Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

BACKGROUND: Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it. OBJECTIVES: To compare progesterone, cerclage and pessary, determine their relative effects and rank them. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study. DATA COLLECTION AND ANALYSIS: We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT). MAIN RESULTS: We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks. CONCLUSIONS: Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae. TWEETABLE ABSTRACT: Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.

Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.

BACKGROUND: About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. OBJECTIVES: To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. SELECTION CRITERIA: Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. MAIN RESULTS: We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I2  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I2  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I2  22%). CONCLUSION: In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. TWEETABLE ABSTRACT: Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.

Oral administration of misoprostol for labor induction: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness, safety, and gastrointestinal tolerance of misoprostol taken orally for induction of labor, against our established protocol, with the interval from induction to vaginal birth as the primary outcome measure. METHODS: Two hundred seventy-five women who presented with indication for induction of labor were assigned randomly to receive either 50 micrograms of misoprostol orally every 4 hours as needed or treatment according to our established protocol (physician-chosen combinations of intracervical or vaginal prostaglandins every 4-6 hours, artificial rupture of membranes, and oxytocin infusion). Sample size was calculated with a two-tailed alpha = .05 and power of 95%. RESULTS: The mean time (+/-standard deviation) to vaginal birth with oral misoprostol was 926 +/- 521 minutes versus 909 +/- 585 minutes with the established protocol, a nonsignificant difference. There were no clinically or statistically significant differences in maternal secondary outcome measures (cesarean rate, frequency of epidural use, perineal trauma, or manual removal of the placenta). There was no difference in frequency of maternal gastrointestinal side effects. Neonatal outcomes, including cord blood acid-base analysis, were not different. CONCLUSIONS: Oral misoprostol may be a new option for labor induction. It appears to be no less effective or safe than our usual regimen for induction of labor at term and is well tolerated. Further studies are warranted to confirm the safety of this approach and to determine optimal dose and frequency of administration.

Vaginal misoprostol for induction of labor: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of the vaginal application of misoprostol for induction of labor at term, with the interval duration from labor induction to vaginal birth as the primary outcome measure. METHODS: Two hundred twenty-two women with indications for induction of labor at term were randomized to receive either misoprostol 50 micrograms per vagina every 4 hours as needed or our standard approach (physician-chosen combinations of intracervical or vaginal dinoprostone every 6 hours, artificial rupture of membranes, and oxytocin infusion). RESULTS: Mean (+/-standard deviation) time to vaginal delivery was 753 +/- 588 minutes for misoprostol versus 941 +/- 506 minutes for the physician-chosen combination (P = .018). Oxytocin infusion was used less frequently (relative risk [RR] 0.48, 95% confidence interval [CI] 0.31-0.74). There was no significant difference in cesarean rate or maternal morbidity. Neonatal outcomes, including cord-blood acid-base analysis, were not significantly different. The estimated cost per patient in Canadian dollars for prostaglandins was $0.22 with misoprostol and $70.00 with standard therapy. CONCLUSION: Vaginal misoprostol is a cost-effective alternative to current labor-induction protocols. We found no evidence of harm to mother or newborn in substantive outcomes.