A meta-analysis of the effects of intramuscular and intravenous injection of oxytocin on the third stage of labor.

BACKGROUND: Clinical studies and trials have shown that oxytocin can effectively reduce postpartum bleeding, whether by intramuscular (IM) injection or intravenous (IV) injection. These two methods are widely used in the prevention and treatment for the third stage of childbirth. However, it is unclear whether the subtle differences between the mode of these routes have any effect on maternal outcomes. OBJECTIVES: To systematically evaluate the efficacy and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labor after vaginal birth. METHODS: Computerized retrieval of PubMed, the Cochrane Library, Web of Science, Embase, and ClinicalTrials.gov was conducted to collect randomized controlled trials (RCT) on the effects of IM and IV oxytocin on the third stage of labor. After independent literature screening, data extraction and evaluation of the bias risk of included studies by two evaluators, RevMan 5.3 software was used for a meta-analysis. RESULTS: Six studies with 7734 women were included in this study. Meta-analysis results showed that: the severe postpartum hemorrhage (PPH) rate [risk ratio (RR) 1.54, 95% confidence interval (95% CI) 1.08-2.20, P = 0.02], PPH rate (RR 1.31, 95% CI 1.11-1.55, P = 0.001), incidence of blood transfusion (RR 2.30, 95% CI 1.35-3.93, P = 0.002) and the need of manual removal of placenta (RR 1.44, 95% CI 1.05-1.96, P = 0.02) for IM group were higher than IV group, but there were no significant differences in the use of additional uterotonics (P = 0.31) and the incidence of serious maternal morbidity and adverse effects between two groups. None of the included studies reported maternal death. CONCLUSION: For clinical practice, intravenous injection oxytocin 10 IU may be a good, safe option in the management of the third stage of labor. Medical conditions, available resources, adverse effects, and women' s preferences should also be considered. If an IV line is already in place at delivery, IV administration may be preferable to IM injection.

Intramuscular injection, intravenous infusion, and intravenous bolus of oxytocin in the third stage of labor for prevention of postpartum hemorrhage: a three-arm randomized control trial.

BACKGROUND: Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes recommended equally and little discussion of potential differences between the two. This trial assesses the effectiveness and safety of 10 IU oxytocin administered as IM injection versus IV infusion and IV bolus during the third stage of labor for PPH prophylaxis. METHODS: In two tertiary level Egyptian maternity hospitals, women delivering vaginally without exposure to pre-delivery uterotonics were randomized to one of three prophylactic oxytocin administration groups after delivery of the baby. Blood loss was measured 1 h after delivery, and side effects were recorded. Primary outcomes were mean postpartum blood loss and proportion of women with postpartum blood loss ≥500 ml in this open-label, three-arm, parallel, randomized controlled trial. RESULTS: Four thousand nine hundred thirteen eligible, consenting women were randomized. Compared to IM injection, mean blood loss was 5.9% less in the IV infusion arm (95% CI: -8.5, - 3.3) and 11.1% less in the IV bolus arm (95% CI: -14.7, - 7.8). Risk of postpartum blood loss ≥500 ml in the IV infusion arm was significantly less compared to IM injection (0.8% vs. 1.5%, RR = 0.50, 95% CI: 0.27, 0.91). No side effects were reported in any arm. CONCLUSIONS: Intravenous oxytocin is more effective than intramuscular injection for the prevention of PPH in the third stage of labor. Oxytocin delivered by IV bolus presents no safety concerns after vaginal delivery and should be considered a safe option for PPH prophylaxis. TRIAL REGISTRATION: clinicaltrials.gov # NCT01914419 , posted August 2, 2013.

Comparison of the effect of breast pump stimulation and oxytocin administration on the length of the third stage of labor, postpartum hemorrhage, and anemia: a randomized controlled trial.

