Intra-amniotic Inflammation Research Articles

Interpretation of Amniotic Fluid White Blood Cell Count in “Bloody Tap” Amniocenteses in Women With Symptoms of Preterm Labor

To estimate whether blood-contaminated amniotic fluid affects the performance of white blood cell (WBC) count in diagnosing intraamniotic inflammation and infection. Three hundred fifty-seven consecutive women pregnant with singletons undergoing amniocentesis to rule out infection were enrolled prospectively. A "bloody tap" was defined as a red blood cell (RBC) count of 1,000 cells/mm or more. Proteomics analysis of amniotic fluid was used in this study as the standard for diagnosing inflammation. Infection was confirmed by positive amniotic fluid culture. An amniotic fluid WBC count correction formula was computed using maternal WBC count, hematocrit, and mean corpuscular volume. The prevalence of a bloody tap amniocentesis was 22% (77 of 357). In the absence of inflammation, the amniotic fluid WBC count was significantly higher in bloody tap (median [interquartile range] 18 [9-58] cells/mm) compared with non-bloody tap specimens (4 [1-10] cells/mm; P<.001). The correction formula reversed this difference to a nonsignificant level (bloody tap 0 [0-17] compared with non-bloody tap 3 [1-10] cells/mm; P=.273). In the setting of inflammation, the observed WBC count of bloody tap samples (778 [197-2,062 cells/mm]) was significantly elevated compared with that of the non-bloody tap specimens (616 [105-1,730] cells/mm; P=.023). Correction of the WBC count in bloody tap amniocenteses improved the test accuracy and positive likelihood ratios for inflammation and infection. A correction algorithm was not useful in amniotic fluid specimens with less than 1,000/RBCs/mm or WBC counts more than 1,100 cells/mm. Given the nonlinear relationship between amniotic fluid WBC and RBC, for a rapid correction of WBC count, the number of neutrophils that need to be subtracted from the observed WBC count is variable. In the setting of an amniotic fluid sample contaminated with 1,000 RBCs/mm or more, WBC count is a less accurate indicator of inflammation and infection. In such samples, correction of WBC count enhances diagnostic performance for inflammation and infection. II.

Patients with an asymptomatic short cervix (≤15 mm) have a high rate of subclinical intraamniotic inflammation: implications for patient counseling

The objective of the study was to determine the frequency and clinical significance of intraamniotic inflammation in asymptomatic women with a sonographic short cervix (SCX) in the midtrimester. This cohort study included 47 asymptomatic women (14-24 weeks) with an SCX (<or=15 mm) who underwent amniocentesis. Women with multiple gestation, cerclage, or cervical dilatation greater than 2 cm were excluded. Intraamniotic inflammation was defined as an elevated amniotic fluid (AF) matrix metalloproteinase-8 concentration (>23 ng/mL). (1) intraamniotic infection was found in 4.3% of patients; (2) among patients with a negative AF culture, the prevalence of intraamniotic inflammation was 22.2%; and (3) patients with a negative AF culture, but with intraamniotic inflammation, had a higher rate of delivery within 7 days (40% vs 5.7%; P=.016) and a shorter median diagnosis-to-delivery interval than those without intraamniotic inflammation (18 vs 42 days; P=.01). Twenty-two percent of patients with a midtrimester SCX have intraamniotic inflammation. The risk of preterm delivery within 7 days for these patients is 40%.

Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor

Distinct processes govern transition from quiescence to activation during term (TL) and preterm labor (PTL). We sought gene sets that are responsible for TL and PTL, along with the effector genes that are necessary for labor independent of gestation and underlying trigger. Expression was analyzed in term and preterm with or without labor (n=6 subjects/group). Gene sets were generated with logic operations. Thirty-four genes were expressed similarly in PTL/TL but were absent from nonlabor samples (effector set); 49 genes were specific to PTL (preterm initiator set), and 174 genes were specific to TL (term initiator set). The gene ontogeny processes that comprise term initiator and effector sets were diverse, although inflammation was represented in 4 of the top 10; inflammation dominated the preterm initiator set. TL and PTL differ dramatically in initiator profiles. Although inflammation is part of the term initiator and the effector sets, it is an overwhelming part of PTL that is associated with intraamniotic inflammation.

