Inhibition of premature labor by terbutaline

Terbutaline was administered to 50 women, all diagnosed as being in labor prior to 36 weeks' gestation. In 47, uterine activity was initially arrested with intravenous therapy. The infusion rate required to arrest uterine activity ranged from 10 to 80 microgram/min and 21 of the 50 patients (42%) required more than one intravenous infusion. The average prolongation of gestation was 3.7 weeks in those successfully treated. Twenty-four delivered within 48 hours after the terbutaline was discontinued. Treatment failures occurred in 11 (22%). Not a single infant died of the respiratory distress syndrome. Side effects were mild and well tolerated.     

A comparison of orally administered misoprostol with vaginally administered misoprostol for cervical ripening and labor induction.

OBJECTIVE: Our purpose was to compare orally administered with vaginally administered misoprostol for cervical ripening and labor induction. MATERIAL AND METHODS: Two hundred twenty subjects with medical or obstetric indications for labor induction and undilated, uneffaced cervices were randomly assigned to receive orally administered or vaginally administered misoprostol. Fifty micrograms of oral misoprostol or 25 microgram of vaginal misoprostol was given every 4 hours. If cervical ripening (Bishop score of >/=8 or cervical dilatation of >/=3) or active labor did not occur, repeated doses were given to a maximum of 6 doses or 24 hours. Thereafter, oxytocin was administered intravenously by a standardized incremental infusion protocol to a maximum of 22 mU/min. RESULTS: Of the 220 subjects evaluated, 110 received orally administered misoprostol and 110 received vaginally administered misoprostol. Fewer subjects who received the oral preparation (34/110, 30.9%) were delivered vaginally within 24 hours of initiation of induction, in comparison with those who received the vaginal preparation (52/110, 47.3%) (P =.01). The average interval from start of induction to vaginal delivery was nearly 6 hours longer in the oral treatment group (mean and SD 1737.9 +/- 845.7 minutes) than in the vaginal treatment group (mean and SD 1393.2 +/- 767.9) (P =.005, log-transformed data). Orally treated patients required significantly more doses than vaginally treated patients (orally administered doses: mean and SD 3.3 +/- 1.7; vaginally administered doses: mean and SD 2.3 +/- 1.2) (P <.0001). Oxytocin administration was necessary in 83 (75.4%) of 110 orally treated subjects and in 65 (59.1%) of 110 vaginally treated subjects (P =.01, relative risk 1. 28, 95% confidence interval 1.06-1.54). Vaginal delivery occurred in 95 (86.4%) orally treated subjects and in 85 (77.3%) vaginally treated subjects (P =.08, relative risk 1.12, 95% confidence interval 0.99-1.27), with the remainder undergoing cesarean delivery. There was no difference in the incidence of uterine contractile abnormalities (tachysystole, hypertonus, or hyperstimulation), intrapartum complications, or neonatal outcomes between the 2 groups. CONCLUSIONS: Oral administration of 50-microgram doses of misoprostol appears less effective than vaginal administration of 25-microgram doses of misoprostol for cervical ripening and labor induction. Further investigation is needed to determine whether orally administered misoprostol should be used for cervical ripening and labor induction.     

Use of vaginally administered chlorhexidine during labor to improve pregnancy outcomes

OBJECTIVE: Our objective was to determine the potential for chlorhexidine used as a vaginal and neonatal wash to reduce adverse outcomes of pregnancy, especially in developing countries. DATA SOURCES: We searched the English literature from January 1950 through October 2005 for all articles related to the use of chlorhexidine. METHODS OF STUDY SELECTION: Every article on chlorhexidine use in pregnancy and in the newborn period was reviewed in detail. The results of every study in which chlorhexidine was used as a vaginal treatment, with or without a neonatal wash, for all pregnancy outcomes except mother-to-child transmission of human immunodeficiency virus, are summarized in this review. TABULATION, INTEGRATION AND RESULTS: Chlorhexidine is a highly effective killer of most bacteria, has an excellent safety profile, rarely is associated with bacterial resistance, is easy to administer, and costs a few cents per application. When used as a vaginal or newborn disinfectant, it clearly reduces bacterial load, including transmission of Group B Streptococcus from the mother to the fetus. Nevertheless, in developed countries, chlorhexidine generally has not been shown to significantly reduce life-threatening maternal or neonatal infections. However, 2 large but not randomized studies, one in Malawi and the other in Egypt, suggest that important reductions in maternal and neonatal sepsis and neonatal mortality may be achievable with vaginal or neonatal chlorhexidine treatment. CONCLUSION: With 4 million neonates and about 700,000 pregnant or recently pregnant women-mostly in developing countries-dying each year, many from infections originating in the vagina, further study of this highly promising treatment is indicated.     