BACKGROUND: This study aimed to compare the effect of breast pump stimulation with that of oxytocin administration regarding the duration of the third stage of labor, postpartum hemorrhage, and anemia after delivery. METHODS: In this study, 108 women were randomly assigned to two groups of breast pump stimulation (n = 54) and oxytocin administration (n = 54). Women in the breast stimulation group received breast pump stimulation (10 min intermittently for each breast with a negative pressure of 250 mmHg), while the women in the oxytocin (control) group received an infusion of 30 IU oxytocin in 1000 mL of Ringer's serum with a maximum rate of 10 mL infusion per min after delivery. The duration of the third stage of labor, blood loss during the third stage of labor and 24 h after delivery, hemoglobin and hematocrit (before and 24 h after delivery), after-birth pain, and the number of breastfeedings during the 24 h after delivery were recorded. The data were analyzed using the chi-square test, independent t-test, and Wilcoxon test. RESULTS: The mean duration of the third stage was 5 ± 1.97 and 5.4 ± 2.5 min in the breast stimulation and women that received intravenous oxytocin respectively (p = 0.75). Most participants had mild postpartum hemorrhage (98.1 and 96.2% in the breast stimulation and women that received intravenous oxytocin, respectively, p = 0.99). Although hemoglobin and hematocrit levels significantly decreased in both groups 24 h after delivery, there was no significant difference between both groups regarding both parameters. After-birth pain was significantly lower and the number of breastfeeding during the 24 h after delivery was significantly more in the breast stimulation group compared to the control group. CONCLUSIONS: Our results demonstrated no differences between breast pump stimulation and oxytocin administration regarding the duration of the third stage of labor, postpartum hemorrhage, anaemia, after-birth pain, and the number of breastfeedings during the 24 h after delivery. TRIAL REGISTRATION NUMBER: The study protocol was registered in the Iranian Randomized Controlled Trial Registry (Ref. No.: IRCT2015050722146N1 ; Registration date: 2015-11-04). The study was registered prospectively and the enrollment date was 23/8/2015.

[Active management of the third stage of labor: Three schemes of oxytocin: randomised clinical trial]. / Tratamiento activo del tercer periodo del trabajo de parto: tres esquemas de oxitocina.

OBJECTIVE: To compare the effectiveness of intramuscular oxytocin against intravenous oxytocin against intravenous traditional oxytocin infusion, in the active management of the third period of the delayed impingement labor work and controlled cord traction. METHODS: Randomized controlled blinded clinical trial. In women age 14 to 40 with full term pregnancy, childbirth attended by ISSSTE's Regional Hospital "Gral. Ignacio Zaragoza", in the period from August to December 2015. RESULTS: 152 deliveries were attended, from which 66 fulfill with selection criteria. Group 1 = 22 patients, group 2 = 21 patients and Group 3 = 23 patients. The total age average was 26.92 + 5.8. For blood volume, statistical differences were significant among the three groups (p = 0.000). Adverse reactions were presented in 1 .5%, without difference between the groups. (P = 0.337). The differences in hemoglobin values and final and initial hematocrit presented differences with statistical significance (p = 0.000 for both). CONCLUSIONS: Nonetheless, the differences obtained in the analysis of the diverse variables among the three types of treatment, the three schemes are effective on the obstetrical hemorrhage prevention.

The ED90 of prophylactic oxytocin infusion after delivery of the placenta during cesarean delivery in laboring compared with nonlaboring women: an up-down sequential allocation dose-response study.

BACKGROUND: Prophylactic administration of oxytocin as a part of active management of the third stage of labor reduces the risk of postpartum hemorrhage. Prophylactic oxytocin is often administered as an infusion rather than a bolus. The aim of the current up-down sequential allocation dose-response study was to test the hypothesis that parturients who receive intrapartum exogenous oxytocin therapy, and who subsequently undergo cesarean delivery for labor dystocia, will have a higher estimated effective dose in 90% of paturients (ED90) for oxytocin infusion in the third stage of labor compared with nonlaboring parturients. METHODS: The study design was a single-blinded, dual-arm, dose-response study using a 9:1 biased-coin sequential allocation method to estimate the ED90 of an infusion of prophylactic oxytocin in women undergoing cesarean delivery with neuraxial anesthesia. The experimental (laboring) group included women scheduled for intrapartum cesarean delivery after prior exposure to exogenous oxytocin, and the control (nonlaboring) group included women scheduled for elective cesarean delivery. The starting infusion rate was 18 IU/h, with an incremental dose of 2 IU/h. The outcome was satisfactory uterine tone 4 minutes after delivery as judged by the obstetrician. Secondary outcomes included requirement for additional uterotonic agents and maternal side effects (e.g., nausea and vomiting, ST-segment depression). Dose-response data for each group were evaluated by a log-logistic function and ED90 estimates derived from the fitted equations using the delta method. RESULTS: Thirty-eight and 32 subjects participated in the nonlaboring and laboring groups, respectively. The oxytocin ED90 was significantly greater for the laboring group (44.2 IU/h [95% confidence interval (CI), 33.8-55.6]) compared with that for the nonlaboring group (16.2 IU/h [95% CI, 13.1-19.3]; difference in dose 28 IU/h [95% CI of difference, 26-29, P < 0.001]). Significantly more women in the laboring group (34%) than in the nonlaboring group (8%) required supplemental uterotonic agents (difference 26% [95% CI of the difference, 7%-44%, P = 0.008]). The overall incidence of side effects was greater in the laboring group (69%) than in the nonlaboring group (34%; difference 25% [95% CI of the difference, 10%-59%, P = 0.004]). CONCLUSIONS: Women with prior exposure to exogenous oxytocin require a higher initial infusion rate of oxytocin to prevent uterine atony after cesarean delivery than women without prior exposure.

