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PubMed1998

Dual roles of amniotic fluid nitric oxide and prostaglandin E2 in preterm labor with intra-amniotic infection.

We hypothesized that induction of nitric oxide synthase and cyclo-oxygenase-2 by bacterial products in intra-amniotic infection could increase the production of proinflammatory nitric oxide and prostaglandin E2 (PGE2) and cause preterm labor. Thus, we sought to determine amniotic fluid levels of nitric oxide metabolites (NOx) and PGE2 in preterm labor patients with and without intra-amniotic infection. Amniotic fluid from 13 preterm labor patients with intra-amniotic infection and 24 without intra-amniotic infection were studied. Intra-amniotic infection was defined as the presence of a positive amniotic fluid culture. Amniotic fluid was tested for NOx, PGE2, glucose, leukocyte counts, Gram stains, creatinine, pH, and specific gravity. NOx was determined using Griess reagent after reduction of nitrate to nitrite with aspergillus nitrate reductase. PGE2 was measured by an enzyme-linked immunoassay. Both amniotic fluid NOx and PGE2 were normalized by amniotic fluid creatinine. We found that amniotic fluid concentrations of NOx and PGE2 were significantly higher in preterm labor patients with intra-amniotic infection compared to those without intraamniotic infection (NOx: median 1.8 micromol/mg creatinine, range 0.7 to 6.8 vs. 1.3 micromol/mg creatinine, range 0.9 to 2.1, p=0.03; PGE2: median 33.5 ng/mg creatinine, range 0.0 to 1048.6 vs. 0.0 ng/mg creatinine, range 0.0 to 33.6, p=0.004). In addition, amniotic fluid NOx and PGE2 were positively correlated (r=0.343, p=0.0398). We conclude that there may be an interaction between the nitric oxide and prostaglandin pathways in intraamniotic infection. Increased production of amniotic fluid pro-inflammatory nitric oxide and PGE2 may play an important role in the pathogenesis of preterm labor in patients with intra-amniotic infection.

Adolescent↗

PubMed2005

Efficacy of aggressive tocolysis for preterm labor with advanced cervical dilatation.

OBJECTIVE: Study the effectiveness of tocolysis for preterm labor with advanced cervical dilatation ( > or = 3 cm) to achieve sufficient latency for the effect of steroids to occur, and delivery of more mature neonates. STUDY DESIGN: We studied 249 singleton pregnancies, 23-36 weeks gestation in preterm labor, stratified by weeks of gestation and degree of cervical dilatation (Group A: 117, < 3 cm; Group B: 132, 3 cm) who were given tocolysis and compared for the length of latency and neonatal outcome. RESULTS: Maternal characteristics were similar between groups except African-American women were admitted with more advanced cervical dilatation. Latency 72 hours was achieved in Group A: > 75% at all gestational ages, and Group B: > 50%. Latency > or = 72 hours, according to the degree of cervical dilatation, was for Group A: 90%, for Group B: 50-75% from > 3-5 cm dilatation, and 40% at 5.1-6 cm dilatation. Neonatal morbidity was mild with a decreased risk of long-term disability. CONCLUSIONS: Aggressive tocolytic therapy for preterm labor with advanced cervical dilatation is efficacious, allows for steroid therapy, and allows delivery of more mature neonates.

Adrenal Cortex Hormones↗

PubMed1992

Randomized comparative trial of indomethacin and sulindac for the treatment of refractory preterm labor.

This study was designed to investigate the efficacy and safety of sulindac in the treatment of preterm labor. Thirty-six women in preterm labor who had failed initial attempts at tocolysis with magnesium sulfate were randomized to receive either oral indomethacin or oral sulindac for 48 hours. The mean gestational ages at admission were 29 and 30 weeks for the sulindac and indomethacin groups, respectively. There was a significantly greater hourly fetal urine output, deepest amniotic fluid pocket, and amniotic fluid index in the sulindac group. A trend toward higher fetal ductus arteriosus flow velocities noted in the indomethacin group was not seen in the sulindac group. The drugs had similar success in delaying delivery for 48 hours or 7 days. The mean birth weights were 2000 and 2323 g for the sulindac and indomethacin groups, respectively. Sulindac appears to be as effective as indomethacin for refractory preterm labor but with fewer fetal side effects.