Tocolysis with terbutaline sulfate in patients with placenta previa complicated by premature labor

Six patients with placenta previa complicated by premature labor underwent tocolysis with terbutaline sulfate. The average prolongation of pregnancy was 3.5 weeks. Five patients were at 31 weeks' gestation or more at the initiation of tocolytic therapy and had infants who survived and were greater than 2,000 gm at birth. All patients received an average blood transfusion of 6.7 units of packed cells each.     

Intravenous terbutaline and simultaneous β1-blockade for advanced premature labor

Seventeen patients in advanced premature labor (cervical dilatation ≥3 cm and effacement ≥50%) were randomized in a double-blind protocol to receive metroprolol (a β₁-adrenergic antagonist) or a placebo in conjunction with intravenous and oral terbutaline (a β₂-agonist) in an attempt to inhibit the side effects of terbutaline. Both groups of patients had a dose-related increase in heart rate and systolic blood pressure and a decrease in diastolic blood pressure. Laboratory studies revealed significant hyperglycemia, hypokalemia, hypocalcemia, and acidosis during the intravenous terbutaline infusion, all of which normalized during oral terbutaline therapy. There were no significant differences in the cardiovascular or metabolic responses to terbutaline between the metroprolol and placebo patients. The mean delay in delivery was 5.7 days, with 59% of patients having delivery delayed for 48 hours or more. The mean prolongation time was shorter, but not statistically significant, for those patients receiving metroprolol. Despite the use of high-dose terbutaline, there were no significant complications of therapy. There was little efficacy of infusion dosages above 40 μg/min or repeated courses of intravenous tocolysis. Although recent reports do not recommend tocolysis in these patients, this study suggests that combined β-mimetics and glucocorticoids may be the optimal care for patients in advanced premature labor, in particular, those with infants of very low birth weight.     

A comparison of vaginally administered misoprostol with extra-amniotic saline solution infusion for cervical ripening and labor induction

OBJECTIVE: The purpose of this study was to compare intravaginal misoprostol with extra-amniotic saline solution infusion with concomitant oxytocin for cervical ripening and labor induction in viable pregnancies. STUDY DESIGN: Two hundred women with indications for labor induction and unfavorable cervices were assigned randomly to vaginal misoprostol or extra-amniotic saline solution infusion. Twenty-five micrograms of misoprostol was administered every 4 hours up to six doses, followed by intravenous oxytocin administration. Patients who had received extra-amniotic saline solution infusion also received intravenous oxytocin along with a maximum 12-hour saline solution infusion through Foley catheters that were placed above the internal cervical os. RESULTS: One hundred women were randomly assigned to misoprostol, and 100 women were assigned randomly to extra-amniotic saline solution infusion. The average interval from start of induction to vaginal delivery was longer in the misoprostol group (1323.3 +/- 700.3 minutes) than in the extra-amniotic saline solution infusion group (970.4 +/- 502.7 minutes; P =.006, log transformed data). Abnormal fetal heart rate tracings were found in 30% of the patients who received misoprostol and in 19% of the patients who received extra-amniotic saline solution infusion (relative risk, 1.6; 95% CI, 1.0-2.4; P =.05). There was more tachysystole in the misoprostol group (8%) than in the extra-amniotic saline solution infusion group (1%; P =.02). There were no differences in the routes of deliveries or neonatal outcomes between groups. CONCLUSION: Extra-amniotic saline solution infusion with oxytocin administration appears more effective and is associated with fewer maternal complications than misoprostol for cervical ripening and labor induction.     

