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PubMed1998

Stimulated polymorphonuclear leukocytes in vaginal secretions from patients with preterm labor.

The purpose of this study was to examine evidence for the presence of activated vaginal leukocytes in women with preterm labor. Vaginal polymorphonuclear leukocytes from 7 patients in preterm labor (24-32 weeks of gestation) as well as from 7 control women with uncomplicated pregnancy were analyzed morphologically using transmission electron microscopy. Peroxidase and NADPH oxidase cytochemistry was also performed. Viable leukocytes were abundant in patients in preterm labor. Phagosomes, phagocytosis of bacteria, attachment of primary granules to the phagosomal membrane, and cell surface projections were observed in the vaginal leukocytes but not in the peripheral blood leukocytes. Peroxidase activity was visible on the cell surface, the phagosomal membrane, and the primary granules. NADPH oxidase activity was demonstrated on the cell surface of leukocytes. Morphological and cytochemical features indicated that vaginal polymorphonuclear leukocytes were stimulated in situ. Such stimulated leukocytes may play a role in the pathogenesis or pathophysiology of preterm labor.

Cell Survival↗
PubMed1986

The preterm cervix and preterm labor: relative risks, predictive values, and change over time.

The accurate prediction and diagnosis of preterm labor continue to frustrate the clinician. This is partly due to a scarcity of cervical data from the early third trimester. A total of 760 prospective, serial, paired, and blinded pelvic examinations were done at 28 to 34 weeks of gestation for 191 patients without a history of preterm labor. If the cervix was dilated greater than or equal to 1 cm (internal os) or effaced greater than 30%, the relative risk of preterm labor was increased to 1.8 to 4.2. Negative predictive values for cervical status were greater than 92%, but positive predictive values were less than or equal to 18%. Change over time was unusual (dilatation increase greater than or equal to 1 cm or effacement increase greater than or equal to 40%), suggesting that a baseline late second-trimester examination could assist in the early but accurate diagnosis of preterm labor should it be suspected later in gestation. These data suggest that even in the low-risk patient, an early cervical examination could be beneficial.

Cervix Uteri↗
PubMed2003

Prediction and early detection of preterm labor.

Studies of cervical sonography, fetal fibronectin, and uterine contraction monitoring during pregnancy have improved our understanding of how preterm labor occurs, but their use in practice remains uncertain. This article reviews the use of these tests to improve the accuracy of diagnosis of preterm labor and to estimate the likelihood of preterm birth in women with historical risk factors. Because the clinical criteria for a diagnosis of preterm labor are inaccurate until labor is well established, over-diagnosis is common. A cervical length measurement of more than 30 mm or a negative fibronectin obtained from a patient with possible preterm labor can avoid over-diagnosis and unnecessary treatment. There is no role for routine use of either cervical sonography or fibronectin to screen pregnant women for preterm birth risk, but women thought to be at increased risk may be reassured by negative test results. Uterine contraction monitoring has low sensitivity for detecting women at risk of preterm birth. Current use of cervical length and fetal fibronectin in pregnancy is limited to situations where a negative result can avoid unnecessary interventions.

Embryonic and Fetal Development↗
PubMed1989

The incidence of positive amniotic fluid cultures in patients preterm labor with intact membranes.

The possible relationship between intrauterine infection and preterm labor has received considerable attention in recent years. The purpose of this study was twofold: first, to determine the frequency of asymptomatic infection in patients who came to the hospital in preterm labor, and second, to determine the significance of a positive amniotic fluid culture in relation to latency period and likelihood of preterm delivery. Patients who came to the hospital in preterm labor with intact membranes between 20 and 35 weeks' gestation underwent transabdominal amniocentesis. Amniotic fluid was sent for Gram stain and culture. Patients received tocolytic therapy as clinically indicated. Of 127 patients cultured, seven (5.5%) had positive amniotic fluid cultures. These patients had a significantly decreased latency period from amniocentesis to delivery (4.4 days versus 28.6 days), and a significantly increased chance of being delivered of preterm infants (100% versus 52.5%), as compared with patients with negative cultures. The rate of positive Gram stain was 7 of 125 positive. However, there was no correlation between positive Gram stain and positive culture results. Similarly, positive Gram stain results were not associated with any difference in the latency period or rate of preterm delivery.