Adult↗

PubMed1989

Coitus, twin pregnancy, and preterm labor.

The effect of coitus on precipitation of preterm labor was studied prospectively in 126 women with twin pregnancies. All of the women attended a special antenatal clinic in a tertiary referral center and were questioned about the frequency of coitus. Of the participants, 40% reported coitus early in the third trimester; the rate decreased to 24% by 36 weeks' gestation. There were no significant differences in the frequency of positive responses between those who went into labor before term when contrasted with those who were delivered of infants at term. The data indicate that coitus is not an important precipitant of preterm labor in this high-risk group and that coitus need not be discouraged in women with twin pregnancies.

Adult↗

PubMed1986

Prostaglandin F metabolite concentration as a prognostic factor in preterm labor.

Concentration of the 13,14-dihydro,15 keto-metabolite of prostaglandin F2 alpha (PGFM) was measured in women being observed for preterm labor. The mean initial PGFM level was significantly higher in patients who delivered preterm (65.9 +/- 9.7 pg/mL; N = 14) than in patients not in preterm labor (32.1 +/- 4.3 pg/mL; N = 11; P less than .01). Plasma PGFM concentrations decreased significantly during ritodrine therapy only in successfully treated patients (P less than .05). All patients with initial PGFM concentrations greater than or equal to 55 pg/mL delivered preterm. Two of four patients not considered to be in preterm labor but who delivered prematurely (within five days of initial evaluation) had initial PGFM concentrations of greater than 55 pg/mL. Concentration determinations of PGFM might be a useful adjunct in identifying early preterm labor and in predicting success of tocolytic therapy.

Dinoprost↗

PubMed2000

Morphology assessed by transvaginal ultrasonography differs in patients in preterm labor with vs. without bacterial vaginosis.

OBJECTIVE: To determine whether cervical morphology in preterm labor patients differs in the presence or absence of bacterial vaginosis. DESIGN: Observational study. SUBJECTS: One hundred and twelve consecutive patients with objectively confirmed preterm labor admitted to a tertiary care centre were included in the study. Patients with placenta previa, active uterine bleeding or indication for an immediate delivery (e.g. severe pre-eclampsia or suspected fetal asphyxia), or severe fetal anomalies were excluded. METHODS: Transvaginal ultrasonography was used to measure cervical length and internal os width. Bacterial vaginosis was diagnosed by Gram stain of a vaginal smear. RESULTS: A total of 36 patients (32%) had bacterial vaginosis. Cervical length in this group was shorter than in patients with normal flora (mean 20.4 +/- 7.2 mm vs. 26.4 +/- 6.7 mm; P = 0.0002), and more patients with bacterial vaginosis had a dilated internal cervical os > or = 5 mm (67% vs. 30%, P = 0.001). There were no significant differences, however, in preterm delivery rate and birth weight between the two groups; the overall preterm delivery rate was 40%. A cervical length < 25 mm was predictive of preterm delivery (P = 0.001, RR 4.2, 95% CI 1.8-9.7). CONCLUSIONS: These data suggest that cervical change in preterm labor is more pronounced in patients with bacterial vaginosis but without a concomitant increase in the risk for preterm delivery. Despite this association, the cervical length measured by transvaginal ultrasonography alone is a useful predictor of preterm delivery, independent of the presence or absence of bacterial vaginosis.

Adult↗

PubMed2005

Hospitalization for women with arrested preterm labor: a randomized trial.

OBJECTIVE: To determine whether hospitalization of women with arrested preterm labor has an effect on delivery at 36 weeks or greater when compared with women discharged home. METHODS: All women with a singleton gestation and a diagnosis of arrested preterm labor with intact membranes between 24 and 33 weeks, 4 days of gestation were randomly assigned to home or hospital management. Upon completion of a dexamethasone course, women assigned to outpatient management were promptly discharged, and women in the inpatient group were advised to continue hospitalization until 34 weeks. Decreased activity was encouraged in both groups. Bed rest was not strictly enforced. The primary outcome was delivery at 36 weeks or greater. RESULTS: A total of 101 women of a planned 188 were enrolled at the time of an interim analysis. There was no difference in the primary study outcome between the 2 groups and the trial was terminated. Among the hospitalized women, 71% reached 36 weeks or greater, compared with 72% of those discharged home (P = .89). The mean cervical dilatation in hospitalized women was 2.7 +/- 0.5 cm, compared with 2.6 +/- 0.5 cm in women discharged home (P = .16). The overall length of hospital stay for the women allocated to hospitalization was 16 +/- 13 days. CONCLUSION: Compared with hospitalization, outpatient management of women with arrested preterm labor and intact membranes had no effect on the rate of preterm birth. LEVEL OF EVIDENCE: I.

