Oral misoprostol and vaginal isosorbide mononitrate for labor induction: a randomized controlled trial.

OBJECTIVE: To estimate whether vaginal isosorbide mononitrate, added to oral misoprostol for cervical ripening and labor induction, shortens time to vaginal delivery. METHODS: A prospective, randomized trial was conducted. Women scheduled for labor induction between 32 and 42 weeks and with unfavorable cervices (modified Bishop score 6 or lower) were randomized to receive oral misoprostol every 4 hours, up to four doses, with or without isosorbide mononitrate every 6 hours, up to two doses. A strict protocol was used, including timing of oxytocin use and amniotomy. Side effects were assessed 6 hours after study initiation. One hundred forty-two patients were required to detect a change in time to vaginal delivery of 4 hours (alpha=.05 and beta=.20). Data were analyzed by intent to treat. Student's t, chi square, Fisher's exact, and Mann-Whitney tests were used where appropriate with P< or =.05 deemed significant. RESULTS: One hundred fifty-six women were randomized; three were excluded after randomization. Seventy-eight women received misoprostol, and 78 received misoprostol with isosorbide mononitrate. Demographic characteristics were similar between groups. The time to vaginal delivery was not reduced when isosorbide mononitrate was added to misoprostol. Cesarean delivery rates and contraction and fetal heart rate abnormalities were similar between groups. Side effects were also similar between groups, except that women given isosorbide mononitrate experienced headaches more often. Neonatal outcomes were similar between groups. CONCLUSION: The addition of vaginal isosorbide mononitrate to oral misoprostol for cervical ripening and labor induction did not reduce time to vaginal delivery and was associated with a greater incidence of headache. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00374621. LEVEL OF EVIDENCE: I.

Daily compared with 8-hour gentamicin for the treatment of intrapartum chorioamnionitis: a randomized controlled trial.

OBJECTIVE: To assess whether daily gentamicin is as effective as 8-hour gentamicin for the treatment of intrapartum chorioamnionitis. METHODS: Women with a clinical diagnosis of chorioamnionitis between 32 and 42 weeks of gestation were randomly assigned in labor to receive either daily gentamicin (5 mg/kg intravenously (IV), then 2 placebo doses IV after 8 and 16 hours) or 8-hour gentamicin (2 mg/kg IV, then 1.5 mg/kg IV after 8 and 16 hours). Both groups received ampicillin (2 grams IV every 6 hours for a total of four doses). Patients who underwent cesarean delivery also received clindamycin (900 mg IV every 8 hours, for a total of three doses). The primary outcome was treatment success, defined by resolution of chorioamnionitis after 16 hours of treatment without development of endometritis. One hundred twenty-six patients were required to have 95% confidence that daily gentamicin is at worst 15% inferior to 8-hour dosing with an alpha of .05 and a beta of 0.2. RESULTS: One hundred twenty-six women were enrolled, of whom 63 received daily gentamicin and 63 received 8-hour gentamicin. One patient was excluded from data analysis. Baseline maternal and obstetric characteristics were similar between groups except for longer mean duration of ruptured membranes in the 8-hour group (679+/-514 compared with 469+/-319 minutes; P =.03). Treatment success was equal between groups (94% daily gentamicin compared with 89% 8-hour gentamicin, P =.53). There were no differences in maternal or neonatal morbidities, including neonatal sepsis and newborn hearing screen. CONCLUSION: Daily and 8-hour gentamicin appear equally effective for the treatment of intrapartum chorioamnionitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00185991. LEVEL OF EVIDENCE: I.

Ultrasound estimation of fetal weight in small for gestational age pregnancies.

OBJECTIVE: Approximately half of small for gestational age (SGA) cases are due to maternal or fetal pathology, and may result in significant neonatal morbidity and mortality. The estimated fetal weight (EFW) measurement is the cornerstone of ultrasonographic findings when diagnosing and managing SGA pregnancies. Our objective was to determine the ultrasound accuracy of EFW in SGA pregnancies. METHODS: A retrospective chart review was performed of all pregnancies complicated by SGA from a single institution (Stanford University) over a 2-year-period (2004-2006). SGA was defined as EFW < or = 10%. 98 neonates whose last ultrasound for EFW occurred within 7 days of delivery were included in the study. The absolute differences between the EFW and birthweight (BW) were analyzed, and the absolute percent errors were calculated as (EFW - BW)/BW x 100. The mean absolute differences and mean absolute percent errors were analyzed across all gestational ages (GA) and EFWs using one-way analysis of variance. RESULTS: The mean absolute percent error for the entire cohort was 8.7% (+/-6.3%). There was no statistically significant difference in the mean absolute percent error across all GAs (<32 weeks, 32-36 weeks, >36 weeks), and EFWs (<1500 g, 1500-2000 g, >2000 g). CONCLUSION: Ultrasound measurement of EFW in SGA pregnancies is consistent across all GAs and EFW measurements.