Amniocentesis↗
PubMed1992

The prevalence and clinical significance of intraamniotic infection with Candida species in women with preterm labor.

Intraamniotic infection is considered a major etiologic factor of preterm birth. Positive amniotic fluid cultures are rarely contaminated with Candida species. The presence of this microorganism is associated with a poor pregnancy outcome. Out of 773 transabdominal amniocenteses performed in women presenting with preterm labor and intact membranes, 77 patients (9.9%) had positive amniotic fluid cultures and in 5 women (6.5%) Candida species were identified. On the other hand, 625 amniocenteses were performed in women with preterm premature rupture of membranes and 178 (28%) had positive cultures. Only in 4 patients was Candida isolated (2.2%) (P = 0.13 Fisher's exact test). The importance of early and accurate diagnosis of intraamniotic infection with Candida is pointed out. A transabdominal amniocentesis for microbiological examination is suggested for every woman presenting with preterm labor or preterm premature rupture of membranes and especially for those who conceived with a retained IUD or cervical cerclage.

Amniotic Fluid↗
PubMed1993

Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.

OBJECTIVE: Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes. STUDY DESIGN: A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos. RESULTS: Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization. CONCLUSION: The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.

Administration, Oral↗
PubMed1989

Oxytocin receptor blockade: a new principle in the treatment of preterm labor?

The concentration of myometrial and decidual oxytocin receptors increases dramatically in normal women in late pregnancy, causing enhanced uterine sensitivity to physiologic levels of oxytocin. Similar increase in myometrial oxytocin receptors has been found in women in preterm labor, indicating a role for oxytocin also in idiopathic preterm labor. A newly synthesized oxytocin analogue, 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin, has been found to be a competitive inhibitor of oxytocin. The present study was conducted to test its efficacy in suppressing uterine contractions during preterm labor in women. Twelve patients with established, uncomplicated preterm labor between 27 and 33 weeks of gestational age were given intravenous infusions of the analogue for 1.5 to 13 hours during continuous external cardiotocographic monitoring. In nine patients inhibition of uterine contractions was achieved and further progression in cervical scores was arrested. In three patients, all at 27 weeks of gestational age, no significant tocolytic effect was observed during a 1.5-hour infusion of the analogue and the patients were then given ritodrine intravenously. No side effects were observed in any of the patients. These preliminary findings support the concept that an increased concentration of uterine oxytocin receptors is an important etiologic factor in uncomplicated preterm labor and therefore oxytocin receptor blockade may be a therapeutic alternative for this condition.

Adult↗
PubMed1984

Comparison of magnesium sulfate, terbutaline and a placebo for inhibition of preterm labor. A randomized study.

Magnesium sulfate has been recommended as a safe and effective agent for inhibiting preterm labor. Its reported adequacy as a tocolytic agent, however, has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated a prospective, randomized study comparing the capabilities of magnesium sulfate, terbutaline and a placebo (5% dextrose in lactated Ringer's solution) for labor inhibition. The study population consisted of 54 patients between 26 and 34 weeks of gestation and in preterm labor. The diagnosis of labor was made if, following hydration, persistent uterine contractions occurred at a frequency of at least three in a ten-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group there were no significant differences between the three treatment groups with regard to capability of delaying delivery at least 48 hours. Also, there were no significant differences between the groups with regard to gestational age at delivery, birth weight and neonatal survival. The fact that delivery occurred in less than 48 hours of approximately one-half the patients under the best of circumstances emphasizes the need for more effective techniques for the inhibition of preterm labor and the need for a better understanding of the mechanisms involved in the initiation of preterm labor.

Adult↗
PubMed2006

Sonographic measurement of cervical length and fetal fibronectin testing in threatened preterm labor.

