Human chorionic gonadotropin in cervicovaginal secretions as a predictor of preterm delivery.

OBJECTIVES: To determine whether human chorionic gonadotropin (hCG) detected in cervicovaginal secretions of patients with symptoms suggestive of preterm labor is a predictor of preterm birth. METHODS: Women presenting to labor and delivery with symptoms of preterm labor were invited to participate. After collecting secretions with a cotton-tipped applicator from the posterior fornix and endocervical canal, we placed the swab in a test tube containing 1 ml of normal saline. From this solution, we performed qualitative and quantitative hCG measurements. Qualitative and quantitative hCG results from women who delivered at term were compared with those delivering prior to 37 weeks' gestation. RESULTS: Samples were obtained and analyzed from 86 women at a mean (+/- standard deviation) gestational age of 30.7+/-2.9 weeks. Of the 86 subjects enrolled, 28 (32.6%) delivered preterm. A positive rapid qualitative assay from cervicovaginal secretions between 24 and 34 weeks' gestation was associated with a significant increase in the incidence of preterm delivery (relative risk 2.62, 95% confidence interval (CI) 1.38, 4.98). The likelihood ratios for a positive and negative test were 2.19 (95% CI 1.35, 3.56) and 0.51 (95% CI 0.30, 0.85) respectively. Using a cut-off of 19 mIU/ml, similar diagnostic accuracy for predicting preterm birth was obtained with the quantitative test 1.93 (95% CI 1.14, 3.26) and 0.62 (95% CI 0.40, 0.98). CONCLUSIONS: Qualitative and quantitative hCG measurements from cervicovaginal secretions may be useful predictors of preterm birth in symptomatic patients. The qualitative hCG test can be used at the bedside with results obtained in minutes.     

Cervicovaginal HCG and cervical length for prediction of preterm delivery in asymptomatic women at high risk for preterm delivery

Objective  To predict the risk of preterm birth (<37 weeks) or early preterm birth (<34 weeks) by cervicovaginal HCG and cervical length measured between 24–28 weeks of gestation in asymptomatic women at high risk for preterm birth. Methods  This study was conducted in the departments’ of Obstetrics & Gynaecology and Immunopathology of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. In 75 pregnant women at high risk for preterm birth because of prior one on more preterm births due to spontaneous labour or ruptured membranes, cervicovaginal HCG and cervical length (by TVS) were measured between 24–28 weeks of gestation. These parameters were correlated individually and in combination for prediction of preterm birth. Results  Of the 75 women, 20 (26.7%) delivered <37 weeks and 6 (8%) delivered <34 weeks. To predict delivery <37 weeks, cervical length <2.95 cm had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 75%, 80.1%, 71.4% and 90.7% respectively, and cervicovaginal HCG >4.75 mIU/ml had a sensitivity, specificity, PPV, and NPV of 70%, 61.81%, 40% and 85% respectively. To predict delivery <34 weeks, cervical length <2.65 cm had a sensitivity, specificity, PPV, and NPV of 50%, 85.50%, 23.08% and 95.16% respectively; and cervicovaginal HCG >14 mIU/ml had a sensitivity, specificity, PPV and NPV of 83.3%, 85.5%, 33.3% and 98.3% respectively. Cervical length was superior to predict delivery <37 weeks, whereas HCG was superior to predict delivery <34 weeks. Their combination was superior to predict preterm birth both <37 weeks or <34 weeks, than either parameter used alone. Conclusion  In high risk asymptomatic women, increased cervicovaginal HCG and reduced cervical length and between 24 to 28 weeks of gestation increased the risk of preterm delivery.     

Vaginal fluid beta-human chorionic gonadotropin level in the diagnosis of premature rupture of membranes

BACKGROUND: To determine whether the measurement of beta-human chorionic gonadotropin (beta-HCG) level in the vaginal washing fluid could be useful for the diagnosis of premature rupture of membranes. METHODS: Totally, 120 pregnant women were enrolled in this study. Subjects were divided into four groups [group I, no preterm labor and term delivery (n = 38); group II, preterm labor and term delivery (n = 12); group III, preterm labor and consequent premature delivery (n = 24); group IV, preterm labor with premature rupture of membranes (PROM) and consequent premature delivery (n = 46)]. After irrigating the posterior vaginal fornix with 3 ml of sterile saline and the obtained vaginal washing fluid, we measured beta-HCG levels. RESULTS: The median and range of vaginal fluid beta-HCG levels were 3.60 (0.09-30.52), 4.42 (0.33-10.02), 15.50 (0.25-378.62), and 512.53 (26.95-3507.20) mIU/ml in group I, group II, group III, and group IV, respectively. Vaginal beta-HCG level was significantly higher in patients with PROM followed by premature delivery (group IV) than patients in other groups (P < 0.01). From the receiver operating characteristic curve, 39.8 mIU/ml was set as a cutoff value. Sensitivity, specificity, positive predictive value, and negative predictive value were 95.5, 94.7, 91.3, and 97.3%, respectively. CONCLUSION: Our study demonstrated that the measurement of vaginal fluid beta-HCG may be reliable, simple, and rapid test in diagnosing PROM and used as a adjunctive test in equivocal cases.     

Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes

OBJECTIVE: We sought to determine whether midtrimester amniotic fluid levels of matrix metalloproteinase-8 were associated with subsequent preterm premature rupture of membranes. STUDY DESIGN: We conducted a case-control study examining 57 asymptomatic women who underwent genetic amniocentesis from 14 to 21 weeks' gestation and subsequently had preterm premature rupture of membranes (<35 wk) and 58 women with subsequent term delivery. Measurement of total matrix metalloproteinase-8 level in amniotic fluid was conducted using a commercially available enzyme-linked immunosorbent assay and association with preterm birth due to preterm premature rupture of membranes was assessed. RESULTS: The overall distribution of matrix metalloproteinase-8 concentrations was similar in women who had preterm premature rupture of membranes and term controls (median 2.39 ng/mL, 25th to 75th percentile 1.1-10.1 vs 2.37 ng/mL, 25th to 75th percentile 1.5-4.7, P = .94). However, 26% of women who had preterm premature rupture of membranes had a matrix metalloproteinase-8 concentration above the 90th percentile (8.7 ng/mL), compared with only 10% of term controls (odds ratio 3.1, 95% CI 1.1-8.7; P = .03). Elevated matrix metalloproteinase-8 remained associated with preterm premature rupture of membranes after adjustment for maternal age, race, parity, gestational age, and year of amniocentesis (odds ratio 3.4, 95% CI 1.2-9.9; P = .03). CONCLUSIONS: The overall distribution of midtrimester amniotic fluid matrix metalloproteinase-8 levels did not differ between women who had preterm premature rupture of membranes and those delivered at term. However, marked elevations of midtrimester amniotic fluid matrix metalloproteinase-8 were highly associated with subsequent preterm premature rupture of membranes, suggesting that the pathophysiologic processes that contribute to preterm premature rupture of membranes may begin in early pregnancy.     

Cervicovaginal fetal fibronectin (FFN) for prediction of preterm delivery in symptomatic cases: a prospective study

OBJECTIVE: To assess the clinical value of cervicovaginal fetal fibronectin (FFN) in the prediction of preterm delivery (PTD) in women with signs and symptoms of preterm labor (PTL). METHOD: This investigation prospectively studied a cohort of a women with symptoms of PTL, between 24 and 37 weeks' gestation with < 3 cm of cervical dilatation and intact membranes. Cases were evaluated in terms of maternal demographic characteristics like age, body mass index, number of parities, previous PTL history, Bishop scores at admission, gestational age at delivery, mode of delivery, use of tocolytic or steroids, presence of histologic chorioamnionitis, neonatal outcomes and delivery before 34 weeks' gestation as well as within seven days of admission. RESULTS: A total number of 68 cases were included in the study. There were no statistically significant differences between positive and negative FFN groups in terms of maternal characteristics, mode of delivery and adverse neonatal outcomes. However, FFN + cases had higher Bishop scores on admission (3.4 +/- 1.2 vs 2.5 +/- 0.3, p = 0.03) and lower gestational age at delivery (33.4 +/- 3.1 weeks vs 36.8 +/- 2.1 weeks, p = 0.002). Likelihood ratio (LR) for positive results was 1.83 (95% CI: 1.61-2.26) for predicting birth before 34 weeks' gestation, with a corresponding negative LR of 0.62 (95% CI: 0.3-1.2). LR for positive results was 4.34 (95% CI: 3.65-5.12) for predicting birth within seven days of testing, with a corresponding negative LR of 0.3 (95% CI: 0.2-0.5). CONCLUSION: Based on the results of cervicovaginal FFN, positive tests represent an increased likelihood of PTD among women with symptoms of threatened preterm labor.     