Amniotic Fluid Angiopoietin-1, Angiopoietin-2, and Soluble Receptor Tunica Interna Endothelial Cell Kinase-2 Levels and Regulation in Normal Pregnancy and Intraamniotic Inflammation-Induced Preterm Birth

Angiopoietin-1 (Ang-1) and Ang-2 act selectively on endothelial cells by engaging the Tunica interna endothelial cell kinase-2 (Tie2) receptor. A soluble form of Tie2 (sTie2) blocks angiopoietin bioactivity. The aim of the study was to characterize changes and expression patterns of Ang-1, Ang-2, and sTie2 in amniotic fluid (AF) and placenta during human pregnancy and intraamniotic inflammation (IAI)-induced preterm birth. We conducted a cross-sectional study at a tertiary university hospital. AF levels of Ang-1, Ang-2, and sTie2 were evaluated in 176 women during second trimester (n = 40), third trimester (n = 37), and preterm labor (positive IAI, n = 50; negative IAI, n = 49). Placenta and cord blood of select women were analyzed. Ang-1, Ang-2, sTie2, and IL-6 were evaluated by ELISA. Real-time PCR measured Ang-1, Ang-2, and Tie2 placental mRNA levels. Placenta was immunostained for Ang-1 and Ang-2. Placental explant cultures were stimulated with lipopolysaccharide, Pam3Cys, and modulators of protein synthesis/secretion (cycloheximide, monensin, and brefeldin A). In normal pregnancy, the levels and ratios of AF Ang-1, Ang-2, and sTie2 varied with gestational age (GA) (P < 0.001). PCR revealed corresponding changes in placental Ang-1 and Ang-2, but not Tie2, mRNA. IAI raised AF Ang-1, Ang-2, and sTie2 above the expected level for GA without affecting their placental mRNA. Ang-2 immunoreactivity appeared enhanced in areas of villous edema. AF Ang-2/Ang-1 ratio was an important determinant of cord blood IL-6 (P < 0.001). Ex-vivo, sTie2 release was increased by Golgi disrupting but not bacterial mimic agents. Ang-1, Ang-2, and sTie2 are physiological constituents of AF that are GA and IAI regulated. Ang-2/Ang-1 ratio may play a role in modulating the fetal inflammatory response to IAI. Placental sTie2 shedding likely involves a Golgi-mediated mechanism.

Pentraxin 3 in maternal circulation: An association with preterm labor and preterm PROM, but not with intra-amniotic infection/inflammation

Objective. Pentraxin 3 (PTX3) is an acute-phase protein that has an important role in the regulation of the innate immune response. The aim of this study was to determine if maternal plasma PTX3 concentration changes in the presence of intra-amniotic infection and/or inflammation (IAI) in women with preterm labor (PTL) and intact membranes, as well as those with preterm prelabor rupture of membranes (preterm PROM).Study design. This cross-sectional study included women in the following groups: (1) nonpregnant (n = 40); (2) uncomplicated pregnancies in the first (n = 22), second (n = 22) or third trimester (n = 71, including 50 women at term not in labor); (3) uncomplicated pregnancies at term with spontaneous labor (n = 49); (4) PTL and intact membranes who delivered at term (n = 49); (5) PTL without IAI who delivered preterm (n = 26); (6) PTL with IAI (n = 65); (7) preterm PROM without IAI (n = 25); and (8) preterm PROM with IAI (n = 77). Maternal plasma PTX3 concentrations were determined by ELISA.Results. (1) Maternal plasma PTX3 concentrations increased with advancing gestational age (r = 0.62, p < 0.001); (2) women at term with spontaneous labor had a higher median plasma PTX3 concentration than those at term not in labor (8.29 ng/ml vs. 5.98 ng/ml, p = 0.013); (3) patients with an episode of PTL, regardless of the presence or absence of IAI and whether these patients delivered preterm or at term had a higher median plasma PTX3 concentration than normal pregnant women (p < 0.001 for all comparisons); (4) similarly, patients with preterm PROM, with or without IAI had a higher median plasma PTX3 concentration than normal pregnant women (p < 0.001 for both comparisons); and (5) among patients with PTL and those with preterm PROM, IAI was not associated with significant changes in the median maternal plasma PTX3 concentrations.Conclusions. The maternal plasma PTX3 concentration increases with advancing gestational age and is significantly elevated during labor at term and in the presence of spontaneous preterm labor or preterm PROM. These findings could not be explained by the presence of IAI, suggesting that the increased PTX3 concentration is part of the physiologic or pathologic activation of the pro-inflammatory response in the maternal circulation during the process of labor at term or preterm.