OBJECTIVE: In women presenting with threatened preterm labor, both fetal fibronectin and sonographic measurement of cervical length have been shown to distinguish between true and false labor. The aim of this study was to determine whether the combination of both tests provides a better prediction than the individual tests alone. METHODS: We examined 195 women with singleton pregnancies presenting at 24-36 (median 31) weeks of gestation with regular and painful uterine contractions, intact membranes and cervical dilatation of less than 3 cm. On admission to the hospital fetal fibronectin positivity in cervicovaginal secretions was determined and transvaginal sonographic measurement of cervical length was carried out. The results were not made available to the attending obstetrician. The primary outcome measure was delivery within 7 days of presentation. RESULTS: Delivery within 7 days occurred in 51.4% (18 of 35) of those with cervical length below 15 mm and 0.6% (1 of 160) of those with cervical length of 15 mm or more, in 21.2% (18 of 85) of the fibronectin positive group and in 0.9% (1 of 110) of the fibronectin negative group. There was a significant association between cervical length and the incidence of fibronectin positivity (r = -0.921, P = 0.003). Logistic regression analysis demonstrated that the only significant contributor to the prediction of delivery within 7 days was cervical length, with no significant contribution from fibronectin positivity, ethnic origin, maternal age, gestational age, body mass index, parity, previous history of preterm delivery, cigarette smoking, or use of tocolytics. CONCLUSIONS: In women with threatened preterm labor assessment of fetal fibronectin in cervicovaginal secretions does not improve the prediction of delivery within 7 days provided by the sonographic measurement of cervical length.

Adult↗
PubMed2004

Role of ERK1/2 in uterine contractility and preterm labor in rats.

The present study tested the hypothesis that ERK activation is an essential step in the onset of labor in a rat model of preterm labor. The administration of RU-486, an antiprogesterone agent, to rats induced preterm delivery 22.2 +/- 0.24 h after treatment. Changes in basal signaling events were studied in myometrial tissue from CO(2)-euthanized rats. Rats treated with RU-486 displayed a dramatically increased in vitro uterine contractility compared with gestational stage-matched, sham-treated rats. In vitro contractility was not significantly different from that during spontaneous labor. During RU-486-induced preterm labor, as previously described for spontaneous labor, ERK phosphorylation levels increased, as did phosphorylation of caldesmon at Ser(789), an ERK phosphorylation site. Also, a small but significant increase in 20-kDa myosin light chain phosphorylation was seen at a constant intracellular pCa of 7. When rats were chronically treated with an agent that prevents ERK activation, U-0126, the onset of RU-486-induced preterm labor was delayed in a statistically significant manner. Chronic in vivo treatment with U-0126 also significantly inhibited the RU-486-induced increase in in vitro contractility and ERK and caldesmon phosphorylation but did not alter the RU-486-induced increase in 20-kDa myosin light chain phosphorylation. These data indicate that ERK activation is a component of the multiple events leading to the development of labor in this rat model. We suggest that the ERK pathway could possibly be used to identify targets for the development of a novel class of tocolytic agents.

Animals↗
PubMed2005

Decreased serum level of macrophage inflammatory chemokine-3beta/CCL19 in preterm labor and delivery.

OBJECTIVE: Chemokines are small soluble molecules which mediate leukocyte migration and may be involved in the pathophysiology of preterm labor. We aimed to determine if serum concentrations of selected chemokines are changed in preterm labor and delivery. STUDY DESIGN: A novel array-based enzyme-linked immunosorbent assay was used to quantitate serum levels of nine chemokines from a single sample: MDC/CCL22, TARC/CCL17, ITAC/CXCL11, I-309/CCL1, IP-10/CXCL10, MIP-1alpha/CCL3, -1beta/CCL4, -3alpha/CCL20 and -3beta/CCL19. Women in preterm labor who delivered (n = 17), women at preterm pregnancy not in labor (n = 13) and women in labor at term (n = 8) participated. RESULTS: In the preterm delivery group of patients, the MIP-3beta/CCL19 concentration was in mean (+/-S.D.) 70.4+/-31.7 pg/mL, which was significantly lower than that in preterm gravidas not in labor of 123+/-34 pg/mL (p < 0.001) and those in labor at term of 118+/-25.6 pg/mL (p < 0.01). The other measured chemokines did not differ significantly. CONCLUSIONS: Of a small number of examined chemokines, we were able to show that one of them, MIP-3beta/CCL19 was significantly lower in women with preterm labor and delivery. Whether or not this chemokine has a potential as biochemical marker of preterm delivery remains to be determined.