Serial serum potassium and glucose levels during treatment of premature labor with oral terbutaline

The effects of prolonged use of orally-administered terbutaline on mothers and their infants were studied. The only side effect observed in all patients was transient maternal tachycardia. Fifty-six percent of the patients experienced palpitations, nervousness and tremors during the first few days of therapy, which thereafter resolved. This is contrary to the serious side effects reported during intravenous infusion of beta-mimetic agents. Maternal serum potassium and plasma glucose levels remained in the normal range during the entire therapy. Neonatal apgar, birthweight and metabolic parameters were all appropriate for gestational age. It appears that orally-administered terbutaline produces no significant maternal biochemical or biophysical changes, or any side effects on the fetus.     

Endocrine and clinical effects of micronized estradiol administered vaginally or orally

OBJECTIVE: To determine the impact of the vaginal route of micronized estradiol (E(2)) administration upon hepatic globulin and lipid production and upon the outcome of oocyte donation cycles in which the recipients received E(2) via this route. DESIGN: Series report. SETTING: University-based assisted reproduction techniques (ART) program. PATIENT(S): Recipients of donor oocytes. INTERVENTION(S): Administration of micronized E(2) via the oral or vaginal route, oocyte donation, and embryo transfer. MAIN OUTCOME MEASURE(S): Measurements of the serum levels of free E(2), sex hormone-binding globulin (SHBG), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), as well as endometrial thickness and pregnancy outcome. RESULT(S): Serum SHBG and lipoprotein levels were unaltered by the vaginal as compared with the oral route of E(2) administration. Serum free E(2) levels were significantly higher after vaginal administration. Ten patients who had previously failed to achieve adequate endometrial thickness with an oral regimen were found to have adequate endometrial thickness after vaginal E(2) administration and seven of them achieved an ongoing pregnancy after embryo transfer. CONCLUSION(S): Vaginal administration of micronized E(2) results in significantly higher free serum E(2) levels when compared to levels achieved after oral E(2) administration. Hepatic globulin and lipoprotein production is similar despite 10-fold higher serum E(2) levels after the vaginal administration. The greater efficiency of E(2) delivery to the endometrium after vaginal administration makes this route a good option for patients who fail to achieve adequate endometrial thickness with oral E(2) administration.     

Beta-adrenoceptor function of leukocytes in pregnant women treated with terbutaline for preterm labor

The correlation between cyclic AMP (cAMP) production in myometrial tissue and that in leukocytes was studied in 21 women delivered by cesarean section for obstetrical reasons. After in vitro beta-adrenoceptor stimulation, cAMP production in myometrial tissue was found to be closely correlated with that in leukocytes (r = 0.96). Using cAMP production in leukocytes as an indicator of the state of the beta receptor function in myometrium, 18 women treated with terbutaline for preterm labor were studied. Repeat analyses of cAMP production were made in leukocytes before, during and after treatment. The results showed a significant reduction in cAMP production 3-5 hours and 1-2 days after terbutaline infusion. The cAMP values remained low during infusion. In women orally treated with terbutaline, a slight reduction in cAMP production was found after the first dose, but there was no significant reduction after 1-14 days of treatment. After cessation of terbutaline treatment, cAMP production remained low during the following 3 days, but after 5-8 days an increase was found in 7 out of 9 patients. It is suggested that a desensitization of the beta-adrenoceptor system in leukocytes appears after beta-adrenoceptor agonist treatment in high doses and that measurement of cAMP production reflects the state of desensitization of the beta-adrenoceptors in myometrial cells too.     

Role of the vaginally administered aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study

In the present nonrandomized pilot study we determined the role of the vaginally administered aromatase inhibitor anastrozole (0.25 mg anastrozole/d for 6 months) in the treatment of women with histologically proven rectovaginal endometriosis. In a series of 10 patients, dysmenorrhea, physical and social functioning, but not chronic pelvic pain and dyspareunia, improved during therapy.     

