Effect of delayed misoprostol dosing interval for induction of labor: a retrospective study.
ABSTRACT: BACKGROUND:Induction of labor occurs in greater than 22% of all pregnancies in the United States. Previous studies have shown that misoprostol is more effective for induction than oxytocin or dinoprostone alone. The World Health Organization recommends vaginal misoprostol 25mcg every 6 hours and the American Congress of Obstetricians and Gynecologists recommends 25mcg vaginal misoprostol every three to 6 hours. Although route of administration and dosage of misoprostol has been extensively studied, little is known about the optimal dosing interval of vaginal misoprostol. METHODS:The primary objective of this study is to determine the effect of delayed vaginal misoprostol dosing, defined as any interval longer than 4.5 h, on time to vaginal delivery. Our hypothesis is that the routine dosing interval of 4 hours shortens times to vaginal delivery compared to delayed dosing, even when adjusted for the time of delay. Secondary objectives include the effect of delayed vaginal misoprostol dosing on cesarean section rate, operative vaginal delivery rate, maternal outcomes, and neonatal outcomes. We conducted a retrospective chart review of 323 inductions of labor at one academic institution. The primary outcome was the proportion of patients who achieved a vaginal delivery within 24 h. The group who received all doses of misoprostol within a 4.5 h dosing window (Routine Dosing Interval Group) was compared with the group who had any dosing deviation (Delayed Dosing Interval Group). RESULTS:Of 133 included patients, 64 subjects received routine interval dosing and 69 subjects received delayed interval dosing. The vaginal delivery rates within 24 h were 56% (36/64) and 20% (14/69), respectively (P < 10- 4). Spontaneous vaginal delivery rates were 86% (55/64) vs. 75% (52/69), respectively (P = .13). Kaplan Meier curves demonstrated statistically significant difference in time to vaginal delivery between groups, with a Cox Proportional Hazard ratio for routine dosing interval of 1.73 (P < 10- 5) unadjusted and 1.34 (P = .01) when adjusted for dosing delay. CONCLUSIONS:This retrospective study demonstrates a significant increase in delay-adjusted time to vaginal delivery when doses of vaginal misoprostol are delayed past 4.5 h.
Project description:The safest, most effective and fastest combined approaches to induction of labor is unknown. In an open-label randomized clinical trial we evaluated the efficacy of combination of extra-amniotic Foley's catheter and vaginal misoprostol compared to vaginal misoprostol alone for cervical ripening and induction of labor on the incidence of failed induction, induction-to-delivery interval and adverse maternal and perinatal outcomes.Pregnant women at gestational age of 28 weeks or greater admitted at Kenyatta National Hospital, Kenya for induction of labor were enrolled then randomized to either a combination of extra-amniotic Foley's catheter inflated by 30 cm3 of normal saline and 25 micrograms of vaginal misoprostol or 25 micrograms of vaginal misoprostol alone. Women underwent 6 hourly reviews and additional misoprostol inserted if required. The primary outcome was incidence of failed induction. Secondary outcomes were induction-to-delivery interval and adverse maternal and perinatal outcomes. We conducted an intent-to-treat analysis and compared means or medians using t-test or Wilcoxon rank, proportions using Chi-square or Fishers test as appropriate. Induction-to-delivery interval were compared using the log-rank test. P-values of <?0.05 and 95% confidence intervals that excluded the null were considered statistically significant.Between February and May 2016, we enrolled 180 of 237 pregnant women admitted for induction of labor and randomized them to either a combination of extra-amniotic Foley's catheter and vaginal misoprostol (n =?90) or vaginal misoprostol alone (n =?90). The socio-demographic and obstetric characteristics were similar between the two groups. Failed induction rates were lower but not statistically significant following combined extra-amniotic Foley's catheter and vaginal misoprostol (8.9%) versus vaginal misoprostol alone (11.1%). The mean induction-to-delivery time was 4.8 h shorter in the combined extra-amniotic Foley's catheter and vaginal misoprostol (mean 18.9, standard deviation (SD) 7.2 h) compared to misoprostol only group (mean 14.1, SD 6.9 h) (log-rank test, p <?0.001). Maternal and perinatal complications were similar between the two groups.Extra-amniotic Foley's catheter and vaginal misoprostol for cervical ripening and induction of labor did not significantly lower the incidence of failed induction but safely shortened induction-to-delivery time compared to vaginal misoprostol only.Trial was retrospectively registered on 14-03-2016 PACTR201604001535825.