Adult↗
PubMed2006

[Diagnosis and management of infection and its role in preterm labor].

OBJECTIVE: Analysis of contemporary knowledge of infection and its role in etiology and pathogenesis of preterm labor. DESIGN: Review article. SETTING: Department of Gynecology and Obstetrics, 1st Faculty of Medicine, Charles University, Prague. METHODS: An overview of published data. CONCLUSION: Infection is considered the most significant cause of preterm labor. The current research tend towards searching for local cervicovaginal markers of infection. An important role in the prenatal care is played by cervical ultrasonography which together with cervicovaginal markers can sort out the group of women with high risk of the preterm labor. Cervicovaginal markers can reveal microbial invasion into higher parts of the birth canals during the intrapartal care and justify the administration of antibiotics especially to women with the premature rupture of membranes. The routine administration of antibiotics was reevaluated in the management of preterm labor. The question of optimal antibiotics remains open.

Bacterial Infections↗
PubMed1991

Randomized comparative trial of indomethacin and ritodrine for the long-term treatment of preterm labor.

A randomized prospective trial was performed to compare the efficacy and safety of ritodrine and indomethacin in the long-term treatment of preterm labor. Forty patients with intact membranes in preterm labor at 23 to 34 weeks' gestation were randomized to receive either intravenous ritodrine or oral indomethacin as the first-line tocolytic agent. Successful intravenous ritodrine therapy was followed by oral terbutaline therapy, and indomethacin-treated patients continued to receive oral indomethacin. Treatment failures were defined as progressive preterm labor or patient intolerance, and these patients were treated with intravenous magnesium sulfate. Ritodrine and indomethacin were equally successful in delaying preterm birth as defined by interval to delivery, gestational age at delivery, delivery delayed greater than 7 days, attainment of 35 weeks of gestation, percentage of patients who required magnesium sulfate therapy, percentage of patients who were readmitted with premature rupture of membranes, absence of recurrent preterm labor, and infant birth weight. More than 80% of mothers who received ritodrine voiced complaints of beta-sympathomimetic side effects, and one patient discontinued treatment as the result of intolerance. There were minimal patient complaints with indomethacin use. No statistically significant differences were noted in neonatal outcome as defined by Apgar scores, umbilical cord pH, intensive care days, ventilator days, or neonatal deaths. However, three cases of primary pulmonary hypertension were observed in the indomethacin group. We had not previously observed this problem with short-term (24 to 48 hours) indomethacin therapy.

Amniotic Fluid↗
PubMed1998

Role of serum ceruloplasmin and its ferroxidase activity on preterm labor.

The role of serum ceruloplasmin and its ferroxidase activity on preterm labor with or without rupture of the membranes was studied. Thirty-seven primigravid women between 31 and 35 weeks of gestation were investigated. Our material is divided into 3 groups. Group A consisted of 12 patients with premature rupture of the membranes; group B consisted of 10 patients with preterm labor but intact membranes, and group C consisted of 15 non-laboring patients. Patients with rupture of the membranes presented with statistically significantly higher serum ceruloplasmin levels compared to those with preterm labor but intact membranes (p < 0.05) as well as to non-laboring patients (p < 0.01). On the contrary, the mean ferroxidase activity level or ceruloplasmin was 518.2+/-183.42, 460.9+/-198.8 and 517.5+/-142.01 micromol/l/min in groups A, B and C, respectively. These values were not significantly different. Our results show a loss of ferroxidase activity of ceruloplasmin in patients with rupture of the membranes and probably suggest a defect in the maternal defense mechanisms.

Adult↗
PubMed2003

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women in preterm labor.

