<0.0001). Non parametric Mann-Whitney U-test demonstrated significant differences in gingival and cervical NO levels between women with PTL and controls (respectively, median 85.1 μmol/L, interquartile range (i.r.) 51.2-177 vs median 50.5 μmol/L, i.r. 34.5-109.65, P<0.0001; and median 102 μmol/L, i.r. 53.05-182.7 vs median 38.9 μmol/L, i.r. 32.87-46.1, P<0.0001). The ability of mean-gingival NO levels to predict PTL was examined by ROC curve analysis: the area under the curve was 0.817 (95% CI 0.774-0.854; P<0.0001). The cut-off level for the greatest sensitivity and specificity for mean-gingival NO levels was 116.04 μmol/L (sensitivity 0.57, specificity 0.94). Positive and negative predictive values were, respectively, 90.65% and 69.73%. Among women with PTL, the risk of PTB increased in women with PD (adjusted relative risk: 3.85, 95% CI 2.11-6.06; P<0.0001). CONCLUSIONS: In this tested population, PTL is associated with PD. The presence of PD in women with PTL increases the risk of premature delivery. NO may be a new marker to explain this association.