Project description:Objective ?To survey obstetrical provider preferences regarding use of misoprostol for induction of labor (IOL). Methods ?An anonymous 25-question survey was distributed at an American College of Obstetricians and Gynecologists (ACOG) joint District V and VII Meeting in 2014 to obstetrics providers. The same survey was sent electronically to local providers. A separate survey was emailed to the labor and delivery nurses at two of the teaching hospitals in Indianapolis. The surveys queried provider demographics, dosing practice for misoprostol, opinions regarding different dosing strategies, and instructions on buccal administration. Results ?A total of 113 (46.5%) providers responded. Of these, 92.9% used misoprostol for IOL, 73% preferred the vaginal route, 20% preferred buccal administration, and 7% oral administration. Only resident physician and midwife providers endorsed buccal route preference. Being a midwife independently predicted a preference for using buccal misoprostol (odds ratio [OR]: 125.8, 95% confidence interval [CI]: 7.9-1992.3). Additionally, 44 nurses completed the survey regarding administration techniques of buccal misoprostol. Also, 54.5% of nurses correctly instructed their patients on buccal administration techniques. Conclusion ?Although not extensively studied, one-fifth of providers, particularly nurse midwives, prefer buccal administration of misoprostol for IOL. The majority of nurses correctly administered buccal misoprostol. There may be a need for further study and education about buccal administration of misoprostol for IOL.
Project description:Background:Mifepristone and misoprostol are recommended for second-trimester medical abortion, but consensus is unclear on the ideal regimen. Objectives:The objectives were to systematically review randomized controlled trials (RCTs) investigating efficacy, safety and satisfaction of medical abortion at ? 12?weeks' gestation. Data sources:We searched PubMed, Popline, Embase, Global Index Medicus, Cochrane Controlled Register of Trials and International Clinical Trials Registry Platform from January 2008 to May 2017. Study eligibility participants and interventions:We included RCTs on medical abortion at ? 12?weeks' gestation using mifepristone and/or misoprostol. We excluded studies with spontaneous abortion, fetal demise and mechanical cervical ripening and those not reporting ongoing pregnancy (OP). Study appraisal and synthesis methods:After extracting prespecified data and assessing risk of bias in accordance with the Cochrane handbook, we used Revman5 software to combine data and GRADE to assess certainty of evidence. Results:We included 43 of the 1894 references identified. Combination mifepristone-misoprostol had lower rates of OP [risk ratio (RR) 0.12, 95% confidence interval (CI) 0.04-0.35] vs. misoprostol only. A 24-h interval between mifepristone and misoprostol had lower OP rate at 24?h than simultaneous dosing (RR 3.13, 95% CI 1.23-7.94). Every 3-h dosing had lower OP rate at 48?h (RR 0.39, 95% CI 0.17-0.88). Limitations:Direct comparisons of buccal misoprostol to sublingual or vaginal routes after mifepristone were limited. Evidence from clinical trials on how to best manage women with prior uterine incisions was lacking. Conclusion:Our analysis supports the use of mifepristone 200?mg 1 to 2 days before misoprostol 400 mcg vaginally every 3?h at ? 12?weeks' gestation. Implications:Where available, providers should use mifepristone plus misoprostol for second-trimester medical abortion. Vaginal misoprostol appears to be most efficacious with fewest side effects, but sublingual and buccal routes are also acceptable.