The frequency and clinical significance of intra-amniotic infection and/or inflammation in women with placenta previa and vaginal bleeding: an unexpected observation

Idiopathic vaginal bleeding, a common complication of pregnancy, increases the risk of small-for-gestational age (SGA) neonate, preeclampsia and preterm delivery and can be the only clinical manifestation of intra-amniotic infection and/or inflammation (IAI). Placenta previa is thought to be protective against ascending intrauterine infection, yet an excess of histologic chorioamnionitis has been reported in this condition. The aim of this study was to determine the frequency and clinical significance of IAI in women with placenta previa and vaginal bleeding in the absence of preterm labor. A retrospective cohort study including 35 women with placenta previa and vaginal bleeding <37 weeks of gestation who underwent amniocentesis was undertaken. Patients with multiple gestations were excluded. Intra-amniotic infection was defined as a positive culture for microorganisms, and intra-amniotic inflammation as an elevated amniotic fluid interleukin (IL)-6 concentration. IL-6 concentrations were determined by ELISA in 28 amniotic fluid samples available. Non-parametric statistics were used for analysis. 1) The prevalence of intra-amniotic infection was 5.7% (2/35), and that of IAI was 17.9% (5/28); 2) the gestational age at delivery was lower in patients with IAI than in those without IAI [29.4 weeks, interquartile range (IQR): 23.1-34.7 vs. 35.4 weeks, IQR: 33.9-36.9; P=0.028]; and 3) patients with placenta previa and IAI had a higher rate of delivery within 48 h (80% (4/5) vs. 19% (4/21); P=0.008) than those without IAI. Patients with placenta previa presenting with vaginal bleeding have intra-amniotic infection in 5.7% of the cases, and IAI in 17.9%. IAI in patients with placenta previa and vaginal bleeding is a risk factor for preterm delivery within 48 h.

Amniotic fluid volume in intra-amniotic inflammation with and without culture-proven amniotic fluid infection in preterm premature rupture of membranes

Previous studies reported that the clinical significance of intra-amniotic inflammation with a negative amniotic fluid (AF) culture is similar to that of intra-amniotic inflammation with microbiologically-proven AF infection. However, the magnitude of the fetal inflammatory response in these two conditions is different as gauged by umbilical cord C-reactive protein (CRP) concentrations. We undertook this study to determine if the frequency of oligohydramnios is different in these two conditions. The amniotic fluid index (AFI) was measured in 205 patients with preterm premature rupture of membranes (PROM) (<or=35 weeks). AF was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an elevated AF matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). Patients were divided into three groups according to the results of AF culture and the presence or absence of intra-amniotic inflammation: 1) without intra-amniotic inflammation and a negative culture (n=109); 2) with intra-amniotic inflammation and a negative culture (n=44); and 3) a positive culture (n=52). Patients with a positive culture had a higher frequency of oligohydramnios and a lower median AFI than those with a negative culture but with intra-amniotic inflammation (P<0.01). However, there was no significant difference in the median AFI or in the frequency of oligo-hydramnios according to the presence or absence of intra-amniotic inflammation among patients with a negative culture (P>0.1). Oligohydramnios was more frequent in patients with culture-proven AF infection than in those with intra-amniotic inflammation and a negative AF culture.

Serial changes of lung morphology and biochemical profiles in a rat model of bronchopulmonary dysplasia induced by intra-amniotic lipopolysaccharide and postnatal hyperoxia

to investigate serial changes of lung morphology and biochemical profiles in a rat model of bronchopulmonary dysplasia (BPD) induced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85%). we evaluated histological changes of the lungs and compared the levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and protein carbonyl in lung tissue on days 1, 7, and 14 after birth in a rat model of BPD. the inhibition of alveolarization was sustained in the LPS plus hyperoxia group from day 7 to 14, whereas alveolarization resumed in the hyperoxia group after oxygen exposure was withdrawn at day 7. Administration of LPS alone did not adversely affect lung morphometry. IL-6 levels showed transient overexpression at day 1 in the LPS-treated groups, but decreased at days 7 and 14. VEGF protein levels were elevated in the LPS-treated groups, but not in the hyper-oxia and control groups at days 1, 7, and 14. Exposure to hyperoxia affected protein carbonyl levels in the hyperoxia group at days 7 and 14. lung injury induced by intra-amniotic inflammation and postnatal hyperoxia may be due to inhibition of alveolarization without recovery even after withdrawal of oxygen.

