A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth

OBJECTIVE: The rarer of 2 alleles of a polymorphism in the promoter of the tumor necrosis factor alpha gene (TNF) has been associated with spontaneous preterm birth following preterm premature rupture of the fetal membranes in some populations. The aim of this study was to assess if the presence of symptomatic bacterial vaginosis amplifies the risk of spontaneous preterm birth in those with a "susceptible" TNF genotype. STUDY DESIGN: A case-control study was performed at our institution. Cases (n=125) were defined as women who delivered before 37 weeks as a result of ruptured membranes or preterm labor, while control subjects (n=250) were defined as women who delivered after 37 weeks. DNA was collected from maternal blood and analyzed for the TNF genotype. Information on symptomatic bacterial vaginosis and other risk factors for preterm birth was obtained by review of the antenatal record. Multiple logistic regression was also used to test the interaction between bacterial vaginosis, the TNF genotype, and preterm birth. RESULTS: Maternal carriers of the rarer allele (TNF-2) were at a significantly increased risk of spontaneous preterm birth [odds ratio (OR) 2.7, 95% CI 1.7-4.5]. The association between TNF-2 and preterm birth was modified by the presence of bacterial vaginosis, such that those with a "susceptible" genotype and bacterial vaginosis had increased odds of preterm birth compared with those who did not (OR 6.1, 95% CI 1.9-21.0). CONCLUSION: This study provides preliminary evidence that an interaction between genetic susceptibilities (ie, TNF-2 carriers) and environmental factors (ie, bacterial vaginosis) is associated with an increased risk of spontaneous preterm birth.     

Polymorphisms in the tumor necrosis factor-alpha gene at position -308 and the inducible 70 kd heat shock protein gene at position +1267 in multifetal pregnancies and preterm premature rupture of fetal membranes

OBJECTIVE: The purpose of this study was to determine the relationship between preterm premature rupture of membranes, tumor necrosis factor-alpha, and heat shock protein-70 gene polymorphisms in multifetal gestations. STUDY DESIGN: Buccal swabs from 101 mother-neonate pairs of multifetal pregnancies were tested for single nucleotide polymorphisms at position -308 of the tumor necrosis factor-alpha gene and +1267 of the heat shock protein-70 gene. Pregnancy outcome data were obtained subsequently. RESULTS: Tumor necrosis factor-alpha allele 2 carriage by the first-born occurred in 10 of 27 pregnancies (37.0%) that resulted in preterm premature rupture of membranes compared with 6 of 67 pregnancies (9.0%) without preterm premature rupture of membranes ( P = .002). The allele frequency of tumor necrosis factor-alpha allele 2 and heat shock protein-70 allele 2 in the first born was higher in pregnancies that were complicated by preterm premature rupture of membranes (18.5% vs 4.5%; P = .003; and 57.7% vs 41.3%; P = .04, respectively). There was no relationship between tumor necrosis factor-alpha allele 2 or heat shock protein-70 allele 2 carriage by the second fetus or mother and preterm premature rupture of membranes. CONCLUSION: Tumor necrosis factor-alpha allele 2 and/or heat shock protein-70 allele 2 carriage by the first-born fetus is associated with preterm premature rupture of membranes in multifetal pregnancies.     

Monocyte chemotactic protein-1 in cervical and amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-amniotic inflammation, and preterm delivery

OBJECTIVE: The purpose of this study was to evaluate the role of monocyte chemotactic protein-1 in cervical and amniotic fluid in women in preterm labor and with preterm premature rupture of membranes. STUDY DESIGN: Women with singleton pregnancies (相似文献   

Tumor necrosis factor in preterm and term labor.