Project description:BACKGROUND:Among the various methods available, the administration of prostaglandins is the most effective for inducing labour in women with an unfavourable cervix. Recent studies have compared treatment with various titrated doses of oral misoprostol with vaginal misoprostol or dinoprostone, indicating that the use of an escalating dose of an oral misoprostol solution is associated with a lower rate of caesarean sections and a better safety profile. The objective of this study is to assess which of these three therapeutic options (oral or vaginal misoprostol or vaginal dinoprostone) achieves the highest rate of vaginal delivery within the first 24?h of drug administration. METHODS:An open-label randomised controlled trial will be conducted in Araba University Hospital (Spain). Women at ?41?weeks of pregnancy requiring elective induction of labour who meet the selection criteria will be randomly allocated to one of three groups: 1) vaginal dinoprostone (delivered via a controlled-release vaginal insert containing 10?mg of dinoprostone, for up to 24?h); 2) vaginal misoprostol (25??g of vaginal misoprostol every 4?h up to a maximum of 24?h); and 3) oral misoprostol (titrated doses of 20 to 60??g of misoprostol following a 3?h on +?1?h off regimen up to a maximum of 24?h). Both intention-to-treat analysis and per-protocol analysis will be performed. DISCUSSION:The proposed study seeks to gather evidence on which of these three therapeutic options achieves the highest rate of vaginal delivery with the best safety profile, to enable obstetricians to use the most effective and safe option for their patients. TRIAL REGISTRATION:NCT02902653 Available at: https://clinicaltrials.gov/show/NCT02902653 (7th September 2016).
Project description:BACKGROUND:This study was undertaken with the objective of comparing efficacy and safety for two different regimens using misoprostol for induction of labour. METHODS:The study was set in two different hospitals in the region of Zeeland, Denmark, and designed as a prospective cohort study. Nulliparous women with unripe cervix, eligible for vaginal delivery and medical induction of labour were included. Exclusion criteria were a previous uterine scar, suspicion of growth restriction of the fetus and prelabour rupture of membranes. One department used 25 mcg oral misoprostol tablets and the other department used 200 mcg slow-release misoprostol vaginal insert, for induction of labour. Primary outcomes were predefined as frequency of cesarean section, tachysystole and delivery within 24?h. Secondary outcomes were: time from induction to delivery, use of additional methods for induction, postpartum hemorrhage, anal sphincter rupture, epidural, pyrexia (rectal temperature?>? 38.5?°C), prolonged rupture of membranes, and use of tocolysis. RESULTS:No significant differences in women achieving vaginal delivery was found. However, a significantly increased risk of tachysystole for the vaginal administration route was observed; 28.4% compared with 2.3%. There were no events of serious neonatal asphyxia. Half of the women induced with vaginal insert delivered within 24?h, compared with 16.8% of the women induced with oral misoprostol. CONCLUSIONS:Induction with vaginal slow-release misoprostol leads to quicker delivery with an increased risk of tachysystole but with similar perinatal outcomes and rates of cesarean sections. Low-dose oral misoprostol appears to be safe, however it leads to an increased use of secondary methods and a tendency of more intrapartum pyrexia. TRIAL REGISTRATION:Clinicaltrials.gov ID: NCT02693587 on February 262,016. EudraCT number 2020-000366-42 on 23 January 2020, retrospectively registered.
Project description:BACKGROUND:Labor induction is defined as any procedure that stimulates uterine contractions before labor begins spontaneously. The vaginal and oral routes of administration of misoprostol are those most used for the induction of labor in routine practice, with the recommended dose being 25??g. Nevertheless, the sublingual route may reduce the number of vaginal examinations required, increasing patient comfort and lowering the risk of maternal and fetal infection. Based on a previous systematic review, the objective of this study was to compare the frequency of tachysystole as the main outcome measure when misoprostol is administered sublingually at the dose of 12.5??g versus vaginally at a dose of 25??g to induce labor in a full-term pregnancy with a live fetus. METHODS:A randomized, placebo-controlled, triple-blind clinical trial was conducted at two maternity hospitals in northeastern Brazil. Two hundred patients with a full-term pregnancy, a live fetus, Bishop score???6 and an indication for induction of labor were included. Following randomization, one group received 12.5??g misoprostol sublingually and a vaginal placebo, while the other group received a sublingual placebo and 25??g misoprostol vaginally. The primary outcome was the frequency of tachysystole. Student's t-test, the chi-square test of association and Fisher's exact test were used, as appropriate. Risk ratios and their 95% confidence intervals were calculated. RESULTS:The frequency of tachysystole was lower in the group using 12.5??g misoprostol sublingually compared to the group using 25??g misoprostol vaginally (RR?=?0.15; 95%CI: 0.02-0.97; p?=?0.002). Failure to achieve vaginal delivery within 12 and 24?h was similar in both groups. Sublingual administration was preferred to vaginal administration by women in both groups; however, the difference was not statistically significant. CONCLUSION:The effectiveness of labor induction with low-dose sublingual misoprostol was similar to that achieved with vaginal administration of the recommended dose; however, the rate of tachysystole was lower in the sublingual group, and this route of administration may prove a safe alternative. TRIAL REGISTRATION:Registration number: NCT01406392, ClinicalTrials.gov. Date of registration: August 1, 2011.