Prevention of postpartum haemorrhage: cost consequences analysis of misoprostol in low-resource settings.

BACKGROUND: While inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of Essential Medicines for use in the prevention of postpartum haemorrhage (PPH) in low-resource settings. This study evaluates the costs and health outcomes of use of oral misoprostol to prevent PPH in settings where injectable uterotonics are not available. METHODS: A cost-consequences analysis was conducted from the international health system perspective, using data from a recent Cochrane systematic review and WHO's Mother-Baby Package Costing Spreadsheet in a hypothetical cohort of 1000 births in a mixed hospital (40% births)/community setting (60% births). Costs were estimated based on 2012 US dollars. RESULTS: Using oxytocin in the hospital setting and misoprostol in the community setting in a cohort of 1000 births, instead of oxytocin (hospital setting) and no treatment (community setting), 22 cases of PPH could be prevented. Six fewer women would require additional uterotonics and four fewer women a blood transfusion. An additional 130 women would experience shivering and an extra 42 women fever. Oxytocin/misoprostol was found to be cost saving (US$320) compared to oxytocin/no treatment. If misoprostol is used in both the hospital and community setting compared with no treatment (i.e. oxytocin not available in the hospital setting), 37 cases of PPH could be prevented; ten fewer women would require additional uterotonics; and six fewer women a blood transfusion. An additional 217 women would experience shivering and 70 fever. The cost savings would be US$533. Sensitivity analyses indicate that the results are sensitive to the incidence of PPH-related outcomes, drug costs and the proportion of hospital births. CONCLUSIONS: Our findings confirm that, even though misoprostol is not the optimum choice in the prevention of PPH, misoprostol could be an effective and cost-saving choice where oxytocin is not or cannot be used due to a lack of skilled birth attendants, inadequate transport and storage facilities or where a quality assured oxytocin product is not available. These benefits need to be weighed against the large number of additional side effects such as shivering and fever, which have been described as tolerable and of short duration.

Synthetic oxytocin: looking beyond the benefits.

While the notion of drug abuse tends to be applied more to substances used outside of medical settings, there is increased concern that synthetic oxytocin is being overused in maternity care settings. This article presents an overview of some of the issues that have been raised within this area, including the risks that have been cited by recent research, social scientists and childbirth commentators, the concerns that are being anecdotally discussed by midwives and, even more importantly, the experiences of women themselves.

Postpartum haemorrhage management, risks, and maternal outcomes: findings from the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To explore the clinical practices, risks, and maternal outcomes associated with postpartum haemorrhage (PPH). DESIGN: Secondary analysis of cross-sectional data. SETTING: A total of 352 health facilities in 28 countries. SAMPLE: A total of 274 985 women giving birth between 1 May 2010 and 31 December 2011. METHODS: We used multivariate logistic regression to examine factors associated with PPH among all births, and the Pearson chi-square test to examine correlates of severe maternal outcomes (SMOs) among women with PPH. All analyses adjust for facility- and country-level clustering. MAIN OUTCOME MEASURES: PPH, SMOs, and clinical practices for the management of PPH. RESULTS: Of all the women included in the analysis, 95.3% received uterotonic prophylaxis and the reported rate of PPH was 1.2%. Factors significantly associated with PPH diagnosis included age, parity, gestational age, induction of labour, caesarean section, and geographic region. Among those with PPH, 92.7% received uterotonics for treatment, and 17.2% had an SMO. There were significant differences in the incidence of SMOs by age, parity, gestational age, anaemia, education, receipt of uterotonics for prophylaxis or treatment, referral from another facility, and Human Development Index (HDI) group. The rates of death were highest in countries with low or medium HDIs. CONCLUSIONS: Among women with PPH, disparities in the incidence of severe maternal outcomes persist, even among facilities that report capacity to provide all essential emergency obstetric interventions. This highlights the need for better information about the role of institutional capacity, including quality of care, in PPH-related morbidity and mortality.

Oral misoprostol versus oxytocin in the management of third stage of labour.