Maintenance nifedipine tocolysis compared with placebo: a randomized controlled trial.

OBJECTIVE: To estimate whether maintenance nifedipine tocolysis after arrested preterm labor prolongs pregnancy and improves neonatal outcomes. METHODS: A prospective, randomized double-blind, multicenter study was conducted. After successful tocolysis, patients were randomly assigned to receive 20 mg nifedipine or an identical-appearing placebo every 4-6 hours until 37 weeks of gestation. The primary outcome was attainment of 37 weeks of gestation. Patients were enrolled between 24 weeks and 34 weeks if they had six or fewer contractions per hour, intact membranes, and less than 4 cm cervical dilation. Exclusion criteria were placental abruption or previa, fetal anomaly incompatible with life, or maternal medical contraindication to tocolysis. Sixty-six patients were required for 80% power to detect a 50% reduction in birth before 37 weeks, with a two-tailed alpha of 0.05. Data were analyzed by intent to treat. RESULTS: Seventy-one patients were randomly assigned. Two patients were excluded after randomization and one was lost to follow-up. Thirty-five patients received placebo, and 33 received nifedipine. There were no maternal demographic differences between groups; the placebo group was significantly more dilated and effaced at study entry. There was no difference in attainment of 37 weeks (39% nifedipine compared with 37% placebo, P>.91), mean delay of delivery (33.5+/-19.9 days nifedipine compared with 32.6+/-21.4 days placebo, P=.81) or delay of delivery for greater than 48 hours or 1, 2, 3, or 4 weeks. Neonatal outcomes were similar between groups. CONCLUSION: When compared with placebo, maintenance nifedipine tocolysis did not confer a large reduction in preterm birth or improvement in neonatal outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00185952 LEVEL OF EVIDENCE: I.

Bacterial flora-typing with targeted, chip-based Pyrosequencing.

BACKGROUND: The metagenomic analysis of microbial communities holds the potential to improve our understanding of the role of microbes in clinical conditions. Recent, dramatic improvements in DNA sequencing throughput and cost will enable such analyses on individuals. However, such advances in throughput generally come at the cost of shorter read-lengths, limiting the discriminatory power of each read. In particular, classifying the microbial content of samples by sequencing the < 1,600 bp 16S rRNA gene will be affected by such limitations. RESULTS: We describe a method for identifying the phylogenetic content of bacterial samples using high-throughput Pyrosequencing targeted at the 16S rRNA gene. Our analysis is adapted to the shorter read-lengths of such technology and uses a database of 16S rDNA to determine the most specific phylogenetic classification for reads, resulting in a weighted phylogenetic tree characterizing the content of the sample. We present results for six samples obtained from the human vagina during pregnancy that corroborates previous studies using conventional techniques.Next, we analyze the power of our method to classify reads at each level of the phylogeny using simulation experiments. We assess the impacts of read-length and database completeness on our method, and predict how we do as technology improves and more bacteria are sequenced. Finally, we study the utility of targeting specific 16S variable regions and show that such an approach considerably improves results for certain types of microbial samples. Using simulation, our method can be used to determine the most informative variable region. CONCLUSION: This study provides positive validation of the effectiveness of targeting 16S metagenomes using short-read sequencing technology. Our methodology allows us to infer the most specific assignment of the sequence reads within the phylogeny, and to identify the most discriminative variable region to target. The analysis of high-throughput Pyrosequencing on human flora samples will accelerate the study of the relationship between the microbial world and ourselves.

Randomized comparison of intravenous terbutaline vs nitroglycerin for acute intrapartum fetal resuscitation.

OBJECTIVE: The purpose of this study was to compare terbutaline and nitroglycerin for acute intrapartum fetal resuscitation. STUDY DESIGN: Women between 32-, 42 weeks' gestation were assigned randomly to 250 microg of terbutaline or 400 microg nitroglycerin intravenously for nonreassuring fetal heart rate tracings in labor. The rate of successful acute intrapartum fetal resuscitation and the maternal hemodynamic changes were compared. Assuming a 50% failure rate in the terbutaline arm, we calculated that a total of 110 patients would be required to detect a 50% reduction in failure in the nitroglycerin group (50% to 25%), with an alpha value of .05, a beta value of .20, and a power of 80%. RESULTS: One hundred ten women had nonreassuring fetal heart rate tracings in labor; 57 women received terbutaline, and 53 women received nitroglycerin. Successful acute resuscitation rates were similar (terbutaline 71.9% and nitroglycerin 64.2%; P = .38). Terbutaline resulted in lower median contraction frequency per 10 minutes (2.9 [25-75 percentile, 1.7- 3.3] vs 4 [25-75 percentile, 2.5- 5]; P < .002) and reduced tachysystole (1.8% vs 18.9%; P = .003). Maternal mean arterial pressures decreased with nitroglycerin (81-76 mm Hg; P = .02), but not terbutaline (82-81 mm Hg; P = .73). CONCLUSION: Although terbutaline provided more effective tocolysis with less impact on maternal blood pressure, no difference was noted between nitroglycerin and terbutaline in successful acute intrapartum fetal resuscitation.

Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor: a randomized controlled trial.

OBJECTIVE: To compare the efficacy and side effects of intravenous magnesium to oral nifedipine for acute tocolysis of preterm labor. METHODS: A multicenter randomized trial was performed. Patients in active preterm labor who were at 24 to 33 weeks and 6 days of gestation were randomly assigned to receive magnesium sulfate or nifedipine. The primary outcome was arrest of preterm labor, defined as prevention of delivery for 48 hours with uterine quiescence. RESULTS: One hundred ninety-two patients were enrolled. More patients assigned to magnesium sulfate achieved the primary outcome (87% compared with 72%, P=.01). There were no differences in delivery within 48 hours (7.6% magnesium sulfate compared with 8.0% nifedipine, P=.92), gestational age at delivery (35.8 compared with 36.0 weeks, P=.61), birth before 37 and 32 weeks (57% compared with 57%, P=.97, and 11% compared with 8%, P=.39), and episodes of recurrent preterm labor. Mild and severe maternal adverse effects were significantly more frequent with magnesium sulfate. Birth weight, birth weight less than 2,500 g, and neonatal morbidities were similar between groups, but newborns in the magnesium sulfate group spent longer in the neonatal intensive care unit (8.8+/-17.7 compared with 4.2+/-8.2 days, P=.007). CONCLUSION: Patients who received magnesium sulfate achieved the primary outcome more frequently. However, delay of delivery, gestational age at delivery, and neonatal outcomes were similar between groups. Nifedipine was associated with fewer maternal adverse effects.

Perinatal outcomes after successful and failed trials of labor after cesarean delivery.

OBJECTIVE: To compare maternal and neonatal outcomes after successful and failed trials of labor after cesarean in women at term, excluding uterine ruptures, and to examine predictors of successful and failed trials of labor. STUDY DESIGN: Matched maternal and neonatal data from 1993-1999 in women with singleton term pregnancies with prior cesarean undergoing trial of labor were reviewed. Women with uterine rupture were excluded. Maternal and neonatal outcomes were analyzed for successful and failed trials. Predictors of success and failure were examined. RESULTS: 1284 women and their neonates were available for analysis. 1094 (85.2%) had a vaginal birth and 190 (14.8%) underwent repeat cesarean. Failed trials of labor were associated with higher incidence of choriamnionitis (25.8% vs. 5.5%, P<.001), postpartum hemorrhage (35.8% vs. 15.8%, P<.001), hysterectomy (1% vs. 0%, P=.022), neonatal jaundice (17.4% vs.10.2%, P=.004) and composite major neonatal morbidities (6.3% vs. 2.8%, P=.014). CONCLUSION: Failed trial of labor in women at term with prior cesarean is associated with increased maternal and neonatal morbidities.

Randomized comparison of intravenous nitroglycerin and subcutaneous terbutaline for external cephalic version under tocolysis.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of intravenous nitroglycerin with that of subcutaneous terbutaline as a tocolytic agent for external cephalic version at term. STUDY DESIGN: We performed a prospective randomized trial. Patients between 37 and 42 weeks of gestation were assigned randomly to receive either 200 microg of intravenous nitroglycerin therapy or 0.25 mg of subcutaneous terbutaline therapy for tocolysis during external cephalic version. The rate of successful external cephalic version and side effects were compared between groups. RESULTS: Of 59 randomly assigned patients, 30 patients received intravenous nitroglycerin, and 29 patients received subcutaneous terbutaline. The overall success rate of external cephalic version in the study was 39%. The rate of successful external cephalic version was significantly higher in the terbutaline group (55% vs 23%; P = .01). The incidence of palpitations was significantly higher in patients who received terbutaline therapy (17.2% vs 0%; P = .02), as was the mean maternal heart rate at multiple time periods. CONCLUSION: Compared with intravenous nitroglycerin, subcutaneous terbutaline was associated with a significantly higher rate of successful external cephalic version at term.