A disproportionate increase in IL-1beta over IL-1ra in the cervicovaginal secretions of pregnant women with altered vaginal microflora correlates with preterm birth

OBJECTIVE: This purpose of this study was to investigate the association between vaginal microflora, concentrations of interleukin-1beta (IL-1beta), and its natural receptor antagonist (IL-1ra) in the cervicovaginal discharge, and spontaneous preterm birth.Study design Vaginal samples collected at 18 to 22 weeks' gestation from 207 women were analyzed to study qualitative and quantitative microbiologic aspects of vaginal microflora and IL-1beta and IL-1ra concentrations. RESULTS: Among women colonized with anaerobic Gram-negative rods and/or Gardnerella vaginalis, an elevated IL-1beta concentration, or a diminished IL-1ra:IL-1beta ratio were associated with preterm delivery. A cut-off IL-1ra:IL-1beta ratio of <8632:1 optimally discriminated the subjects with subsequent spontaneous preterm deliveries from subjects who delivered at term, with a sensitivity of 78%, specificity of 51%, positive predictive value of 21%, and negative predictive value of 95%. CONCLUSION: A disproportionate increase in IL-1beta over IL-1ra in response to vaginal colonization with anaerobic Gram-negative rods and/or G. vaginalis at 18 to 22 weeks' gestation is associated with spontaneous preterm delivery.     

Qualitative human chorionicgonadotropin testing of cervicovaginal washings for the detection of preterm premature rupture of membranes

OBJECTIVE: This study was performed to determine whether a qualitative human chorionicgonadotropin (hCG) test using cervicovaginal washings obtained from pregnant women is a useful predictor of recent preterm premature rupture of the membranes (PPROM). STUDY DESIGN: A prospective observational analysis of qualitative hCG testing on cervicovaginal washings in patients with either known PPROM or with intact membranes was performed. Patients with singleton gestations between 24 and 34 completed weeks were included. PPROM patients had documented confirmatory tests, including visualized pooling of amniotic fluid in the vaginal vault that was nitrazine-positive and demonstrated ferning. Those with vaginal bleeding or an anomalous fetus were excluded. Before collection, all patients were screened for bacterial vaginosis and trichomoniasis. Washings were then collected from the posterior vaginal fornix with the use of a 5-mL sterile saline irrigation and aspiration technique. Samples were then agitated manually and applied to the Quickvue Onestep qualitative pregnancy test (Quidell, San Diego, Calif) with a threshold of 25 mIU/mL. Data were analyzed with the t test, chi 2, and Fischer exact tests. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were calculated. When applicable, all 2-tailed P <.05 were considered significant. RESULTS: Fifty-two patients were enrolled in the study with 24 in the PPROM group and 28 in the control group. The 2 groups were similar with respect to demographic characteristics and wet preparation results. The mean gestation age was 31.4 +/- 2.4 (X +/- SD) and 30.8 +/- 2.7 weeks in the PPROM and control groups, respectively. The hCG test was positive in 19 (79%) of the PPROM patients and in 1 (3.6%) of the controls (sensitivity 79%, specificity 96%, PPV 95%, NPV 84%). CONCLUSION: Qualitative hCG testing of cervicovaginal washings appears to be an useful predictor of PPROM.     

Human chorionic gonadotropin assay in cervical secretions for accurate diagnosis of preterm labor.

OBJECTIVES: We planned to determine whether the concentration of human chorionic gonadotropin (hCG) in cervical secretions could be a useful marker for accurate diagnosis of preterm labor, and whether the use of cervical hCG assay in combination with the Bishop score would improve the prediction of delivery within 7 days, and to determine the cut-off values for hCG in prediction of delivery within 100 h, 7 and 14 days, as well as before 35 and 37 weeks of gestation in a group of women at high risk for preterm delivery. METHODS: The study was conducted in the perinatology department of Zeynep Kamil Women and Children Diseases Education and Research Hospital between February 2002 and February 2003. One hundred and two subjects with a diagnosis of threatened preterm labor with intact membranes were included in the study. For hCG measurements, a cotton swab was rolled intracervically for 10 s to absorb fluid. Bishop scores were assessed. The correlation test was employed for the variables influencing hCG values. The ROC curve analysis was used to establish an optimal cut-off concentration for cervical hCG and an optimal cut-off level for Bishop score. The continuous variables were analyzed by the unpaired, independent, two-tailed t-test and categorical data were analyzed by the chi-square test. RESULTS: A significant positive correlation was present between the cervical hCG concentrations and Bishop scores (r=0.72, P<0.0001), and a highly negative correlation between the cervical hCG concentrations and the time interval from sampling time until delivery (r=-0.80, P<0.0001) was detected. The cut-off value for cervical hCG concentration and its sensitivity, specificity, positive and negative predictive values, accuracy, relative risk and likelihood ratio for accurate determination of delivery within 100 h were > or =32 mIU/ml, 98%, 55%, 70%, 96%, 77%, 19.68 and 2.18, respectively. However, these values were > or =32 mIU/ml, 97%, 84%, 89%, 95%, 92%, 17.37 and 6.06, respectively, for prediction of delivery within 7 days; > or =30 mIU/ml, 97%, 79%, 87%, 94%, 89%, 15.15 and 4.62, respectively, for prediction of delivery within 14 days; > or =33 mIU/ml, 89%, 92%, 94%, 83%, 90%, 5.83 and, 11.55, respectively, for prediction of delivery before 35 weeks; and finally > or =27 mIU/ml, 76%, 50%, 85%, 37%, 71%, 1.34 and 1.52, respectively, for prediction of delivery before 37 weeks. CONCLUSIONS: Cervical hCG expression seems to be rewarding in accurate diagnosis of preterm labor. This test has the advantage of low cost and wide availability.     