OBJECTIVES: To compare oral misoprostol versus intramuscular oxytocin in the management of third stage of labour. METHODS: The quasi-experimental study was conducted at the Obstetrics and Gynaecology Unit II, Civil Hospital, Karachi, from June 20 to December 19, 2006. A total of 70 patients diagnosed in active phase of labour who fulfilled the inclusion criteria were selected by non-probability convenience sampling. These patients were divided into 2 groups of 35 patients each, for Oxytocin (Group 1) and misoprostol (Group 2). Main and secondary outcome measures were analysed. SPSS 10 was used for statistical analysis. RESULTS: Average amount of blood loss(ml) was 267.14 +/- 140.35 with Oxytocin versus 302.86 +/- 160.4, with Misoprostol, this difference was statistically insignificant (p = 0.236). Average drop in haemoglobin concentration (g/dl) with Oxytocin was 1.55 +/- 0.38 vs 1.66 +/- 0.61 with Misoprostol (p = 0.684). Drop in haematocrit (%) was 4.18 +/- 0.64 with Oxytocin vs. 4.50 +/- 0.92 with Misoprostol (p = 0.133). There was also insignificant difference in duration of third stage of labour, between oxytocin and Misoprostol groups (5.37 +/- 2.20 vs. 5.23 +/- 2.46, p = 0.451) Shivering, in Misoprostol group occured in n = 11 (31.4%) vs n = 3 (8.6%) with Oxytocin (p = 0.017) and pyrexia in n = 6 (17.1%) with misoprostol vs n = 0, with oxytocin (p = 0.025) thus significantly higher in misoprostol group. CONCLUSION: There were no major differences in oral misoprostol and intramuscular oxytocin in the management of third stage of labour.

Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage.

BACKGROUND: Active management of the third stage of labour has been shown to reduce the risk of postpartum haemorrhage (PPH) greater than 1000 mL. One aspect of the active management protocol is the administration of prophylactic uterotonics, however, the type of uterotonic, dose, and route of administration vary across the globe and may have an impact on maternal outcomes. OBJECTIVES: To determine the effectiveness of prophylactic oxytocin at any dose to prevent PPH and other adverse maternal outcomes related to the third stage of labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials including pregnant women anticipating a vaginal delivery where prophylactic oxytocin was given during management of the third stage of labour. The primary outcomes were blood loss > 500 mL and the use of therapeutic uterotonics. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, assessed trial quality and extracted data. Data were checked for accuracy. MAIN RESULTS: This updated review included 20 trials (involving 10,806 women). Prophylactic oxytocin versus placebo Prophylactic oxytocin compared with placebo reduced the risk of PPH greater than 500 mL, (risk ratio (RR) 0.53; 95% confidence interval (CI) 0.38 to 0.74; six trials, 4203 women; T² = 0.11, I² = 78%) and the need for therapeutic uterotonics (RR 0.56; 95% CI 0.36 to 0.87, four trials, 3174 women; T² = 0.10, I² = 58%). The benefit of prophylactic oxytocin to prevent PPH greater than 500 mL was seen in all subgroups. Decreased use of therapeutic uterotonics was only seen in the following subgroups: randomised trials with low risk of bias (RR 0.58; 95% CI 0.36 to 0.92; three trials, 3122 women; T² = 0.11, I² = 69%); trials that performed active management of the third stage (RR 0.39; 95% CI 0.26 to 0.58; one trial, 1901 women; heterogeneity not applicable); trials that delivered oxytocin as an IV bolus (RR 0.57; 95% CI 0.39 to 0.82; one trial, 1000 women; heterogeneity not applicable); and in trials that gave oxytocin at a dose of 10 IU (RR 0.48; 95% CI 0.33 to 0.68; two trials, 2901 women; T² = 0.02, I² = 27%). Prophylactic oxytocin versus ergot alkaloids. Prophylactic oxytocin was superior to ergot alkaloids in preventing PPH greater than 500 mL (RR 0.76; 95% CI 0.61 to 0.94; five trials, 2226 women; T² = 0.00, I² = 0%). The benefit of oxytocin over ergot alkaloids to prevent PPH greater than 500 mL only persisted in the subgroups of quasi-randomised trials (RR 0.71, 95% CI 0.53 to 0.96; three trials, 1402 women; T² = 0.00, I² = 0%) and in trials that performed active management of the third stage of labour (RR 0.58; 95% CI 0.38 to 0.89; two trials, 943 women; T² = 0.00, I² = 0%). Use of prophylactic oxytocin was associated with fewer side effects compared with use of ergot alkaloids; including decreased nausea between delivery of the baby and discharge from the labour ward (RR 0.18; 95% CI 0.06 to 0.53; three trials, 1091 women; T² = 0.41, I² = 41%) and vomiting between delivery of the baby and discharge from the labour ward (RR 0.07; 95% CI 0.02 to 0.25; three trials, 1091 women; T² = 0.45, I² = 30%). Prophylactic oxytocin + ergometrine versus ergot alkaloids: There was no benefit seen in the combination of oxytocin and ergometrine versus ergometrine alone in preventing PPH greater than 500 mL (RR 0.90; 95% CI 0.34 to 2.41; five trials, 2891 women; T² = 0.89, I² = 80%). The use of oxytocin and ergometrine was associated with increased mean blood loss (MD 61.0 mL; 95% CI 6.00 to 116.00 mL; fixed-effect analysis; one trial, 34 women; heterogeneity not applicable).In all three comparisons, there was no difference in mean length of the third stage or need for manual removal of the placenta between treatment arms. AUTHORS' CONCLUSIONS: Prophylactic oxytocin at any dose decreases both PPH greater than 500 mL and the need for therapeutic uterotonics compared to placebo alone. Taking into account the subgroup analyses from both primary outcomes, to achieve maximal benefit providers may opt to implement a practice of giving prophylactic oxytocin as part of the active management of the third stage of labour at a dose of 10 IU given as an IV bolus. If IV delivery is not possible, IM delivery may be used as this route of delivery did show a benefit to prevent PPH greater than 500 mL and there was a trend to decrease the need for therapeutic uterotonics, albeit not statistically significant.Prophylactic oxytocin was superior to ergot alkaloids in preventing PPH greater than 500 mL; however, in subgroup analysis this benefit did not persist when only randomised trials with low risk of methodologic bias were analysed. Based on this, there is limited high-quality evidence supporting a benefit of prophylactic oxytocin over ergot alkaloids. However, the use of prophylactic oxytocin was associated with fewer side effects, specifically nausea and vomiting, making oxytocin the more desirable option for routine use to prevent PPH.There is no evidence of benefit when adding oxytocin to ergometrine compared to ergot alkaloids alone, and there may even be increased harm as one study showed evidence that using the combination was associated with increased mean blood loss compared to ergot alkaloids alone.Importantly, there is no evidence to suggest that prophylactic oxytocin increases the risk of retained placenta when compared to placebo or ergot alkaloids.More placebo-controlled, randomised, and double-blinded trials are needed to improve the quality of data used to evaluate the effective dose, timing, and route of administration of prophylactic oxytocin to prevent PPH. In addition, more trials are needed especially, but not only, in low- and middle-income countries to evaluate these interventions in the birth centres that shoulder the majority of the burden of PPH in order to improve maternal morbidity and mortality worldwide.