Pentraxin 3 in amniotic fluid as a marker of intra-amniotic inflammation in women with preterm premature rupture of membranes

Objective To determine whether amniotic fluid levels of pentraxin 3 (PTX3) are of value in the prenatal diagnosis of acute histological chorioamnionitis in preterm premature rupture of membranes (PPROM). Methods Forty pregnant women with PPROM between 24 and 36 weeks of pregnancy without (n = 21) and with (n = 19) histological chorioamnionitis (PPROM group) and 42 women between 16 and 20 weeks of pregnancy (midtrimester group) were included in the study. We compared amniotic fluid PTX3 levels in the PPROM group with versus without histological chorioamnionitis, and between the PPROM and the midtrimester groups using nonparametric tests (Mann-Whitney test), given the non-normal distribution of the analyte. Results Patients with histological chorioamnionitis had a significantly higher median amniotic fluid PTX3 concentration than patients without the histological signs of chorioamnionitis (3.69 ng/mL [0.51–106.8] versus 0.8 ng/mL [0.36–121.0]; P = 0.015). Patients in the PPROM group reached a significantly higher median amniotic fluid concentration of PTX3 compared with those in the midtrimester group (1.0 ng/mL [0.36–121.0] versus 0.67 ng/mL [0.4–2.8]; P = 0.007). Conclusion Histological chorioamnionitis is associated with a significant increase of amniotic fluid pentraxin 3 levels. Amniotic fluid pentraxin 3 appears to be a marker of intra-amniotic inflammation.

485: Lack of intra amniotic inflammation (IAI) during the mid 2nd trimester of women with spontaneous preterm birth (PTB)

The relationship between PTB and IA is confirmed by many investigators. Some estimate >70% PTBs <32w are associated with a fetal inflammatory response syndrome (FIRS) or IAI. Further, recent studies demonstrate panels of amniotic fluid (AF) inflammation biomarkers (e.g. the MR Score [human defensins 1 & 2 and calgranulins A & C) are superior to all other tests for the identification of FIRS / IAI, and the only test that predicts neonatal course. We test the hypothesis IAI is already present by the mid 2nd trimester of women destined for PTB.

521: One of every four patients with an asymptomatic short cervix (15mm) has subclinical intra-amniotic inflammation: implications for patient counseling and management

The clinical management of a patient with a sonographic short cervix is a common obstetrical challenge. A fraction of patients with a short cervix have evidence of intra-amniotic inflammation (Kiefer, AJOG, 2009); however, the outcome of these patients has not been characterized. The purpose of this study was to determine the frequency and clinical significance of intra-amniotic inflammation in asymptomatic women in the mid-trimester of pregnancy with a sonographic short cervix.

122: Is fetal fibronectin (FFN) a marker of intra-amniotic inflammation in patients with midtrimester short cervix?

Both fFN and amniotic fluid (AF) cytokines can predict interval to delivery in patients with midtrimester short cervix. However, no studies have shown if fFN is related to intra-amniotic inflammation. Therefore, we examined the relationship between fFN and AF cytokines in patients presenting with midtrimester short cervix.

527: Interleukin-6 trans-signaling molecules soluble GP130 and soluble IL-6 receptor in the amniotic fluid (AF) of women with intra-amniotic inflammation (IAI) and preterm premature rupture of membranes (PPROM)

527: Interleukin-6 trans-signaling molecules soluble GP130 and soluble IL-6 receptor in the amniotic fluid (AF) of women with intra-amniotic inflammation (IAI) and preterm premature rupture of membranes (PPROM)

642: The risk of microbial invasion of the amniotic cavity, intra-amniotic inflammation and histologic chorioamnionitis in term pregnant women with intact membranes during labor

642: The risk of microbial invasion of the amniotic cavity, intra-amniotic inflammation and histologic chorioamnionitis in term pregnant women with intact membranes during labor

506: Non-invasive prediction of intra-amniotic infection/inflammation in women with preterm premature rupture of membranes: a comparison with amniotic fluid white blood cell count

To develop a model based on non-invasive variables to predict the probability of intra-amniotic infection and/or inflammation in women with preterm premature rupture of membranes (PPROM), and to compare its predictive ability with amniotic fluid (AF) white blood cell (WBC) count.