Comparison of the pharmacokinetics of crinone 8% administered vaginally versus Prometrium administered orally in postmenopausal women(3)

OBJECTIVE: Compare the pharmacokinetics of vaginal progesterone gel (Crinone 8%, 90 mg) with that of oral progesterone (Prometrium, 100 mg). DESIGN: Open-label, randomized, parallel-group protocol. SETTING: Outpatient clinic. PATIENT(s): Twelve healthy postmenopausal women. INTERVENTION(s): Six subjects each were randomized to receive progesterone, which was administered either as 90 mg of progesterone gel (Crinone 8%) given vaginally or 100 mg progesterone in a capsule (Prometrium) given orally. MAIN OUTCOME MEASUREMENT(s): Serum progesterone levels were measured by both radioimmunoassay (RIA) and liquid chromatography-mass spectrometry (LC-MS). RESULT(s): Progesterone given vaginally resulted in greater bioavailability with less relative variability in absorption than oral progesterone (mean AUC(0-24) = 1.48 +/- 0.16 ng. h/mL per milligram vs. 0.035 +/- 0.0052 ng. h/mL per milligram). Mean C(max) for oral progesterone was much lower than that of vaginal progesterone (i.e., 2.20 +/- 3. 06 ng/mL vs. 10.51 +/- 0.46 ng/mL). Mean T(max) occurred earlier for oral progesterone than for Crinone (1.00 +/- 0.41 hours vs. 7.67 +/- 3.67 hours). Radioimmunoassay is inappropriate for determining serum progesterone levels after oral administration, because it provided erroneously high values that were approximately eightfold higher than those obtained with LC-MS. CONCLUSION(s): Crinone (progesterone gel) given vaginally results in greater bioavailability with less relative variability than oral progesterone, thus providing more reliable delivery of progesterone, compared with oral progesterone. Measuring circulating progesterone with use of direct RIA is not appropriate after oral progesterone administration.     

Lewis phenotype in women with preterm labor and premature rupture of the membranes

Objective: The purpose of this study was to evaluate the possible association between Lewis phenotype status in pregnant women and preterm labor (PTL) or preterm rupture of the membranes (PROM).Methods: Red blood cell (RBC) Lewis phenotype was determined in 113 pregnant women admitted for PTL or PROM and in 121 controls. The results were controlled for the influence of race on Lewis phenotype.Results: Pregnancy was associated with a higher frequency in women with the a-b- phenotype. There was no association between RBC Lewis phenotype and the occurrence of PTL or PROM.Conclusions: A susceptibility to PTL or PROM is not due to a lack of Lewis antigen expression on the plasma membrane of the vaginal mucosa.     

Effects of vaginally administered high estradiol doses on hormonal pharmacokinetics and hemostasis in postmenopausal women

OBJECTIVE: To study the effect of high doses of estradiol released from vaginal rings on the pharmacokinetics of hormones, and the long-term effect on hormones and hemostasis in postmenopausal women. DESIGN: A pilot, nonrandomized study. SETTING: Healthy volunteers in an academic research environment. PATIENTS: Postmenopausal women.Eight women were treated with 17 beta-estradiol from three vaginal rings, releasing 7.5 micro g per ring for a total of 22.5 micro g over 24 hours. The rings were changed every morning for 14 days. MAIN OUTCOME MEASURE(S): Hemostatic changes were recorded. RESULT(S): Estradiol was rapidly absorbed, and statistically significant increases in the levels were found after 15 minutes; C(max) was obtained after 1 hour and a steady state after 24 hours. No statistically significant changes were found in the levels of coagulation factors V, von Willebrand factor, and activated factor VII; nor were any changes observed for activated protein C resistance, coagulation inhibitors protein C, protein S, or plasminogen activator inhibitor-1. No indication of increased thrombin formation was demonstrated by analyses of prothrombin fragment 1+2, fibrin D-dimer, and soluble fibrin. CONCLUSION(S)No statistically significant changes in hemostasis were observed from the vaginal administration of estradiol using a dose equivalent to transdermal administration with a release rate of 100 micro g per 24 hours.     

Treatment of premature labor in insulin-dependent diabetic women

This retrospective study was designed to analyze the safety and efficacy of beta-sympathomimetic agents used to treat premature labor in insulin-dependent diabetic women. The study evaluated 12 insulin-dependent diabetic women who experienced 15 pregnancies complicated by premature labor. A group of 30 insulin-dependent diabetic women who delivered at term served as matched controls. Treatment consisted of parenteral and oral administration of beta-sympathomimetic drugs (ritodrine and isoxsuprine). Premature labor was diagnosed, and tocolytic treatment was initiated at a mean gestational age of 31.5 +/- 0.9 weeks. The mean gestational age at the time of delivery was 35.8 +/- 0.5 weeks. Delivery was delayed in the study group by a mean of 30.5 +/- 6.6 days. No fetal or infant deaths occurred in the study group, and there was no difference between the two groups in the incidence of neonatal morbidity. No maternal complications occurred. There were no significant differences in hemoglobin A1 levels between the two groups at any period of gestation. Thus, beta-sympathomimetic drugs may be used safely to treat premature labor in patients with insulin-dependent diabetes, provided they are administered under strictly controlled clinical settings.     