OBJECTIVE: Our objective was to determine if labor (term and preterm) and microbial invasion of the amniotic cavity were associated with changes in amniotic fluid concentrations of tumor necrosis factor. STUDY DESIGN: Amniotic fluid was retrieved by transabdominal amniocentesis from 269 women in the following groups: midtrimester (n = 38), preterm labor with intact membranes (n = 52), preterm premature rupture of membranes (n = 74), term in active labor (n = 84), and term not in labor (n = 21). Fluid was cultured for aerobic and anaerobic bacteria and for Mycoplasma species. Tumor necrosis factor was measured with a commercially available enzyme-linked immunosorbent assay validated for amniotic fluid (sensitivity 60 pg/ml). RESULTS: Amniotic fluid from pregnant women in the second and third trimesters who were not in labor did not contain tumor necrosis factor. Among women in preterm labor, 92.3% (12/13) of patients with a positive amniotic fluid culture had detectable tumor necrosis factor in the amniotic fluid (median 820 pg/ml, range less than 60 to 2340 pg/ml). In contrast, only 10.2% (4/39) of women with a negative amniotic fluid culture had detectable tumor necrosis factor. Histopathologic chorioamnionitis was found in all patients who had a positive amniotic fluid culture, and tumor necrosis factor was detectable in the amniotic fluid of all but one of these patients. Among women in active labor at term, 25% (21/84) had detectable tumor necrosis factor in the amniotic fluid. Tumor necrosis factor was detected more frequently in the amniotic fluid of patients with a positive amniotic fluid culture than in patients with a negative culture (46.6% [7/15] vs 20.2% [14/69], p = 0.047). Amniotic fluid concentrations of tumor necrosis factor were significantly higher in patients with preterm premature rupture of membranes, labor, and a positive amniotic fluid culture than in the other subgroups of patients with preterm premature rupture of membranes. CONCLUSION: Parturition in the setting of microbial invasion of the amniotic cavity is associated with activation of the cytokine network as demonstrated by the detection of tumor necrosis factor in human amniotic fluid.     

High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery

OBJECTIVE: This study was conducted to determine whether there is a relationship between the concentration of fetal cell-free DNA in maternal serum and the duration of pregnancy in women who are at high risk for preterm delivery because of either preterm labor or preterm premature rupture of the membranes. STUDY DESIGN: Sera were collected and frozen from 71 women with a male fetus. Maternal serum fetal cell-free DNA concentration was measured with the use of real-time polymerase chain reaction amplification of DYS1. Fetal cell-free DNA concentrations were converted to multiples of the median. The following groups were studied: group 1: women with preterm labor and intact membranes who were delivered at > or = 36 weeks of gestation (n = 21); group 2: women with preterm labor who were delivered at <36 weeks of gestation (n = 29); and group 3: women with preterm premature rupture of the membranes in labor (n = 20) or not in labor (n = 1) who were delivered prematurely (<36 weeks of gestation). Kaplan-Meier and Cox regression analyses were used to analyze the relationship between fetal cell-free DNA concentrations and the likelihood of preterm delivery. RESULTS: A cut-off value for fetal cell-free DNA of 1.82 multiples of the median was chosen for analysis. The cumulative rate of early preterm delivery (<30 weeks of gestation) was significantly higher for women with fetal cell-free DNA concentrations of > or = 1.82 multiples of the median than those with fetal cell-free DNA concentrations below this cut-off (45% [95% CI, 36%-74%] vs 18% [95% CI, 11%-25%]; P = .008]. The cumulative rate of preterm delivery (<36 weeks of gestation) was also significantly higher at > or = 1.82 multiples of the median (73% [95% CI, 52%-93%] vs 66% [95% CI, 54%-79%]; P = .02). After adjustment for covariates, Cox analysis showed that fetal cell-free DNA at > or = 1.82 multiples of the mechanisms of disease that are associated with a mean hazard rate of delivery of 1.57 (P = .005). CONCLUSION: High concentrations of fetal cell-free DNA in maternal serum are associated with an increased risk of spontaneous preterm delivery. This observation may have implications for the understanding of the mechanisms of disease that is associated with preterm labor.     