Evaluation of quantitative ultrasound tissue characterization of the cervix and cervical length in the prediction of premature delivery for patients with spontaneous preterm labor

OBJECTIVE: This study was to evaluate the predictive value of the uterine cervix tissue with the use of quantitative ultrasound gray level analysis for preterm delivery. STUDY DESIGN: Sixty-eight patients with preterm labor between 20 and 35 weeks of gestation were included. When two-dimensional transvaginal ultrasound measurement of cervical length was completed, a region of interest of constant size was defined in the midsection of the posterior wall, and the tissue-specific gray scale was determined. Preterm delivery of <37 weeks of gestation was sought. RESULTS: Twenty-eight patients (41.2%) were delivered preterm. The risk for preterm delivery was increased significantly in patients with cervical length of /=4 (odds ratio, 3.44; 95% CI, 1.21-9.75), and with decreased mean gray scale value (odds ratio, 12.13; 95% CI, 3.69-39.88). Parity and uterine contractions were not significant as predictors for preterm delivery, although the risk for preterm delivery increased with higher parity (odds ratio, 1.8; 95% CI, 0.68-4.79). The risk for preterm delivery remained nearly the same by uterine contractions (odds ratio, 0.92; 95% CI, 0.28-3.01). A mean scale value of 相似文献   

Maternal serum ferritin concentration in patients with preterm labor and intact membranes.

OBJECTIVE: To determine the relationship between maternal serum ferritin concentrations in the second trimester and the risk of preterm delivery (PTD). METHODS: A prospective observational study was conducted. Fifty consecutive women with singleton pregnancies, who were admitted to the Maternal Fetal Medicine Unit due to preterm labor in the second trimester, were included. Maternal serum samples for determination of ferritin concentrations were obtained. Multiple logistic regression analysis was performed to control for confounders. RESULTS: Out of fifty patients enrolled in the study, 38% (19/50) delivered prematurely. Eight women (16%) had maternal serum ferritin concentrations above 30 ng/ml in the second trimester. Among them, 75% (n = 6) subsequently presented with preterm delivery (odds ratio (OR) = 6.7 with 95% confidence interval (CI) 1.1-56.2, p = 0.04). Only two patients with increased maternal ferritin concentrations delivered at term. However, 13 patients with second trimester ferritin concentrations below 30 ng/ml had preterm delivery. No significant differences in mean maternal ferritin concentrations were found between patients who delivered preterm and those that delivered at term, 31.9 +/- 50.6 vs. 13.6 +/- 15.2, respectively (p = 0.064). Using a multivariable analysis, controlling for anemia, leucocytosis and maternal age, increased serum ferritin concentrations were found to be an independent risk factor for PTD (OR = 8.6; 95% CI 1.4-52.5; p < 0.019). No significant correlation was found between serum ferritin concentrations and gestational age at birth (Pearson correlation coefficient r = -0.093; p = 0.522). CONCLUSIONS: Maternal ferritin concentrations above 30 ng/ml in the second trimester can serve as a marker for preterm delivery. However, since no correlation was found between serum ferritin concentrations and gestational age at birth, the routine use of serum ferritin as a marker for preterm delivery warrants further investigation.     