Comparison of 25 and 50 microg vaginally administered misoprostol for preinduction of cervical ripening and labor induction.

Our purpose was to compare the efficacy of 25 microg and 50 microg intravaginally administered misoprostol tablets for cervical ripening and labor induction. Either 25-microg (n: 58) or 50-microg (n: 56) misoprostol tablets were randomly administered intravaginally to 114 subjects with an unripe cervix for labor induction. The physician was blinded to the medication. Intravaginal misoprostol was given every 4 h until the onset of labor. The mean Bishop score before misoprostol administration was 2.1 +/- 1.6 in the 25-microg group and 2.0 +/- 1.4 in the 50-microg group (p > 0.05). With the 25-microg dose the time until delivery was significantly longer (991.2 +/- 514.4 min vs. 703.12 +/- 432.6 min in the 50-microg group). The use of oxytocin augmentation was significantly higher in the 25-microg group (63.8%) than the 50-microg group (32.1%; p < 0.05). The proportions of patients with tachysystoles and hypersystoles were not significantly different between the two groups (19 and 6.9%, respectively, in the 25-microg group and 25 and 17.8%, respectively, in 50-microg group; p > 0.05). Overall, in the 25-microg group more women achieved vaginal delivery (79.3 vs. 60.7%; p < 0.05). The rate of cesarean sections due to non-reassuring fetal status was higher in the 50-microg misoprostol group (28.6 vs. 10.3%; p < 0.05). The number of neonates with a low 1-min Apgar score (<7) was significantly higher in the 50-microg misoprostol group (26.8 vs. 8.6%; p < 0.05), but 5-min Apgar scores and umbilical artery blood gas values at the time of delivery were not significantly different between the groups (p > 0.05). One patient in the 25-microg group suffered a ruptured uterus. Intravaginal administration of 25 microg of misoprostol is a clinically effective labor induction regimen and has the least adverse effects and complications.     

Social support during premature labor: effects on labor and the newborn

Prematurity is the single most frequent abnormality associated with birth, and is associated with both neonatal deaths and developmental deficits. In uncomplicated labors at term, the presence of a supportive companion has been found to lead to reduced length of labor, reduced need for medication for pain management, and improved neonatal well being. The relationships have not been explored in premature labor. Women in premature labor between 26 and 37 weeks of gestation were randomly assigned to a control group (n = 11) or to a supported group (n = 14), who were accompanied during labor by a supportive companion. Support during labor was associated with fewer abnormally long labors, less frequent use of medication for pain management during labor, and improved neonatal wellbeing.     

Comparative bioavailability of orally and vaginally administered progesterone.

OBJECTIVE: To study the pharmacokinetics of progesterone (P) in healthy premenopausal female volunteers to compare the bioavailability of orally or vaginally administered hormone. DESIGN: Subjects were randomly allocated to receive either oral P or a vaginal pessary then crossed over to the alternate preparation 1 month later. SETTING: The study was conducted in outpatient setting. SUBJECTS: All subjects were healthy, normal female volunteers who underwent a physical and gynecological examination before the study. None were using oral contraceptives. Ten subjects (mean age 32.6 +/- 7.3 years) entered the study and all completed it. INTERVENTIONS: Progesterone was administered as 200 mg of micronized hormone or as a pessary containing 400 mg. MAIN OUTCOME MEASURE: Plasma levels of P were measured by radioimmunoassay to test the apriori hypothesis of similar bioavailability. RESULTS: Peak plasma P concentrations attained within 4 hours after oral administration ranged from 8.5 to 70.6 ng/mL, whereas after vaginal administration the peak levels were attained within 8 hours and ranged from 4.4 to 181.1 ng/mL. Considerable interindividual variation was noted. Area under the plasma concentration-time curve for the two formulations was not significantly different (F = 1.09; P greater than 0.1; ANOVA). CONCLUSIONS: The two formulations had similar bioavailability.