Adolescent↗

PubMedDate not supplied

The treatment of preterm labor using a portable subcutaneous terbutaline pump.

The perinatal mortality rate related to preterm delivery has led researchers to investigate new methods of tocolysis. A new concept in managing preterm labor uses continuous administration of terbutaline sulfate via a portable subcutaneous infusion pump. Use of the terbutaline pump to treat 13 preterm labor patients at the Baylor College of Medicine demonstrated an efficacy rate of 9 for a population failing all other methods of tocolysis. This unique treatment modality offers new hope for patients experiencing recalcitrant preterm labor.

Female↗

PubMed1989

Randomized comparison of oral terbutaline and ritodrine for preventing recurrent preterm labor.

We compared oral ritodrine and terbutaline for the prevention of recurrent preterm labor. Women between 20 and 35 weeks' gestation who successfully completed a course of intravenous tocolysis were eligible for inclusion. One hundred two patients were randomized to oral ritodrine (20 mg every four hours) or oral terbutaline (5 mg every four hours). The groups showed no significant differences with respect to recognized risk factors for preterm labor or prognostic factors for the failure of tocolysis. Initial treatment failures occurred more frequently in the ritodrine group (nine vs. two, P = .0527). There were no statistically significant differences in the treatment results or frequency of side effects. We conclude that ritodrine appears to be less effective than terbutaline upon the initiation of oral therapy and that oral ritodrine and terbutaline are equivalent in safety and efficacy when used on a long-term basis for preventing recurrent preterm labor.

Administration, Oral↗

PubMed1999

Tocolytics for preterm labor: a systematic review.

OBJECTIVE: To examine the effectiveness of any tocolytic compared with a placebo or no tocolytic for preterm labor. DATA SOURCES: We checked MEDLINE (1966-1998) and the Cochrane Controlled Trials Register for articles, using the search terms "randomized controlled trial" (RCT), "preterm labor," "tocolysis," "betamimetics," "ritodrine," "terbutaline," "hexaprenaline," "isoxuprine," "prostaglandin synthetase inhibitors," "indomethacin," "sulindac," "calcium channel blockers," "nifedipine," "oxytocin receptor blockers," "atosiban," "nitroglceride," and "magnesium sulfate." METHODS OF STUDY SELECTION: We included all RCTs that compared effect of a tocolytic with a placebo or no tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. TABULATION, INTEGRATION, AND RESULTS: Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. CONCLUSION: Although tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.

Clinical Trials as Topic↗

PubMed1986

Preterm labor in the quadriplegic parturient.

The occurrence of preterm labor is not uncommon in the pregnant quadriplegic. Early diagnosis is hampered by the inability of most quadriplegics to sense uterine contractions in the usual way. A patient we recently treated for preterm labor learned to recognize contractions by the associated symptoms of autonomic hyper-reflexia: flushing, headache, and piloerection. Tocolytic therapy was successful and a favorable neonatal outcome occurred. Increased awareness by the physician and the pregnant quadriplegic patient is encouraged so that symptoms of autonomic hyper-reflexia may be recognized as potentially indicative of uterine contractions.

Adult↗

PubMed1988

Differing fetal growth patterns in pregnancies complicated by preterm labor.