How effective are the components of active management of the third stage of labor?

BACKGROUND: Active management of the third stage of labor is recommended for the prevention of post-partum hemorrhage and commonly entails prophylactic administration of a uterotonic agent, controlled cord traction, and uterine massage. While oxytocin is the first-choice uterotonic, it is not known whether its effectiveness varies by route of administration. There is also insufficient evidence regarding the value of controlled cord traction or uterine massage. This analysis assessed the independent and combined effectiveness of all three interventions, and the effect of route of oxytocin administration on post-partum blood loss. METHODS: Secondary data were analyzed from 39202 hospital-based births in four countries and two clinical regimens: one in which oxytocin was administered following delivery of the baby; the other in which it was not. We used logistic regression to examine associations between clinical and demographic variables and post-partum blood loss ≥ 700 mL. RESULTS: Among those with no oxytocin prophylaxis, provision of controlled cord traction reduced hemorrhage risk by nearly 50% as compared with expectant management (P < 0.001). Among those with oxytocin prophylaxis, provision of controlled cord traction reduced hemorrhage risk by 66% when oxytocin was intramuscular (P < 0.001), but conferred no benefit when oxytocin was intravenous. Route of administration was important when oxytocin was the only intervention provided: intravenous administration reduced hemorrhage risk by 76% as compared with intramuscular administration (P < 0.001); when combined with other interventions, route of administration had no effect. In both clinical regimens, uterine massage was associated with increased hemorrhage risk. CONCLUSIONS: Recommendations for active management of the third stage of labor should account for setting-related differences such as the availability of oxytocin and its route of administration. The optimal combination of interventions will vary accordingly.

A behavioral intervention to improve obstetrical care.