Time to delivery after the first course of antenatal corticosteroids: a cohort study

The optimal time interval between administration of antenatal corticosteroids and delivery is 1 to 7 days. This study evaluates the timing of the first course of antenatal corticosteroids in clinical practice. We performed a retrospective cohort study of consecutive women who had received antenatal corticosteroids and/or delivered between 24 and 34 weeks of gestation. Time between administration of corticosteroids and delivery was compared between women with different causes of anticipated preterm deliveries: symptomatic preterm labor with intact membranes; preterm premature rupture of the membranes; (pre)eclampsia; hemolysis, elevated liver enzymes, and low platelet count; intrauterine growth restriction; vaginal blood loss; and suspected fetal distress. We included 439 women of whom 348 (79%) completed the course of corticosteroids. In women with a complete course, 143 (41%) delivered within 7 days. The median interval between the course and delivery was 11 days and varied between 41 days in women with vaginal blood loss, 25 days in women with spontaneous preterm labor with intact membranes, and 8 days in women with preeclampsia ( P < 0.001). In women with spontaneous preterm labor with intact membranes and in women with vaginal blood loss, we can benefit substantially from a more accurate discrimination of women who need corticosteroids immediately and women who do not.     

孕产妇血清中MMP-3、TNF-α、IL-10的表达与早产和早产胎膜早破的关系

目的探讨基质金属蛋白酶-3（MMP-3）、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（lL-10）在孕产妇血清中的表达与早产、胎膜早破的关系。方法选择单胎头位初产妇80例作为研究对象,按孕周、胎膜是否破裂和产妇是否临产分为早产临产组（sPTD）、早产胎膜早破组（PPROM）、先兆早产组（TPL）和妊娠28～36＋6周无产兆组（对照组）,每组各20例。用ELISA法检测孕妇血清中MMP-3及TNF-α、lL-10的水平。结果①早产临产组、早产胎膜早破组、先兆早产组和对照组血清中MMP-3的浓度分别为（242.25±72.40）ng/ml、（225.95±85.43）ng/ml、（197.85±57.08）ng/ml、（186.80±54.33）ng/ml;TNF-α的浓度分别为（1332.35±346.65）pg/ml、（1365.00±211.80）pg/ml、（1188.15±269.43）pg/ml、（1061.85±210.02）pg/ml;IL-10的浓度分别为（563.65±116.50）pg/ml、（566.80±123.03）pg/ml、（521.00±105.14）pg/ml、（483.50±119.17）pg/ml;②早产组血清中MMP-3,TNF-α浓度高于对照组,以TNF-α升高更明显（P〈0.01）;而IL-10在前两组中有增高趋势,但与后两组相比差异无统计学意义（P〉0.05）;③血清中MMP-3、TNF-α、IL-10浓度呈两两正相关。结论①孕产妇血清中MMP-3及TNF-α浓度与早产、胎膜早破密切相关;②孕产妇血清中MMP-3、TNF-α及IL-10在临产、胎膜早破中可能起协同作用。     

Predictive value of serum interleukin-6 and -8 levels in preterm labor or rupture of the membranes

BACKGROUND: The aim of this prospective study was to examine if serum concentrations of cytokines are of value in the identification of patients at risk for preterm delivery. METHODS: Interleukin- 1beta,2,4,6,8 and tumor necrosis factor alpha were determined between 25 and 37 weeks of gestation in the serum of 72 consecutive patients with preterm labor, 38 patients with preterm rupture of the membranes, and 24 healthy pregnant women as a control group. Material was collected within 18 hours after hospitalization and was immediately centrifuged and shock frozen. RESULTS: Significantly increased serum levels were found for interleukin-6 and -8 in patients with preterm labor or preterm rupture of the membranes when compared to the control group (p<0.001 and p<0.005, respectively). In patients with preterm rupture of the membranes and interleukin-6 levels above the median of 4.0 pg/ml the delivery occurred significantly earlier than in patients with lower levels (1 versus 5.5 days; p=0.005). Patients of both pathology groups with detectable (>18 pg/ml). Interleukin-8 levels had a shorter pregnancy duration when compared to other patients (p=0.05 for preterm labor and p=0.04 for preterm rupture of the membranes). Interleukin-1beta,2,4, and tumor necrosis factor alpha were not correlated with clinical outcome. CONCLUSIONS: Increased serum interleukin-6 and -8 levels are associated with a shorter interval between onset of preterm rupture of the membranes and delivery and should therefore be further evaluated for their use in clinical practice.     