BACKGROUND: Previous studies indicate an association between intra-amniotic microbial invasion and/or inflammation and spontaneous preterm birth, but there is a limited amount of data available from Europe. The aim of this study was to investigate the occurrence of intra-amniotic microorganisms and cytokines (interleukin-6 and interleukin-8) in a Swedish population of women in preterm labor and their correlation with preterm birth. METHODS: Amniotic fluid was retrieved transabdominally from 61 patients in preterm labor before 34 weeks of gestation. Polymerase chain reaction analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. Interleukin-6 and interleukin-8 were analyzed with enzyme-linked immunosorbent assay. RESULTS: Microorganisms in amniotic fluid were detected in 10 patients (16%). Patients with detected bacteria in the amniotic fluid had significantly higher levels of interleukin-6 and interleukin-8. There was also an association between interleukin-6/-8, the amniocentesis-delivery interval ( or= 1.5 ng/mL or interleukin-8 >or= 1.3 ng/mL was associated with an increased risk of delivery within 7 days (interleukin-6: relative risk 7.3; 95% confidence interval: 2.8-19; sensitivity 83%, specificity 87%; interleukin-8: relative risk 14, 95% confidence interval: 3.6-55, sensitivity 91%, specificity 87%). CONCLUSIONS: The occurrence of intra-amniotic microbial invasion and inflammation in this population of Swedish women in preterm labor was similar to data reported from populations with a higher incidence of preterm delivery. Amniotic interleukin-6 and interleukin-8 correlated with the presence of microorganisms and with preterm birth.

Adult↗
PubMed1992

[Evaluation of usefulness of enzymatically determining estriol in urine and placental lactogen in serum of pregnant women with threatened preterm labor].

In 40 pregnant women in the pregnancy period from 16 to 28 weeks with threatened preterm labor diagnosed after clinical investigations and recording of cardiotocogram the values of oestriol in 24-hour urine and placental lactogen in the serum was measured. These values were compared to analogous determinations in a group 40 healthy women with similar duration of pregnancy. Statistically significantly lower values of placental lactogen were found in the serum of pregnant women with threatened preterm labor. The values of oestriol in 24-hour urine were also lower, but the differences were not statistically significant. In conclusion the authors state that enzymatically determined placental lactogen in the serum is a useful method of monitoring of pregnancy with threatened preterm labor. Determination of oestriol was without any greater diagnostic significance in the case of threatened preterm labor.

Adult↗
PubMed1997

15-hydroxyprostaglandin dehydrogenase: implications in preterm labor with and without ascending infection.

There is evidence that intrauterine infection, which stimulates PG synthesis may play a role in the pathogenesis of some preterm labor. Local tissue concentrations of PGs are controlled not only by the rate of synthesis, but also by catabolism, which is regulated by 15-hydroxyprostaglandin dehydrogenase (PGDH). We hypothesized that a decrease of PGDH activity could contribute to an increase in PG output at the time of preterm labor (PTL) especially in association with infection. We measured PGDH activity with a zero order kinetic enzymatic assay, PGDH messenger ribonucleic acid by in situ hybridization and PGDH distribution and localization with immunohistochemistry in human placenta and fetal membranes from women at term before (n = 10) or after (n = 16) labor compared to preterm labor at less than 36 weeks without (n = 16) and with (n = 11) chorioamnionitis. PGDH activity in chorion was significantly lower in PTL than at term and was further reduced when PTL was associated with inflammation. Immunoreactive PGDH and PGDH messenger ribonucleic acid localized predominantly to chorionic trophoblasts at term and were reduced in PTL women with or without infection. These effects were not observed in the placenta. Loss of PGDH with infection was associated with infiltration of chorion by polymorphonuclear leukocytes, resulting in a compromised structural integrity, although the amniotic epithelium was generally intact. We conclude that a reduction in PGDH in the human fetal membranes may occur in some cases of preterm labor and may contribute to an increase in net PG accumulation and drive to myometrial contractility.

Extraembryonic Membranes↗
PubMed1999

Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor.

OBJECTIVE: To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor. METHODS: Thirty-one women with preterm labor before 35 weeks' gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis. RESULTS: Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy. CONCLUSION: Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.

Adult↗