Fetal fibronectin in cervicovaginal secretions as a predictor of preterm birth

Objective To determine whether fetal fibronectin detected in cervicovaginal secretions of patients with symptoms suggestive of preterm labour is a predictor for preterm birth.
Design A blind prospective observational study.
Setting A teaching hospital.
Participants One hundred and forty-one women presenting to the delivery suite between 24 and 37 weeks of gestation (112 were between 24 and 34 weeks of gestation) with symptoms suggestive of preterm labour, with intact membranes and cervical dilatation of < 2 cm.
Intervention Specimens of cervicovaginal secretions were collected from the ectocervix and posterior fornix. Fetal fibronectin levels were measured by an ELISA and samples were considered positive if the level of fetal fibronectin present was ≥ 0.05 μg/ml.
Main outcome measures Gestation at birth and sampling-birth interval.
Results The preterm birth (before 3 7 weeks of gestation) rate in the population studied was 19±1%. Fetal fibronectin predicted preterm birth with sensitivity of 63%, specificity of 95±6%, positive predictive value of 77±3%, and negative predictive value of 91±6%. Analysis of the data from women at less than 34 weeks of gestation showed similar results. A negative test accurately excluded (97±9%) the chance of subsequent birth during the three weeks interval following sampling.
Conclusions The presence of fetal fibronectin in the cervicovaginal secretions of women admitted with symptoms suggestive of preterm labour indicates a significant risk for subsequent preterm birth. The absence of fetal fibronectin in this group is a very strong indication that subsequent preterm birth is unlikely to occur. Fetal fibronectin test, if combined with clinical findings, has a potentially important role in clinical management of women with symptoms suggestive of preterm labour.     

The preterm prediction study: elevated cervical ferritin levels at 22 to 24 weeks of gestation are associated with spontaneous preterm delivery in asymptomatic women

OBJECTIVE: Low serum ferritin levels correlate with low iron stores, whereas high levels are associated with an acute-phase reaction. Our objective was to determine whether elevated levels of ferritin in the genital tract may be a potent marker to identify patients at risk for spontaneous preterm delivery. STUDY DESIGN: We performed a nested case-control study involving 182 women who had spontaneous preterm delivery and 182 term control subjects matched for race, parity, and recruitment center, and selected from 2929 women enrolled in the Preterm Prediction Study of the National Institute of Child Health and Development Maternal-Fetal Medicine Units Network. Cervical fluid ferritin was measured by use of radioimmunoassay. RESULTS: Cervical ferritin levels were significantly higher in women who subsequently had spontaneous early preterm delivery (<32 weeks, mean +/- SD, 37.7 +/- 31.1 vs 21.5 +/- 24.1 ng/mL, P =.002; and <35 weeks, 43.2 +/- 62.7 vs 28.2 +/- 36.7 ng/mL, P =.004) than in term controls. A cervical ferritin of >75th percentile in the controls (>35.5 ng/mL) was found in 52.9% (9/17) of the women delivered <29 weeks vs 17.7% (3/17) of the controls (odds ratio [OR] 5.3 [95% CI 1.1-25.2]) and in 43.5% (20/46) of the women delivered <32 weeks versus 10.9% (5/46) of the controls (OR 6.3, 95% CI 2.1-18.9). Cervical ferritin levels had a weaker association with spontaneous preterm delivery <35 weeks (OR 2.8 [95% CI 1.5-5.1]) and <37 weeks (OR 1.6, 95% CI 1.0-2.5]). Cervical ferritin levels correlated significantly with cervical lactoferrin, interleukin-6 (IL-6), and defensin levels. CONCLUSIONS: Elevated cervical ferritin levels at 22 to 24 weeks of gestation in asymptomatic women are associated with subsequent spontaneous preterm birth. The strong correlation of cervical ferritin with other inflammatory markers provides support for the hypothesis of infection as a mediator of preterm delivery.     

Association between colonization with group B streptococci during pregnancy and preterm delivery among Danish women

OBJECTIVE: We studied the relationship between group B streptococcal colonization and preterm delivery. STUDY DESIGN: In this prospective study at a single hospital in Odense, Denmark, cervicovaginal cultures were obtained at < or = 24 weeks' gestation from all the women, at delivery from women with preterm deliveries, and from a random sample of women delivering at term. RESULTS: In 2846 singleton births, there was no significant association between group B streptococcal colonization at 相似文献   

Maternal plasma and amniotic fluid dehydroepiandrosterone-sulfate concentrations in preterm labor and delivery