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.     

Occupational fatigue and preterm premature rupture of membranes. National Institute of Child Health and Human Development Maternal-Fetal Medicine, Units Network

OBJECTIVE: The aim of this study was to prospectively determine the relationship between occupational fatigue and spontaneous preterm delivery segregated into the etiologically distinct categories of spontaneous preterm labor, preterm premature rupture of membranes, and indicated preterm delivery. STUDY DESIGN: A total of 2929 women with singleton pregnancies at 22 to 24 weeks' gestation were enrolled in a multicenter (10 sites) Preterm Prediction Study. Patients reported the number of hours worked per week and answered specific questions designed to determine the following 5 sources of occupational fatigue described by Mamelle et al: posture, work with industrial machines, physical exertion, mental stress, and environmental stress. Fatigue was quantified (0-5 index) according to the number of these sources positively reported. Simple and Mantel-Haenszel chi2 tests were used to test the univariate association and hypothesis of a linear trend between sources of occupational fatigue and spontaneous preterm delivery. Covariables were considered by multivariate logistic regression analysis. Women who did not work outside the home were considered separately from those who worked but did not report any sources of occupational fatigue. RESULTS: Each source of occupational fatigue was independently associated with a significantly increased risk of preterm premature rupture of membranes among nulliparous women but not among multiparous women. The risk of preterm premature rupture of membranes increased (P = .002) with an increasing number of sources of occupational fatigue-not working outside the home, 2.1%; working but not reporting fatigue, 3.7%; working with 1 source of fatigue, 3.2%; working with 2 sources of fatigue, 5.2%; working with 3 sources of fatigue, 5.1%; and working with 4 or 5 sources of fatigue, 7.4%. There was also a significant relationship (P = .01) between preterm premature rupture of membranes and an increasing number of hours worked per week among nulliparous women. Neither spontaneous preterm labor nor indicated preterm delivery was significantly associated with occupational fatigue among either nulliparous or multiparous women. CONCLUSION: The occupational fatigue index of Mamelle et al discriminated a group of nulliparous women at increased risk for preterm premature rupture of membranes. The relationship between preterm premature rupture of membranes and occupational fatigue or hours worked may provide guidelines according to which nulliparous women and their employers can be advised.     

Evaluation of amniotic fluid cytokines in preterm labor and intact membranes.

OBJECTIVE: To compare the amniotic fluid (AF) concentration of pro-inflammatory cytokines between women with preterm labor and intact membranes that delivered within 7 days, with those that delivered after 7 days of the amniocentesis according to the result of the AF culture. METHODS: Fifty-two women with preterm labor and intact membranes between 21 and 35 weeks of gestation were included in the study. Transabdominal amniocentesis was performed to rule out intra-amniotic infection, and AF concentrations of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF) were determined with sensitive and specific enzyme-linked immunosorbent assays. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Ureaplasma urealyticum, and Mycoplasma hominis. Exclusion criteria included preterm premature rupture of membranes, vaginal bleeding, multiple gestations, uterine anomalies, fetal congenital anomalies, ominous fetal heart rate tracings and fetal deaths. Proportions were compared using chi2 or Fisher's exact test. Receiver operator characteristic (ROC) curve analysis was performed for each cytokine for the prediction of delivery within 7 days. RESULTS: Sixty-two percent (32/52) of women delivered within 7 days and 38% (20/52) delivered after 7 days of amniocentesis. All women that delivered after 7 days of the procedure had negative AF cultures. In contrast, 28% (9/32) of women that delivered within 7 days had positive AF cultures and 72% (23/32) had negative AF cultures. Women that delivered within 7 days regardless of AF cultures had a lower birth weight and a shorter amniocentesis-to-delivery interval than those that delivered after 7 days of amniocentesis. Among women that delivered within 7 days, those with positive AF cultures had a lower gestational age at delivery and a higher frequency of histologic chorioamnionitis than those with negative AF cultures. The AF concentrations of all cytokines were significantly higher in women that delivered within 7 days with positive AF cultures than in those with negative AF cultures. Similarly, the AF concentrations of IL-1alpha, IL-6, and IL-8 were significantly higher in women that delivered within 7 days than those that delivered after 7 days of the amniocentesis, regardless of the AF culture results. Diagnostic indexes were calculated for all cytokines using critical values derived from ROC curve analysis for the prediction of delivery within 7 days. CONCLUSIONS: Women with preterm labor and intact membranes that delivered within 7 days had higher AF concentrations of pro-inflammatory cytokines than those who delivered after 7 days of the amniocentesis regardless of the AF culture results.     