434: The frequency and clinical significance of intra-amniotic inflammation in twin pregnancies with preterm labor and intact membranes

434: The frequency and clinical significance of intra-amniotic inflammation in twin pregnancies with preterm labor and intact membranes

Differential expression pattern of genes encoding for anti-microbial peptides in the fetal membranes of patients with spontaneous preterm labor and intact membranes and those with preterm prelabor rupture of the membranes

Objective. Increased amniotic fluid concentrations of anti-microbial peptides, components of the innate immune system, have been reported in patients with preterm labor (PTL) with intact membranes and intra-amniotic infection and/or inflammation (IAI), as well as in patients with preterm prelabor rupture of the membranes (PPROM). This study was designed to confirm these results using a targeted approach, detecting DEFA1, DEFB1, GNLY, and S100A9 gene expression in the choriamniotic membranes in pregnancies complicated with PTL and intact membranes or PPROM, with and without histologic chorioamnionitis.Study design. Human fetal membranes were obtained from patients in the following groups: (1) PTL with intact membranes (n = 15); (2) PTL with intact membranes with histologic chorioamnionitis (n = 12); (3) PPROM (n = 17); and (4) PPROM with histologic chorioamnionitis (n = 21). The mRNA expression of α-defensin-1, β-defensin-1, calgranulin B and granulysin in the fetal membranes was determined by qRT-PCR.Results. (1) The expression of α-defensin-1 mRNA in the fetal membranes was higher in patients with PTL and intact membranes with histologic chorioamnionitis, than those without chorioamnionitis (19.4-fold, p < 0.001); (2) Among patients with histologic chorioamnionitis, patients with PTL and intact membranes had a higher α-defensin-1 mRNA expression than those with PPROM (5.5-fold, p = 0.003); (3) Histologic chorioamnionitis was associated with a higher calgranulin B mRNA expression in the chorioamniotic membranes of patients with both PTL and intact membranes (7.9-fold, p = 0.03) and PPROM (7.6-fold, p < 0.0001); (4) The expression of calgranulin B mRNA in the fetal membranes was higher in patients with PTL and intact membranes without histologic chorioamnionitis than in those with PPROM without histologic chorioamnionitis (2.7-fold, p = 0.03); (5) There were no differences in the expression of β-defensin-1 and granulysin in the chorioamniotic membranes between the study groups even in the presence of histologic chorioamnioniotis.Conclusions. (1) Among patients with histologic chorioamnionitis, the mRNA expression of α-defensin-1 and calgranulin B in the fetal membranes of patients with PTL and intact membranes as well as that of calgranulin B in the fetal membranes of patients with PPROM is higher than in the membranes of those without histologic chorioamnionitis; (2) histologic chorioamnionitis is associated with differences in the pattern of α-defensin-1 mRNA expression in the fetal membranes in patients with PTL and intact membranes and those with PPROM.

High tissue factor activity and low tissue factor pathway inhibitor concentrations in patients with preterm labor

Objective. Preterm labor (PTL) has been associated with an increased thrombin generation in the maternal circulation and amniotic fluid. Tissue factor (TF) is a potent initiator of the coagulation cascade, which can trigger the hemostatic system to generate thrombin. The aims of this study were to determine whether spontaneous PTL with intact membranes is associated with changes in the maternal plasma concentrations and activity of TF as well as tissue factor pathway inhibitor (TFPI).Methods. This cross-sectional study included women in the following groups: (1) normal pregnancies (n = 86); (2) term pregnancies in spontaneous labor (TIL) (n = 67) and not in labor (TNL) (n = 88); and (3) patients with spontaneous PTL and intact membranes (n = 136) that were classified into three sub-groups: (a) PTL without intra-amniotic infection and/or inflammation (IAI) who delivered at term (n = 49); (b) PTL without IAI who delivered preterm (n = 54); and (c) PTL with IAI who delivered preterm (n = 33). Plasma concentrations of TF and TFPI were measured by ELISA, and their activity was measured by chromogenic assays. Non-parametric statistics were used for analysis.Results. (1) Among women at term, those with spontaneous labor had a higher median maternal plasma TF and a lower median TFPI concentration than those without labor. (2) Patients with PTL had a significantly lower median maternal plasma TFPI concentration than that of normal pregnant women, regardless of the presence of IAI. (3) There was no significant difference in the median maternal plasma TF concentration between patients with a normal pregnancy and those with PTL. (4) In contrast, the median maternal plasma TF activity was higher among patients with PTL than in women with normal pregnancies, regardless of the presence of IAI or preterm delivery. (5) However, maternal plasma TFPI activity did not differ among the study groups.Conclusion. Women with preterm parturition, in contrast to those in labor at term, have a higher TF activity and a lower TFPI concentration, without a significant change in the median maternal plasma TF concentration. These observations suggest that the increased thrombin generation reported in patients with PTL may be the result of activation of the extrinsic pathway of the coagulation cascade. In addition, the increased thrombin generation reported in patients with PTL could be due to insufficient anti-coagulation, as reflected by the low maternal plasma TFPI concentration.