Previous studies have demonstrated diminished ultrasonic fetal growth parameters in women delivering preterm. In this study, we tested the following hypothesis: In pregnancies complicated by spontaneous preterm labor, 1) unsuccessful tocolysis is likely to be associated with diminished fetal growth, and 2) successful tocolysis is likely to occur when fetal growth is normal. Ultrasound examinations were performed in 78 pregnancies complicated by preterm labor before 35 weeks' gestation. Tocolysis was attempted unless contraindicated or unless cervical dilatation was advanced (4 cm or greater). Pregnancies delivering before 36 weeks' gestation were compared with those delivering after this gestational age. Among the 48 pregnancies delivered before 36 weeks' gestation, a significantly greater proportion had ultrasonic growth parameters lower than normal values at corresponding gestational ages. In contrast, those pregnancies that had successful tocolysis and delivered near term demonstrated a normal distribution of ultrasound growth parameters. In pregnancies complicated by preterm labor, ultrasonic documentation of diminished fetal growth may identify the subgroup at increased risk for preterm delivery.

Adult↗

PubMed1989

Dilemmas in the pharmacological management of preterm labor.

It is the thesis of the author that the use of Ritodrine in the treatment of premature labor is potentially dangerous and possibly even lethal. Ritodrine is being overused in the attempt to control and delay premature labor. Only 25 to 50 per cent of patients complaining of premature labor pains actually proceed to true preterm labor. Because there is no definitive screening test to firmly establish the diagnosis of preterm labor, many women are treated unnecessarily with a drug that many obstetricians question as to its efficacy, safety, and cost. If it is used, it must be in a hospital with adequate facilities both in manpower and the ability to identify and treat the medical and obstetrical complications. Ritodrine is too potentially dangerous to be used as an attempt to "do something" it there are questionable indications.

Clinical Protocols↗

PubMed1994

Tocolysis for recurrent preterm labor using a continuous subcutaneous infusion pump.

This study attempted to determine the best method of treatment for patients with recurrent preterm labor: administration of terbutaline via an automated, programmable, subcutaneous infusion pump or oral terbutaline. In this retrospective, controlled study, 32 patients diagnosed with recurrent preterm labor, as determined by persistent uterine contractions with cervical change, were treated with a programmable infusion pump adjusted to control uterine contraction frequency to < or = 4 contractions per hour. Patients in this group were matched for age, race, parity, gestational age and cervical dilation at diagnosis of recurrent preterm labor in subjects taking oral terbutaline. The patients receiving oral terbutaline were given an average of 6.5 mg every four to six hours to maintain uterine quiescence, while those in the pump group were given basal rates of terbutaline and in addition received four to six boluses per day (< 3 mg/d total dose) to achieve this outcome. Patients using the pump were more likely to reach term and less likely to fail tocolytic therapy than were those taking oral terbutaline. The terbutaline pump appeared to be more successful in prolonging pregnancies to term after the diagnosis of recurrent preterm labor than did oral terbutaline.

Administration, Oral↗

PubMed2001

Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes.

OBJECTIVE: The purpose of this study was to determine the frequency and clinical significance of intraamniotic inflammation in patients with preterm labor and intact membranes. STUDY DESIGN: Amniocentesis was performed in 206 patients with preterm labor and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. The diagnosis of intraamniotic inflammation was made in patients with a negative amniotic fluid culture on the basis of amniotic fluid concentrations of interleukin-6 (>2.6 ng/mL, derived from receiver operating characteristic curve analysis). Statistical analysis was conducted with contingency tables and survival techniques. RESULTS: Intra-amniotic inflammation (negative amniotic fluid culture but elevated amniotic fluid interleukin-6) was more common than intra-amniotic infection (positive amniotic fluid culture regardless of amniotic fluid interleukin-6 concentration; 21% [44/206 women] vs 10% [21/206 women]; P <.001). The amniocentesisto-delivery interval was significantly shorter in patients with intra-amniotic inflammation than in patients with a negative culture and without an inflammation (median, 20 hours [range, 0.1-2328 hours] vs median, 701 hours [range, 0.1-3252 hours], respectively; P <.0001). Spontaneous preterm delivery of <37 weeks was more frequent in patients with intra-amniotic inflammation than in those with a negative culture and without inflammation (98% vs 35%; P <.001). Patients with intra-amniotic inflammation had a significantly higher rate of adverse outcome than patients with a negative culture and without intra-amniotic inflammation. Adverse outcomes included clinical and histologic chorioamnionitis, funisitis, early preterm birth, and significant neonatal morbidity. There were no significant differences in the rate of adverse outcomes between patients with a negative culture but with intra-amniotic inflammation and patients with intra-amniotic infection (positive culture regardless of amniotic fluid interleukin-6 concentration). CONCLUSION: Intra-amniotic inflammation/infection complicates one third of the patients with preterm labor (32%; 65/206 women), and its presence is a risk factor for adverse outcome. The outcome of patients with microbiologically proven intra-amniotic infection is similar to that of patients with intra-amniotic inflammation and a negative amniotic fluid culture. We propose that the treatment of patients in preterm labor be based on the operational diagnosis of intra-amniotic inflammation rather than the diagnosis of intra-amniotic infection because the latter diagnosis cannot be undertaken rapidly.