Uterine activity after preterm premature rupture of the membranes

Preterm premature rupture of the membranes complicates few pregnancies but is a major contributor to overall perinatal morbidity and mortality. Although a reduced incidence of preterm premature rupture of fetal membranes has been reported in women who had antepartum uterine activity monitoring, there are few data regarding uterine activity after preterm premature rupture of fetal membranes. Therefore daily uterine activity monitoring was performed in 101 consecutive women with preterm premature rupture of fetal membranes between 26 and 34 weeks' gestation. The mean gestational ages at rupture and delivery were 31.4 +/- 2.3 and 33.7 +/- 4.5 weeks, respectively. A significant increase in contraction frequency was identified within 24 hours of onset of preterm labor (p less than 0.005). A contraction frequency of four or more per hour predicted the onset of labor within 24 hours with a sensitivity of 72%, a specificity of 90%, a positive predictive value of 54%, and a negative predictive value of 95%. These results indicate that most women with preterm premature rupture of fetal membranes exhibit a baseline contraction frequency that is similar to that of women with intact membranes and premature labor. An abrupt increase in contraction frequency is a warning of impending labor.     

Further observations on the fetal inflammatory response syndrome: a potential homeostatic role for the soluble receptors of tumor necrosis factor alpha

OBJECTIVE: The fetal inflammatory response syndrome is a subclinical condition frequently present in preterm labor and preterm premature rupture of the membranes and is associated with increased perinatal morbidity and mortality. Tumor necrosis factor alpha is a mediator of septic shock and death, and it exerts its biologic effects by interacting with 2 receptors, TNF-R1 and TNF-R2. Soluble tumor necrosis factor receptors can buffer the biologic activity and protect against the deleterious effects of tumor necrosis factor alpha. The purpose of this study was to determine the behavior of soluble tumor necrosis factor receptors in fetuses with and without fetal inflammatory response syndrome. STUDY DESIGN: Fetal blood sampling was performed in patients with preterm labor (n = 95) and preterm premature rupture of the membranes (n = 39). Control samples were obtained from fetuses who were undergoing blood sampling for clinical indications and had normal outcomes (n = 21). Fetal inflammatory response syndrome was defined as a fetal plasma interleukin 6 concentration >11 pg/mL. Concentrations of interleukin 6 and TNF-R1 and TNF-R2 were determined by use of sensitive and specific immunoassays. Analysis of covariance was used for statistical analysis. RESULTS: (1) TNF-R1 and TNF-R2 were detectable in all samples, and their concentrations decreased with advancing gestational age (r = -0.8 and r = -0.7; P<.0001 and P<.001, respectively). (2) The mean fetal plasma concentrations of TNF-R1 and TNF-R2 were significantly higher in fetuses with fetal inflammatory response syndrome than in those without the syndrome after adjustment for gestational age and fetal membrane status (TNF-R1: no fetal inflammatory response syndrome, mean +/- SE, 3473.7+/-128.8 pg/mL; vs fetal inflammatory response syndrome, mean +/- SE, 4079.9+/-190.7 pg/mL; P<.005; TNF-R2: no fetal inflammatory response syndrome, mean +/- SE, 6033.2+/-235.4 pg/mL; vs. fetal inflammatory response syndrome, mean +/- SE, 7783.1+/-342.8 pg/mL; P<.0001). (3) Fetuses of patients who delivered within 72 hours of cordocentesis had significantly higher concentrations of TNF-R1 and TNF-R2 receptors than those with longer latency periods (P<.05 for each). CONCLUSION: The fetal inflammatory response syndrome is associated with increased availability of the soluble receptors of tumor necrosis factor alpha in fetal plasma. These factors may attenuate the deleterious effects of tumor necrosis factor alpha.     