Project description:OBJECTIVE:To determine the effectiveness and economic impact of two methods for induction of labour in hypertensive women, in low-resource settings. DESIGN:Cost-consequence analysis of a previously reported multicentre, parallel, open-label randomised trial. SETTING & POPULATION:A total of 602 women with a live fetus, aged ?18 years requiring delivery for pre-eclampsia or hypertension, in two public hospitals in Nagpur, India. METHODS:We performed a formal economic evaluation alongside the INFORM clinical trial. Women were randomised to receive transcervical Foley catheterisation or oral misoprostol 25 mcg. Healthcare expenditure was calculated using a provider-side microcosting approach. MAIN OUTCOME MEASURES:Rates of vaginal this delivery within 24 hours of induction, healthcare expenditure per completed treatment episode. RESULTS:Induction with oral misoprostol resulted in a (mean difference) $20.6USD reduction in healthcare expenditure [95% CI (-) $123.59 (-) $72.49], and improved achievement of vaginal delivery within 24 hours of induction, mean difference 10% [95% CI (-2 to 17.9%), P = 0.016]. Oxytocin administration time was reduced by 135.3 minutes [95% CI (84.4-186.2 minutes), P < 0.01] and caesarean sections by 9.1% [95% CI (1.1-17%), P = 0.025] for those receiving oral misoprostol. Following probabilistic sensitivity analysis, oral misoprostol was cost-saving in 63% of 5,000 bootstrap replications and achieved superior rates of vaginal delivery, delivery within 24 hours of induction and vaginal delivery within 24 hours of induction in 98.7%, 90.7%, and 99.4% of bootstrap simulations. Based on univariate threshold analysis, the unit price of oral misoprostol 25 mcg could feasibly increase 31-fold from $0.24 to $7.50 per 25 mcg tablet and remain cost-saving. CONCLUSION:Compared to Foley catheterisation for the induction of high-risk hypertensive women, oral misoprostol improves rates of vaginal delivery within 24 hours of induction and may also reduce costs. Additional research performed in other low-resource settings is required to determine their relative cost-effectiveness. TWEETABLE ABSTRACT:Oral misoprostol less costly and more effective than Foley catheter for labour induction in hypertension.