Amniocentesis↗

PubMedDate not supplied

Aminophylline treatment of preterm labor.

Prevention of neonatal mortality linked to prematurity may be achieved by treating preterm labor, thus allowing fetal lungs to spontaneously develop, or by administering drugs able to enhance pulmonary maturation. The methylxantine derivative aminophylline has been reported to reduce uterine contractility and increase the concentrations of saturated phosphatidylcholine in fetal lungs. Its effectiveness in treating preterm labor and preventing respiratory distress syndrome (RDS) has been evaluated in comparison to the widely used drug ritodrine. In 39 pregnant women with preterm labor the efficacy of aminophylline and ritodrine in delaying the delivery seemed similar. However, while two of the babies born from ritodrine treated mothers died because of RDS, all babies born from aminophylline-treated mothers survived. These data might then confirm the effectiveness of aminophylline treatment to prevent RDS.

Aminophylline↗

PubMed1993

A murine model of preterm labor: inflammatory mediators regulate the production of prostaglandin E2 and interleukin-6 by murine decidua.

Inflammatory processes may be important in the initiation and propagation of uterine contractions and preterm labor in human pregnancies. Recently, a murine model of preterm labor has been described. The purpose of our study was to determine whether murine decidua responds to inflammatory mediators, such as lipopolysaccharide (LPS) and the inflammatory cytokines interleukin (IL)-1 beta and tumor necrosis factor (TNF). Allogeneic pregnant mice (C3H/Hen females mated with C57/B6 males) were killed at 12-14 days of pregnancy, decidual tissue was isolated, and explants were placed on the polycarbonate membrane of Costar Transwell inserts. Initial validation studies of this explant system, including biochemical and histologic evaluations, indicated that the decidual tissue remained intact, viable, and responsive to IL-1 beta for at least 5 days in explant culture. Treatment of murine decidual explants with LPS, IL-1 beta, and TNF resulted in significant increases in the production of prostaglandin E2 (PGE2) and IL-6. Thus the regulation of PGE2 and IL-6 production from murine decidua by LPS and inflammatory cytokines is similar to findings previously reported for human decidua. Our findings are consistent with the view that the pathophysiology of infection-induced preterm labor in the mouse may be similar to that in human pregnancy and supports the continued development of murine models of preterm labor.

Animals↗

PubMed1989

Amniotic fluid concentrations of prostaglandin F2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and 11-deoxy-13,14-dihydro-15-keto-11, 16-cyclo-prostaglandin E2 (PGEM-LL) in preterm labor.

Although prostaglandins (PGs) are considered the key mediators of human parturition at term, there is a paucity of data regarding their participation in the mechanisms responsible for preterm labor. The purpose of this study was to establish if preterm labor is associated with changes in the amniotic fluid concentrations of prostaglandins. PGF2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-prostaglandin E2 (PGEM-ll) were measured by using specific and sensitive radioimmunoassays. Amniotic fluid was retrieved by transabdominal amniocentesis from 55 women with preterm labor and intact membranes. Patients were divided into three groups according to the response to tocolysis and the presence or absence of an intra-amniotic infection. Amniotic fluid concentrations of PGFM and PGEM-ll were significantly greater in women with preterm labor and intra-amniotic infection than in women without infection. In addition, patients unresponsive to tocolysis without intra-amniotic infection also had a significantly greater concentration of PGFM and PGEM-ll in amniotic fluid than those responsive to tocolysis. Amniotic fluid concentrations of PGF2 alpha were greater in women with intra-amniotic infection than in women without intra-amniotic infection. In the absence of intra-amniotic infection, no difference in amniotic fluid PGF2 alpha concentrations could be found between women who responded to tocolytic treatment and those who did not.

Amnion↗