The purpose of this study was to determine whether preterm parturition is associated with changes in maternal plasma and amniotic fluid dehydroepiandrosterone-sulfate concentrations. A cross sectional study was constructed according to the gestational age at admission and response to tocolysis. Group 1 consisted of women admitted with preterm labor and intact membranes between 28 and 31 weeks and 6 days gestational age (n=40). Group 2 included 40 patients with preterm labor between 32 and 36 weeks gestational age. Both groups were classified into two subgroups: preterm delivery within seven days of admission and term delivery. Commercially available immunoassay kits validated for amniotic fluid analysis of DHEA-S, were used to measure maternal plasma and amniotic fluid DHEA-S concentrations. Maternal plasma DHEA-S concentrations were significantly higher in women with preterm labor who delivered preterm than in those who delivered at term. (Group 1: median 800 ng/ml [range 100–1100] vs. median 200 ng/ml [70–800],P<0.001; Group 2: median 850 ng/ml [300–1700] vs. median 300 ng/ml [90–1100],P<0.001). In contrast, no significant differences were detected in amniotic fluid DHEA-S concentrations. Our data suggest that the rise in maternal plasma DHEA-S concentrations observed in patients with preterm labor may be related to the effects of stress during labor.     

Plasma protein Z concentrations in pregnant women with idiopathic intrauterine bleeding and in women with spontaneous preterm labor.

OBJECTIVES: Preterm parturition has been associated with decidual vascular disorders and excessive thrombin generation. The objective of this study was to examine maternal plasma concentrations of protein Z in normal pregnancies, as well as in those presenting with spontaneous preterm labor (PTL) and intrauterine bleeding during pregnancy. STUDY DESIGN: A cross-sectional study was designed to include patients with preterm labor and intact membranes and those with idiopathic intrauterine bleeding during pregnancy. Protein Z plasma concentrations were measured in the following groups: (1) normal pregnant women (n = 71); (2) patients at term with (n = 67) and without labor (n = 88); (3) patients with spontaneous PTL before 34 weeks who were classified into: (a) PTL with intra-amniotic infection/inflammation (IAI; n = 35), (b) PTL without IAI (n = 54), and (c) patients with PTL who delivered at term (n = 49); and (4) patients with idiopathic intrauterine bleeding in the second and third trimester who were divided into: (a) subsequent spontaneous PTL and delivery, and (b) term delivery. Maternal plasma protein Z concentration was measured by a specific and sensitive immunoassay. Moreover, the amniotic fluid concentration of protein Z was determined in a subset of patients with preterm labor (n = 30). RESULTS: (1) There was no correlation between maternal plasma protein Z concentration and gestational age in normal pregnant women. (2) The mean maternal plasma concentration of protein Z was significantly lower in women during spontaneous labor at term than in those not in labor (mean 2.15 microg/mL (95% CI 2.01-2.29) vs. mean 2.45+/-0.52 microg/mL (95% CI 2.34-2.56), respectively; p = 0.001). (3) Women with PTL without IAI who delivered preterm had a significantly lower mean protein Z concentration than normal pregnant women (mean 2.12 mug/mL (95% CI 1.98-2.26) vs. mean 2.39 microg/mL (95% CI 2.28-2.5); p = 0.008). (4) Of interest, PTL with IAI was not associated with lower plasma concentrations of protein Z, nor were those with PTL who delivered at term (p > 0.05 for each). (5) No differences were found in the maternal plasma concentrations of anti-protein Z antibodies between normal pregnancies and those with spontaneous PTL. (6) Patients with idiopathic intrauterine bleeding who had spontaneous PTL and delivery had a significantly lower mean plasma protein Z concentration than those who delivered at term (mean 1.24 microg/mL (95% CI 1.08-1.4) vs. mean 1.49+/-0.47 microg/mL (95% CI 1.33-1.65), respectively; p = 0.03). (7) Amniotic fluid was found to contain immunoreactive protein Z. CONCLUSIONS: (1) Patients with PTL leading to preterm delivery in the absence of IAI had a significantly lower plasma concentration of protein Z than those with normal pregnancies. (2) Patients with idiopathic intrauterine bleeding and subsequently spontaneous PTL and delivery had a significantly lower plasma concentration of protein Z than those with idiopathic intrauterine bleeding who delivered at term. (3) Protein Z was present in the amniotic fluid of patients with PTL. Collectively, these observations suggest that a subgroup of patients with PTL have a hemostatic disorder that involves bleeding/thrombosis as a mechanism of disease.     

Association of the Gln27Glu polymorphism of the beta-2-adrenergic receptor with preterm labor.