Elevation of total nitrite and nitrate concentration in vaginal secretions as a predictor of premature delivery

We measured the total concentration of nitrite and nitrate, metabolites of nitric oxide, in vaginal secretions from pregnant women at 22 to 32 weeks' gestation. Total nitrite and nitrate concentrations in patients with preterm premature rupture of membranes and in those with preterm labor and subsequent premature delivery were significantly higher than concentrations in patients who were delivered at term. Elevated total nitrite and nitrate concentration may predict premature delivery.     

Relationships of vaginal Lactobacillus species, cervical Chlamydia trachomatis, and bacterial vaginosis to preterm birth

The frequency of genital infection was compared among women in premature labor who delivered preterm (before 37 weeks), women in preterm labor who delivered at term, and control women who delivered at term. Both groups of women in premature labor were younger and had more previous preterm births than did control women. Women in premature labor who delivered preterm were more likely to experience rupture of membranes, intrapartum fever, and postpartum fever than were control women. The presence of bacterial vaginosis (odds ratio 2.3) and Chlamydia trachomatis (odds ratio 3.9) was positively associated, and Lactobacillus sp (odds ratio 0.2) was negatively associated, with birth before 37 weeks, using multivariable analysis to control for confounding variables.     

Human beta-defensin-2: a natural antimicrobial peptide present in amniotic fluid participates in the host response to microbial invasion of the amniotic cavity.

OBJECTIVE: Human beta-defensin-2 (HBD-2) is a potent antimicrobial peptide that is part of the innate immune response. The purpose of this study was to determine whether HBD-2 is present in amniotic fluid and if its concentration changes with microbial invasion of the amniotic cavity (MIAC) and labor. STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 318 patients in the following groups: (1) mid-trimester (n=75); (2) term not in labor (n=28) and in labor (n=51); (3) preterm labor and intact membranes without MIAC who delivered at term (n=36), who delivered preterm without MIAC (n=52), and preterm labor with MIAC who delivered preterm (n=25); and (4) preterm premature rupture of membranes (preterm PROM) with (n=25) and without MIAC (n=26). MIAC was defined as a positive amniotic fluid culture for microorganisms. Amniotic fluid HBD-2 concentrations were determined using a sensitive and specific ELISA. Non-parametric statistics were used for analysis. RESULTS: (1) HBD-2 was detected in all amniotic fluid samples; (2) the concentration of HBD-2 did not change with gestational age from mid-trimester to term (p=0.8); (3) intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of HBD-2 in both women with preterm labor and intact membranes, and women with preterm PROM (p<0.05 for each comparison); (4) patients with preterm labor and a negative amniotic fluid culture who delivered preterm had a higher median amniotic fluid HBD-2 concentration than those with preterm labor who delivered at term (p=0.001); and (5) among patients with preterm labor without MIAC, those who had intra-amniotic inflammation (amniotic fluid white blood cell count>100 cells per mL) had a higher median amniotic fluid concentration of HBD-2 than those without this condition (p<0.002). CONCLUSION: (1) Amniotic fluid contains HBD-2, a natural antimicrobial peptide, and this may account for some of the antimicrobial activity of amniotic fluid; (2) amniotic fluid HBD-2 concentrations are increased in women with MIAC, regardless of the membrane status (intact membranes or PROM); and (3) we propose that amniotic fluid HBD-2 is part of the innate immune system within the amniotic cavity.     

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.