BACKGROUND: Implementation of evidence-based obstetrical practices remains a significant challenge. Effective strategies to disseminate and implement such practices are needed. METHODS: We randomly assigned 19 hospitals in Argentina and Uruguay to receive a multifaceted behavioral intervention (including selection of opinion leaders, interactive workshops, training of manual skills, one-on-one academic detailing visits with hospital birth attendants, reminders, and feedback) to develop and implement guidelines for the use of episiotomy and management of the third stage of labor or to receive no intervention. The primary outcomes were the rates of prophylactic use of oxytocin during the third stage of labor and of episiotomy. The main secondary outcomes were postpartum hemorrhage and birth attendants' readiness to change their behavior with regard to episiotomies and management of the third stage of labor. The outcomes were measured at baseline, at the end of the 18-month intervention, and 12 months after the end of the intervention. RESULTS: The rate of use of prophylactic oxytocin increased from 2.1% at baseline to 83.6% after the end of the intervention at hospitals that received the intervention and from 2.6% to 12.3% at control hospitals (P=0.01 for the difference in changes). The rate of use of episiotomy decreased from 41.1% to 29.9% at hospitals receiving the intervention but remained stable at control hospitals, with preintervention and postintervention values of 43.5% and 44.5%, respectively (P<0.001 for the difference in changes). The intervention was also associated with reductions in the rate of postpartum hemorrhage of 500 ml or more (relative rate reduction, 45%; 95% confidence interval [CI], 9 to 71) and of 1000 ml or more (relative rate reduction, 70%; 95% CI, 16 to 78). Birth attendants' readiness to change also increased in the hospitals receiving the intervention. The effects on the use of episiotomy and prophylactic oxytocin were sustained 12 months after the end of the intervention. CONCLUSIONS: A multifaceted behavioral intervention increased the prophylactic use of oxytocin during the third stage of labor and reduced the use of episiotomy. (ClinicalTrials.gov number, NCT00070720 [ClinicalTrials.gov]; Current Controlled Trials number, ISRCTN82417627 [controlled-trials.com].).

Use of oxytocin during early stages of labor and its effect on active management of third stage of labor.

OBJECTIVE: The purpose of this study was to evaluate whether the use of oxytocin during the first and second stages of labor is associated with a higher incidence of postpartum hemorrhage (PPH) in pregnant women who received active management of third stage of labor (AMTSL). STUDY DESIGN: A secondary data analysis from vaginal deliveries in a hospital-based cohort study from 24 maternity hospitals in South America. The primary outcomes that were analyzed were moderate PPH (≥500 mL of blood loss), severe PPH (≥1000 mL of blood loss), and need of blood transfusion. RESULTS: A total of 11,323 vaginal deliveries were included. The incidence of moderate and severe PPH was 10.8% and 1.86%, respectively. Overall, 36% of deliveries received AMTSL. There was no association between induced/augmented labor and moderate PPH (P = .753), severe PPH (P = .273), and blood transfusion (P = .603) in the population that received AMTSL. CONCLUSION: AMTSL should be recommended, regardless of whether pregnant women received oxytocin during the first and second stages of labor.

Rectal versus oral misoprostol for active management of third stage of labor: a randomized controlled trial.

AIM OF THE STUDY: To test that rectal misoprostol is effective for active management of third stage of labor, and probably with less side effects than oral misoprostol. MATERIALS AND METHODS: As much as 658 patients were randomly allocated to receive either 600 µg misoprostol orally or rectally 5 min after cord clamping and cutting. The primary outcome was incidence of postpartum hemorrhage. Secondary outcomes included amount of blood loss, duration of third stage of labor, incidence of side effects, pre- and post-delivery hemoglobin, and the use of additional uterotonics. RESULTS: A total of 331 patients received 600 µg of misoprostol orally, while 327 rectally. Both groups were comparable in demographic data and neonatal outcome. Oral misoprostol was associated with significantly more blood loss than rectal (P = 0.016). Shivering and pyrexia occurred in 161 (52.1%) and 86 (27.8%) women receiving oral misoprostol, and in 81 (26.2%) and 47 (15.2%) of those who received rectal misoprostol, respectively (P = 0.000 and 0.001). CONCLUSION: Rectal misoprostol is effective in the management of third stage of labor, and with a significant decrease in side effects. Lesser dose and other routes could be explored in the future.

Carbetocin versus syntometrine in the management of third stage of labor following vaginal delivery.

OBJECTIVE: To assess and compare the efficacy and safety of a single intramuscular dose of carbetocin to a single intramuscular dose of syntometrine in managing the third stage of labor following vaginal delivery among women with low risk factors for postpartum hemorrhage. STUDY DESIGN: Prospective double-blind randomized controlled study. SUBJECTS AND METHODS: The study included 240 healthy women with viable normal singleton pregnancies achieving normal vaginal delivery at or beyond 37 weeks' gestation during the period from May 2009 to December 2009 at TAIBA Hospital in Kuwait. Women were randomized to receive either a single dose of carbetocin or syntometrine intramuscularly following the delivery of the anterior shoulder of the baby. Outcome measures compared included postpartum hemorrhage requiring additional uterotonic therapy, incidence of postpartum hemorrhage, amount of intrapartum blood loss as well as adverse effects profile. RESULTS: There was a statistically highly significant difference in the estimated mean blood loss between the carbetocin and syntometrine groups, with a blood loss of 81.5 ml higher in the syntometrine group. The mean drop of hemoglobin concentration 24 h after delivery was 0.8 g/dl in carbetocin group and 1.1 g/dl in syntometrine group, and the difference was statistically highly significant. Women in the carbetocin group were less likely to experience nausea and vomiting. CONCLUSION: Single dose of intramuscular carbetocin 100 µg may be more effective as compared to a single intramuscular dose of syntometrine in reducing postpartum blood loss with a smaller drop in hemoglobin levels and less adverse effects.