OBJECTIVES: To investigate a potential association between the beta-2-adrenergic receptor (B2AR) polymorphisms occurring at amino acid positions 16 (Arg16Gly) and 27 (Gln27Glu) and preterm labor. METHODS: Eighty patients with preterm labor and 76 control subjects were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A significant association was found between Gln27Glu substitution and preterm labor (P=0.001). The frequency of Gly16 and Glu27 alleles were found to be higher in patients than in control women (0.54 vs. 0.48 and 0.42 vs. 0.26, respectively), and the odds ratio for the occurrence of preterm labor was 2.14 (95% CI, 1.32-3.46; P=0.002) for the Glu 27 allele. An early delivery was noted in 52.5% of patients. CONCLUSION: The Gln27Glu polymorphism of the B2AR gene may have a role in molecular pathogenesis of preterm labor. Glu27 allele in patients with preterm labor might be a risk factor for deliveries before 37 weeks of gestation.     

Perinatal outcomes in women with preterm rupture of membranes between 24 and 32 weeks of gestation and a history of vaginal bleeding

OBJECTIVE: The purpose of this study was to compare perinatal outcomes among women with conservatively treated preterm premature rupture of membranes at 24 to 32 weeks of gestation in the presence or absence of vaginal bleeding. STUDY DESIGN: This is a secondary analysis of 581 women with and without vaginal bleeding within 1 week of admission with preterm premature rupture of membranes at 24 to 32 weeks of gestation who were enrolled in a multicenter trial of antibiotic therapy during conservative treatment. The main outcome was latency to delivery. Other outcome variables included clinical abruptio placentae, amnionitis, perinatal death, severe intraventricular hemorrhage, and respiratory distress syndrome. RESULTS: Outcome data were available for 581 patients (n=50 with bleeding). Latency to delivery was not affected by the presence or absence of bleeding. In general, a history of bleeding was associated with higher frequencies of subsequently diagnosed abruptio placentae (12% vs 3.5%; P=.01), perinatal death (16% vs 4.9%; P=.006), intraventricular hemorrhage (14.3% vs 5.9%; P=.03), and respiratory distress syndrome (69.4% vs 40.4%; P<.0001), when compared with those women with nonbleeding events. Women with bleeding were less likely to be black (42% vs 60%; P=.002) and had a lower mean gestational age at preterm premature rupture of membranes (27.6 vs 28.5 weeks; P=.02) when compared with white, Hispanic, and other. After an adjustment of data was made for potentially confounding factors, women with recent bleeding were more likely to be diagnosed with abruptio placentae at delivery (odds ratio, 2.8; 95% CI, 1.03-7.8; P=.04), and their infants were more likely to have respiratory distress syndrome (odds ratio, 3.1; 95% CI, 1.5-6.6; P=.004). CONCLUSION: Vaginal bleeding before preterm premature rupture of membranes is associated with increased rates of neonatal respiratory distress syndrome and abruptio placentae, but not with reduced latency to delivery.     

An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery.

OBJECTIVE: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid matrix metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. STUDY DESIGN: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. RESULTS: The median amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (matrix metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, <0.3-45.2 ng/mL], P <.01; interleukin-6: median, 0.32 ng/mL [range, 0.04-2.52 ng/mL] vs median, 0.18 ng/mL [range, 0.01-1.81 ng/mL], P <.01; angiogenin: median, 11.1 ng/mL [range, 4.5-30.7 ng/mL] vs median, 6.7 ng/mL [range, 1.3-21.9 ng/mL], P <.001). Amniotic fluid matrix metalloproteinase-8 concentrations higher than 23 ng/mL had the highest specificity and odds ratio (sensitivity, 42% [8/19]; specificity, 99% [94/95]; OR, 68.4 [95% CI, 7.8-599.1]) in the identification of the patients with preterm delivery after genetic amniocentesis. CONCLUSIONS: Elevated mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery (<32 weeks). An elevated matrix metalloproteinase-8 level of >23 ng/mL is a powerful predictor of spontaneous preterm delivery (<32 weeks) with an odds ratio of 68.4. Amniotic fluid studies can be used to improve the risk assessment for preterm delivery in women who undergo mid-trimester amniocentesis for genetic indications.     