Project description:To assess the effectiveness and safety of prostaglandins used for labour induction.Systematic review with Bayesian network meta-analysisThe Cochrane Pregnancy and Childbirth Group's Database of Trials (which incorporates the results of a broad generic search for all pregnancy and postpartum trials). Sources included are CENTRAL, Medline, Embase, NHS Economic Evaluation Database, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials.Randomised clinical trials of prostaglandin or prostaglandin analogues used for third trimester cervical ripening or labour induction versus placebo or no treatment, alternative prostaglandin dose or administration, or a different type of prostaglandin. We included studies recruiting women with a viable fetus, but had no other restrictions relating to indication for labour induction or language of publication. Outcomes assessed were serious neonatal morbidity (trialist defined) or perinatal death; serious maternal morbidity (trialist defined) or death; vaginal delivery not achieved within 24 hours, caesarean section, and uterine hyperstimulation with fetal heart rate changes.280 randomised clinical trials were included (48 068 women) in the review. Maternal and neonatal mortality and serious morbidity were rarely reported and are summarized narratively. Unresolved inconsistency was observed for the hyperstimulation outcome. Relative to placebo, the odds of failing to achieve a vaginal delivery were lowest for vaginal misoprostol (?50 µg) (odds ratio 0.06 (95% credible interval 0.02 to 0.12)), with a 39% absolute probability of event (95% credible interval 1% to 94%). Compared with placebo, odds of caesarean section were lowest for titrated oral misoprostol solution (<50 µg) (odds ratio 0.65 (0.49 to 0.83)), with an absolute probability of event of 15% (3% to 40%).Low dose(<50 µg) titrated oral misoprostol solution had the lowest probability of caesarean section, whereas vaginal misprostol (?50 µg) had the highest probability of achieving a vaginal delivery within 24 hours. These findings have important implications for a series of current national and international guidelines for induction of labour and future research in this area.PROSPERO 2013:CRD42013005116.
Project description:To evaluate the effectiveness of four commonly used induction methods.This randomized trial compared four induction methods: misoprostol alone, Foley alone, misoprostol-cervical Foley concurrently, and Foley-oxytocin concurrently. Women undergoing labor induction with full-term (37 weeks of gestation or greater), singleton, vertex-presenting gestations, with no contraindication to vaginal delivery, intact membranes, Bishop score 6 or less, and cervical dilation 2 cm or less were included. Women were enrolled only once during the study period. Our primary outcome was time to delivery. Neither patients nor health care providers were blinded to assigned treatment group because examinations are required for placement of all methods; however, research personnel were blinded during data abstraction. A sample size of 123 per group (n=492) was planned to compare the four groups pairwise (P?.008) with a 4-hour reduction in delivery time considered clinically meaningful.From May 2013 through June 2015, 997 women were screened and 491 were randomized and analyzed. Demographic and clinical characteristics were similar among the four treatment groups. When comparing all induction method groups, combination methods achieved a faster median time to delivery than single-agent methods (misoprostol-Foley: 13.1 hours, Foley-oxytocin: 14.5 hours, misoprostol: 17.6 hours, Foley: 17.7 hours, P<.001). When censored for cesarean delivery and adjusting for parity, women who received misoprostol-Foley were almost twice as likely to deliver before women who received misoprostol alone (hazard ratio 1.92, 95% confidence interval [CI] 1.42-2.59) or Foley alone (hazard ratio 1.87, 95% CI 1.87 1.39-2.52), whereas Foley-oxytocin was not statistically different from single-agent methods.After censoring for cesarean delivery and adjusting for parity, misoprostol-cervical Foley resulted in twice the chance of delivering before either single-agent method.ClinicalTrials.gov, https://clinicaltrials.gov, NCT01916681.
Project description:The efficacy and safety of misoprostol alone for missed abortion varied with different regimens. To evaluate existing evidence for the medical management of missed abortion using misoprostol, we undertook a comprehensive review and meta-analysis. The electronic literature search was conducted using PubMed, the Cochrane Library, Embase, EBSCOhost Online Research Databases, Springer Link, ScienceDirect, Web of Science, Ovid Medline and Google Scholar. 18 studies of 1802 participants were included in our analysis. Compared with vaginal misoprostol of 800?ug or sublingual misoprostol of 600?ug, lower-dose regimens (200?ug or 400?ug) by any route of administration tend to be significantly less effective in producing abortion within about 24?hours. In terms of efficacy, the most effective treatment was sublingual misoprostol of 600?ug and the least effective was oral misoprostol of 400?ug. In terms of tolerability, vaginal misoprostol of 400?ug was reported with fewer side effects and sublingual misoprostol of 600?ug was reported with more side effects. Misoprostol is a non-invasive, effective medical method for completion of abortion in missed abortion. Sublingual misoprostol of 600?ug or vaginal misoprostol of 800?ug may be a good choice for the first dose. The ideal dose and medication interval of misoprostol however needs to be further researched.