Timing of prophylactic uterotonics for the third stage of labour after vaginal birth.

BACKGROUND: Administration of the uterotonic drugs is one of the main components of the active management of the third stage of labour. The timing of uterotonics varies considerably across the globe and it may have significant implications on the well-being of the mothers and their babies. OBJECTIVES: To assess the effect of the timing of administration of prophylactic uterotonics (before compared to after placental delivery) on the outcomes related to the third stage of labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009). SELECTION CRITERIA: Randomised controlled trials examining the timing of prophylactic uterotonic drugs in the third stage of labour. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked MAIN RESULTS: We included three trials involving 1671 participants; oxytocin was the only uterotonic drug that was used. The dose and route of administration of oxytocin varied among the included studies. Administration of oxytocin before and after the expulsion of placenta does not significantly influence the incidence of postpartum haemorrhage (blood loss greater than 500 ml) (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.62 to 1.04; n = 1667, three trials); retained placenta (RR 1.54, 95% CI 0.76 to 3.11; n = 1667, three trials); length of third stage of labour (minutes) (mean difference (MD) -0.30, 95% CI -0.95 to 0.36; n = 1667, three trials); postpartum blood loss (ml) (MD 22.32, 95% CI -58.21 to 102.86; n = 181, two trials); changes in haemoglobin (g/dL) (MD 0.06, 95% CI -0.60 to 0.72; n = 51, one trial); blood transfusion (RR 0.79, 95% CI 0.23 to 2.73; n = 1667, three trials); the use of additional uterotonics (RR 1.10, 95% CI 0.80 to 1.52; n = 1667, three trials); the incidence of maternal hypotension (RR 2.48, 95% CI 0.23 to 26.70; n = 130, one trial) and the incidence of severe postpartum haemorrhage (blood loss 1000 ml or more) (RR 0.98, 95% CI 0.48 to 1.98; n = 130, one trial). No data on other maternal or neonatal outcome measures were available. AUTHORS' CONCLUSIONS: Administration of oxytocin before and after the expulsion of placenta did not have any significant influence on many clinically important outcomes such as the incidence of postpartum haemorrhage, rate of placental retention and the length of the third stage of labour. However, the number of available studies were limited. The only uterotonic drug used was oxytocin, mainly through intravenous infusion, therefore its extrapolation to other routes of administration should be interpreted cautiously. More studies are required to examine other maternal and neonatal outcomes using consistent approaches.

Carbetocin versus rectal misoprostol for management of third stage of labor among women with low risk of postpartum hemorrhage.

OBJECTIVE: To compare effectiveness and safety of carbetocin and misoprostol for prevention of postpartum hemorrhage (PPH) among low-risk women. METHODS: Randomized controlled trial among 150 pregnant women with low risk of PPH admitted for vaginal delivery at Kasr Al Ainy Hospital, Cairo, Egypt, between July 2018 and May 2019. Participants were assigned to two groups by a web-based randomization system ensuring allocation concealment. After neonatal delivery, the carbetocin group received one ampoule of carbetocin (100 µg/mL) intravenously and the misoprostol group received two rectal tablets of misoprostol (800 µg) for active management of the third stage. Blood pressure, blood loss, and hemoglobin levels were monitored. The primary outcome measure was need for additional uterotonic drugs. RESULTS: The carbetocin group had significantly less blood loss (P<0.001), shorter third stage (P<0.001), and less need for additional uterotonics (P=0.013) or uterine massage (P=0.007). The two drugs were hemodynamically safe. Hemoglobin levels after delivery were comparable in the two groups (P=0.475). Adverse effects were more common in the misoprostol group (P<0.001). CONCLUSION: Among low-risk women, carbetocin seems to be a better alternative to misoprostol for active management of the third stage of labor; it reduced blood loss and use of additional uterotonic drugs. CLINICALTRIALS.GOV: NCT03556852.

Misoprostol to prevent and treat postpartum haemorrhage: a systematic review and meta-analysis of maternal deaths and dose-related effects.