Impact of threatened preterm labor and lower genital tract biocenosis on the concentrations of selected proinflammatory cytokines in cervicovaginal fluid of pregnant women

AIM: Recent studies have suggested that proinflammatory cytokines might play a crucial role in the mechanism of preterm labour and delivery. Lower genital tract infection could also influence the cytokines levels. The main aim of this study was to compare the concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6 and IL-8 in cervicovaginal fluid of pregnant women with threatened preterm labour (TPL) with group of women with normal course of pregnancy (reference group) and to determine impact of lower genital tract microflora on cytokines concentration. MATERIAL AND METHODS: Cervicovaginal fluids were obtained by lavage from 40 pregnant women at 22 to 34 weeks' gestation. Those samples were analyzed for the concentrations of selected cytokines using standard enzyme-linked immunosorbent assay technique. Lower genital tract microbiology was diagnosed using Gram stain method according to Spiegel's criteria. TPL was defined as uterine contractions treated by tocolysis. RESULTS: Threatened preterm labour (TPL) was diagnosed in 22 (55.0%) cases. Mean gestational age at the time of cytokines measurement was 28.6 weeks. Mean concentrations of IL-1 alpha, IL-1 beta and IL-8 measured in cervicovaginal fluid of pregnant women with TPL and in reference group were similar (89.43 vs. 91.17 pg/ml; 42.05 vs. 41.01 pg/ml and 621.8 vs. 697.8 pg/ml, respectively). Vaginal levels of IL-6 was higher among women with preterm labour (21.1 pg/ml vs. 13.9 pg/ml) as compared to reference group. Bacterial vaginosis (BV) was diagnosed in 11 women (27.5%) while grade I microflora in 19 (47.5%). There was a positive correlation between BV and IL-1 alpha and IL-1 beta concentration but no with IL-6 and IL-8. CONCLUSIONS: Vaginal levels of IL-6 were found to be significantly elevated among women with threatened preterm labour while IL-1 alpha and IL-1 beta among women with BV. The usefulness of cytokines measurement in cervicovaginal fluid of pregnant women for prediction of preterm delivery should be clarified in further after excluding the impact of lower genital tract infections on cytokines concentrations.     

The preterm prediction study: granulocyte colony-stimulating factor and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

OBJECTIVE: Granulocyte colony-stimulating factor is elevated in the amniotic fluid and plasma of women with chorioamnionitis and active preterm labor. We investigated the relationship between plasma granulocyte colony-stimulating factor and subsequent spontaneous preterm birth in pregnant women without symptoms. STUDY DESIGN: We performed a nested case-control study involving 194 women who had a singleton spontaneous preterm birth and 194 matched term control subjects from the patient pool (n = 2929) enrolled in the Preterm Prediction Study. Plasma collected at 24 and 28 weeks' gestation was analyzed for granulocyte colony-stimulating factor, and the results were compared with subsequent spontaneous preterm birth. RESULTS: Compared with term control subjects, women who were delivered of their infants spontaneously at <28 weeks' gestation had increased mean granulocyte colony-stimulating factor values at 24 weeks' gestation (84.7 +/- 38.4 vs 67.7 +/- 28.6 pg/mL; P =.049), and women who were delivered of their infants at <32 weeks' gestation had increased mean plasma granulocyte colony-stimulating factor values at 28 weeks' gestation (80.4 +/- 24.1 vs 55.9 +/- 16.5 pg/mL; P =. 001). At 24 weeks' gestation a granulocyte colony-stimulating factor value >75th percentile in control subjects (approximately 80 pg/mL) was found in 48.9% (23/47) of all women delivered of their infants at <32 weeks' gestation versus 14.9% (7/47) of the term control subjects (adjusted odds ratio, 6.2; 95% confidence interval, 1.8-20. 8). At 28 weeks' gestation a granulocyte colony-stimulating factor value >75th percentile was found in 36.8% (7/19) of women delivered of their infants at <32 weeks' gestation versus 5.3% (1/19) of term control subjects (adjusted odds ratio, 25.7; 95% confidence interval, 1.5-470.4). When measured at 24 or 28 weeks' gestation, granulocyte colony-stimulating factor did not predict spontaneous preterm birth at 32 to 34 weeks' gestation or at 35 to 36 weeks' gestation. CONCLUSION: In pregnant women without symptoms at 24 and 28 weeks' gestation, elevated plasma granulocyte colony-stimulating factor levels are associated with subsequent early (<32 weeks' gestation) spontaneous preterm birth, especially within the next 4 weeks, but not with late spontaneous preterm birth. These data provide further evidence that early spontaneous preterm birth is associated with an inflammatory process that is identifiable by the presence of a cytokine in maternal plasma several weeks before the early spontaneous preterm birth; however, later spontaneous preterm birth is not associated with this process.