Pentraxin 3 in amniotic fluid: a novel association with intra-amniotic infection and inflammation

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor (PRR) that has an important role in immunoregulation and vascular integrity. The aim of this study was to determine if PTX3 is present in amniotic fluid (AF) and whether its concentration changes with gestational age (GA), in the presence of preterm or term labor, and in cases of intra-amniotic infection/inflammation (IAI) associated with spontaneous preterm labor (PTL) or preterm prelabor rupture of membranes (PROM). This cross-sectional study included the following groups: 1) mid-trimester (n=45); 2) uncomplicated pregnancies at term with (n=48) and without (n=40) spontaneous labor; 3) women with PTL and intact membranes who: a) delivered at term (n=44); b) delivered preterm without IAI (n=40); or c) delivered preterm with IAI (n=62); 4) women with preterm PROM with (n=63) and without (n=36) IAI. PTX3 concentration in AF was determined by ELISA. Non-parametric statistics were used for analyses. 1) Among women with PTL and intact membranes, the median AF PTX3 concentration was significantly higher in women with IAI than in those without IAI (7.95 ng/mL vs. 0.38 ng/mL; P<0.001) and than in those who delivered at term (0.55 ng/mL; P<0.001); 2) women with preterm PROM and IAI had a higher median AF PTX3 concentration than those without IAI (9.12 ng/mL vs. 0.76 ng/mL; P<0.001); 3) the median AF PTX3 concentration did not change with GA (mid-trimester: 0.79 ng/mL vs. term not in labor: 0.58 ng/mL; P=0.09); and 4) labor at term was not associated with a significant change of AF PTX 3 concentration (in labor: 0.54 ng/mL vs. not in labor: 0.58 ng/mL, P=0.9). PTX3 is a physiologic constituent of the AF, and its median concentration is elevated in the presence of IAI, suggesting that PTX3 may play a role in the innate immune response against IAI.

Cervical length and gestational age at admission as predictors of intra‐amniotic inflammation in preterm labor with intact membranes

To evaluate cervical length and gestational age as predictors of intra-amniotic inflammation in patients admitted because of preterm labor and intact membranes. Ninety-three pregnant women with preterm labor and intact membranes were included in our study. Cervical length was measured on admission by transvaginal sonography and transabdominal amniocentesis was performed within the first 48 h following admission. Positive amniotic fluid cultures defined intra-amniotic infection. Levels of intra-amniotic interleukin-6 (IL-6) were measured, and a receiver-operating characteristics (ROC) curve was constructed to determine the best cut-off point of IL-6 for predicting intra-amniotic infection. This value was then used as a basis for determining a cut-off of IL-6 for defining intra-amniotic inflammation. Considering inflammatory status, perinatal outcomes were evaluated and compared. Logistic regression was used to investigate associations of different explanatory variables with inflammatory status. A non-invasive approach for detection of intra-amniotic inflammation in women admitted because of preterm labor with intact membranes was evaluated. Intra-amniotic infection and inflammation rates were 14% and 28%, respectively. ROC curve analysis showed that the best cut-off value for IL-6 was 13.4 ng/mL for predicting intra-amniotic infection, which was comparable to the cut-off of 11.3 ng/mL reported previously by other authors (which we used to define inflammation). Regardless of the intra-amniotic microbial status, perinatal outcomes in women who developed intra-amniotic inflammation were worse than in those who did not. Cervical length < 15 mm and gestational age at admission < 28 weeks were independently associated with intra-amniotic inflammation. A strategy considering these two non-invasive parameters (either women admitted < 28 weeks or women admitted between >or= 28 and < 32 weeks with a cervical length < 15 mm) could detect 84.0% of women with intra-amniotic inflammation with a positive predictive value of 48.8%, providing improved diagnostic indices compared to either variable considered alone. Cervical length and gestational age at admission can be used as a non-invasive method to assess the risk of intra-amniotic inflammation in preterm labor and intact membranes.