OBJECTIVE: To review maternal deaths and the dose-related effects of misoprostol on blood loss and pyrexia in randomized trials of misoprostol use for the prevention or treatment of postpartum haemorrhage. METHODS: We searched the Cochrane Controlled Trials Register and Pubmed, without language restrictions, for '(misoprostol AND postpartum) OR (misoprostol AND haemorrhage) OR (misoprostol AND hemorrhage)', and we evaluated reports identified through the Cochrane Pregnancy and Childbirth Group search strategy. Randomized trials comparing misoprostol with either placebo or another uterotonic to prevent or treat postpartum haemorrhage were checked for eligibility. Data were extracted, tabulated and analysed with Reviewer Manager (RevMan) 4.3 software. FINDINGS: We included 46 trials with more than 40,000 participants in the final analysis. Of 11 deaths reported in 5 trials, 8 occurred in women receiving >or= 600 microg of misoprostol (Peto odds ratio, OR: 2.49; 95% confidence interval, CI: 0.76-8.13). Severe morbidity, defined as the need for major surgery, admission to intensive care, organ failure or body temperature >or= 40 degrees C, was relatively infrequent. In prevention trials, severe morbidity was experienced by 16 of 10,281 women on misoprostol and by 16 of 10,292 women on conventional uterotonics; in treatment trials, it was experienced by 1 of 32 women on misoprostol and by 1 of 32 women on conventional uterotonics. Misoprostol recipients experienced more adverse events than placebo recipients: 8 of 2070 versus 5 of 2032, respectively, in prevention trials, and 5 of 196 versus 2 of 202, respectively, in treatment trials. Meta-analysis of direct and adjusted indirect comparisons of the results of randomized trials showed no evidence that 600 microg are more effective than 400 microg for preventing blood loss > 1000 ml (relative risk, RR: 1.02; 95% CI: 0.71-1.48). Pyrexia was more than twice as common among women who received > 600 microg rather than 400 microg of misoprostol (RR: 2.53; 95% CI: 1.78-3.60). CONCLUSION: Further research is needed to more accurately assess the potential beneficial and harmful effects of misoprostol and to determine the smallest dose that is effective and safe. In this review, 400 microg of misoprostol were found to be safer than > 600 microg and just as effective.

Optimization of third-stage management after second-trimester medical pregnancy termination.

OBJECTIVE: Comparison of 3 regimens for third-stage management after second-trimester intravaginal misoprostol termination. STUDY DESIGN: Prospective randomized trial. Three third-stage management strategies were compared: 10 units of intramuscular oxytocin (group 1), 600 microg oral misoprostol (group 2), or no additional medication (group 3) after fetal expulsion. Primary study outcome was the incidence of placental retention. RESULTS: Two hundred fifty-one women were randomly assigned to the groups. There was a significant difference in placental retention rates: group 1, 8 of 83 (10%) vs group 2, 24 of 83 (29%) vs group 3, 26 of 85 (31%); P = .002. Blood loss was significantly lower in group 1, 100 mL (interquartile ranges, 50-200) vs group 2, 200 mL (interquartile ranges, 100-370) vs group 3, 200 mL (interquartile ranges, 100-375); P < .001. Requirement for blood transfusion: group 1, 1 of 83 (1%) vs group 2, 1 of 83 (1%) vs group 3, 5 of 85 (6%); P = .103. CONCLUSION: Intramuscular oxytocin administered after fetal delivery after second-trimester medical termination significantly increases placental expulsion rates and decreases short-term postpartum blood loss.

A randomized controlled trial of prophylactic sublingual misoprostol versus intramuscular methyl-ergometrine versus intramuscular 15-methyl PGF2alpha in active management of third stage of labor.

OBJECTIVE: To compare the efficacy and side effects of 0.2 mg methyl-ergometrine IM, 400 microg misoprostol sublingual and 125 microg 15 methyl PGF2alpha IM in active management of third stage of labor. METHOD: Two hundred low risk pregnant women with induced or spontaneous labor were randomized to receive either 400 microg misoprostol sublingually or 0.2 mg methyl-ergometrine intramuscularly or 125 microg 15-methyl PGF2alpha intramuscularly, after the delivery of anterior shoulder of baby. The main outcome measures were: blood loss more than 500 ml, need for additional oxytoxic drug, change in hemoglobin level and side effects due to drugs. RESULTS: The median estimated blood loss, blood loss more than 500 ml, need for additional oxytocic drug and change in hemoglobin levels were similar in all three groups. The significant side effects in the misoprostol group were shivering, pyrexia (temperature > 38 degrees C) and vomiting, which were self-limiting. Diarrhea was significantly more in the 15 methyl PGF2alpha group. Three women in methyl-ergometrine group underwent manual removal of placenta. One woman in misoprostol group received blood transfusion. CONCLUSION: Sublingual misoprostol appears to be as effective as intramuscular methyl-ergometrine and intramuscular 15-methyl PGF2alpha in the prevention of postpartum hemorrhage. It can be a good alternative in resource poor setting.